MRC/info4africa KZN Community Forum | May 2012


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Dr Shay Ganesh, Clinical Manager at medical Research Council in the HIV Prevention, Treatment and Wellness Unit presented on local and global HIV prevention efforts, focusing on previous, current and future programmes. Dr Ganesh  looked towards Pre-Exposure Prophylaxis as a possible future prevention programme and gave some insight into possible programmatic and public health challenges involved in rolling out new HIV prevention programmes.

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MRC/info4africa KZN Community Forum | May 2012

  1. 1. HIV Prevention Update Presented By: Dr. S.Ganesh Medical Research Council( SA) HIV Prevention Research Unit Durban HIV PREVENTION UPDATE
  2. 2. Discussion Focus • Background • Current prevention strategies • Recent updates • Roll out , Access and Challenges
  3. 3. A global view of HIV infection 2.4
  4. 4. Background • Worldwide, an estimated 34 million people are living with HIV, more than two thirds of whom live in sub-Saharan Africa. • Since the epidemic began in the early 1980s, more than 60 million people have been infected with HIV and nearly 30 million people have died of HIV-related causes. • Even as inroads are made, as a global crisis, HIV/AIDS shows few signs of slowing down Ref:
  5. 5. In • Approximately 2.7 million people were newly infected with HIV in 2010 – more than 7,000 every day. • The number of new infections continues to outstrip advances in treatment: • For every person starting HIV treatment, there are two new infections • Ref:
  6. 6. Women and HIV • Although the rate of new HIV infections is stabilizing or decreasing in many countries around the world, the global epidemic continues to have its greatest toll on sub-Saharan Africa, a region that accounts for 67 percent of all new HIV infections and 80 percent of the world‟s HIV-positive women. Ref:
  7. 7. • Women account for 59 percent of adults with HIV in sub-Saharan Africa, where unprotected heterosexual intercourse is the primary driver of the epidemic. • Young women are especially vulnerable. In southern Africa, young women are up to five times more likely to become infected with HIV than young men. • Among both men and women aged 15-24 in sub-Saharan Africa, 71 percent are women.
  8. 8. MSM and HIV • Throughout the globe, racial and ethnic minorities and men who have sex with men are disproportionately affected. • Men who have sex with men account for more than half of all new HIV infections in the U.S. each year, as well as nearly half of people living with HIV. • This population bears the burden of the epidemic in many other parts of the world, such as Europe, Latin America, Australia and New Zealand. Ref:
  9. 9. Importance of HIV prevention • Antiretroviral treatment alone will not be able to stem this epidemic • No intervention is likely to be fully protective • Need multiple approaches to HIV prevention (eg., male circumcision, HSV-2 suppression, PrEP) • Need short-term interventions while working towards effective HIV vaccines and microbicides • Need interventions that target reduced HIV infectiousness & decreasing HIV susceptibility
  10. 10. Current HIV Prevention Modalities • Biomedical Prevention • Abstinence • Condoms • Behavioral modification • Diagnosis and treatment of STIs • HSV suppression • PREP/PEP • Circumcision • Vaccines • Microbicides
  11. 11. Microbicides Needle exchange programmes Testing and treatment of genital infections (STIs) Cervical Barriers: vaginal diaphragms HSV-2 Suppressive therapy Exposure prophylaxis MTCT PEP PrEP Immunisation: Vaccines Voluntary Counselling and Testing (VCT) Behavioural Intervention Abstain Be faithful Condomise HIV PREVENTION Male circumcision
  12. 12. Rationale for Chemoprophylaxis for HIV Prevention • Continuous oral prophylaxis works against malaria and HIV PMTCT • Efficacy demonstrated in animal models • Can be combined with other prevention strategies • Could be used by both genders • Potentially could be effective against vaginal, anal, & parenteral transmission
  13. 13. Male Circumcision: Clinical Trials Population HIV Prevalence (%) Site Recruited End Date/Results HIV (-) men 7.3 Kenya (Kisumu) 2,784 53% reduction in HIV acquisition HIV (-) men 9 Uganda (Rakai) 4,996 48% reduction in HIV acquisition HIV (-) men 4.5 South Africa 3,274 60% protection from HIV acquisition Ref: Prof G. Ramjee ( 2006) Challenges Safety and Ethical Challenges Cultural and religious acceptability Effect on female partners From evidence to public health action
  14. 14. Biological data on HIV risk reduction  Removal of HIV target cells from foreskin  Keratinisation of skin surface – rapid drying  STI Epidemiological evidence  HIV prevalence  in circumcised men Meta analysis (Weiss et al, 2000)  38 (mainly African) studies – circumcision  risk of HIV Ref : Prof G Ramjee ( 2008) Male Circumcision for HIV Prevention
  15. 15. Challenges for HIV Vaccine Development  Virus HIV is hyper-variable Which HIV antigens needed for protection? No ideal animal model for HIV/AIDS Multiple forms/routes for transmission Replication cycle yields integration- permanently  Host Natural immunity doesn‟t eradicate HIV Correlate of protection- undefined Superinfection can occur Ref Prof G Ramjee ( 2008)
  16. 16. Microbicides: A Promising Strategy • Microbicides are products being developed to prevent or reduce the sexual transmission of HIV or other sexually transmitted infections (STIs) when used in the vagina or rectum.
