HIV Care ; Challenges for Sri Lanka 2013 by College of Venereologists

HIV care; Challenges for Sri Lanka

Presidential address1 Dr Jayadarie Ranatunga Consultant Venereologist

Overview of the presentation  HIV situation in Sri Lanka  Overview of the challenges in HIV care  Challenges ahead for Sri Lanka – New infection rate – Evolving evidence and changing treatment criteria and options – HIV and ageing – Changing pattern of mortality and morbidity with ART – Sexual and Reproductive Issues – Drug Resistance – Opportunistic infections 02

HIV situation in Sri Lanka

History of HIV Epidemic in Sri Lanka

1986

• First AIDS case reported (A Foreigner)

• First Sri Lankan with HIV reported

1987

1989

• Identified at SJH on 10th February 1987 by Consultant physician Dr. HHR Samarasinghe, TPEPCP, History of homosexual contact in Homosexual club in Bangkok,

• First locally acquired HIV infection 04

Estimated New HIV Infections per Year 1200

1,107

No. HIV infections/Year

1000 878 800

727

600 400

303

334

479 455 439 407 419 428 388 363

515

562

628

200 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

Comparison of 2001 and 2011 Estimations

1. Living with HIV

2. New HIV infections

4. Adult HIV %

2001

2011

% Increase

1900

4200

120%

330

560

70%

0.01% <0.03%

200% 06

The present situation (at the end of 2012)  The total number of diagnosed HIV positive adults 1649  The total number of HIV positive children (<15 yrs age) 58  The total number of HIV positive adults under our care today 1073  The total number of HIV positive children under our care today 40  The total number of HIV positives on ART 387

Challenges

Challenges  Increasing number of new cases – Sri Lanka is among the four countries in SEA which records an increase in identification of new patients.  Significant number of Key populations practicing HIV risk behaviours – FSW, MSM, DU, BB,

Challenges contd...  Antiretroviral drugs – ART coverage – Changing ART regimens, and treatment criteria – ART associated other issues (cost, availability of options, toxicities and the management, metabolic syndrome etc…) – ARV Resistance  HIV and ageing 10

New Infection Rate

Changes in the incidence rate of HIV infection among adults 15–49 years old, 2001–2011, selected countries Increasing >25% Bangladesh Georgia Guinea-Bissau Indonesia Kazakhstan Kyrgyzstan Philippines Republic of Moldova

Sri Lanka

Stable Angola Belarus Benin Congo France Gambia Lesotho Nigeria Tajikistan Uganda United Republic of Tanzania USA

Decreasing 26–49%

Decreasing ≥50%

Burundi Cameroon Democratic Republic of the Congo Jamaica Kenya Malaysia Mali Mexico Mozambique Niger Sierra Leone South Africa Swaziland Trinidad and Tobago

Bahamas Barbados Belize Botswana Burkina Faso Cambodia Central African Republic Djibouti Dominican Republic Ethiopia Gabon Ghana Haiti India Malawi Myanmar Namibia Nepal Papua New Guinea Rwanda Suriname Thailand Togo Zambia Zimbabwe

Source: UNAIDS Report on the Global AIDS Epidemic 2012

New HIV Infections

New HIV cases reported per quarter

No. of HIV cases reported

60 50

42 36

40 30

20 10 0 3Q

2010

2011

2012 14

Evolving treatment options and criteria

The changes in ART initiation â&#x20AC;&#x201C; year 2010 (WHO guidelines) ď&#x201A;§ The modifications of ART initiation 1. To start ART at a CD4 count < 350 2. To start ART for all high risk groups, sero discordant couples, people on therapy for Hepatitis B, Tuberculosis all pregnant mothers who were started on ART for MTCT, Renal Disease

WHO 2013: Summary of Changes TARGET POPULATION (ARV-NAÏVE)

2010 ART GUIDELINES

CD4 ≤500 cells/mm3 (CD4 ≤ 350 cells/mm3 as a priority)

HIV Asymptomatic

CD4 ≤350

Symptomatic HIV

WHO clinical stage 3 or 4 regardless of CD4 cell count

No change

Pregnant and breast feeding women with HIVART continued

CD4 ≤350 cells/mm3 or WHO clinical stage 3 or 4

Regardless of CD4 cell count or WHO clinical stage ART to be continued after starting for PMTCT

