Paediatrics booklet by John Snow, Inc

YINQABA

The Kingdom of Swaziland

SWAZILAND PAEDIATRIC HIV/AIDS TREATMENT GUIDELINES 2006

MOHSW aids

N LA

SNAP

OG RA MME

I SWAZ

R NA TION AIDS P AL

Swaziland Paediatric HIV/AIDS Treatment Guidelines 2007

Ministry of Health and Social Welfare

Acknowlwedgements The Paediatric HIV/AIDS Treatment guidelines has been put together by a dedicated team of clinicians and partners, with the expert help of the WHO consultant paediatrician Dr. Hilda Mujuru from Zimbabwe. The in-country leading team was composed of the following: 1. 2. 3. 4. 5. 6.

Dr. Delouis Terlonge Dr. Joris Vandelanotte Dr. Raymond Byaruhanga Dr. Fabian Mwanyumba Dr. Mohammed Ali Mahdi Dr. Velephi Okello

- Baylor Children's Centre of Excellence Clinic, Mbabane - ICAP - ICAP - UNICEF - EGPAF - National ART Co-ordinator SNAP

Further consultations were made from the following team of clinicians: 1. Dr. Augustine Ntilivamunda - WHO 2. Dr. Joyce Mareverwa - Paediatrician Good Shepherd Hospital 3. Dr. Patrick Okoth - Mbabane Government Hospital 4. Dr. Getahun - Raleigh Fitkin Memorial Hospital 5. Dr. Simba Takuva - Mbabane Government Hospital 6. Dr. Rosemary Mukasa - National TB Programme 7. Dr. Peggy Chibuye - EGPAF 8. Dr. Akingba - Mbabane Government Hospital 9. Dr. Yohannes Ghebrengus - Raleigh Fitkin Memorial Hospital 10. Dr. Ganizani Mlawanda - Mbabane Government Hospital 11. Dr. Sikhathele Mazibuko - Mbabane Government Hospital 12. Dr. Kamal Mohammed - Sithobela Health Centre 13. Dr. B. Radebe - Simunye Health Services 14. Ms. Faith Dlamini - NERCHA 15. Ms. Sibongile Mndzebele - M&E SNAP 16. Ms. Rejoice Nkambule - HTC SNAP 17. Ms. Bonisile Nhlabatsi - PMTCT 18. Mr. Richard Walwema - National Reference Laboratory 19. Matron Abigail Shongwe - Piggs Peak Government Hospital Finally, we would like to acknowledge WHO Country Office for their technical and financial support throughout the development process for these guidelines.

Foreword The Ministry of Health and Social Welfare has realized the plight of the children infected with HIV and AIDS in the country and is thus stepping up efforts to reduce the number of children who are infected with HIV through mother to child transmission. Prevention of mother to child transmission is therefore a priority to ensure that children born to HIV positive mothers are HIV free and healthy. The clinical management of children infected with HIV and AIDS has been difficult due to the lack of comprehensive guidelines for paediatric HIV and AIDS treatment, lack of capacity among health workers to provide quality care for these children and inadequate choice of paediatric ARV drugs from which to choose from. These paediatric guidelines have been developed through consultations with the medical personnel in the different health care facilities in the country and with partners involved in improving the health of children in the country. It is therefore based on experience of paediatric ART in resource-limited settings and considers what works for the situation of Swaziland. The new guidelines also take into account the new developments in paediatric HIV and AIDS in the world, and considers the use of new types of ARV drug combinations that are expected to be easier to adhere to by children on ART. Also covered in these guidelines are issues around the care and treatment of adolescents, as the number of perinatally HIV infected children growing into adolescence is increasing. It is also worth noting that as this is an evolving era, new information is constantly becoming available and as this happens, the information will be made available to the users of these guidelines. The understanding of these guidelines will be further complimented by capacity building of health workers on paediatric HIV and AIDS. It is expected that trainings of health workers will continue to cover a greater percentage of the health workers involved in ART service delivery in the country, which will help to improve the care of children with HIV and AIDS in Swaziland. Finally, we would like to thank the dedicated team that worked tirelessly to produce these paediatric guidelines, the first of its kind in Swaziland.

Abbreviations 3TC ABC AFASS AFB AIDS ALT ANC ART ARV AST AZT BAL BCG BD BSA CD4 CDC cm CMV CNS CrAg CSF CT CTX CXR d4T ddl dl DNA DPT E EFV ELISA FBC FDC g INH Hb HBV HCW HIV HSV ICD IM IMCI IMR

Lamivudine, Epivir Abacavir, liagen Acceptable, feasible, affordable, sustainable and safe Acid Fast Bacilli Acquired Immune Deficiency Syndrome Alanine aminotransferase Ante natal care Anti-Retroviral Therapy Anti-RetroViral Aspartate Amino Transferase Zidovudine, Retrovir Broncho Alveolar Lavage Bacille de Calmette et Guerin Twice per Day Body Surface Area Cluster of Differentiation Center for Disease Control Centimeter Cytomegalovirus Central Nervous System Cryptococcal Antigen Cerebrospinal Fluid Computed Tomography Co-trimoxazole, Bactrim, Septrin Chest x-ray Stavudine, Zerit Didanosine, Videx Deciliter Deoxyribonucleic Acid Diphteria Pertussis Tetanus Ethambutol Efavirenz, Sustiva Enzyme-Linked ImmunoSorbent Assay Full Blood Count Fixed Dose Combination Gram Isoniazide Hemoglobin Hepatitis B Virus Health Care Worker Human Immunodeficiency Virus Herpes Simplex Virus Immune Complex Dissociated Intramuscular Integrated Management of Childhood Illnesses Infant Mortality Rate

iii

INH IRIS IU IV Kg LGE LIP LP LPV/r LTB m² MAC Mg Ml mm³ MOHSW MRI MTCT NNRTI NPA NPEP NRTI NVP OD OI PCP PCR PEP PGL PI PML PMTCT PO PPD Qid R RNA RTHC SD STI TB TDS TLC TMP TMP-SMX TST UN

Isoniazid Immune reconstitution inflammatory syndrome Intemational Units intravenous kilograms Lineal gingival erythema Lymphoid Interstitial Pneumonitis lumbar puncture lopinavir boosted with ritonavir (Kaletra) Laryngeotracheobronchitis meters squared Mycobacterium Avium Complex milligrams milliliter millimeters cubic Ministry of Health and Social Welfare magnetic resonance imaging Mother To Child Transmission Non-Nucleoside Reverse Transcriptase Inhibitor Nasal Pharyngeal Aspirate non-occuptional post exposure prophylaxis Nucleoside Reverse Transcriptase Inhibitor nevirapine, Viramune once per day Opportunistic Infection Pneumocystis Jirovecii (Carinii) Pneumonia Polymerase Chain Reaction Post Exposure Prophylaxis Persistent Generalised Lymphadenopathy Protease Inhibitor Progressive Multifocal leukoencephalopathy Prevention of Mother To Child Transmission orally Purified Protein Derivate four times a day Rifampicin Ribonucleic Acid Road To Health Card Standard deviation Sexually Transmitted Infection Tuberculosis three times a day Total Lymphocyte Count Trimethoprim Trimethoprim- Sulfamethoxazole Tuberculin Skin Testing United Nations

UNAIDS UNICEF URTI WHO ZDV Z-N Z

Joint United Nations Program on HIV/AIDS United Nations Children's Fund Upper Respiratory Tract Infection World Health Organization zidovudine, Retrovir (AZT) Ziehl Nielsen Pyrazinamide

Table of Contents Acknowledgements Foreword Abbreviations List of tables List of figures List of Appendices

i ii iii viii ix x

Chapter 1: Introduction

Chapter 2: Care of the HIV exposed child 4 2.1 Infant Diagnosis 5 A. Diagnosis of HIV infection in children less than 18 months old 5 B. Establishing HIV infection with antibody testing in children 18 months of age and older 7 2.2 Contrimoxazole Prophylaxis 9 A. Who should receive Cotrimoxazole and for how long 9 B. Cotrimoxazole dosage 9 C. Contra indications to use of cotrimoxazole 10 D. Information for parents 10 E. Reaction to contrimoxazole 10 2.3 Suggested follow up schedule for the HIV exposed child 10 2.4 Natural History of HIV in children 12 A. Rapid progressors - 25% 12 B. Intermediate progressors - 50-70% 12 C. Slow down progressors - 5-10% 12 Chapter 3: Care of the HIV infected child 3.1 Identify HIV infected children 3.2 Clinical staging 3.3 Immunological staging A. Cd4 cell counts B. Total Lymphocyte Count 3.4 Deciding when to initiate ART A. Cd4 percentage is available B. Cd4 cell count/percentage is not available 3.5 ART preparation A. History B. Physical exam C. Initial evaluation and laboratory tests D. Counselling screening E. Discolsure to the child

13 13 14 16 16 16 17 17 18 19 19 19 20 20 21

3.6 Eligibility for ART A. Clinical criteria B. Social Criteria 3.7 Antiretroviral therapy (ART) A. Recommended first line regimen B. Monitoring patients on ART C. Substitution D. Treatment failure: when to switch (change) to 2nd line treatment E. Recommemned 2nd line treatment in cases of treatment failure 3.8 TB in HIV infection A. Signs and symptoms suggestive of TB B. Diagnosis C. Scoring system for the diagnosis of TB in children D. Treatment of TB E. ART in TB/HIV co-infected children

22 22 22 22 23 23 24 25 27 28 28 28 29 29 29

Chapter 4: Nutrition in HIV 4.1 Causes of poor nutritional status in HIV infected children 4.2 Assessment of the nutritional status 4.3 Nutritional rehabilitation 4.4 Infant feeding A. The different feeding options

32 32 32 33 33 33

Chapter 5: Care and treatment for adolescents 5.1 Risk factors for HIV Infection 5.2 Counselling and Disclosure 5.3 Medical management of Adolescents 5.4 Adolescent needs in Swaziland

36 36 37 37 37

Chapter 6: Non-occupational post-exposure prophylaxis 6.1 Rationale for PEP for non-occupational exposure to HIV 6.2 Management of non-occupational exposure to HIV 6.3 Counselling and Testing 6.4 Monitoring

40 40 40 41 42

vii

List of Tables Table 1: Table 2: Table 3: Table 4: Table 5: Table 6: Table 7: Table 8: Table 9: Table 10: Table 11: Table 12: Table 13: Table 14: Table 15: Table 16: Table 17: Table 18:

Dosage for Cotrimoxazole prophylaxis (given once daily) Suggested follow up schedule and content of visits for exposed infants and children Mortality rates for untreated HIV infected children Clinical signs and symptoms suggestive of HIV infection in children according to specificity WHO clinical staging for infants and children with established HIV infection WHO classification of HIV associated in immunodeficiency in infants and children Total lympocyte Count (TLC) criteria of severe HIV immunodeficiency requiring initiation of ART for use in infants and children with clinical stage 2 and where Cd4 measurement is not available. Recommendations for ART initiation according to WHO paediatric stage and age when Cd4 cell count/perecntage is available Recommendations for ART initiation according to WHO paediatric stage when Cd4 cell/count/percentage is not available Clinical criteria for presumptive diagnosis of severe HIV disease in infants and children less than 18 months of age requiring ART in situations where virological testing is not available. Minimum and suggested baseline laboratory tests Suggested ART preparation counselling sessions. Routine follow up visit schedule for infants and children on ART Severe toxicities in infants and children associated with specific first-line ARV drugs and suggested first-line drug substitutions Using the WHO Paediatric Clinical Staging System to guide decision-making regarding switching to second-line therapy for treatment failure Scoring system for the diagnosis of TB in children (a score of 7 or more indicates a high likelihood of TB). Source: South African National TB Control Program Practical Guidelines 2004 Guidelines for the initiation for PEP Laboratory monitoring of patients on PEP

viii

9 11 12 13 15 16 16 17 18 18 20 20 23 25 26 29 40 42

List of Figures Figure 1: Figure 2: Figure 3: Figure 4: Figure 5: Figure 6: Figure 7:

HIV diagnosis in infants and young children less than 18 months who are not breastfeeding 6 HIV diagnosis in infants and young children less than 18 months who are breastfeeding 7 HIV diagnosis in non breastfeeding children of 18 months or older 8 HIV diagnosis in breastfeeding children of 18 months or older 8 Follow-up schedule exposed infants 11 IMCI check list for HIV infection in children 14 Algorithm for evaluation and treatment of possible non-occupational HIV esposure 41

List of Appendices Appendix 1: Appendix 2: Appendix 3: Appendix 4: Appendix 5:

Presumptive and Definitive Criteria For Recognizing And Treating HIV/AIDSRelated Clinical Events In Infants And Children With Established HIV Infection Drug Formulation and Dosages Serious Acute and Chronic Toxicities due to ARV Drugs that ma\y require therapy modification Side effects (Adverse Events) of Antiretroviral Agents Sexual Maturity (Tanner Staging) in adolescents

Chapter 1: Introduction About 2.3 million children below the age of 15 years are living with HIV/AIDS and 2.1 million of them are in SubSaharan Africa. There are 16 000 children living with HIV/AIDS in Swaziland and an estimated 65 000 AIDS orphans (UNAIDS 2004 Report). Swaziland's infant mortality rate (IMR) is 108 per 1000 live births and under 5 mortality is 156 per 1000 live births (2004) (UNICEF SOWC 2006). HIV related mortality contributes significantly to both the IMR and Under 5 mortality. It is paramount that the HIV prevention, treatment and care of children are scaled up if significant reduction in childhood mortality is to be achieved. The majority of children get HIV infection through mother to child transmission (MTCT). This accounts for >95% of infections in children. There is 10% risk of transmission in utero, 20% intrapartum (labour and delivery), and 15 - 20% post-partum during breastfeeding. In Swaziland, the HIV prevalence among pregnant women is 39.2% (National surveillance, 2006) and the annual number of deliveries is estimated to be about 40,000. Therefore approximately 17,000 babies will be born to HIV-infected mothers and an estimated 6,800 of these will be HIV infected. Even HIV-negative infants born to HIV-infected mothers have a 2- to 5-fold increased risk of mortality as a direct consequence of the mother's HIV infection (either severe disease or early death). Prevention of HIV infection is paramount if efforts to reduce HIV in children are to succeed. Swaziland has adopted the WHO strategic 4-prong approach to the prevention of HIV infection in women and infants: ? Prong 1: primary prevention of HIV-infection ? Prong 2: prevention of unintended pregnancies among HIV positive women ? Prong 3: Reduction of MTCT among HIV positive pregnant women ? Prong 4: Care and support for HIV positive women and their families Details on the implementation of these 4 prongs can be found in the national PMTCT guidelines. The other modes of HIV transmission to children include: ? Sexual abuse by infected person ? HIV contaminated blood and blood products ? Use of non-sterile instruments ? Traditional scarifications ? Wet nursing by an infected person (breastfeeding by woman other than the biological mother)

Chapter 2: Care of the HIV exposed child An HIV-exposed infant is 1. An infant who is born to an HIV-positive mother or 2. An infant who tests positive for HIV antibodies even if the mother's status is unknown HIV exposure can be established by: 1. Confirming the HIV status of the mother (either tested during PMTCT) 2. If status of the mother is unknown and mother is available: counsel and test mother to confirm HIV exposure status of child 3. If the mother is not available: counsel the caregiver and do a rapid test on the child to confirm the HIV exposure status (for children < 18 months)

Children above 18 months who are HIV antibody positive are HIV infected HIV exposed infants and children should be followed up and managed according to The TenPoint Package for Comprehensive Paediatric AIDS Care: 1. Confirm HIV status as early as possible 2. Monitor the child's growth and development 3. Ensure that immunizations are started and completed according to the recommended schedule 4. Provide prophylaxis for opportunistic infections (PCP, MAC, and TB) 5. Actively look for and treat infections early 6. Counsel the mother and family on

Optimal infant feeding to minimize Maternal to Child Transmission (MTCT), prevent malnutrition and promote growth and development

Good personal and food hygiene to prevent common infections. Encourage the caretaker to seek prompt treatment for any infections or other health related problems

When the child should be followed up 7. 8. 9. 10.

