Living with HIV

Living With HIV

Dr V Harindra FRCP, FRCP(Glasg) Consultant Physician St. Mary’s Hospital Portsmouth. UK

THE FIRST YEARS • Unexpectedly Diagnosed January 2006 at age 38 • Initial Reactions; – “Is my partner safe?”

– “You Stupid Idiot! You have friends who died of AIDS. How could you let this happen to you?”

– “Who did I get it from?”

– “Who do I tell? Who needs to know?”

– “How many years will I live for?”

• Started ARV Therapy January 2007 – Drug switch within 1st 6 months due to side effects.

• Relationship ended • Read every bit of HIV related information I could get my hands on • Slowly came to terms with diagnosis

7 YEARS ON • Generally positive outlook • 100% adherent having maintained undetectable viral load and CD4 averaging 800 • Longevity expectations?

– Hopefully I will live ‘near-normal’ lifespan but I’m not banking on it!

– Nevertheless, I’m making long-term plans

• It doesn’t define who I am – But it has an unavoidable impact on my daily life

• Disclosure?

– I’ve mostly disclosed to friends but not to family (my parents would only worry so what’s the point?)

– I’ve disclosed to work, mainly for practical reasons due to inability to travel to certain destinations

DOWNSIDES • Rejection and Stigma – Surprisingly from the gay community

• General increase in anxiety overall – Health • Toxicity of drugs • Body fat changes • reduced energy levels • Co morbidities (Meniere’s disease) • Neuro-cognitive impairment?

– Financial • what if I need to stop working?

• I need to pay off my mortgage early • I’m maxing-out my pension AVCs • Practical issues – Medical appointments – Adherence – Restrictions in travel (avoidance of travel to certain countries)

HOW DID I COME TO TERMS WITH DIAGNOSIS? • I’m lucky!

– Thanks to medical advances, I’m alive and have a ‘near-normal’ life expectancy!

• Re-evaluation of what’s important in life • The support of a fantastic partner – (who is HIV negative)

• The support of friends • The support of a brilliant HIV healthcare team

THE FUTURE? • Monotherapy?

– Early indications are that this is a viable approach?

– Minimise toxicity and side effects

• Eradication of HIV? – Unlikely in my lifetime

• Maintain optimum health – Lifestyle choices (e.g. diet, exercise) – Stop smoking!

• Continue Planning for the Future

Living With HIV • HIV infection has become a chronic disease with a good prognosis provided – Treatment is started sufficiently early in the course of the disease – The patient is able to maintain lifelong adherence to ART

• Life expectancy in the general population varies by – Age, sex, and race – Substantial differences between low and high income countries

• The pattern of the HIV epidemic varies by country • The risk of death in successfully treated patients is similar to that of people with unhealthy lifestyles or other chronic conditions such as diabetes

HAART

HIV

Inflammation

OIs

Immune Dysfunction

Neoplasia

Endothelial Dysfunction Coagulation Platelet Reactivity

HIV

CVD CKD

Liver Disease Death

HIV Disease Contributes to Non-AIDS Events Low CD4+ T-cell nadir Coinfections (hepatitis, CMV, EBV, and HPV)

Persistent inflammation

Increased comorbidities Cumulative HAART exposure

Lifestyle (smoking, etc.)

Aging

Adapted from Deeks SG, et al. BMJ. 2009;338:a3172. Operskalski EA. Curr HIV/AIDS Rep. 2011;8:12-22

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 100%

Non-AIDS malignancy Non-AIDS infection

90%

Liver Heart

80% 70%

CNS Kidney

60%

Proportion

50%

Intestine/pancreas Lung

40% 30%

Suicide Substance use

20%

Accident/homicide Other

10% 0% 1984-1995

Weber R, et al. HIV Med. 2013;14:195-207.