HIV/TB COInfection

Presence of active TB disease, regardless of CD4 cell count

No change

HIV/HBV COinfection

Evidence of chronic active Evidence of severe chronic HBV liver HBV disease, regardless disease, regardless of CD4 cell count of CD4 cell count

Sero – discordant couples, high risk populations

cells/mm3

2013 ART GUIDELINES

No recommendation established

Regardless of CD4 cell count or WHO clinical stage

Challenges faced with new recommendations  New budgets for ART  Adherence issues with the start of ART in asymptomatic patients  Starting ART in high risk groups specially in drug users and MSM  More long term side effects due to ART  As the life expectancy increases, the age related complications will be more

HIV and ageing

Interplay of Age With Morbidity

HIV infection

 Risk of “comorbidities” increases as individuals get older Ageing

Antiviral treatment

 HIV does not cause these illnesses  However, HIV and/or ART may increase the risk

HIV and Accelerated Age-related Conditions 1. Development of Fraility (muscle weakness, weight loss, fatigue, and low levels of physical activity)

2. 3. 4. 5. 6. 7.

Insulin resistance, DM, CVD Chronic kidney disease Bone disease Cognitive impairment and dementia HIV-related and unrelated malignancies Liver disease and Hepato cellular carcinoma

chronic ALT elevation, steatosis, steatohepatitis, increased drug-related toxicity, more severe liver disease in aging patients with HBV, HCV 1. 4-fold increase in morbidity and mortality due to liver disease among older patients

1. Drug-drug interactions due to the other medications 21

Changing pattern of mortality and morbidity among PLHIV

Changing Patterns of the Causes of Death in the Swiss HIV Cohort Causes of Death in Participants in the Swiss HIV Cohort Study in 3 Different Time Periods, and in the Swiss Population in 2007 AIDS

Proportion

100%

Non-AIDS malignancy

90%

Non-AIDS infection

80%

Liver

70%

Heart CNS

60%

Kidney

50%

Intestine/pancreas

40%

Lung

30%

Suicide

20%

Substance use

Accident/homicide

10%

Other

0% 1984-1995

1996-2004

2005-2009

Swiss 2007

Yrs of Death of HIV-Positive Persons vs Swiss Population Weber R, et al. HIV Med. 2013;14:195-207.

Unknown

Emerging co-morbidities in HIV Neurocognitive dysfunction

Renal dysfunction

Impairment present in â&#x2030;Ľ50% HIV+ patients3

30% of HIV+ patients have abnormal kidney function1

Cardiovascular disease 75% increase

Reduced bone mineral density Increased prevalence

63% of HIV+ patients2

Cancer

in risk of acute MI4

Increased risk of nonAIDS-defining cancers e.g. anal, vaginal, liver, lung, melanoma, leukemia, colorectal and renal5 24

Lifetime HIV care Requires an integrated multidisciplinary approach Endocrinologis t

Nephrologi st

HIV physician Cardiologi st

Plastic surgeon

Nutritionali st

Smoking cessation

Gynecologist Neurologi st

Hepatolog ist 26

Adpated From Anna Maria Geretti. London

Questions for the future?  Are newer ART regimens associated with specific Cardiovascular Disease profiles?  For HIV-infected individuals with CVD or at high risk for CVD, when is the optimal time to start ART and what is the optimal ART regimen?  Should treated HIV infection be considered a CVD risk equivalent similar to DM?

Osteoporosis in HIV-Positive Patients  Osteoporosis and fractures are common in HIV-positive patients and will increase with aging  Risk factors include – HIV: chronic infection, ART (TDF, certain PIs, any ART initiation) – Behavioral- smoking, alcohol

 Screening: dual-energy x-ray absorptiometry should be considered in all HIV-positive postmenopausal women and in men aged older than 50 yrs

McComsey G, et al. Clin Infect Dis. 2010;51:937-946.