Conduct WHO staging for the infected child Offer antiretroviral (ARV) treatment for the infected child, if eligible Provide psychosocial support to the infected child and mother Refer the infected child for higher levels of specialized care if necessary, or for other social- or community-based support programs

2.1. Infant Diagnosis

HIV exposed children have maternal antibodies passively transferred to them from their mother. These maternal antibodies are no longer detectable in the baby after 18 months of age. The tests used to detect antibodies are the Rapid and ELISA tests. If performed before 18 months, these tests may detect maternal and/or infant antibodies and therefore cannot confirm infection in the baby. However, antibody tests done after 18 months detect infection in the baby as maternal antibodies should have been cleared. In non breastfeeding infants or after cessation of breastfeeding for at least 3 months, an HIV antibody test should be done at 12 months; if negative then the baby is not HIV infected. A repeat antibody test should be done at 18 months. Ideally virological testing should be done for definitive diagnosis of HIV infection in children < 18 months of age. This will confirm infection if the test is positive. A negative test only confirms absence of infection if the child is not breastfeeding or at least 3 months after cessation of breastfeeding. Breastfeeding babies continue to be at risk of HIV transmission through breast milk. The virological tests that can be done are HIV DNA PCR, HIV RNA PCR, and ICD p24. Availability of these tests is still limited in Swaziland. HIV DNA PCR is the test of choice for the Ministry of Health and Social Welfare and will be made available in 2007. These tests are more reliable if done from the age of 6 weeks (usual post natal visit). Virological tests should therefore be done as early as possible from 6 weeks of age. The purpose of early infant diagnosis is to identify children who are HIV infected, so that they can start ART early. Waiting until 18 months to confirm the diagnosis using antibody tests is often too late. In the absence of virological testing, a presumptive HIV diagnosis based on clinical criteria can be made pending a confirmatory test. In all circumstances, regular close clinical monitoring of HIV exposed infants is critical. Do not delay referral to an ART centre for CD4 assessment and care and treatment if the child has The purpose of early infant ? growth retardation (slower than expected diagnosis is to identify HIV growth or failure to thrive) infected children, so that they ? delayed development or loss of can start care and treatment developmental milestones ? clinical signs or symptoms suggestive of AIDS

A. Diagnosis of HIV infection in children less than 18 months old Figure 1 and Figure 2 on pages 6 and 7 are flow charts that assists with the steps to take to confirm HIV infection in children <18 months depending on whether or not they are breastfeeding if virological tests are available. In absence of virological testing, a presumptive diagnosis can be made based on clinical criteria

Non Breastfeeding Infant Virological test from 6 weeks

Positive

Negative

Child is HIV infected Plan for care, treatment and support

Child is presumed not HIV infected Do antibody test at 12 months

Negative

Positive

Child is not HIV infected

Repeat antibody test after 18 months of age

Negative

Positive

Child is not HIV infected

Child is HIV infected Plan for care, treatment and support

Repeat antibody test after 18 months

Figure 1: HIV diagnosis in infants and young children less than 18 months who are not breastfeeding.

Breastfeeding Infant Virological test from 6 weeks

Positive

Negative

Child is HIV infected Plan for care, treatment and support

At 12 months: did cessation of breastfeeding occur at least 3 months earlier? Yes

Do antibody test

Antibody test 3 months after complete cessation of breastfeeding

Negative

Positive

Repeat antibody test 18 months

Child is not HIV infected

Positive

Negative Child is not HIV infected

Repeat antibody test after 18 months(confirmation)

Child is HIV infected Plan for care, treatment and support

Figure 2: HIV diagnosis in infants and young children less than 18 months who are breastfeeding.

B. Establishing HIV infection with antibody testing in children 18 months of age and older In children older than 18 months of age, do the following: 1. Confirm HIV infection using antibody testing. 2. A child that is confirmed HIV antibody positive (i.e. two positive Rapid tests such as Determine and Unigold or positive ELISA) is HIV infected. 3. Refer all HIV infected children for treatment, care and support 4. A negative antibody test implies that the child is not HIV infected. However, if the child is still breastfeeding, she/he is still exposed to HIV infection, so repeat HIV antibody testing at least 3 months after complete cessation of breastfeeding.

Non-Breastfeeding Infant HIV antibody test

Positive

Negative

Child is HIV infected Plan for care, treatment and support

Child is not HIV infected

Figure 3: HIV diagnosis in non breastfeeding children of 18 months or older.

Breastfeeding Infant HIV antibody test

Negative

Positive Child is HIV infected Plan for care, treatment and support

Repeat HIV test at least 3 months after complete cessation of breastfeeding

Positive

Negative

Child is HIV infected Plan for care, treatment and support

Child is not HIV Infected

Figure 4: HIV diagnosis in breastfeeding children of 18 months or older.

2.2 Cotrimoxazole Prophylaxis

Cotrimoxazole prophylaxis prevents Pneumocystis jiroveci Pneumonia (PCP), toxoplasmosis and other bacterial infections in HIV positive children. All infants exposed to HIV must receive prophylactic cotrimoxazole.

A. Who Should Receive Cotrimoxazole and for how long?

All HIV exposed infants (all infants whose mothers are known to be HIV positive) § From 6 weeks of age § Until HIV infection has been definitely ruled out (see infant diagnosis) AND the child is no longer breastfeeding

All HIV infected children below 5 years of age § From time of HIV diagnosis All HIV infected children > 5 years of age § From time of HIV diagnosis § With clinical signs and symptoms suggestive of HIV infection § Indefinitely if there is no ART available for the child § Until the child has evidence of immune restoration under ART (CD4 > 350 at least 6 months after ART initiation – see chapter on ART)

B. Cotrimoxazole Dosage The dosage for Cotrimoxazole prophylaxis is given in table 1. Dosage can be either according to weight or according to age. Give Cotrimoxazole syrup or Cotrimoxazole tablets (the tablets can be crushed). Once daily Weight (kg)

Age

strength Oral suspension Pediatric tablet Single tablet 100/20 200/40 per 5 ml 400/80

< 6 months

2.5 ml

5 - 15kg

6 months - 5 years

5 ml

15 - 30

5 - 15 years

10 ml

30kg ³

>15 years

<5kg

Table 1: Dosage for Cotrimoxazole prophylaxis (given once daily)

C. Contra Indications To Use Of Cotrimoxazole Cotrimoxazole should not be given to children with: Sulfa allergy Severe renal or liver insufficiency

D. Information For Parents Cotrimoxazole prevents serious infections. It helps your child feel better and live longer. It is not an antiretroviral treatment. It does not cure AIDS. The dose will increase when your child grows. Use either a spoon or a syringe to measure the dose You can crush a tablet and mix it with food before giving it to your child You can give cotrimoxazole with or without food Some children develop adverse reactions to cotrimoxazole. Bring the child back if he/she develops a serious rash

E. Reactions To Cotrimoxazole Stop cotrimoxazole if the child has a severe reaction. Dapsone 2mg/kg can be used as an alternative to cotrimoxazole. Desensitisation can be done with cotrimoxazole being introduced gradually under medical supervision. WHO recommends desensitization in adolescents but not in younger children. Desensitization should not be attempted in individuals with a history of Grade 4 severe reaction to cotrimoxazole or any other sulfa drugs.

2.3 Suggested follow up schedule for the HIV-exposed child

Follow up should be well planned. Exposed children should be followed up monthly in their first year of life. Always check the mother's own health during the follow up visits and ensure that she also gets appropriate care and support. Encourage the mother to come with her other children on her next visit. Assess and provide care to the siblings as needed. The suggested follow up visit schedule is provided in table 2 (see next page):

Counsel the mother on feeding issues and care of the newborn § Weigh the child § Counsel and assist with any feeding issues § Counsel the mother on HIV testing. Take blood for a virological test (if available) § Monitor growth and development. Weigh baby and chart the weight on RTHC § Full clinical examination for any signs suggestive of HIV infection § Immunisation—give all due immunizations HBV 1, DPT 1, POLIO 1 § If BCG not given at birth, do not give it if baby symptomatic § Start cotrimoxazole prophylaxis § Health education: §

2 weeks 6 weeks

10 weeks

14 weeks

Monthly visits after 14 weeks

On general hygiene § Seeking treatment early for any illness in both mother and baby § Counsel mother on feeding issues § Provide results of virological test (if tested at 6 weeks). Counsel the mother (If virological test § not done at 6 weeks, counsel and test the baby.) Monitor growth and development. Weigh baby and chart the weight on RTHC § Full clinical examination for any signs suggestive of HIV infection § Immunisations - give all due immunizations HBV 2, DPT 2, POLIO 2 § Cotrimoxazole prophylaxis if HIV positive, HIV negative and still breastfeeding or status § unknown General Health Education § Counsel mother on feeding issues § Counsel and test the baby (if virological tests available and not already done) or provide results § if tests already done Growth and development monitoring – weigh and plot weight on RTHC § Full examination for any signs suggestive of HIV infection § Immunisations – give all due immunizations HBV 3, DPT 3, POLIO 3 § Cotrimoxazole prophylaxis if HIV positive, HIV negative and still breastfeeding or status § unknown General Health Education § Growth and development monitoring: weigh and plot on RTHC § Full examination for any signs suggestive of HIV infection § Cotrimoxazole prophylaxis §

Table 2: Suggested follow-up schedule and content of visits for exposed infants and children

DNA PCR

HIV rapid test Monthly

Birth 2 wks 6 wks 10 wks 14 wks

12 m

3 Monthly

HIV rapid test

18 m

24 m Yearly

Immunisations Cotrimoxazole Prophylaxis Figure 5: Follow-up schedule exposed infants

Please note: All HIV exposed and infected children should receive all the scheduled immunisations. HIV-infected children who have signs and symptoms of AIDS should receive all immunizations except BCG.

Exposed children need to be referred for assessment (clinical and CD4) when they: Have a growth retardation (slower than expected growth or failure to thrive) Have delayed development or lose developmental milestones Have clinical signs or symptoms suggestive of AIDS Try to establish if an infant is infected as early as possible, to provide appropriate care and treatment.

2.4 Natural History of HIV in children The natural history of HIV in children (without any intervention) shows that the progression of disease differs in children. Three distinct groups have been identified.

A. Rapid Progressors – 25% These children develop early onset CNS involvement and OIs with CD4 lymphopenia in the first year of life. The majority of them die within the first year of life and almost all of them by the second year of life.

B. Intermediate Progressors – 50 -70% These children are asymptomatic for the first 4/5 years of life.

C. Slow Progressors – 5-10% These children are asymptomatic for 8/10 years. It is therefore important to continuously assess children of any age for HIV infection, have a high index of suspicion, and consider provider initiated counselling and testing and cotrimoxazole prophylaxis. Mortality in HIV infected children is very high. Studies in resource-constrained countries indicate that the risk of death is 52.5% at 2 years and 66-75% at 5 years in untreated HIV-infected infants. Delayed diagnosis of HIV infection, poor nutrition, and high levels of severe bacterial respiratory and gastrointestinal tract infections are likely reasons for the higher early mortality. The majority of children are Failure to identify HIV- infected children early results in the following HIV/AIDS mortality rates based on age (Newell et al, 2004 and Spira et al, 1999) At 1 year At 2 year At 5 year At 10 years

35.2% 52.5% 66 – 75% 85%

Table 3: Mortality rates for untreated HIV infected children.

either rapid or intermediate progressors.