1996-2004

2005-2009

Swiss 2007

Unknown

Top 10 Causes of Death Sri Lanka

United Kingdom

1. War

24%

1. Coronary Heart Disease

20%

2. Coronary Heart Disease

12%

2. Stroke

12%

3. Hypertension

07%

3. Influenza & Pneumonia

08%

4. Lung Disease

07%

4. Lung Cancer

08%

5. Stroke

06%

5. Alzheimer's/ Dementia

06%

6. Other Injuries

06%

6. Lung Disease

06%

7. Diabetes Mellitus

05%

7. Colon-Rectum Cancer

04%

8. Influenza & Pneumonia

03%

8. Breast Cancer

03%

9. Renal Disease

03%

9. Prostate Cancer

02%

10. Liver Disease

02%

10. Oesophagus Cancer

02%

HIV & Cardiovascular Disease ‘HIV’ risk factors ?

‘Standard’ risk factors - Smoking - Family history - Hypertension - Diabetes - Obesity - Male and age - Hyperlipidaemia

Vascular disease

- Increased prevalence of standard risk factors - HIV - HAART (PI > others?)

- HAART-related Hyperlipidaemia [+/- Insulin resistance, metabolic consequences of fat redistribution, hypertension, inflammatory process]

HIV & Cardiovascular Disease • The risk of CVD is greater in PLHIV – Meta-analysis of literature: • RR 1.61 for CVD in untreated HIV pts vs uninfected controls; • RR 2.0 for CVD in treated HIV pts vs controls

• CVD is more likely to be acquired with lower CD4 counts – CD4 count < 350 cells/μL – CD4 count > 350 cells/μL

1.58 (95% CI 1.09, 2.30) 1.28 (95% CI 0.81, 2.02)

• Use of PI and non-PI-based ARTs was associated with CVD – PI 6.22 (95% CI 3.13, 12.39) – Non – PI 3.18 (95% CI 1.99, 5.09) – Estimated combined RR of MI for PI- vs. non-PI-based ART to be 1.79 (95% CI 1.05, 1.72)

Lichtenstein KA, et al. Low CD4+ T cell count is a risk factor for cardiovascular disease events in the HIV outpatient study. Clin Infect Dis 2010; 51: 435–447.

Vaughn G, Detels R. Protease inhibitors and cardiovascular disease: analysis of the Los Angeles County adult spectrum of disease cohort. AIDS Care 2007; 19: 492–499., Islam FM , et al. HIV Med. 2012;13:453-468.

Risk Factors for Kidney Disease • • • • • •

Diabetes Mellitus Hypertension Smoking BMI Age Race (African-Caribbean or south Asian origin)

• CKD is present in 15-18% of HIV+

patients – eGFR <60

2-6%

– Proteinuria

10-14%

Proteinuria is defined as: • Urine albumin:creatinine ratio >30mg/mmol or • albumin concentration >200mg/l or • Urine protein:creatinine ratios >45 mg/mmol

HIV-Related Renal Disease • HIV-associated nephropathy (HIVAN), -- focal segmental glomerulosclerosis presenting with nephrotic syndrome and progressive renal insufficiency • One third of HIV-infected patients with renal disease have glomerular diseases other than HIVAN – – – – –

Membranoproliferative glomerulonephritis Minimal change disease Membranous glomerulopathy amyloidosis, immune-complex glomerulonephritis IgA nephropathy

• Antiretroviral therapy is associated with less rapid progression of HIVAN

Winston JA, Klotman ME, Klotman PE. HIV-associated nephropathy is a late, not early, manifestation of HIV-1 infection. Kidney Int. 1999;55:1036-1040.

United States Renal Data System. 2000 Annual Data Report/Atlas. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md, April 2000. Available at: http://www.usrds.org/adr.htm

Cumulative ARV Exposure and Risk of CKD • Cumulative exposure to TDF, ATV, LPV/RTV, or IDV each associated with increased risk of CKD • Renal toxicities are rare with NNRTIs, entry inhibitors, and integrase inhibitors • Risk of CKD after stopping TDF remained elevated for 1 yr – Within 12 mos: IRR 4.05 (2.51-6.53) – After 12 mos: IRR 1.12 (0.63-1.99)

• Risk of CKD after stopping ATV or LPV/RTV similar to pts never exposed

Mocroft A, et al. AIDS 2010;24:1667-1678, Gallant J, et al. AIDS 2012.

