HIV as a chronic disease Implications for public health

1. HIV as a chronic diseaseImplications for public health Massimo N Ghidinelli MD HIV/AIDS STI Pan American Health Organization World Health Organization J2J Global Health Media Training Washington D.C., 11 June 2011

2. OUTLINE • Overview of HIV epidemic, morbidity, mortality and modes of transmission • Natural history of HIV infection, progression to AIDS • Anti Retroviral Therapy (ART), applications and impact on HIV/AIDS • Response to HIV: global steps and achievements in treatment and care • Challenges and future directions

4. Adults and children estimated to be living with HIV  2009 Eastern Europe & Central Asia 1.4 million [1.3 million – 1.6 million] Western & Central Europe 820 000 [720 000 – 910 000] North America 1.5 million [1.2 million – 2.0 million] East Asia 770 000 [560 000 – 1.0 million] Middle East&North Africa 460 000 [400 000 – 530 000] Caribbean 240 000 [220 000 – 270 000] South & South-East Asia 4.1 million [3.7 million – 4.6 million] Sub-Saharan Africa 22.5 million [20.9 million – 24.2 million] Central & South America 1.4 million [1.2 million – 1.6 million] Oceania 57 000 [50 000 – 64 000] Total: 33.3 million[31.4 million – 35.3 million]

5. Estimated number of adults and children newly infected with HIV  2009 Eastern Europe & Central Asia 130 000 [110 000 – 160 000] Western & Central Europe 31 000 [23 000 – 40 000] North America 70 000 [44 000 – 130 000] East Asia 82 000 [48 000 – 140 000] Middle East&North Africa 75 000 [61 000 – 92 000] Caribbean 17 000 [13 000 – 21 000] South & South-East Asia 270 000 [240 000 – 320 000] Sub-Saharan Africa 1.8 million [1.6 million – 2.0 million] Central & South America 92 000 [70 000 – 120 000] Oceania 4500 [3400 – 6000] Total: 2.6 million [2.3 million – 2.8 million]

6. Over 7000 new HIV infections a day in 2009 • About 97% are in low and middle income countries • About 1000 are in children under 15 years of age • About 6000 are in adults aged 15 years and older, of whom: • ─ almost 51% are among women • ─ about 41% are among young people (15-24)

7. Routes of Exposure and HIV INFECTION ROUTE RISK OF INFECTION Sexual Transmission a. Female-to-male transmission………..1 in 700 to 1 in 3,000 b. Male-to-female transmission……...….1 in 200 to 1 in 2,000 Male-to-male transmission………...….1 in 10 to 1 in 1,600 Fellatio??…………………………….. 0 (CDC) or 6% (SF) Parenteral transmission Transfusion of infected blood………….95 in 100 Needle sharing………………………….1 in 150 c. Needle stick…………………………..…1 in 200 d. Needle stick /AZT PEP…………………1 in 10,000 Transmission from mother to infant a. Without AZT treatment………...…….1 in 4 b. With AZT treatment………………….Less than 1 in 10 Royce, Sena, Cates and Cohen, NEJM 336:1072-1078, 1997

8. Natural History of HIV infection Source: Fauci, et al, Immu. Mech HIV Inf, 1996

9. Acute HIV syndrome : oral candidiasis

10. AIDS: Wasting Syndrome

11. AIDS: Pneumocystis Jirovecci

12. AIDS: Kaposi’s Sarcoma

13. Milestones in the response to HIV1981-2010 HIV discovery Diagnostics Viral load Epidemiology Pathogenesis Prevention Effective therapy Potential eradication Development of a vaccine

14. HIV medicine armamentarium DLV NVP ddC TDF ABC ZDV d4T ETV ddI EFV FTC 3TC ’87 ’93 ’04 ’05 ’88 ’89 ’90 ’91 ’92 ’94 ’95 ’96 ’97 ’98 ’99 ’00 ’01 ’02 ’03 ’06 ’07 ’08 NRTI ATV NFV LPV/r SQV DRV NNRTI FPV APV TPV PI RTV T-20 MVC Entry inhibitor IDV Integrase inhibitor RAL

15. FDA Approved Antiretroviral Medications NRTI Abacavir ABC Didanosine DDI EmtricitabineFTC Lamivudine 3TC Stavudine D4T Zidovudine AZT Tenofovir TDF NNRTI Efavirenz EFV Nevirapine NVP Etravirine ETR Integrase inhibitor Raltegravir RAL Protease Inhibitor Atazanavir ATV Darunavir DRV Fosamprenavir FPV Indinavir IDV Lopinavir/rtv LPV/rtv Nelfinavir NFV Ritonavir RTV Saquinavir SQV Tipranavir TPV Fusion Inhibitor Enfuvirtide T-20 CCR 5 antagonist Maraviroc MVC

16. Evolution of HIV Care 1980 2010 Health Care • Chronic • Proactive • Focus on behavior • Standardized care • Practical • Pt role central Disease Care • Acute • Reactive • Focus on dx/rx • Customized care • Spiritual • MD role central Kathleen Clanon, MD 2007 16

17. Patients on HAART Deaths per 100 PY HIV Treatment Saves Lives Mortality and HAART Use Across Time HIV Outpatient Study, CDC, 1994-2003 Palella et al, JAIDS 2006; 43:27.