It is important that infected children are identified early and given appropriate care, treatment and support

Chapter 3: Care of the HIV infected Child 3.1.Identify HIV infected children

HIV infected children can be identified through: PMTCT program § Exposed children with growth or developmental retardation § Symptomatic children identified on clinical examination during follow up of the exposed child. § Asymptomatic children who had a positive virological test § positive rapid test or ELISA after 18 months (If breastfeeding repeat the ELISA 612 wks after cessation of breastfeeding) Routine medical care via Provider-Initiated Testing and Counselling § Symptomatic children identified during routine clinical care on inpatients admissions or outpatients visit e.g. immunization visits or any other medical visits. PEP program. § Confirmed HIV positive children identified during post exposure prophylaxis care following sexual abuse or other exposures. The table below summarizes clinical signs that may suggest HIV infection and assist in identifying HIV infected children. Specificity for HIV Infection

Signs/conditions very specific to HIV infection

Signs/conditions common in HIV-infected children and uncommon in uninfected children

Signs/conditions common in HIV-infected children but also common in ill uninfected children

Signs/Conditions § Pneumocystis jiroveci Pneumonia (PCP) § Oesophageal candidiasis § Extrapulmonary cryptococcosis § Invasive salmonella infection § Lymphoid interstitial pneumonitis § Herpes zoster (shingles) with multi-dermatomal involvement § Kaposi’s sarcoma § Lymphoma § Progressive multifocal encephalopathy § Severe bacterial infections, esp. if recurrent § Persistent or recurrent oral thrush § Bilateral painless parotid enlargement § Generalized persistent non-inguinal lymphadenopathy § Hepatosplenomegaly (in non-malaria endemic areas) § Persistent and/or recurrent fever § Neurologic dysfunction § Herpes zoster (shingles), single dermatome § Persistent generalized dermatitis unresponsive to treatment § Chronic, recurrent otitis with ear discharge § Persistent or recurrent diarrhoea § Severe pneumonia § Tuberculosis § Bronchiectasis § Failure to thrive § Marasmus

Table 4: Clinical signs and symptoms suggestive of HIV infection in children according to specificity

IMCI guidelines can also be used to identify children with possible HIV infection, start them on cotrimoxazole prophylaxis and arrange for HIV testing. If identified using the IMCI algorithm, these children can be further assessed, staged and provided with appropriate treatment and care (see IMCI guidelines for further details). Consider symptomatic HIV Infection in every child found to have: Recurrent diarrhoea or persistent diarrhoea Acute ear infection (with pus discharge) Fever for more than 30 days Low weight/growth faltering.

Ask

Has the child had more than one episode of severe chest infection requiring antibiotics (pneumonia) in the past 3 months? Has the child had one or more episodes of persistent or acute diarrhoea in the past 3 months?

Any Three signs: Symptomatic HIV infection

Has the child had fever (recurrent or intermittent) for more than one month? Does the child have acute or chronic or recurrent ear infection? History or evidence of past or present herpes zoster?

Classify As

History or evidence of severe seborrheic dermatitis? History of TB in the child? Mother known to be HIV positive?

Then look and feel Has the child a low weight-for-age or is growth faltering? (weight curve flat or falling for 2 consecutive months)

Two signs or fever: HIV infection unlikely

Any enlarge lymp glands in more than one of the following sites: neck, axillae groins? Is there oral thrush? Is there Parotid enlargement?

Figure 6: IMCI check list for HIV infection in children

3.2 Clinical staging

Always stage HIV-infected children when you assess them, at every visit. This helps to: See the clinical progression of disease Assists with decision making on commencement of ART even without CD4 counts. Assists in assessing clinical improvement on ART. Assists in providing a prognosis for the child

Primary HIV infection Asymptomatic Acute retroviral syndrome Clinical Stage 1 Asymptomatic Persistent generalized lymphadenopathy Clinical Stage 2 Unexplained persistent hepatosplenomegaly Papular pruritic eruptions Extensive wart virus infection Extensive molluscum contagiosum Recurrent oral ulcerations Unexplained persistent parotid enlargement Lineal gingival erythema Herpes zoster Recurrent or chronic upper respiratory tract infections (otitis media, otorrhoea, sinusitis, tonsillitis ) Fungal nail infections Clinical Stage 3 Moderate unexplained malnutrition not adequately responding to standard therapy Unexplained persistent diarrhoea (14 days or more) Unexplained persistent fever (above 37.5 intermittent or constant, for longer than one month) Persistent oral candida (outside first 6- 8 weeks of life) Oral hairy leukoplakia Acute necrotizing ulcerative gingivitis/periodontitis Lymph node TB Pulmonary tuberculosis Severe recurrent presumed bacterial pneumonia Symptomatic lymphoid interstitial pneumonitis Chronic HIV-associated lung disease including bronchiectasis Unexplained anaemia (<8g/dl), neutropenia (<500/mm3) or chronic thrombocytopenia (<50 000/ mm3) HIV-associated cardiomyopathy or HIV-associated nephropathy Clinical Stage 4 Unexplained severe wasting, stunting or severe malnutrition not responding to standard therapy Pneumocystis pneumonia Recurrent severe presumed bacterial infections (e.g. empyema, pyomyositis, bone or joint infection, meningitis, but excluding pneumonia) Chronic herpes simplex infection; (orolabial or cutaneous of more than one month's duration or visceral at any site) Extrapulmonary tuberculosis* Kaposi sarcoma Oesophageal candidiasis (or candida of trachea, bronchi or lungs) Central nervous system toxoplasmosis (outside the neonatal period) HIV encephalopathy Cytomegalovirus (CMV) infection; retinitis or CMV infection affecting another organ, with onset at age over 1 month. Extrapulmonary cryptococcosis including meningitis Disseminated endemic mycosis (extrapulmonary histoplasmosis, coccidiomycosis, penicilliosis) Chronic Cryptosporidiosis Chronic Isosporiasis Disseminated non-tuberculous mycobacteria infection Acquired HIV-associated rectal fistula Cerebral or B cell non-Hodgkin lymphoma Progressive multifocal leukoencephalopathy

*This excludes lymph node TB which is Clinical Stage 3 disease Table 5: WHO clinical staging for infants and children with established HIV infection

3.3 Immunological staging HIV infected infants and children should be monitored regularly with CD4 cell counts/percentages to measure HIV associated immunodeficiency. If CD4 cell counts/percentages are not available, then Total Lymphocyte Counts (TLC) can be used.

A. CD4 Cell Counts The criteria for immunological staging for infants and children change with age. Use CD4 percentages for children 5 years and below. Age-related CD4 values Classification of HIV-associated immunodeficiency

< 11 months (%) > 35

12 - 35 months (%) > 30

Mild

30 - 35

25 - 30

20 - 25

350 - 499

Advanced

25 - 30

20 - 25

15 - 20

200 - 349

Not significant

Severe (%) Severe (CD4 count)

36 - 59 months (%) > 25

> 5 years (cells/mm3) > 500

<25

<20

<15

<15%

<1500

<750 cells/mm 3

<350 cells/mm 3

<200 cells/mm3

cells/mm 3

Table 6: WHO classification of HIV associated immunodeficiency in infants and children.

Start ART in infants and children classified as severe HIV associated immunodeficiency, regardless of clinical stage. CD4 percentages below the indicated levels of severe HIV associated immunodeficiency are associated with increased risk of disease progression and mortality.

B. Total Lymphocyte Count When CD4 is not available, total lymphocyte count (TLC) can be used to complement the clinical staging in deciding to initiate ART especially in children with stage 2 disease. TLC is used in children below 8 years of age (table 7). Immunological marker Total Lymphocyte Count (TLC)

<11 months

Age-specific recommendation to initiate ART 12 -35 months 36 - 59 months 5 - 8 years

<4000 cells/mm 3

<3000 cells/mm3

<2500 cells/mm3

<2000 cells/mm3

Table7: Total Lymphocyte Count (TLC) criteria of severe HIV immunodeficiency requiring initiation of ART for use in infants and children with clinical stage 2 and where CD4 measurement is not available.

A drop of TLC below the significantly increases the risk of disease progression and mortality. TLC is only used to monitor disease progression and ART initiation; it is not used for monitoring children who are already on ART.

3.4. Deciding when to initiate ART

Decisions on when to start ART are based on clinical (clinical staging, see table 5) and immunological (CD4 percentage TLC, see table 6 & 7) assessment. Recommendations on when to start depend on the availability of CD4 and on the age of the child.

Initiating ART is not an emergency

A. Cd4 percentage is available The following children should start ART: All children with clinical stage 3 or 4 disease, irrespective of CD4 count/percentage Children with clinical stage 1 or 2 disease, if the CD4 immunological stage is â&#x20AC;&#x153;severeâ&#x20AC;?. It is important to identify, treat and stabilise any opportunistic infection before initiating ART. It is important to obtain a baseline CD4 cell count at ART start, even if the CD4 is not required to start ART. The recommendations are summarised in Table 8 Who paediatric stage

Age- specific treatment recommendation

Treat all

CD4 guided

Table 8: Recommendations for ART initiation according to WHO paediatric stage and age, when CD4 cell count/percentage is available.

B. Cd4 Cell Count/percentage is Not Available. All children in stage 3 or 4 should be started on ART. Children in stage 2 should be started based on TLC (see table 7). The recommendations are summarised in Table.9 Who paediatric stage

treatment recommendation

Treat all

TLC guided

Do not treat

Table 9: Recommendations for ART initiation according to WHO paediatric stage when CD4 cell/count/percentage is not available.

In children less than 18 months, a presumptive diagnosis can be made as per WHO recommendation below if virological tests are not available but there is a confirmed Rapid or ELISA antibody test. HIV infection in the child should be confirmed as early as is possible. A presumptive diagnosis of severe HIV disease should be made if: The infant is confirmed HIV antibody positive; And Diagnosis of any AIDS-indicator condition(s) can be made or The infant is symptomatic with two or more of the following: Oral thrush; Severe pneumonia; Severe sepsis. Other factors that support the diagnosis of severe HIV disease in an HIV seropositive infant include: Recent HIV-related maternal death or advanced HIV disease in the mother CD4 < 20%. Confirmation of the diagnosis of HIV infection should be sought as soon as possible Table 10: Clinical criteria for presumptive diagnosis of severe HIV disease in infants and children less than 18 months of age requiring ART in situations where virological testing is not available.

3.5. ART preparation

ART should never be started as an emergency. The principles of ART are: Ensure that patient satisfies eligibility criteria Provide ongoing support to the patient and family to maintain adherence ARV drugs are not a cure for HIV. However, when both patients and healthcare providers use them properly they are associated with excellent quality of life.

ART has limitations: Drug interactions and drug resistance may decrease the potency of ARV drugs Patients must adhere to Patients on ART may develop adverse drug ART to avoid treatment reactions failure and drug Patients must take at least 95% of their pills to resistance minimize the emergence of drug resistance, which may result in treatment failure. Adherence is the key to successful therapy. In fact, patients with adherence between 70 and 89% have the highest likelihood of developing resistance. Therefore patients must be counselled on the importance of nothing less than 100% adherence. Health care workers must thoroughly assess and examine infants and children and their caregivers before starting ART. This assessment and examination includes:

A. History Identify one or two caregivers who will provide care and treatment to the child Thorough patient medical history History of TB/ household contact Nutritional assessment Psychosocial assessment Assess adherence to medication already provided to the child (e.g. CTX) Assess the accessibility of supportive processes, such as counselling services, nutritional supplements, cotrimoxazole prophylaxis and family support groups Provide care and treatment to the caregiver(s) if needed. Their health is particularly important for survival of the child.

B. Physical exam Vital signs Weight, length/height, and head circumference. Always plot the weight on the child's road to health chart (immunisation card) Complete clinical assessment including WHO staging Neurodevelopment assessment Exclude TB Sex Maturation Rating (Tanner Staging)

C. Initial evaluation and laboratory tests. The following laboratory investigations should be done as a baseline before ART initiation. Suggested additional baseline tests (can be done if tests are readily available)

Minimum baseline laboratory tests Hb

FBC

ALT/AST

Liver Function Tests (LFT)

Serum Creatinine

Electrolytes Pregnancy Test

CD4

Viral Load PPD, Mantoux test

Table 11: Minimum and suggested baseline laboratory tests

Do a Chest X ray (CXR) if there are clinical indications.

D. Counselling and screening Health care workers must screen and counsel patients and caregivers to ensure eligibility and readiness for ART. This usually takes a few visits and counselling sessions. A minimum of 3-4 pre-ART sessions is usually needed. Depending on different factors sometimes more sessions are needed. A general guide of visits is given below, but this should be flexible depending on individual patient needs. Counselling for the correct use of suspensions might need even more sessions. Time

Activity

Assess eligibility for ART and prepare the caregiver and family in 3 counselling sessions. -6 weeks

Counselling 1

-4 weeks

Counselling 2

-2 weeks

Counselling 3 Counselling 4 Treatment Initiation-ART

0 weeks Table 12: Suggested ART preparation counselling sessions

Appropriate individual adherence counselling is one of the most essential elements of a successful anti-retroviral therapy program. Most occurrences of treatment failure occur due to poor adherence. Proper adherence counselling must include the following messages: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.

Basic education about HIV, the ARVs, and their function Education that HIV is now a chronic illness and is no longer fatal if treated and monitored properly That ARV drugs, once used properly, prolong survival and improve quality of life That better adherence to a regimen guarantees greater success of therapy That ARV drugs are not a cure for HIV, that they suppress the amount of HIV to a harmless level if taken properly That once started these drugs are taken for life Explanation and demonstration of correct administration of medicines to the child, especially use of syringes or measuring spoons or caps Explanation and demonstration of practical medication management tools (pill boxes, timers (e.g. cellphone reminders), medication diaries Mechanisms to cope with HIV/AIDS Emotional support should be provided to the care givers in order to deal with issues such as importance of positive living and to ensure that the educational and recreational needs of the child are met That ARVs have known side effects that require regular follow-up with a physician Education and motivation about responsible sexual behaviour, e.g. delay of sexual encounter or abstinence, use of safer sexual practices in adolescents and sexually active youth Awareness of safer options regarding reproduction and infant feeding (for young mothers) The caretaker must realize that the child should not be limited in participating in activities unless medically contraindicated by the health care worker The importance of financial and social support of the treatment The caretaker's role in the ARV therapy and adherence

Adherence counselling and support should be provided on an ongoing basis. Key messages should be repeated regularly. Counselling and support should continue even after the child started on ART.

E. Disclosure to the child Disclosing the HIV status to the child is a very important but sensitive issue. Disclosure should start as soon as the child's development allows. Research shows that at the age of 8 years, most children can be fully disclosed to. But the decision to disclose to a child should be tailored to the individual development of the child. Children should be counselled about HIV/AIDS and ART over time in an age-appropriate manner. It becomes more important to counsel a child on HIV/AIDS and ART if (s)he starts asking more questions about the disease or begins feeling different because of the disease.

