1. Harvard University Initiative for Global Health Global Health Challenges Social Analysis 76: Lecture 7

2. Harvard University Initiative for Global Health Biology, Clinical Manifestations and Interventions Overview Viral Life Cycle Natural History of Disease Modes of Transmission Preventive Interventions Treatment Interventions Global Distribution and Trends in HIV The Unfolding Epidemic Sub-Saharan Africa Asia History of the Health System Response Challenges and Controversies Vaccines and Microbicides Prevention versus Treatment Scaling Up Societal Impact

3. Harvard University Initiative for Global Health HIV disease is characterized by a gradual decline in immune function. Crucial immune cells called CD4+ T cells are disabled and killed during the course of infection. Healthy uninfected individuals have 800-1200 CD4 cells per mm3 of blood. During HIV infection CD4 declines progressively. When CD4<200/mm3 the individual becomes afflicted by opportunistic infections and cancers. HIV Disease

4. Harvard University Initiative for Global HealthPrimaryinfectionAsymptomatic HIV infection SymptomaticHIV/AIDS Years Months Viral load ‘set point’ 20 3 6 12 3 4 5 6 7 8 9 10 11 12 13 14 200 400 600 800 1000 HIV-1 RNA 10 3 10 4 10 5 10 6 10 7 CD4

5. Harvard University Initiative for Global Health Transmission is through sexual contact, blood contact (intravenous drug use, unsafe healthcare injections, unsafe blood transfusions) and maternal to child transmission. Probability of transmission per heterosexual coital act is 1/1000. Annual probability of transmission for a discordant heterosexual couple averaging 9 coital acts per month is 10.2%. Transmission probability increases as a function of viral load. Modes of Transmission

6. Harvard University Initiative for Global Health Probability as high as 8/1000 in early stage of infection. Male-to-female and female-to-male transmission probability where studied in Africa is equal Transmission probabilities are also a function of type of sex: much lower for oral sex, higher for anal sex, dry sex may increase risk Transmission Co-Factors

7. Harvard University Initiative for Global Health Presence of genital ulceration from other sexually transmitted diseases increases transmission probability by 2-4 times. Male circumcision probably reduces the probability of transmission from female to the male. Mother to child transmission without intervention is approximately 30%. Transmission Co-Factors

8. Harvard University Initiative for Global Health Change sexual behaviour (mass media, voluntary counseling and testing, peer-to-peer outreach, school, work and youth programmes: Promotion of abstinence Delayed sexual debut Decrease number of partners Decrease number of high-risk sexual contacts Change probability of transmission per coital act: Treatment of STDs – mixed trial results Male circumcision – 1 positive trial, 2 pending Promote condom use – Promote safer sexual practices - ?? Decrease transmission from mother to child – during delivery or through breastfeeding Antiretroviral prophylaxis for mother and child HIV Preventive Interventions

9. Harvard University Initiative for Global Health

10. Egger et al 2002, Lancet

11. Harvard University Initiative for Global Health Results of HAART in Treatment Naïve Patients, Europe and USA Egger et al 2002, Lancet

12. Harvard University Initiative for Global Health Biology, Clinical Manifestations and Interventions Overview Viral Life Cycle Natural History of Disease Modes of Transmission Preventive Interventions Treatment Interventions Global Distribution and Trends in HIV The Unfolding Epidemic Sub-Saharan Africa Asia History of the Health System Response Challenges and Controversies Vaccines and Microbicides Prevention versus Treatment Scaling Up Societal Impact

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14. Recent population-based blood surveys in developing countries suggest that prevalence from ANC clinics may be too high. True prevalence may be 30% lower than suggested by ANC data. Antenatal Clinic Sero-Surveillance and Population Sero-Surveys

15. Harvard University Initiative for Global Health HIV Sero-prevalence in Adults, 2005

16. Harvard University Initiative for Global Health HIV Sero-Prevalence 2005

17. Harvard University Initiative for Global Health

18. Uganda since 1992 has had a remarkable decline in sero-prevalence. Many, many analyses of this decline which claim different relative contributions of: delay of first sexual contact, decrease in the number of concurrent sexual partners (‘zero grazing campaign’), increase in condom use. ABC debate: A is for abstinence, B is for ‘be faithful’, and C is for condoms. Uganda

19. Harvard University Initiative for Global Health

23. Biology, Clinical Manifestations and Interventions Overview Viral Life Cycle Natural History of Disease Modes of Transmission Preventive Interventions Treatment Interventions Global Distribution and Trends in HIV The Unfolding Epidemic Sub-Saharan Africa Asia History of the Health System Response Challenges and Controversies Vaccines and Microbicides Prevention versus Treatment Scaling Up Societal Impact