  17. 17. What might a microbicide look like? A microbicide could assume a number of different forms: Gel or cream Film Suppository Pre-loaded diaphragm or cervical cap Sponge or vaginal ring slowly releasing active ingredient What would be the ideal characteristics of a microbicide? active against a range of sexually transmitted pathogens not irritating to mucosal surfaces available in both spermicidal and non-spermicidal formulations effective over relatively long periods acceptable to potential users (odor, color, taste, portability) biodiffusible bioadhesive stable at high temperatures able to maintain or enhance normal vaginal ecology; and not be absorbed systemically Tablet, capsule, film
  18. 18. • The idea for a microbicide-like product was first proposed more than 20 years ago by reproductive health specialists and advocates who recognized the need for female-controlled HIV prevention methods. • One of the first products considered was the spermicide nonoxynol-9 because researchers believed it might also be effective against HIV. • Unfortunately, research showed it was neither safe nor effective against HIV. Other trials of different so-called first generation microbicides also proved unsuccessful. • These included products intended to strengthen natural defenses in the vagina or create a barrier to protect target cells in the vagina Ref:
  19. 19.                   South Africa Zimbabwe Malawi Uganda Kenya Cameroon Benin Nigeria Tanzania Zambia Burkina Faso  CARRAGUARD CELLULOSE SULFATE 2% & 0.5% PRO2000 BUFFERGEL & 0.5% PRO2000 C31G (SAVVY) 1% TENOFOVIR GEL Ref: Prof G Ramjee      India  Philadelphia, USA PHASE IIB/III MICROBICIDE TRIALS: GLOBALLY
  20. 20.     CARRAGUARD CELLULOSE SULFATE 2% & 0.5% PRO2000 BUFFERGEL & 0.5% PRO2000        Durban MtubatubaHlabisa Johannesburg Pretoria Cape Town Johannesburg: RHRU Pretoria: MEDUNSA Cape Town: UCT Mtubatuba: Africa Centre Durban/Hlabisa: MRC Ref : Prof G Ramjee PHASE IIB/III MICROBICIDE TRIALS: SOUTH AFRICA
  21. 21. Earlier Clinical Trials of First-Generation Products • MDP 301 – A Phase III trial of PRO 2000 that involved 9,395 African women. The study found no evidence that PRO 2000 reduced the risk of HIV. Conducted by the Microbicides Development Programme, and reported in December 2009. Ref:
  22. 22. HPTN 035 • A Phase IIb trial of PRO 2000 and BufferGel that involved more than 3,000 women in Africa and the United States. Reported in February 2009, the results found PRO 2000 was 30 percent effective compared to a placebo, although this was not statistically significant. BufferGel was found to have no protective effect. Conducted by the MTN. Ref:
  23. 23. Savvy (C-31G) • Two Phase III trials of Savvy closed, the first in 2005 and the second in 2006, after interim reviews indicated little convincing evidence that Savvy protected against HIV. Both studies were conducted by FHI 360. Ref:
  24. 24. Cellulose Sulfate • In 2007, two Phase III trials of cellulose sulfate were closed early after a Data Safety and Monitoring Board (DSMB) review of the study conducted by CONRAD suggested an increased risk of HIV infection among women using the gel. As a precaution, the second study, conducted by FHI 360, was also closed, although its DSMB review found no evidence of increased risk. Ref:
  25. 25. Carraguard • A Phase III trial of Carraguard, a microbicide developed from carrageenan, a derivative of seaweed, that showed the product was safe and acceptable to women, but did not reduce their risk of acquiring HIV. Conducted by the Population Council Ref:
  26. 26. The State of the Field: Clinical Trials of ARV-Based Vaginal Microbicides • CAPRISA 004 – A Phase IIb trial that assessed the safety and effectiveness of tenofovir gel used before and after vaginal sex. • The study, which involved 889 women from South Africa, found tenofovir gel reduced the risk of HIV by 39 percent compared to a placebo. • However, results, which were reported in July 2010, also indicated that the true level of effectiveness of tenofovir gel – when used before and after sex – could be anywhere between 6 and 60 percent. • CAPRISA 004 provided the first proof of concept that a microbicide can help prevent HIV, a finding that was considered a major milestone for the field. Ref:
  27. 27. VOICE (MTN-003) • Vaginal and Oral Interventions to Control the Epidemic – is a major HIV prevention trial designed to evaluate the safety and effectiveness of two different ARV-based approaches for preventing sexual transmission of HIV in women: daily use of an ARV tablet (tenofovir or Truvada) or daily use of an ARV-based vaginal gel (tenofovir gel). • The study began in September 2009 and enrolled 5,029 women in Uganda, South Africa and Zimbabwe. • Testing of tenofovir tablets was halted after an independent review of study data in September 2011 concluded that although the tablets were safe they were no more effective than placebo in preventing HIV. • Similarly, a November 2011 routine review indicated that tenofovir gel was safe but not effective among the women in the study. VOICE continues to evaluate Truvada. • Final results are due in early 2013. Ref:
  28. 28. FACTS 001 • A Phase III study testing the same regimen as in CAPRISA 004, in which women use tenofovir gel before and after sex. FACTS 001 was launched October 2011 and seeks to enroll a minimum of 2,200 women at nine sites in South Africa. Being conducted by the Follow-on Africa Consortium for Tenofovir Studies. Results are expected in 2014 Ref:
  29. 29. CAPRISA 008 • A proposed three-year follow-up study of former participants from CAPRISA 004 that will test the feasibility and effectiveness of providing tenofovir gel in family planning clinics. Ref:
  30. 30. NEW PRODUCTS • Vaginal Rings • ASPIRE (MTN-020) – A Study to Prevent Infection with a Ring for Extended Use (ASPIRE) - is a Phase III effectiveness trial of a vaginal ring containing dapivirine. It is the first Phase III trial of a vaginal ring for preventing HIV. The study, being led by the MTN, is expected to be launched at several sites in Africa beginning mid-2012. About 3,476 women will be enrolled, who will be randomly assigned to insert either the dapivirine ring or a placebo ring every four weeks for at least one year. The dapivirine ring was developed by the International Partnership for Microbicides (IPM). Ref:
  31. 31. • The Ring Study (IPM 027) – As part of its strategy to license the dapivirine ring, IPM plans to conduct The Ring Study in parallel with ASPIRE, the study will collect long-term safety and efficacy data among approximately 1,650 women at multiple research centers in Africa. IPM expects to begin enrolling women into The Ring Study in the first quarter of 2012 Ref:
  32. 32. Challenges with HIV Prevention? • HIV Prevention at the Cross-Roads • Critically need evidence-based prevention strategies • Behavior change can be effective • Increased condom use among serodiscordant couples • Need to understand role of & interventions for multiple, concurrent partnerships • Biomedical interventions that have partial efficacy • Male circumcision of HIV-negative heterosexual men (clinical trial data) • ART (based on observational & ecologic data) • New biologic interventions being tested for efficacy • PrEP, microbicides (tenofovir gel), HIV vaccines, ART at higher CD4 (HPTN 052) • No single strategy will work alone • Multi-component, integrated, partially effective biomedical & behavioral interventions • Evidence-based approach to design of combination HIV prevention & testing effectiveness of a package
  33. 33. Combination Prevention? • Principles of Combination HIV Prevention • 1) Important to “know one‟s HIV epidemic” • HIV prevalence & incidence • Populations at highest risk • Whether they know they‟re at risk & their HIV serostatus • Modifiable risk factors (community & individual levels) • Evidence for different prevention interventions • 2) To slow HIV epidemic (Ro<1), need interventions with demonstrated efficacy to reduce infectiousness & susceptibility • ART for HIV+, MC for HIV- men at high risk (eg., in discordant couples) • Consider synergy, redundancy & antagonism when combine interventions • 3) Consider coverage, efficacy & cost-effectiveness in „scaling up‟ interventions
  34. 34. From Research to roll out Research to Rollout A schematic road map Clinical Trial Safety and Efficacy Real-world Effectiveness
  35. 35. Successes from 2011 What Works in HIV prevention, 2/12 Study Effect size (CI) Prime-boost Vaccine (Thai RV144, 2009) 1% tenofovir gel (CAPRISA 004, 2010) TDF/FTC oral PrEP (iPrEx, 2010) Medical male circumcision (Orange Farm, 2005; Rakai, Kisumu, 2007) TDF/FTC oral PrEP (TDF2, CDC, 2011) TDF oral PrEP (Partners PrEP, 2011) TDF/FTC oral PrEP (Partners PrEP, 2011) Immediate ART for HIV+ partner (HPTN 052, 2011) 31% (1, 51) 39% (6, 60) 44% (15, 63) 57% (42, 68) 63% (22, 83) 62% (34, 78) 73% (49, 85) 96% (82, 99) 0% 10 20 30 40 50 60 70 80 90 100% Efficacy
  36. 36. Access and Programmatic issues: Challenges and questions? • Who will receive HIV prevention? • How will they be monitored? • How often should HIV testing be done? • Side effects and tolerability? • Cost effectiveness?
  37. 37. To conclude…… • We now have an unprecedented opportunity ,based on solid scientific data to control and ultimately end the AIDS pandemic.(Tony Fauci ,NIH, 2011)
  38. 38. To conclude…….. • Our efforts have helped set the stage for the historic opportunity the world has today: To change the course of this pandemic and usher in an AIDS- free generation.“ ( Hillary Clinton,2011)
  39. 39. ACKNOWLEDGMENTS • Prof G Ramjee • Microbicides Trials Network
  40. 40. Thank You