Problems associated with delayed disclosure to children include: Failure to adhere to medications Poor coping skills Increase in risky behaviours Greater morbidity and mortality

3.6. Eligibility for ART ART eligibility depends on both clinical and social criteria.

A. Clinical Criteria These criteria were discussed in section on page 17.

B. Social Criteria These criteria are very important in order to ensure good adherence and treatment success. Ensure that the child has a primary caregiver who is counselled and takes responsibility for giving medications, bringing the child for review and the general upkeep of the child (nutrition, immunisations etc.) The family must identify a secondary caregiver to ensure good continued support for the child if the primary caregiver is not available. Both caregivers should be properly counselled and adequately prepared for ART. Patient should be on cotrimoxazole during the pre-art preparation period and adherence counselling and monitoring should be done. If an eligible patient meets these criteria and is ready to start ART, then you can initiate ART.

3.7 Antiretroviral therapy (ART) Three main classes of anti-retroviral drugs are commonly used: 1. Nucleoside reverse transcriptase inhibitors - NRTIs 2. Non-nucleoside reverse transcriptase inhibitors - NNRTIs 3. Protease Inhibitors - PIs It is recommended to start with 2 NRTIs and 1 NNRTI. PIs are usually reserved for 2nd line following treatment failure.

A. Recommended First Line Regimen The recommended first line regimen for Swaziland is d4T/3TC/NVP. The preferred d4T formulation is either as part of Fixed Drug Combination tablets or as pediatric capsules. The FDC tablets for children weighing 10 kg and above are available (Triomune 30, Triviro 30) If these are not available, then the child should be given d4T suspension, provided adequate storage (refrigeration) can be guaranteed. Reconstituted d4T suspension loses its potency after 24 hours if it is not refrigerated. If the family cannot provide adequate d4T storage, then the child should be given AZT instead of d4T.

Stavudine + Lamivudine + Nevirapine d4T + 3TC + NVP Children who have been exposed to ARV drugs during PMTCT or through breastfeeding should be started on the standard recommended treatment.

B. Monitoring Patients On Art Patients on ART need to be monitored regularly. Infants should be monitored monthly for clinical and laboratory assessment, adherence and weighing. Older children should be monitored monthly for the first 3 months (clinical and laboratory assessment, adherence and weighing). If they are stable there after, their weight and adherence should be monitored on a monthly basis. Clinical and laboratory assessment can be done at 3 months intervals. Monitoring visit 2 weeks after initiating therapy 4 weeks

8 weeks 12 weeks After 12 weeks:

Monthly 3 monthly

Specific Activities Step up the dose of NVP if no side effects Clinical evaluation Adherence monitoring Weighing of child Clinical evaluation Adherence monitoring Weighing of child Clinical evaluation Adherence monitoring Weighing of child Evaluation Weighing of child â&#x20AC;&#x201C; Adherence monitoring Clinical evaluation

6 monthly

Laboratory monitoring ALT FBC

ALT FBC CD4 ALT FBC

CD4, ALT, FBC

Table 13: Routine follow up visit schedule for infants and children on ART

Counseling sessions: children and their caretakers should be counselled every time they visit the facility. See counselling guidelines for further details.

Clinical Monitoring Clinical monitoring and evaluation at every visit should encompass: Complete clinical examination Developmental assessment Check weight, height and head circumference and update growth charts Ensure that medicines are being correctly administered and stored Check for any drug side effects or problems with the regimen Recheck and recalculate drug doses. Review and re-enforce adherence (proper adherence counselling done by all ART team members) Re-supply ART and Cotrimoxazole Treat any inter-current infections Normal monthly growth and development monitoring in Under 5s clinic should continue. Children can be followed up more regularly if need be. Laboratory Monitoring The schedule for laboratory monitoring is as follows: Cd4 count/percentage and viral load (where available) at 6-monthly intervals after the initial one. FBC and ALT at 2, 8 and 12 weeks then 6 monthly. Other tests may be done as clinically indicated

C. Substitution Substitution is the replacement of a drug that has caused toxicity with another drug from the same class that does not have the same adverse effects. An example in our situation would be stavudine (d4T) substitution for zidovudine (AZT) if anaemia occurs with AZT. The table on page 24 summarizes the toxicities of the first line drugs and the suggested substitutions. ART Toxicities/ Adverse Events (See Appendix 3) Moderate to severe ART toxicities may need substitution of the ARV responsible for the toxicity. This is not the same as changing (or switching) to 2nd line for treatment failure. Substitution can compromise future 2nd line regimens. Be careful in choosing the right drug. Contact an HIV paediatric specialist if in doubt.

First-line ARV drug AZT

NVP

3TC d4T

Most frequent significant toxicity for the ARV drug Severe anaemia or neutropaenia Lactic acidosis

Suggested first-line ARV drug substitution

d4T or ABC ABC Severe gastrointestinal intolerance d4T or ABC Acute symptomatic hepatitis EFV Preferred substitution by NRTI to: Hypersensitivity reaction 路 a third NRTI (disadvantage, may be less Severe or life-threatening rash potent) (Stevens-Johnson Syndrome or 路 PI (disadvantage, premature start of 2nd line ARV drug) No major toxicities in children except rarely pancreatitis Lactic acidosis ABC Peripheral neuropathy Pancreatitis AZT or ABC Lipoatrophy/metabolic syndrome

Table 14: Severe toxicities in infants and children associated with specific first-line ARV drugs and suggested firstline drug substitutions.

D. Treatment Failure: When To Switch (change) To 2nd Line Treatment Factors that contribute to treatment failure Poor adherence Inadequate drug levels Prior existing drug resistance or inadequate potency of the drugs chosen Genetic differences in drug metabolism Use of mixed formulations of same drug WHO recommends using clinical criteria to identify treatment failure. When Cd4 count/percentage is available, it is used in addition to the clinical assessment to define treatment failure. Before considering treatment failure it is important to ensure that: the child has received therapy for at least 6 months (24 weeks) adherence has been assessed as being optimal any intercurrent opportunistic infections have been identified and treated the child is receiving adequate nutrition When treatment failure is confirmed, it is necessary to switch to a second-line regimen

Treatment failure is identified based on clinical criteria supported by CD4 criteria

Treatment failure Based on Clinical Criteria Treatment failure should be considered when clinical symptoms that are suggestive of a more severe clinical stage develop in a child on therapy for at least 6 months. This usually presents as development of new or recurrent WHO Paediatric Clinical stage T3 or T4 events whilst the child is on ART (see table 5 on page 15). Lack of or decline in growth rate in children who show initial response to treatment (T3 or T4) Loss of neurodevelopmental milestones or development of encephalopathy (T4) Occurrence of new opportunistic infections, malignancies or recurrence of infections e.g. oral candidiasis refractory to treatment or oesophageal candidiasis (T3 or T4). WHO Clinical staging for infants or children on ART is designated in codes from T1 to T4. summarises the management options for children on ART who are assessed and staged according to T stage. Clinical stages in this table refer to a new or recurrent condition in the WHO clinical staging (see table 5 on page 15) at the time of evaluating the infant or child on ART. WHO Clinical Stage on ART No new events or PGL (T 1) New stage 2 events (T 2)

New stage 3 events (T 3)

New stage 4 event (T 4)

Management options

§ Do not switch to a new regimen § Maintain scheduled follow up § Treat and manage staging event § Do not switch to new regimen § Assess and offer adherence support § Assess nutritional status and offer support § Schedule earlier visit for clinical review and consider CD4 § Treat and manage staging event and monitor response § Check if on treatment 24 weeks or more § Assess and offer adherence support § Assess nutritional status and offer support § Check CD4 - where available § Consider switching regimen § Institute more frequent follow up § Treat and manage staging event § Check if on treatment 24 weeks or more § Assess and offer adherence support § Assess nutritional status and offer support § Document CD4 - where available § Switch regimen

Table 15: Using the WHO Paediatric Clinical Staging System to guide decision-making regarding switching to second-line therapy for treatment failure

Notes: Differentiation of opportunistic infections from immune reconstitution syndrome is important. In considering changing treatment because of growth failure, it should be ensured that the child is not failing to grow due to lack of adequate nutrition, and that any intercurrent infections have been treated and resolved.

Pulmonary or lymph node TB, Clinical Stage 3 conditions, may not be an indication of treatment failure, and thus not require consideration of second-line therapy; response to tuberculosis therapy should be used to evaluate the need for switching of therapy. CD4 is best performed once the acute phase of the presenting illness is resolved. Immunological Failure The basis for recognising treatment failure is clinical assessment. CD4 results supplement the clinical criteria. Base your decision on 2 different CD4 measurements before deciding to switch to a second line regimen. Consider treatment failure if: CD4 drops to values at or below the age related CD4 threshold levels (See page 16) Or Confirmed return of CD4 % to baseline Or More than 50% decline in CD4 % Or No improvement in CD4 values despite at least 6 months of therapy NOTE: CD4 but not TLC is used for monitoring and defining treatment failure. TLC, while useful in the absence of CD4 measurement to guide when to initiate therapy, should not be used for the evaluation of response to ARV therapy as change in TLC is a poor predictor of treatment success. Virological Failure Not currently recommended for use to change to 2nd line by WHO.

E. Recommended 2nd Line Treatment In Cases Of Treatment Failure Abacavir + Didanosine + Ritonavir boosted Lopinavir (ABC + ddI + Kaletra) Patients on 2nd line treatment need very close monitoring. Laboratory Investigations Laboratory investigations should be done as per monitoring schedule for first line regimens. A Lipid profile (Total Glycerides and Cholesterol) at 4 weeks and 6 monthly thereafter needs to be added to monitor PI toxicity (Kaletra) includes lipid profile since the 2nd line regimen includes a PI. Step Up Adherence Poor adherence has been identified as one of the major causes of treatment failure. It is therefore very important to step up adherence in patients with poor adherence (adherence less than 80%), clinical indications of treatment failure or patients who start a 2nd line treatment.

Suggestions for stepping up adherence are listed below: Re-educate the primary and secondary caregivers about the importance of adherence. Re-emphasize the long-term benefits Evaluate the support structures in place. § Are they appropriate? § How can they be improved? § What alternatives are there? Consider the use of pillboxes and/or daily dosing diary. Insist on caregiver participation in a support group Consider doing a psychological profile. Re-assess the family situation (through social worker and therapeutic counselor). Home visits where possible (spot pill counts to be done at home).

3.8 TB in HIV infection

Also see National TB guidelines

The incidence of TB infection has increased with the HIV pandemic. TB is the most common opportunistic infection among HIV-infected people and accounts for a third of HIV related deaths. The progression of TB from infection to active disease is more rapid in younger children than older children and adults. Recognition of TB is more difficult in children

A. Signs And Symptoms Suggestive Of TB Signs and symptoms in infants and children are often non-specific: Chronic cough Weight loss/ wasting/failure to thrive (always check the RTHC) Persistent fever Failure to respond to conventional antibiotics

B. Diagnosis It is difficult to make a diagnosis of TB in infants and children because: Poor sputum production Gastric washings give poor yield CXR is non-specific Tuberculin skin test - may not respond due to poor immunity A high index of suspicion is necessary: Contact with a person with TB or with signs and symptoms of TB in the household Suggestive clinical signs Sputum for Z-N stain for AFBs and TB culture TST (Mantoux) § Use 5 IU of PPD intradermally § Response >5 mm induration is considered positive. § Negative Mantoux does not exclude TB

CXR § Non specific § Hilar adenopathy § Infiltrative changes

C. Scoring System For The Diagnosis Of TB In Children Various scoring systems have been used to assist in screening and strengthening the likelihood of TB in children. Unfortunately these scoring systems have not been validated. An example of the South African scoring system that can be used is given below. Feature General Weeks of illness Nutritional Status (weight for age) Family history of TB

0 <2 >80%

1 2-4 60 - 80%

None

Reported by family

Tuberculin test Malnutrition Unexplained Fever

Score

3 >4 <60%

Score

Proved sputum positive Positive Not improving after 4 weeks No response to treatment

Local

Lymph nodes Joint or bone swellings Abdominal mass or ascites CNS signs, abnormal CSF Broad mediastinum Angle due to enlarged hilar deformity of glands spine Total

Table 16: Scoring system for the diagnosis of TB in children (a score of 7 or more indicates a high likelihood of TB). Source: South African National TB Control Program Practical Guidelines 2004.

D. Treatment Of TB HIV infected children, diagnosed with TB, should have TB treated first where possible before starting ART. Use the recommended national standard treatment guidelines using a combination of the following drugs: Rifampicin (R) INH (H) Pyrazinamide (Z) Ethambutol (E) –only for re treatment cases

Standard TB regimens for children: New Pulmonary TB: 2RHZ/4RH Retreatment cases 3RHZE/5RHE

Note: Ethambutol is not routinely used in children below 8 years except in re-treatment cases. The dosage of ethambutol should be calculated strictly per Kg body weight in children. Close monitoring for loss of vision is necessary.

E. ART in TB /HIV Co- Infected Children The management of TB in HIV infected children, and the treatment of severe HIV infection with antiretroviral drugs is complicated by the potential for multiple drug interactions. Rifampicin interacts with the NNRTI (especially with nevirapine) and PI classes. Use of PI or Nevirapine together with rifampicin may result in sub-therapeutic antiretroviral drug levels and potentially in HIV treatment failure. The choice of ART regimen in TB/HIV co-infected children is also complicated by the limited options for paediatric drug formulations and/or dosing information (particularly for children less than 3 years of age) for antiretroviral drugs. This further limits ART options for co-infected children. When to start This depends on the child's clinical condition and immunological stage: TB treatment takes priority HIV Clinical stage 3 and 4 or severe immunological suppression (based on CD4 â&#x20AC;&#x201C; see on page ): Consider ART after stabilizing the patient for at least 2-8 weeks on TB treatment. The decision on whether to commence after 2 weeks of anti-TB treatment or to finish the intensive phased is based on clinical assessment of individual patients. Patients with Clinical Stage 3 (Lymph Node TB or pulmonary TB) with good response to anti TB Rx could delay ART initiation and should be re-evaluated after TB treatment. In stable patients complete TB treatment before commencing on ART. Advantages of delaying ART in patients on TB treatment. Reduces pill burden Improves adherence Better monitoring and differentiation of any adverse effects Recommended start regimen for children on TB treatment If patients needs to take TB treatment and ARTs together, then the recommended regimens are AZT, 3TC and Ritonavir boosted Kaletra in children 3 years or younger and AZT, 3TC and EFZ in children older than 3 years. The Ritonavir/Lopinavir ratio in Kaletra is 1:4. This needs to be boosted to a 1:1 ratio; therefore, Ritonavir needs to be added to the Kaletra tablets.