Sexual and reproductive health issues in HIV

Women with HIV infection  70-80% are sexually active  Research shows that level of contraceptive use is variable  Unintended pregnancy frequently reported  Proper research has not been undertaken in Sri Lanka related to fertility issues.  Pre-conception counselling, natural reproduction and assisted reproduction are the important areas for discussion 31

The facilities in Sri Lanka  Some of the couples are willing to have children  In Sri Lanka, up to now, there are 12 couples seeking fertility care but facing many problems due to the lack of facilities like sperm filtration in the government sector  Sperm washing is not available in Sri Lanka. 32

ART failure and drug resistance

The cohort of HIV positives on ART  There are 387 HIV positives on ART in Sri Lanka  The number of people on first line regimen is 232  The number on substituted therapy 131  The number of people who switched to 2nd line regimen 24

The reasons for substituting and switching regimens ď&#x201A;§ Evidence of immunological, virological or clinical failure and side effects of the drugs ď&#x201A;§ Virological assessment is not available in a regular basis ď&#x201A;§ But it is done free of charge

New ART regimens ď&#x201A;§ Antiretroviral drug therapy (ART) of HIV continues to improve, with current regimens offering greater

convenience, tolerability, and even the ability to retain activity when resistance has developed, compared with the first highly active ART (HAART) regimens available a decade ago.

Drug resistance ď&#x201A;§ Primary resitance ď&#x201A;§ Transmitted resistance

Drug resistance

 Drug resistance testing is not available in Sri Lanka

 It is available in the region  The cost for a resistance test is 75, 000 LKR

Challenges ahead of us ď&#x201A;§ It is a challenge to study the local resistance pattern ď&#x201A;§ Alternative regimens should be made available to be used in 1. Second line failure

2. Drug drug interactions and 3. Co- morbid conditions where some of the combinations cannot be used

ď&#x201A;§ Making pediatric preparations available 39

2.5. Opportunistic Infections

Opportunistic infections ď&#x201A;§ The number of people who are diagnosed with opportunistic infections in 2012 is 38 most of them have presented and diagnosed at very late stages ď&#x201A;§ The most common OIs found in Sri Lanka are Oesophageal candidiasis , Tuberculosis,, pneumocystis jeroveccei pneumonia and Cryptococcal meningitis

The challenges faced in managing OIs ď&#x201A;§ The facilities for diagnosing OI s is not at an optimal level in Sri Lanka ď&#x201A;§ The National reference laboratory should be equipped with facilities for diagnosing opportunistic infections which are common in Sri Lanka- eg 1. TB culture

2. PCR for TB 3. Culture for Non- TB mycobacteria 4. Cryptococcal Antigen 42

Hopes in the horizon

Vaccine for HIV; What might a successful vaccine do? ď&#x201A;§ Production of antibodies Bind virus; neutralize or stop virus from infecting cells; eliminate virus ď&#x201A;§ Produce cytotoxic T lymphocytes (CTL)

which recognise cells infected with virus and kill them

HIV vaccine development approaches  Protein sub unit  Synthetic peptide  Naked DNA  Inactivated virus  Live attenuated virus

 Live vectored vaccine

Challenges in HIV vaccine research  Viral genetic diversity  Immune protection  Neutralising antibodies  Vaccine testing

HIV functional cure Berlin Patient  Timothy Ray Brown who underwent stem cell transplant as treatment for AML from a donor who was homozygos for CCR5 delta 32 mutation  Did not receive HIV treatment for five years and viral load remains undeteactable and HIV culture remains negative  But is stem cell transplant practical for all HIV positives?

Gero Hütter is a German hematologist. Huetter and his medical team transplanted bone marrow deficient in a key HIV receptor to a leukemia patient, Timothy Ray Brown, who was also infected with HIV

MISSISSIPPI baby  Combined ART in first few hours of life appears to have eliminated HIV. CROI -2013  A baby born to HIV positive mother received three ART(AZT,3TC,NVP) very early in life within 30 hrs of birth .  Now she is two and half years old and off medication for more than one year without evidence of HIV infection and undetectable viral load BUT

 Could this be possible for many ? 48

To combat the epidemic ď&#x201A;§ Elimination of stigma and discrimination among health professionals and the general population should be taken

as a priority and the National STD/AIDS control programme has and is taking all the efforts towards this.

My request to this learned audience  Take every effort to diagnose people with HIV  Minimize stigma and discrimination in health care settings and among general population  Help the National Programme in implementing the preventive and curative services in the field of HIV

Make your contribution To the effort in achieving three zeros

Zero new infections

Zero HIV related deaths Zero discrimination

Acknowledgements  Dr K A M Ariyaratna  Dr Ajith Karawita  Dr N Abeygunasekara  Dr Thilani Ratnayaka  Dr Darshani Wijewickreme

Thank you