Liver Related Disease • Alcohol abuse • Infectious hepatitis • Drug-induced liver disease • Non-Alcoholic fatty liver disease

• A significant increase in the death rates from LRD in PLHIV • The risk of liver-related toxicities is considerably higher in patients coinfected with HBV and/or HCV • HAART reduced the death rate from LRD by increasing the CD4 cell count

• Death rates due to LRD might increase with longer exposure to HAART – Progression of liver disease due to hepatitis B or C over time – Direct liver toxicity of antiretrovirals – some other factor - ? Fatty liver

Mental Health in HIV • Most at risk for HIV infection often have high rates of mental illness • Most common mental disorders seen in people with HIV infection are – Mood disorders – Anxiety disorders, including post-traumatic stress disorder (PTSD); – Alcohol or other substance use disorders

• One third of patients with HIV infection suffer from major depression – Increased morbidity and mortality from HIV infection

• Direct effect of HIV on the brain can cause cognitive impairment – HIV-associated dementia – Milder or asymptomatic cognitive impairment can be more difficult to assess

• HAART reduces the rate of development of HIV dementia and can reverse cognitive deficits – Milder forms of cognitive impairment appear to be more refractory to treatment

Natural History of Untreated HIV Infection in Older vs Younger Patients • The natural history of HIV infection is generally unfavourable for older patients • Following acute infection, average HIV-1 RNA plasma titers are 0.4-0.5 log10 copies/mL higher in older (aged > 40 years) vs younger (16-20 years) patients • CD4+ cell counts are 40 cells/mm3 lower in individuals aged 40 years or older compared with individuals younger than 40 years of age (P < .01) • Older persons have faster rates of CD4+ cell count decline and more rapid progression to AIDS and death • Every 10 years of increased age, there was a 32% increased risk of developing AIDS and a 47% greater risk of death (independent of the CD4+ cell count and HIV-1 RNA level)

Touloumi 2004, CASCADE- 2000/ 2003, UKCHIC 2007, COHERE 2008

HIV and Aging 窶｢ Cohort study of HIV and comorbidities in the Netherlands (N = 452 HIVnegative and 489 HIV-positive persons) 窶｢ Significantly more Non-AIDS窶電efining malignancies, Diabetes, Hypertension, Cardiovascular disease, Renal disease , Osteoporosis 窶｢ Increase in drug toxicity Number of Comorbidities per Patient

100

HIV Negative

HIV Positive 3+ 2 1 0

80 %

60 40 20

0

Mean Number of Age-Associated Noncommunicable Comorbidities 0.68 0.80 1.03 1.15 1.47 0.89 1.35 1.52 Number of Participants 166 108 70 53 34 159 111 86 Schouten J, et al. AIDS 2012. Abstract THAB0205.

1.65

2.04

62

52

Living With HIV Healthy Lifestyle Adherence to Therapy

Early Diagnosis

Patient Monitoring

HAART

Living With HIV

Monitoring

Patient - HIV Markers - CVD – BP/Lipids - Liver screen - DM – FBS - Renal – eGFR/ Proteinuria -Mental health - Screening for Malignancy -- Bone -

Living With HIV HAART

Choice of HAART

NRTI Sparing Induction - Maintenance (PI Monotherapy) Non NRTI/PI regimens Choice of ART based on - Comorbidities - Age - Gender

Life expectancy across the globe - 2012

United Kingdom comes in 30th at 80.17 years

Monaco has the highest life expectancy in the world at 89.68 years. Chad has the lowest level of life expectancy at 48.69 years.

United Kingdom comes in 30th at 80.17 years. America ranks 51st in the table with 78.49 years Sri Lanka ranks 83 with 75.94 years

THANK YOU