Child < 3 years: AZT + 3TC + Ritonavir boosted Kaletra Child > 3 years: AZT + 3TC + EFZ IRIS should be considered especially if CD4 is very low at commencement of ART Decisions on 2nd line ART regimens in TB should be referred to a specialist.

Evaluate the possibility of delaying ART initiation depending on the clinical status and CD4, and on clinical and immunological response to TB therapy. Children already on ART who need to start TB treatment These children should continue with ART but a review of their ART regimen is needed. Replace nevirapine with EFV in children >3yrs.

F. TB Prophylaxis Routine INH prophylaxis in HIV infected children is not recommended. INH prophylaxis against TB should be given to all children less than 5 years old who are exposed to TB in their household as per national TB guidelines (regardless of HIV status). Active disease must be ruled out first. INH for TB prophylaxis is given as a single oral daily dose of 10 mg/kg for 6 months.

Cotrimoxazole prophylaxis should always be continued in infants and children on TB treatment

Chapter 4: Nutrition in HIV Nutrition plays a crucial role in child health and in HIV/AIDS in particular. The interaction between nutrition, infection and immunity is well recognized.

4.1. Causes of poor nutritional status in HIV infected children Poor nutrient (food) intake Reduced appetite Oral sores Limited food availability Encephalopathy with feeding problems Malabsorption Nausea and vomiting Diarrhoea, recurrent and persistent Increased nutritional requirements Chronic infections e.g TB Fever, increased catabolism Malignancies Depression Loss parents (Orphans) Side - effects of drugs

4.2. Assessment of the nutritional status Assess nutritional status, weigh child and offer nutrition counselling at EVERY visit Record the weight on the Road to Health Chart Always measure: Weight Height Head circumference (children<2yrs) Check the weight for height on growth charts. Weight for height >90% -- nutrition is good Weight for height <70% -- severe wasting Check the weight for age if height not available Weight for age >80% -- nutrition is good Weight for age <60% -- marasmus Check for Bilateral pitting pedal oedema --- kwashiorkor Check for signs of visible severe wasting (see IMCI guidelines)

Check the child's RTHC. Decide whether there is good weight gain, or growth faltering (slower than expected rate of growth or drop in weight). Counsel the caregiver accordingly. If child is on ART, assess with other findings whether this is an indicator of poor response to ART.

4.3 Nutritional rehabilitation. Guidelines for management of severe malnutrition should be used. Precise information of caloric needs for HIV-infected children is not available. Severely malnourished children need admission and intensive management. HIV-infected children have increased energy needs. Refer to IMCI feeding recommendations for the dietary advice. General advice General Hygiene on handling food. Always wash hands with soap and water Use safe water that is boiled or filtered Small frequent feeds might be better tolerated. Increase gradually.

4.4 Infant feeding Refer to infant feeding guidelines. Breast-feeding increases the risk of HIV transmission to baby by up to 20%. The risk of transmission through breast milk increases with the duration of breastfeeding. Maternal factors like recent infection, advanced maternal disease, low CD4 count, high viral load and mastitis increase the risk of infection. Mothers should be counselled on infant feeding choices. Correct and adequate information should be given to enable the mother to make an informed choice of the feeding option. Feeding counselling should start during ANC care. Support the mother appropriately depending on the option she will have chosen.

A. The Different Feeding Options Considering the risk of HIV through breastfeeding and the risk of morbidity and mortality from other causes UN (WHO/UNICEF and others) recommends the following for HIV infected mothers: - â&#x20AC;&#x153;Exclusive breastfeeding is recommended for HIV-infected women for the first 6 months of life unless replacement feeding is acceptable, feasible, affordable, sustainable and safe for them and their infants before that time. -

When replacement feeding is acceptable, feasible, affordable, sustainable and safe, avoidance of all breastfeeding by HIV-infected women is recommended.

At six months, if replacement feeding is still not acceptable, feasible, affordable, sustainable and safe, continuation of breastfeeding with additional complementary foods is recommended, while the mother and baby continue to be regularly assessed. All breastfeeding should stop once a nutritionally adequate and safe diet without breast milk can be provided.”

Adequate counselling is therefore essential to be able to equip the mother to make an informed choice on the appropriate feeding option and to support her on the choice she will have made. Support the mother who has chosen to breastfeed. Counsel the mother on the importance of exclusive breastfeeding for up to 6 months. Breastfeeding should be discontinued as soon as is feasible. As part of supporting this mother AFASS of replacement feeding should be continuously assessed. Encourage growth and development monitoring monthly in Under 5 clinic. Support the mother who has chosen not to breastfeed. Counsel mother on replacement feeding. Discuss all the AFASS criteria. Assist her in choosing the appropriate feeding option for her baby. Infant feeding options are: § Formula feeding § Home-modified animal milk (fresh or processed animal milk that is modified by adding water, sugar and micronutrient) § Expressing and heat-treating breast milk to kill HIV virus.

Mixed feeding increase the risk of HIV transmission and should be discouraged

Chapter 5: Care and Treatment for Adolescents The World Health Organization defines “adolescents” as individuals aged 10 – 19 years and “young people” as those aged 10 – 24 years, but the definitions are not quite that simple. Adolescents are a special population. Adolescents are not “older children” nor are they “little adults”. In fact, adolescence is a period of transitioning from childhood to adulthood, with many physical, mental, and emotional changes. There are three stages of adolescence: 1. Early adolescence (age 10-13 years), where there are many questions about the changes that are occurring. There is emphasis on relationships with peers, or a shift in attachments. Thinking is very concrete, and they tend to act impulsively 2. Middle adolescence (age 14-16 years), where pubertal development is nearing completion. Abstract reasoning is developing, but there is still some immaturity in the ability to deal with the outside world. There is increased concern with self-image. 3. Late adolescence (age 17-21 years), where body image and gender role are defined. Individual relationships become more important than peer group. Cognitive development is usually complete at this time, and thus better awareness of the consequences of actions. There is overall comfort with self and with others.

5.1. Risk Factors for HIV Infection These include developmental stage, biologic and physical characteristics, individual attributes, and their environment. Adolescents often have issues such as denial, adherence, sexuality, peer pressure, school issues, and other responsibilities that may affect behaviour. Low self esteem has been shown to increase the probability of risk-taking behaviour that includes sexual experimentation or substance abuse. Lack of education about proper conduct and practices also puts many adolescents at risk of acquiring HIV. Many believe that they are invincible and that “it won't happen to me”. While boys tend to initiate sex earlier than girls, and adolescents growing up in rural areas are more likely to be sexually active than those growing up in urban areas, girls are more vulnerable. Biologically, the immature female cervix is more vulnerable to HIV infection than in older women. Gender imbalance often makes many young women feel powerless to insist on safer sex practices like abstinence or condom use. Girls are more likely to marry and to become pregnant, increasing the risk of HIV infection. In Swaziland, this time can be very difficult for most adolescents. For example, orphaned adolescents are often forced to become leaders of the household or are often thrust into adult responsibilities. Attempts at survival can lead to sex work, homelessness, and exploitation. Adolescence is a critical turning point in the lives of children, so much that proper guidance now in diminishing risky behaviours can lead to more positive outcomes later. The establishment of adolescent and youth-friendly services (sexual, reproductive, counselling and testing) is important in improving universal access to adolescents.

5.2. Counselling and Disclosure Specialists agree that physicians should fully disclose to teenage patients and parents should answer children's questions truthfully and honestly. The adolescent should also be counselled about disclosing his or her status to others, e.g. friends and family, about the costs and benefits of disclosure, and that there is no compulsory disclosure. However, the patient must be counselled on responsibility to sexual partners. Patients are less likely to disclose if they engage in casual sexual encounters. The counsellor should discuss issues of legal and moral obligation to the partner, but even with good counselling this process can be very difficult. In Swaziland, the age of informed consent is 16 years, where the patient no longer needs permission from guardian. They are fully expected to make decisions for themselves. However, there are some adolescents as young as 11 years of age who are mothers and are expected to care for others. As such, adolescents of all ages must be empowered to take care of themselves, to be responsible for their own health care, and to be responsible participants in society and community as well. They must be allowed to ascertain their own serostatus. They must be involved in discussions about medication adherence and the importance of regular visits to the health facility. However, they should also be encouraged to disclose to other family members to improve their social support.

5.3. Medical Management of Adolescents HIV is known to cause delays in development and sexual maturity. This is why many adolescents appear physically much younger than their chronologic age. This impacts the dosage of prescribed medications, especially antiretroviral therapy. If the child is in Tanner Stage I, II or III (See appendix 5 on page 75), they should still be dosed on the paediatric mg/kg (per weight) or on the body surface area. At Tanner Stages IV and IV, they are treated with adult dosing if the weight > 60 kg. In the case of antiretroviral therapy, again remember that not all adolescents will be mature enough to have the knowledge and understanding of the life-time commitment of HIV therapy, so it is best to individualize counselling and services to the individual patient.

5.4. Adolescent Needs in Swaziland Adolescent HIV programs in Swaziland need to acknowledge the rights of each client: Information, especially reproductive health services that provide information, education and counselling on sexual and reproductive health issues, STI, HIV, contraception, pregnancy testing and counselling, antenatal and postnatal care. Access to care regardless of sex, sexual orientation, or any other reasons. Choice Safety Privacy Confidentiality Dignity to be treated with courtesy and attentiveness, not merely as a statistic Comfort while receiving services in an adolescent friendly environment. Continuity of care for as long as the care is needed Opinions that should be expressed

HIV counselling and testing services should cater to adolescents who are sexually active, pregnant, or who have children, and allow them to consent for HIV testing. Support services for adolescents in Swaziland should be multidisciplinary and comprehensive. Health care providers should be equipped to supply the adolescents with contact information for relevant organizations providing support services that are appropriate for their needs.

Chapter 6: Non-occupational post-exposure prophylaxis 6.1. Rationale for PEP for non-occupational exposure to HIV When exposure occurs in the occupational setting to HCWs, the HIV status of the source person can usually be determined. This is rarely the case following non-occupational exposure. People who are exposed to blood (e.g. through violence, needle sticks, dirty knives or blades) or victims of sexual abuse are included in the category of non-occupational exposure to HIV. Unfortunately sexual abuse is not uncommon in Swaziland. During the 6 month period from September 2004 to March 2005, out of over 360 reported cases of sexual abuse in Swaziland, over 180 occurred in young people under the age of 20 years. In a country with a high prevalence rate of HIV among the most sexually active group and a high occurrence of rape cases, health workers should offer post-exposure prophylaxis (PEP) to victims of rape. Rape causes genital tract trauma that increases the risk of HIV transmission to the victim.

6.2. Management of non-occupational exposure to HIV Victims should be taken immediately to the nearest referral PEP centre even before questioning by the police. Qualified medical staff should examine the victim carefully, document her/his clinical condition, and establish evidence for violence. The medical personnel should perform a thorough examination of the genital area. Samples should be acquired for laboratory analysis. If the victim is less than 18 years of age, every attempt should be made to encourage the patient to involve the caretaker or caretakers. The examination and laboratory tests should be offered routinely; if an adult victim refuses to be tested for HIV, no PEP will be offered. Antiretroviral therapy should be offered according to the algorithm in Figure 6: HIV Positive Source*

HIV status of the source unknown

HIV negative

<72 hours of Recommend 2 ARV drugs Recommend 2 ARV drugs reported exposure (ZDV or d4T plus 3TC) (ZDV or d4T plus 3TC)

No PEP

>72 hours of reported exposure

No PEP

Not recommended**

Table 17: Guidelines for the initiation of PEP

* If there is a substantial risk of HIV transmission, a 3-drug regimen may be considered by adding efavirenz, lopinavir/ritonavir, nelfinavir, or indinavir ** Clinical judgment must be taken into account. If there is a high risk of HIV transmission, and if the benefits of using 2 drug ARV outweigh the costs in this scenario, it is within the health worker's discretion to provide PEP.

Figure 7: Algorithm for evaluation and treatment of possible non-occupational HIV exposure

Substantial exposure risk

72 Hours since exposure

Negligible exposure risk

72 Hours since exposure

Source patient known to be HIV positive

Source patient of unknown HIV status

nPEP recommended

Case-by-case determination

nPEP not recommended

Negligible Risk for HIV Exposure

Substantial Risk for HIV Exposure Exposure of

Exposure of

vagina. rectum, eye, mouth or other mucous membrane,nonintact skin, or percutaneous contact

vagina. rectum, eye, mouth or other mucous membrane, intact or nonintact skin, or percutaneous contact

with blood, semen, vagina secretions, rectal secretions, breast milk, or any body fluid that is visibly contaminated with blood

with urine, nasal secretions, saliva, sweat, or tears, if not visibly contaminated with blood Regardless of the known or suspected HIV status of the source

when the source is known to be HIV-infected

6.3. Counselling and Testing Pre- and post-test HIV test counselling and appropriate psychosocial support for victims of abuse should be offered to the victim and the parents/guardians. Confidentiality must be assured and an anonymous form should be filled in. Advise the victim to take STI prophylaxis. Perform a pregnancy test in females. Counselling should include the risk of transmission and acknowledgement of the options open to the victim and her/his family. Assistance should be made in reporting the assault to the proper authorities.

6.4

Monitoring

Non-occupational exposure laboratory evaluation should be as indicated in .