19. Mono Dual Triple therapy Impact of ART on TB Incidence TB among AIDS patients in Brazil Pulmonary TB Disseminated TB www.aids.gov.br/boletim/bol_htm/boletim.htm

21. Pill Burden: Changes in the landscape 1996: AZT-3TC-Indinavir 20066: TDF-FTC-EFV NOON NIGHT NIGHT MORNING

22. ART Applications • Treatment of HIV disease (HAART) • Prevention of Mother-to-Child-Transmission (PMTCT) • Post-exposure Prophylaxis (PEP) • Pre-exposure Prophylaxis (PrEP, iPrEP) • Prevention ART-population based ART

23. Promising results for the prevention of mother-to-child transmission of HIV since 1994 Courtesy: James Mc Intyre

25. Routes of Exposure and HIV INFECTION ROUTE RISK OF INFECTION Sexual Transmission a. Female-to-male transmission………..1 in 700 to 1 in 3,000 b. Male-to-female transmission……...….1 in 200 to 1 in 2,000 Male-to-male transmission………...….1 in 10 to 1 in 1,600 Fellatio??…………………………….. 0 (CDC) or 6% (SF) Parenteral transmission Transfusion of infected blood………….95 in 100 Needle sharing………………………….1 in 150 c. Needle stick…………………………..…1 in 200 d. Needle stick /AZT PEP…………………1 in 10,000 Transmission from mother to infant a. Without AZT treatment………...…….1 in 4 b. With AZT treatment………………….Less than 1 in 10 Royce, Sena, Cates and Cohen, NEJM 336:1072-1078, 1997

26. Pre-Exposure Prophylaxis • Daily anti-HIV medication taken by HIV-negatives • Started prior to potential exposure • Continued throughout periods of risk • Added to existing prevention efforts • Concept proven effective in other situations: • Malaria • Prevention of mother-to-child transmission of HIV • Would be an addition to, not a replacement for, existing prevention strategies

27. iPrEx: Efficacy of oral TDF-FTC PrEP in HIV negative MSM Use of TDF-FTC was associated with a 44% risk of HIV acquisition (MITT analysis) In adherent individuals protection was close to 90% Grant, N Engl J Med 2010; 363:2587-259

28. Ongoing and Planned Efficacy Trials of PrEP USA Thailand Botswana Kenya Malawi South Africa Tanzania Uganda Zambia Zimbabwe Brazil Ecuador Peru

31. Impressive scaling up of ART during the last decade

33. Launching PEPFAR “AIDS can be prevented. Anti-retroviral drugs can extend life for many years. And the cost of those drugs has dropped from $12,000 a year to under $300 a year -- which places a tremendous possibility within our grasp. Ladies and gentlemen, seldom has history offered a greater opportunity to do so much for so many” January 28, 2003 "

34. Universal Access 2005 G8 Summit at Gleneagles, Final Communiqué: “…working with WHO, UNAIDS and other international bodies to develop and implement a package of HIV prevention, treatment and care, with the aim of as close as possible to universal access to treatment for all those who need it by 2010.”

35. Number of people receiving antiretroviral therapy in low- and middle-income countries, by region, 2002–2009

36. Estimated percentage coverage with antiretroviral therapy in low- and middle-income countries by region, based on WHO 2010 and 2006 guidelines, 2008 and 2009

37. Retention on antiretroviral therapy up to 48 months, 2008 and 2009

38. Percentage of pregnant women living with HIV receiving antiretrovirals for preventing mother-to-child transmission of HIV in low- and middle-income countries by region, 2005, 2008 and 2009

40. Before After

41. Challenges Long term toxicity, early initiation of ART Burden of NCD in HIV Ensure retention and adherence and development of drug resistance Sustainability

42. Long-term complications of HAART Dyslipidaemia/CHD Abnormalities of Body Fat Distribution Hepatotoxicity

43. Rationale to start ART earlier PREVENTAIDS CANCERS RENAL CARDIAC LIVER CNS WAIT TOXICITY RESISTANCE COST START PREVENTTB MTCT New HIV cases

44. The Problem of Late Diagnosis CD4+ cell counts typically low among treatment-naive patients first presenting for HIV care 500 400 300 CD4+ Cell Count (cells/mm3) 200 100 0 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 Calendar Year Moore RD, et al. CROI 2008. Abstract 805. Graphic reproduced with permission.

45. When Is Antiretroviral Therapy Started? • Review of data from 2003-2005 from 176 sites in 42 countries (N = 33,008) • Since 2000, CD4+ cell count at initiation in developed countries stable at approximately 150-200 cells/mm3, increasing in sub-Saharan Africa from 50-100 cells/mm3 200 180 187 160 19 120 100 85 95 55 100 130 100-125 > 200 87-97 180 Egger M, et al. CROI 2007. Abstract 62.

46. HIV patients carry higher burden of NCD

47. HCV-Related Cirrhosis Complications expected over next 10 years Projected Number of Cases of HCC andDecompensated Cirrhosis due to HCV 160,000 140,000 120,000 Decompensated cirrhosis 100,000 Cases (n) 80,000 60,000 40,000 Hepatocellular cancer 20,000 0 1950 1960 1970 1980 1990 2000 2010 2020 2030 Year Davis GL, et al. Gastroenterology2010.

48. Incidence of Fatal Malignancies Among HIV Patients (N=23,437) 20 ADM, n=112 nADM, n=193 18 16 14 12 10 Event Rate/1,000 PYFU 8 6 4 2 0 Age Group <30 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 ADM, AIDS-defining malignancies; nADM, non-AIDS defining malignancies; PFYU, person-years of follow-up Monforte A. 14th CROI, 2007. Abstract 84.

49. Retention: need of increase both preART and ART retention In selected countries, retention on ART at 48 months approaches 75% (UNAIDS) Approximately only 1/3 of elegible patients initiate ARV timely. Kranzer et al (2010)

50. Poor Adherence Leads to Virologic Failure N = 81 Patients on Protease Inhibitor-Based RX Paterson Dl et al. Ann Intern Med 2000;133:21-30.