24. Harvard University Initiative for Global Health WHO created the Global Programme on AIDS in the late 1980s In 1996, United Nations created a new agency to spearhead the global response to HIV. The main focus of efforts was on raising awareness of the epidemic and advocating for a comprehensive approach to prevention. Many countries were slow to recognize the magnitude of the epidemic. Global Response to HIV (1)

25. Harvard University Initiative for Global Health Success of ARVs in extending survival for HIV infected individuals in rich countries has increased international focus on HIV. Massive increase in sero-prevalence and rise in mortality in East and Southern Africa has made it impossible for politicians to ignore the epidemic. WTO Doha round of negotiations reflected developing country demands for access to effective medications. Global Response to HIV (2)

26. Harvard University Initiative for Global Health In 2001, Global Fund for AIDS, Tuberculosis and Malaria created to channel new resources to these three diseases. GFATM has disbursed more than $2 billion by end of 2005. In 2003, President Bush announced President’s Emergency Plan for AIDS Relief (PEPFAR), US$ 15 billion over 5 years. Global Response to HIV (3)

27. Harvard University Initiative for Global Health JW Lee took over as new Director-General of WHO July 21, 2003. His stated main priority is delivering ARVs to poor countries. This is a major shift from a focus on prevention to treatment. Slogan capturing this policy shift is 3 by 5. A target of 3 million individuals on ARVs by December 2005. Global Response to HIV (4)

28. Harvard University Initiative for Global Health Number of People on ARVs in Low and Middle- Income Countries

29. Harvard University Initiative for Global Health Percent Needing ARVs Who Receive Them

30. Harvard University Initiative for Global Health Biology, Clinical Manifestations and Interventions Overview Viral Life Cycle Natural History of Disease Modes of Transmission Preventive Interventions Treatment Interventions Global Distribution and Trends in HIV The Unfolding Epidemic Sub-Saharan Africa Asia History of the Health System Response Challenges and Controversies Vaccines and Microbicides Prevention versus Treatment Scaling Up Societal Impact

31. Harvard University Initiative for Global Health Two vaccine trials completed with no significant benefits. General pessimism on the prospects for a vaccine in the short to medium term. Interest in vaginal microbicides. Proponents argue that they would empower women in settings where they are unable to demand that male sexual partners use condoms. No effective microbicide has yet been through clinical trials (Phase III). Vaccines and Microbicides

32. Harvard University Initiative for Global Health Common debate in HIV policy is the balance of emphasis on prevention and treatment. Most commentators argue for a mixture of both; at issue is the emphasis on one or the other. To help clarify the debate, can consider two polar extremes: prevention first, treatment second vs treatment first, prevention second. Prevention vs Treatment

33. Harvard University Initiative for Global Health. Thailand used as model case. Proponents argue emphasis should be on preventing infection and then on providing ARVs to those who have been infected. Thailand used as model case. Criticisms: 1)failure of prevention programs in the majority of countries with large epidemics; 2) poor understanding of differences in sexual behaviour across different countries; and 3) weak evidence on the effectiveness of specific prevention programs. Prevention First, Treatment Second

34. Harvard University Initiative for Global Health emphasis should be on delivering ARVs to those who need them. Proponents argue emphasis should be on delivering ARVs to those who need them. Proposed benefits: 1) reduce mortality dramatically in the infected; 2) encourage voluntary testing and counseling for HIV infection which will lead to decreased transmission; 3) increase national commitment and resources to tackling HIV and thus increase spending on prevention programs as well; and 4) dramatically raise morale of health workers in beleaguered health systems improving their overall effectiveness Treatment First, Prevention Second

35. Harvard University Initiative for Global Health : 1) overriding emphasis on ARV treatment will suck dollars, health workers and energy out of prevention efforts and other priority health programs; Critics’ arguments: 1) overriding emphasis on ARV treatment will suck dollars, health workers and energy out of prevention efforts and other priority health programs; 2) emphasizing treatment can lead to increases in risky sexual behaviour and thus transmission of the virus; and 3) resources invested in ARVs will be wasted because most afflicted countries do not have the human resources and managerial infrastructure to effectively deliver a life long complex intervention. Treatment First, Prevention Second (2)

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37. Dramatic success of scaling up ARV programs in Sub-Saharan Africa to approximately 20% coverage. Challenges to further expansion especially outside of urban areas. Many PEPFAR funded programs use physicians and nurses, human resource shortages may limit this model. Successful models using community health workers have so far been local. Scaling Up