Test

Baseline

During nPEP

E ,S$ E

E E

E, S

HIV antibody testing Complete bloob count differencial Serum liver enzymes Blood urea nitrogen /creatinine Sexually transmitted diseases screen (gonorrhea, chlamydia, syphilis) Hepatitis B serology Hepatitis C serology Pregnancy test (for women of reproduc tive age) HIV viral load HIV resistance testing CD4+T lymphocyte count

E, S E, S E

4-6 Weeks after exposure E

3 Months after exposure

6 Months after exposure

E E

E** E** E**

E E

S S S

E** E** E**

* Other specific tests might be indicated dependent on the antiretrovirals prescribed. Literature pertaining to individual agents should be consulted. E = exposed patient, S = source $ HIV antibody testing of the source patient is indicated for sources of unknown serostatus. Additional testing for pregnancy, sexually transmitted diseases, and hepatitis B should be performed as clinically indicated. ** If deternined to be HIV infected on follow-up testing: perform as clinically indicated once diagnosed. Table 18: Laboratory monitoring of patients on PEP.

Appendix 1 Presumptive and Definitive Criteria for Recognizing And Treating HIV/AIDSRelated Clinical Events In Infants And Children With Established HIV Infection Primary HIV infection Clinical event Clinical diagnosis Asymptomatic infection Acute retroviral syndrome

Acute febrile illness 2 - 4 weeks postexposure, often with lymphadenopathy, pharyngitis and skin rashes

Clinical Stage 1 Clinical event Asymptomatic

Persistent generalized lymphadenopathy (PGL)

Definitive diagnosis In children 18 months or over seroconversion from HIV antibody negative to antibody-positive. A positive virological test for HIV virus or its components (RNA or DNA or ICD HIV p 24 antigen) confirmed by a second virological test obtained from a separate determination. Profound temporary lymphopaenia and other transient blood abnormalities may occur.

Clinical diagnosis No HIV related symptoms reported and no signs on examination. Swollen or enlarged lymph nodes >1 cm at two or more noncontiguous sites, without known cause.

Clinical Stage 2 Clinical Clinical diagnosis event Unexplained Enlarged liver and spleen without persistent obvious cause. Hepatosplenomeg aly Papular Papular pruritic vesicular lesions. Also pruritic common in uninfected children: scabies eruptions and insect bites should be excluded.

Fungal nail infections

Angular cheilitis

Treatment and prophylaxis Supportive Care of symptoms

Fungal paronychia (painful, red and swollen nail bed) or onycholysis (painless separation of the nail from the nail bed). Proximal white subungual onychomycosis is uncommon without immunodeficiency. Splits or cracks on lips at the angle of the mouth with depigmentation, usually responding to antifungal treatment but may recur.

Definitive diagnosis

Treatment and prophylaxis

Not required.

Cotrimoxazole prophylaxis

Not required.

Definitive diagnosis Not required.

Not required.

Treatment and prophylaxis

Supportive skin care: Antihistamine to treat pruritis §

(Chlorpheniramine, Diphenhydramine, Promethazine, Cetirizine, Loratidine) Hydrocortisone 1% cream § applied once daily for no more than 5 to 7 days Petroleum jelly, vegetable oil, § lotion Not required Topical antifungal treatment until resolution Nystatin TDS § Miconazole TDS § Clotrimazole TDS § Not required.

Topical Anti -fungal therapy Clotrimazole § Nystatin § ketoconazole § Gentian violet §

Clinical Stage 2 continued Clinical Clinical diagnosis event Lineal gingival Erythematous band that follows the Erythema contour of the free gingival line; may be (LGE) associated with spontaneous bleeding. Extensive Characteristic warty skin lesions; small wart virus fleshy grainy bumps, often rough, flat on infection sole of feet (plantar warts); facial, more than 5% of body area or disfiguring.

Extensive molluscum contagiosum infection Recurrent oral ulcerations (two or more in six months) Unexplained parotid enlargement Herpes zoster

Recurrent upper respiratory tract infection (URTI)

Definitive diagnosis Not required.

Treatment and prophylaxis

Not required.

Supportive Care

Characteristic skin lesions: small fleshcoloured, pearly or pink, dome-shaped or umbilicated growths, may be inflamed or red; facial, more than 5% of body area or disfiguring Aphthous ulceration, typically with a halo of inflammation & yellow-grey pseudomembrane.

Not required.

Antiretroviral therapy Dermatology referral Podophyllin 10%-25% applied ยง by practitioner then washed off 1-4 hours later at 0.5 mL per treatment Cauterisation ยง Antiretroviral therapy Gentle curettage

Not required.

Gentian violet Chlorhexidine solution mouth rinse

Asymptomatic bilateral swelling that may spontaneously resolve and recur, in absence of other known cause, usually painless Painful rash with fluid-filled blisters, dermatomal distribution, can be haemorrhagic on erythematous Current event with at least one episode in past 6 months. Symptom complex; fever with unilateral face pain and nasal discharge (sinusitis) or painful swollen eardrum (otitis media), sore throat with productive cough (bronchitis), sore throat (pharyngitis) and barking crouplike cough (LTB). Persistent or recurrent ear discharge.

Not required.

Supportive Care

Not required Analgesia Moderate disease: oral acyclovir ยง 80 mg/kg/day divided into 4-5 Not Treat with standard antibiotics for required. suspected aetiology

Clinical Stage 3 Clinical event Unexplained moderate malnutrition

Clinical diagnosis Weight loss: low weight-for-age up to - 2 standard deviations (SDs), not explained by poor or inadequate feeding and or other infections, and not adequately responding to standard management.

Definitive diagnosis Treatment and prophylaxis Confirmed by Nutritional support documented loss of body weight of –2SD, failure to gain weight on standard management and no other cause identified during investigation.

Unexplained persistent diarrhoea

Unexplained persistent (14 days or more) diarrhoea (loose or watery stool, three or more times daily), not responding to standard treatment.

Confirmed by stools observed and documented as unformed. Culture and microscopy reveal no pathogens.

Unexplained persistent fever (intermittent or constant, for longer than one month)

Reports of fever or night sweats for longer than one month, either intermittent or constant, with reported lack of response to antibiotics or antimalarials. No other obvious foci of disease reported or found on examination. Malaria must be excluded in malarious areas. Exclude TB Persistent or recurring creamy white to yellow soft small plaques which can be scraped off (pseudomembranous), or red patches on tongue, palate or lining of mouth, usually painful or tender (erythematous form). Fine small linear patches on lateral borders of tongue, generally bilaterally, which do not scrape off. Non acute, painless "cold" enlargement of lymph nodes, usually matted, localized to one region. May have draining sinuses. Response to standard anti-TB treatment in one month. Nonspecific symptoms, e.g. chronic cough, fever, night sweats, anorexia and weight loss. In the older child also productive cough and haemoptysis. Abnormal CXR. Response to standard anti-TB treatment in one month. Cough with fast breathing, chest indrawing, nasal flaring, wheezing, and grunting. Crackles or consolidation on auscultation. Responds to course of antibiotics. Current episode plus one or more in previous 6 months

Confirmed by documented fever of >37.5 0C with negative blood culture, negative malaria slide and normal or unchanged CXR, and no other obvious foci of disease.

Oral candida (outside first 6-8 weeks of life)

Oral hairy leukoplakia Lymph node TB

Pulmonary TB

Severe recurrent presumed bacterial pneumonia

Nutritional support Rehydration Oral rehydration § Intravenous if necessary § Specific antibiotic treatment for suspected pathogen Antiretroviral therapy Anti-pyretic paracetamol § ibuprofen §

Confirmed by microscopy Analgesia or culture. Antifungal therapy Nystatin oral solution § Miconazole gel § Clotrimazole § ketoconazole § None

ARV therapy

Confirmed by histology or Anti-TB treatment fine needle aspirate for Test and treat household contacts per Ziehl Neelsen stain. national protocol Culture.

Confirmed by positive sputum smear or culture.

Anti-TB treatment Test and treat household contacts per national protocol

Confirmed by isolation of Supportive Care bacteria from appropriate Antibiotic regimen appropriate for clinical specimens suspected pathogens (induced sputum, BAL, lung aspirate).

Clinical Stage 3 continued Clinical event Clinical diagnosis Acute necrotizing Severe pain, ulcerated gingival ulcerative gingivitis papillae, loosening of teeth, or stomatitis, or spontaneous bleeding, bad odour, acute necrotizing and rapid loss of bone and/or soft ulcerative tissue. periodontitis Symptomatic LIP No presumptive diagnosis.

Chronic HIVassociated lung disease (including bronchiectasis)

Unexplained anaemia (<8g/dl), or neutropenia (<1000/mm3) or chronic thrombocytopenia (<50 000/ mm3)

Definitive diagnosis None.

Diagnosed by CXR: bilateral reticulonodular interstitial pulmonary infiltrates present for more than two months with no response to antibiotic treatment and no other pathogen found. Oxygen saturation persistently <90%. May present with cor pulmonale and may have increased exercise-induced fatigue. Characteristic histology. History of cough productive of Confirmed by CXR copious amounts of purulent sputum may show honeycomb (bronchiectasis only), with or without appearance (small clubbing, halitosis, and crepitations cysts) and/or persistent and/or wheezes on auscultation; areas of opacification and/or widespread lung destruction, with fibrosis and loss of volume. No presumptive diagnosis. Diagnosed on laboratory testing, not explained by other non-HIV conditions, or not responding to standard therapy with haematinics, antimalarials or anthelmintics as outlined in IMCI.

Treatment and prophylaxis Analgesia Appropriate antibiotics Chlorhexidine solution ARV therapy

Antibiotic treatment of superinfections Prednisolone ยง 1-2 mg/kg/day for 2-6 weeks ยง titrate to lowest possible dose ยง gradually taper over several weeks Appropriate antibiotic therapy Supportive care ARV therapy

Nutritional support Vitamin supplementation Supportive Care ARV therapy

Clinical Stage 4 Clinical event Unexplained severe wasting, stunting or severe malnutrition not adequately responding to standard therapy

Clinical diagnosis Persistent weight loss not explained by poor or inadequate feeding, other infections and not adequately responding in two weeks to standard therapy. Characterized by: visible severe wasting of muscles, with or without oedema of both feet, and/or weight-for-height of –3 SDs, as defined by WHO IMCI guidelines. Dry cough, progressive difficulty in breathing, cyanosis, tachypnoea and fever; chest indrawing or stridor. (Severe or very severe pneumonia as in IMCI). Usually of rapid onset especially in infants under six months of age. Response to high-dose cotrimoxazole +/- prednisolone.

Definitive diagnosis Confirmed by documented weight loss of >-3 SD +/oedema

Treatment and prophylaxis Nutritional support ARV therapy

Confirmed by: CXR typical bilateral perihilar diffuse infiltrates; microscopy of induced sputum or BAL or NPA, or histology of lung tissue.

Recurrent severe presumed bacterial infection, e.g. empyema, pyomyositis, bone or joint infection, meningitis but excluding pneumonia Chronic herpes simplex infection; (orolabial or cutaneous of more than one month's duration or visceral at any site)

Fever accompanied by specific symptoms or signs that localize infection. Responds to antibiotics. Current episode plus one or more in previous 6 months.

Confirmed by culture of appropriate clinical specimen.

Oxygen supplementation Trimethoprim-sulfamethoxazole 15-20 mg/kg/d (based on § trimethoprim component) IV divided Q6 - Q8 x 21 days Corticosteroids for severe disease 1-2 mg/kg BD (max 40 mg) x 5 § days, then 1-2 mg/kg OD (max 40 mg) x 5 days, then 0.5-1 mg/kg OD (max 20 mg) to completion of treatment Clindamycin 25-40 mg/kg/day IV/IM div every § 6-8 hours, max 4.8 g/d 10-30 mg/kg/d PO div q6-8 h, § max 1.8 g/d Analgesia Antipyretic Appropriate antibiotic regimen

Severe and progressive painful orolabial, genital, or anorectal lesions caused by HSV infection present for more than one month.

Confirmed by culture and/or histology

Oesophageal candida (or candida of trachea, bronchi or lungs).

Chest pain and dysphagia (difficulty in swallowing), odynophagia (pain on swallowing food and fluids), or retrosternal pain worse on swallowing (food and fluids) responds to specific treatment. In young children,

Confirmed by macroscopic appearance at endoscopy, microscopy of specimen from tissue or macroscopic

Pneumocystis pneumonia (PCP)

Analgesia Antipyretic Treatment Mild: oral acyclovir 40-80 § mg/kg/day divided into TDS for 7 to 10 days (maximum 1200 mg/kg/day) Severe: IV acyclovir 15-30 § mg/kg/day divided TD, given over one hour, for 7 to 14 days Analgesia Antifungal Fluconazole § Loading dose: 10 mg/kg IV/PO Maintenance (24 hours after loading dose) 3-6 mg/kg/day IV/PO OD max 12 mg/kg/day x 4

Clinical Stage 4 continued Clinical event Clinical diagnosis Definitive diagnosis Extrapulmonary/ Systemic illness usually with Confirmed by positive disseminated TB prolonged fever, night sweats, microscopy showing weight loss. Clinical features of AFB or culture of organs involved, e.g. sterile pyuria, Mycobacterium TB from pericarditis, ascites, pleural blood or other relevant effusion, meningitis, arthritis, specimen except orchitis. Responds to standard sputum or BAL. Biopsy anti-TB therapy. and histology. Kaposi sarcoma Typical appearance in skin Not required but may be or oropharynx of persistent, confirmed by : initially flat, patches with a § typical red-purple pink or blood-bruise colour, lesions seen on skin lesions that usually bronchoscopy or develop into nodules. endoscopy; § dense masses in lymph nodes, viscera or lungs by palpation or radiology; § histology. CMV retinitis or Retinitis only. Definitive diagnosis CMV infection CMV retinitis may be required for other sites. affecting another diagnosed by experienced Histology. CSF organ, with onset at clinicians: progressive floaters polymerase chain age over 1 month. in field of vision, light flashes reaction (PCR). and scotoma; typical eye lesions on serial fundoscopic examination; discrete patches of retinal whitening with distinct borders, spreading centrifugally, often following blood vessels, associated with retinal vasculitis, haemorrhage and necrosis. CNS toxoplasmosis Fever, headache, focal Not required but with onset at age neurological signs, confirmed by over 1 month. convulsions. Usually computed responds within 10 days tomography (CT) to specific therapy. scan showing single/multiple lesions with mass effect/enhancing with contrast.

Treatment and prophylaxis Anti-TB as per national protocol

Antiretroviral therapy consider lopinavir/ritonavir if possible Refer for Chemotherapy

Treatment

§ Ganciclovir : 5 mg/kg BID IV x 14 days Secondary Prophylaxis § <12 years old: Ganciclovir 5 mg/kg/dose OD IV or 6 mg/kg/dose IV OD x 5 days per week § >12 years old: Ganciclovir 1000 mg PO TDS with food

Dexamethasone or corticosteroids for cerebral edema or mass effect. Children:<12 years old § Pyrimethamine 1-2 mg/kg PO BD x 2 days then 1 mg/kg/day PO x 2 months then 1 mg/kg/day PO 3 days/week (max 50 mg) 0.5 mg/kg PO BD x 4 weeks AND § Sulfadiazine 100 mg/kg oral loading dose then 50 mg/kg PO BD AND § Folinic acid 5-10 mg PO/IM 3 times /week Children >12 years old: § Pyrimethamine 200 mg PO loading dose then 50-100 mg PO OD AND § Folinic acid 10 mg PO OD AND § Sulfadiazine 1-1.5 g PO q 6 hours OR/PLUS § Clindamycin 600 mg PO/IV q 6 hours Primary Prophylaxis: Same as PCP Secondary Prophylaxis (for life) <12 years old: § Pyrimethamine: 1 mg/kg PO OD (max 25 mg) AND

Clinical Stage 4 continued Clinical event Clinical diagnosis Extrapulmonary Meningitis: usually sub cryptococcosis acute, fever with including meningitis increasing severe headache, meningism, confusion, behavioural changes that responds to cryptococcal therapy.

HIV encephalopathy

Definitive diagnosis Treatment and prophylaxis Confirmed by CSF Treatment microscopy (India ink § Amphotericin B 0.25 – 1.0 mg/kg/day or Gram stain), serum IV x 14 days (start with test dose of 0.1 or CSF CRAG or mg/kg IV over 20 minutes, then culture. remainder of 1st dose), max. 1.5 mg/kg/day PLUS § Flucytosine 25 mg/kg PO four times per day x 14 days § AFTER 14 DAYS Fluconazole 12 mg/kg/day for 8-10 weeks then suppressive therapy (max 600 mg/day for children, 400 mg/day for adolescents) Alternative regimen § Fluconazole 12 mg/kg PO/IV x 1, then 6 mg/kg/day until 10-12 weeks after negative cultures then suppressive therapy Secondary Prophylaxis (Suppresssive regimen) § Fluconazole 6 mg/kg/day for life Confirmed by ARV therapy brain CT scan or MRI demonstrating atrophy and basal ganglia calcification and excluding other causes.

At least one of the following, progressing over at least two months in the absence of another illness: § failure to attain, or loss of, developmental milestones, loss of intellectual ability; or § progressive impaired brain growth demonstrated by stagnation of head circumference; or § acquired symmetric motor deficit accompanied by two or more of the following: paresis, pathological reflexes, ataxia, gait disturbances. Disseminated mycosis No presumptive Diagnosed by: (coccidiomycosis, histoplasmosis, diagnosis. § Histology: penicilliosis) usually granuloma formation. § Isolation: antigen detection from affected tissue; culture or microscopy from clinical specimen or blood culture

Treatment: Amphotericin followed by fluconazole or itraconazole or ketoconazole Secondary Prophylaxis for life

Clinical Stage 4 continued Clinical event Clinical diagnosis Disseminated mycobacteriosis No presumptive other than TB diagnosis

Chronic cryptosporidiosis

No presumptive diagnosis.

Chronic Isospora

No presumptive diagnosis.

Definitive diagnosis

Treatment and prophylaxis For MAC Nonspecific clinical symptoms including Clarithromycin 7.5 mg/kg (max 500 progressive weight mg) PO BD PLUS loss, fever, anaemia, Ethambutol 15-25 mg/kg day PO OD night sweats, fatigue or (max 1 g/day) diarrhoea; plus culture If unrsponsive may add rifabutin or of typical mycobacteria Rifampicin species from stool, OR instead of clarification: Azithromycin blood, body fluid or 20 mg/kg/dose OD other body tissue, Clarification 7.5 mg/kg/dose PO BID excluding lung. (max 1 g/day) OR Azithromycin 20 mg/kg/dose PO once per week (max 1200 mg/dose) OR Rifabutin (>6 years old) 300 mg PO OD Secondary Prophylaxis may be stopped in >12 years old after 12 months of ART and Cd4 count >100 cells/uL for 6 months Same as primary prohpylaxis but must add ethambutol 15 mg/kg/dose PO OD (max 900 mg/dose) Confirmed in children with chronic diarrhoea lasting longer than one month by microscopic examination. Confirmed in children with chronic diarrhoea by microscopic examination.

Antiretroviral therapy Paromomycin 25-35 mg/kg/day PO div TDS or QID x 14-28 days Nutritional supplementation Supportive care

Cerebral or B cell non-Hodgkin No presumptive lymphoma diagnosis.

Diagnosed by CNS imaging: at least one lesion with mass effect on brain scan; histology of relevant specimen

Chemotherapy

Progressive multi focal leukoencephalopathy (PML)

Diagnosed by MRI or CT scan, and biopsy. Viral PCR for Jacob Creutzfeldt virus.

TMP-SMX (co-trimoxazole) 6 to 10 mg/kg/day TMP PO div BD x 2 to 4 weeks, max 1 DS tablet PO BD Antiretroviral therapy

ARV therapy No presumptive diagnosis.

Appendix 2: Drug Formulation and Dosages Source: Antiretroviral therapy of HIV infection in infants and children in resource-limited settings: towards universal access. Recommendation for a public health approach. 2006. World Health Organisation.

weight (kg ) x height (cm) BSA = 3600 Nucleoside Reverse Transcriptase Inhibitors

Lamivudine (3TC) Formulations Oral solution: Tablet:

10 mg/ml 150 mg

Age (weight), dose and dose frequency Target dose: 4 mg/kg/dose twice daily to a maximum of 150 mg twice daily Dose at 30 days: 2 mg/kg/dose twice daily Dose at 30 days: 4 mg/kg/ dose twice daily Dose at 50 kg: 150 mg twice daily Note: Once-daily dosing is not yet approved for children but encouraging pharmacokinetic data are now available (175).

Other comments General: Well tolerated No food restrictions Also active against hepatitis B Oral solution: Store solution at room temperature (i.e. 25oC; use within one month of opening) Tablets: Store at 25 oC (permitted range: 15 oC to 30 oC) Can be crushed and contents mixed with a small amount of water of food and immediately taken Pharmacokinetic data: Available for all ages

Lamivudine: Recommended dosing based on weight bands

Weight range (kg)

Dose (ml, tablets)

Formulation

Bottom

Top

Target dose 4 mg/kg/dose twice daily to a maximum 150mg/dose twice daily

a.m.

p.m.

5.9

10 mg/ml solution

3 ml

6.9

10 mg/ml solution

3 ml

7.9

10 mg/ml solution

4 ml

8.9

10 mg/ml solution

4 ml

9.9

10 mg/ml solution

4 ml

10.9

10 mg/ml solution

5 ml

11.9

10 mg/ml solution

5 ml

5 ml 6 ml

13.9

10 mg/ml solution

6 ml

150 mg tablets

0.5

16.9

150 mg tablets

0.5

19.9

150 mg tablets

0.5

24.9

150 mg tablets

0.5

29.9

150 mg tablets

34.9

150 mg tablets

Stavudine (d4T) Formulations Oral solution: 1 mg/ml Capsules: 15 mg, 20 mg, 30 mg, 40 mg Age (weight), dose and dose frequency Target dose: Dose at 30 kg: Dose at 30 kg: Adults 60 kg

1 mg/kg/dose 1 mg/kg/dose twice daily 30 mg/dose twice daily currently 40 mg twice daily recommended; (using 30 mg dosage leads to delay or reduction of toxicity, although limited data on efficacy are available).

Other comments General: Well tolerated Do not use stavudine with zidovudine (AZT) due to an antagonistic effect Oral solution: Palatable and well tolerated but requires refrigeration after reconstitution Power for oral solution should be protected from excessive moisture and stored in tightly closed containers at 25oC (permitted range: 15oC to 30oC) After constitution, needs refrigeration and storage in original container; discard any unused portion after 30 days Must be well shaken prior to each use Capsules: Can be opened and mixed with small amount of food or water (stable in solution for 24 hours if kept refrigerated) Pharmacokinetic data: Available for all ages

Non-nucleoside Reverse Transcriptase Inhibitors

Fixed drug combinations

Appendix 3 Serious Acute and Chronic Toxicities due to ARV Drugs that may require therapy modification Source: Antiretroviral therapy of HIV infection in infants and children in resource-limited settings: towards universal access. Recommendations for a public health approach. 2006. World Health Organisation Remark: Alternative explanations for toxicity must be excluded before concluding that it is secondary to the ARV drug. This table describes management of the ART regimen but does not indicate detailed clinical toxicity management. Possible clinical manifestations (Most common ARV drug or drugs associated with the toxicity)

Possible laboratory abnormalitiesa

Implications for antiretroviral drug treatment

Accute serious adverse reactions Acute symptomatic hepatitis (NNRTI class, particulary NVP, more rarely EFV; NRTIs or PI class) § Jaundice § Liver enlargement § gastrointestinal symptoms § Fatigue, anorexia § My have hypersensitivity component (rash, fever, systemic symptoms), usually occur within 6-8 weeks. § May have accompanying lactic acidosis (see below) if seconadry to NRTI drug.

§ Elevated transaminases § Elevated bilirubin.

§ Discontinue all ARV until

symtoms resolve § If possible, monitor

transaminases, bilirubin § If receiving NVP, it should NOT

be readministered to the patient in future. § Once symptoms resolve, either: - restart ART with change to alternative ARV (if on NVP regimen, this is required): or - restart current ART regimen with close observation; if symptoms recur, substitute alternative ARV b

Acute pancreatitis (NRTI class, particularly d4T, ddl; more rarely 3TC) § Severe nausea and vomiting § Severe abdominal pain § May have accompanying lactic

acidosis (see below)

§ Elevated transaminases § Elevated eosinophil count

§ Discontinue all ARVs uuntil symptoms resolve § If possible, monitor serum pancreatic, lipase § Once symptoms resolve, restart ART with substitution of an alternative NRTI, preferably one without pancreatic toxicityb

Possible clinical manifestations (Most common ARV drug or drugs associated with the toxicity)

Possible laboratory abnormalitiesa

Implications for antiretroviral drug treatment

Hypersensitivity reaction (ABC or NVP) § ABC: Combination of acute § Elevated onset of both respiratory and transaminases gastrointestinal symptoms after § Elevated eosinophil restarting ABC, including fever, count fatigue myalgia, nausea, vomiting, diarrhoea, abdominal pain, pharyngitis, cough, dyspnoea; rash (usually mild) may or may not occur; progressive worsening of symptoms soon after receiving ABC dose, usually occurs within 6-8 weeks § NVP: Systemic symptoms of fever, myalgia, arthralgia, hepatitis, with or without rash. Possible clinical manifestations (Most common ARV drug or drugs associated with the toxicity)

Possible laboratory abnormalitiesa

§ Immediately discontinue all ARVs until symptoms resolve § NVP or ABC should NOT be readministered to the patient in future. § Once symptoms resolve, restart ART with substitution of an alterantive ARV for ABC or NVPb

Implications for antiretroviral drug treatment

Lactic acidosis (NRTI class, particularly d4T) § Generalized fatigue and weakness § Gastrointentinal features (nausea,

vomiting, diarrhoea, abdominal pain, hepatomegaly, anorexia, poor weight gain and/or unexplained weight loss) § May have hepatitis or pancreatitis (see above) § Respiratory features (tachypnoea and dyspnoea) § Neurological symptoms (including motor weakness)

§ Increased anion gap § Lactic acidosis § Elevated

aminotransferase § Elevated CPK § Elevated LDH

§ Discontinue all ARVs until

symptoms resolve § Symptoms associated with lactic

acidosis may continue or worsen despite discontinuation of ART § Once symptoms resolve, restart ART with substitution of an alternative NRTI with lower mitochondrial toxicity risk (e.g. ABC or AZT) b

Possible clinical manifestations (Most common ARV drug or drugs associated with the toxicity)

Possible laboratory abnormalitiesa

Implications for antiretroviral drug treatment

Severe rash/Stevens-Johnson syndrome (NNRTI class, particularly NVP, less common EFV) § Rash usually occurs during first 6-8

§ Elevated

weeks of treatment § Mild to moderate rash: erythematours, maculopapular, confluent, most often on the body and arms, with no systemic symptoms § Severe rash: extensive rash with moist desquamation, angiooedema, or serum sickness-like reaction; or rash with constitutional findings such as fever, oral lesions, blistering, facial oedema, conjunctivitis. § Life-threatining Stevens-Johnson syndrome or toxic epidermal necrolysis

aminotransferases

§ If mild or moderate rash, ART can

continue without interruption staying at induction dose until rash settles but with close observation, and only increase to maintenance dose once tolerated § For severe or life-threatening rash, discontinue all ARVs until symptoms resolve § NVP should NOT be readministered to the patient in the future. § Once symptoms resolve, restart ART with substitution of an alternative ARV for NVP (note: most experts would not change to another NNRTI drug if patient had severe or life-threatening StevensJohnson syndrome with NVP) b

Severe life-threatening anaemia (AZT) § Severe pallor, tachycardia § Significant fatigue § Congestive heart failure

§ Low haemoglobin

§ If refractroy to symtomatic

treatment (e.g. tranfusion) discontinue AZT only and substitute an alternative NRTI b

Severe neotropenia (AZT) § Sepasis/infection

§ Low neutrophil

§ If refactory to symptomatic

treatment (e.g. transfusion), discontinue AZT only and substitute an alternative NRTI b

Possible clinical manifestations (Most common ARV drug or drugs associated with the toxicity)

Possible laboratory abnormalitiesa

Implications for antiretroviral drug treatment

Possible clinical manifestations (Most common ARV drug or drugs associated with the toxicity)

Possible laboratory abnormalitiesa

Implications for antiretroviral drug treatment

Chronic late serious adverse reactions Lipodystrophy/metabolic syndrome (d4T; pls) § Fat accumulation and/or fat loss

§ Hyper-

§ Substitution of ABC or AZT for d4T

in distinct regions of the body: - increase fat around the abdomen, buffalo hump, breast hypertrophy - fat loss from limbs, buttocks and face occurs to a variable extent § Insulin resistence, including diabetes mellitus § Potential risk for later coronary artery disease

triglyceridaemia § Hypercholesterolaemia § Low HDL levels § Hyperglycaemia

may prevent progression of lipoatrophy § Substitution of an NNRTI for a PI may decrease serun lipid abnormalities

Severe peripheral neuropathy (d4T, ddl; mre rarely 3TC) § Pain tingling, numbness of hands

§ None

§ Stop suspect NRTI only abd

or feet; refusal to walk § Distal sensory loss § Mild muscle weakness and areflexia may occur.

susbtitute a different NRTI that is not associated with neurotoxity b § Symptoms may take several weeks to resolve

Appendix 4 Side effects (Adverse Events) of Antiretroviral Agents Mild side effects such as headache, fatigue, gastrointestinal upsets and diarrhoea occur fairly frequently, but the serious side effects occur rarely. Mild side effects usually occur early in treatment and often wear off and should be treated symptomatically. Side effects of antiretroviral drugs are summarized with the specific drug information later in this booklet. Grading of Adverse Events Grade 1 Mild Transient or mild discomfort; no limitation in activity; no medical intervention/therapy required Grade 2 Moderate Mild to moderate limitation in activity-some assistance may be needed; no or minimal medical intervention/therapy required. Grade 3 Severe Marked limitation in activity; assistance usually required; medical intervention/therapy required; hospitalization possible. Grade 4 Life-threatening Extreme limitation in activity, significant assistance required; significant medical intervention/therapy required; hospitalization or hospice care probable. Action on Grading of Adverse Events Grades 1 and 2: · Child remains on therapy. · Repeat the test. · Reassess clinically within 2 weeks Grade 3: · Test/exam should be repeated within 1 week. · If still Grade 3, stop all antiretroviral drugs and seek expert medical advice. Grade 4: · Stop all drugs immediately and seek specialist advice. · If the patient restarts therapy after the event has resolved, and the same grade 4 event recurs, appropriate changes or withdrawal of antiretroviral therapy may need to be made. Decisions should be made on an individual basis, and discussed with experts as required. Severity Grading of selected clinical and laboratory toxicities most commonly seen with recommended ARVs for children Source: Antiretroviral therapy of HIV infection in infants and children in resource-limited settings: towards universal access. Recommendations for a public health approach. 2006. World Health Organisation

Parameter

Mild

Severe and potentially life-threatening

Moderate

Severe

Symptoms causing greater than minimal interference with usual social and functional activities: may require minimal intervention and monitoring

Symptoms causing inability to perform usual social and functional activities: requires medical care and possible hospitalization

Symptoms causing inability to perform basic self-care functions: b requires medical or operative intervention to prevent permanent impairment, persistent disability or death

General guidance on estimating severity grade Characterization of symptoms and general guidance on management

Symptoms causing no or minimal interference with usual social and functional activities:a No therapy needed, monitor

Haematologyc Standard international units are listed in italics

Absolute neutrophil count

750 - < 1000/mm 3 0.75 x 10 9 - < 1 x 10 9 / I

500 - 749/mm3 0.5 x 10 9 - 0.749 x 10 9 /l

500 - 749/mm3 0.5 x 10 9 - 0.749 x 10 9 / l

< 250/mm3 <0.250 x 10 9 / l

Haemoglobin (child >60 days of age)

8.5 - 10.0 g/dl 1.32 - 1.55 mmol/l

7.5-<8.5 g/dl 1.16 - <1.32 mmol/l

6.5 - <7.5 g/dl 1.01 - <1.16 mmol/l

<6.5 g/dl <1.01 mmol/l Or severe clinical symptoms attributable to anaemia (e.g. cardiac failure), refractory to supportive therapy

Platelets

100 000-125 000/mm3 100 x 10 9 - 125 x 10 9/l

50 000 - <100 000/mm3 50 x 10 9 - <100 x 10 9/l

25 000 - <50 000/mm3 25 x 10 9 - <50 x 10 9/l

<25 000/mm3 <25 x 10 9/l or bleeding

ALT (SGPT)

1.25 - 2.5 x ULN

2.6 - 5.0 x ULN

5.1 - 10.0 x ULN

> 10.0 x ULN

AST (SGOT)

1.25 - 2.5 x ULN

2.6 - 5.0 x ULN

5.1 - 10.0 x ULN

> 10.0 x ULN

Bilirubin (>2 weeks of age)

1.1 - 1.5 x ULN

1.6 - 2.5 x ULN

2.6 - 5.0 x ULN

> 5.0 x ULN

Lipase

1.1 - 1.5 x ULN

1.6 - 3.0 x ULN

3.1 - 5.0 x ULN

> 5.0 x ULN

Pancreatic amylase

1.1 - 1.5 x ULN

1.6 - 2.0 x ULN

2.1 - 5.0 x ULN

> 5.0 x ULN

Gastrointestinalc Laboratory

Source: Adapted from Division of AIDS, National Institute of Allergy and

Infectious Diseases, Table for grading the severity of adult and paediatric adverse events, Bethesda, Maryland, USA; December 2004 a

Activities that are appropriate to age and culture (e.g. feeding self with culturally appropriate eating implement, walking or using hands).

Usual social and functional activities in young children include those

Values are provided for children in general except where age groups are specifically noted.

that are appropriate to their age and culture (e.g. social interactions, play activities, learning tasks).

Parameter

Moderate

Mild

Severe

Severe and potentially life-threatening

Clinical

Diarrhoea > 1 year of age

Transient or intermittent episodes of unformed stools OR increase of < 3 stools over baseline per day

Persistent episodes of unformed to watery stools OR increase of 4-6 stools over baseline per day

Grossly bloody diarrhoea OR increase of > 7 stools per day OR intravenous fluid replacement indicated

Life-threatening consequences (e.g. hypotensive shock)

< 1 year of age

Liquid stools (more unformed than usual) but usual number of stools

Liquid stools with increased number of stools OR mild dehydration

Liquid stools with moderate dehydration

Liquid stools resulting in severe dehydration with aggressive rehydration indicated OR hypotensive shock

Nausea

Transient (< 24 hours) or intermittent nausea with no or minimal interference with oral intake

Persistent nausea resulting in decreased oral intake for 24 - 48 hours

Persistent nausea resulting in minimal oral intake for > 48 hours OR aggressive rehydration indicated (e.g. intravenous fluids)

Persistent nausea with no or minimal oral intake resulting in dehydration with aggressive rehydration indicated

Pancreatitis

Not applicable

Symptomatic AND hospitalization not indicated (other than emergency treatment)

Life-threatening consequences (e.g. circulatory failure, haemorrhage, sepsis)

Vomiting

Transient or intermittent vomiting with no or minimal interference with oral intake

Frequent episodes of vomiting with no or mild dehydration

Persistent vomiting resulting in orthostatic hypotension OR aggressive rehydration indicated (e.g. intravenous fluids)

Life-threatening consequences (e.g. hypotensive shock)

Acute systemic allergic reaction

Localized urticaria (weals) lasting a few hours

Localized urticaria with medical intervention indicated OR mild angio oedema

Generalized urticaria OP angio-oedema with medical intervention indicated OR symptomatic mild bronchospasm

Acute anaphylaxis OR lifethreatening bronchospasm or laryngeal oedema

Cutaneous reaction - rash

Localized macular rash

Diffuse macular, maculopapular, or morbilliform rash OR target lesions

Diffuse macular, maculopapular, or morbilliform rash with vesicles or limited number of bullae OR superficial ulcerations of mucous membrane limited to one site

Extensive or generalized bullous lesions OR StevensJohnson syndrome OR ulceration of mucous membrane involving two or more distinct mucosal sites OR toxic epidermal necrolysis (TEN)

Allergic/dermatological

Source: Adapted from Division of AIDS, National Institute of Allergy and

Infectious Diseases, Table for grading the severity of adult and paediatric adverse events, Bethesda, Maryland, USA; December 2004 a

Activities that are appropriate to age and culture (e.g. feeding self with culturally appropriate eating implement, walking or using hands).

Usual social and functional activities in young children include those

Values are provided for children in general except where age groups are specifically noted.

that are appropriate to their age and culture (e.g. social interactions, play activities, learning tasks).

Parameter

Mild

Moderate

Severe

Severe and potentially life-threatening

Neurological Alteration in personality, behaviour or mood b

Alteration causing no or minimal interference with usual social and functional activitiesb

Alteration causing greater than minimal interference with usual social and functional activities b

Alteration causing inability to perform usual social and functional activities b AND intervention indicated

Behaviour potentially harmful to self or others OR life-threatening consequences

Altered mental status

Changes causing no or minimal interference with usual social and functional activitiesb

Mild lethargy or somnolence causing greater than minimal interference with usual social and functional activities b

Onset of confusion, memory impairment, lethargy, or somnolence causing inability to perform usual social and functional activitiesb

Onset of delirium, obtundation or coma

Neuromuscular weakness (including myopathy and neuropathy)

Asymptomatic with decreased strength on examination OR minimal muscle weakness causing no or minimal interference with usual social and functional activitiesb

Muscle weakness causing greater than minimal interference with usual social and functional activities b

Muscle weakness causing inability to perform usual social and functional activitiesb

Disabling muscle weakness causing inability to perform basic self-care functions OR respiratory muscle weakness impairing ventilation

Neurosensory alteration (including painful neuropathy)

Asymptomatic with sensory alteration on examination OR minimal paraesthesia causing no or minimal interference with usual social and functional activities

Sensory alteration or paraesthesia causing greater than minimal interference with usual social and functional activities

Sensory alteration or paraesthesia causing inability to perform usual social and functional activities

Disabling sensory alteration or paraesthesia causing inability to perform basic self-care functionsc

Other laboratory parameters Standard international units are listed in italics Cholesterol (fasting, paediatric <18 years old)

170 - < 200 mg/dl 4.40 - 5.15 mmol/l

200 - 300 mg/dl 5.16 - 7.77 mmol/l

> 300 mg/dl > 7.77 mmol/l

Not applicable

Glucose, serum, high: non-fasting

116 - < 161 mg/dl 6.44 - <8.89 mmol/l

161 - <251 mg/dl 8.89 - < 13.89 mmol/l

251 - 500 mg/dl 13.89 - 27.75 mmol/l

> 500 mg/dl > 27.75 mmol/l

Glucose, serum, high: fasting

110 - < 126 mg/dl 6.11 - < 6.95 mmol/l

126 - <251 mg/dl 6.95 - < 13.89 mmol/l

251 - 500 mg/dl 13.89 - 27.75 mmol/l

> 500 mg/dl > 27.75 mmol/l

Lactate

<2.0 x ULN without acidosis

> 2.0 x ULN without acidosis

Increased lactate with pH<7.3 without lifethreatening consequences or related condition present

Increased lactate with pH <7.3 with life-threatening consequences (e.g. neurological findings, coma) or related condition present

Triglycerides (fasting)

Not applicable

500-751 mg/dl 5.65-<8.49 mmol/l

751 - 1200 mg/dl 8.89 - 13.56 mmol/l

> 1200 mg/dl > 13.56 mmol/l

Source: Adapted from Division of AIDS, National Institute of Allergy and

Infectious Diseases, Table for grading the severity of adult and paediatric adverse events, Bethesda, Maryland, USA; December 2004 a

Activities that are appropriate to age and culture (e.g. feeding self with culturally appropriate eating implement, walking or using hands).

Usual social and functional activities in young children include those

Values are provided for children in general except where age groups are specifically noted.

that are appropriate to their age and culture (e.g. social interactions, play activities, learning tasks).

Appendix 5 Sexual Maturity Rating (Tanner Staging) in adolescents Source: Antiretroviral therapy of HIV infection in infants and children in resource-limited settings: towards universal access. Recommendations for a public health approach. 2006. World Health Organisation.

References 1. Antiretroviral therapy of HIV infection in infants and children in resource-limited settings: towards universal access. Recommendations for a public health approach (2006 revision). Final Version 2006, WHO 2. Nutritional aspects of HIV-infected children receiving highly active antiretroviral therapy. Tracie L. Miller 3. HIV/AIDS AND NUTRITION. A Review of the literature and Recommendations for Nutritional Care and support in Sub-Saharan Africa. Ellen G Piwoz and Elizabeth A Preble 4. Treating opportunistic Infections among HIV exposed and infected children. Recommendations from CDC, the National Institutes of Health and the Infectious Diseases Society of America MMWR Dec 3, 2004 Vol 53; No. RR -14 5. Handbook on Paediatric AIDS in Africa, ANECCA 6. Guidelines for CTX prophylaxis - final draft (May 2004); WHO 7. Guidelines for the management of HIV â&#x20AC;&#x201C; infected children; National Department of Health, South Africa 2005 8. The Paediatric Clinical Manual, The International Center for Aids Programs, September 2004; Elaine Abrams, Wafaa El-Sadr, Miriam Rabkin 9. Newell, M. L., Brahmbhatt, H., & Ghys, P. D. 2004, "Child mortality and HIV infection in Africa: a review", AIDS., vol. 18 Suppl 2:S27-34., p. S27-S34. 10. Spira, R., Lepage, P., Msellati, P., Van De, P. P., Leroy, V., Simonon, A., Karita, E., & Dabis, F. 1999, "Natural history of human immunodeficiency virus type 1 infection in children: a five-year prospective study in Rwanda. Mother-to-Child HIV-1 Transmission Study Group", Pediatrics., vol. 104, no. 5, p. e56.

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