1 / 24

MICROBICIDES FOR HIV PREVENTION

MICROBICIDES FOR HIV PREVENTION. Z Mike Chirenje MD FRCOG University of Zimbabwe Harare, Zimbabwe chirenje@uz-ucsf.co.zw. HIV incidence and HIV prevalence by age and sex, South Africa 2005. 30. Prevalence (females). Prevalence (males). 25. Incidence (females). Incidence (males). 20.

wardah
Download Presentation

MICROBICIDES FOR HIV PREVENTION

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. MICROBICIDES FOR HIV PREVENTION Z Mike Chirenje MD FRCOG University of Zimbabwe Harare, Zimbabwe chirenje@uz-ucsf.co.zw

  2. HIV incidence and HIV prevalence by age and sex, South Africa 2005 30 Prevalence (females) Prevalence (males) 25 Incidence (females) Incidence (males) 20 HIV Prevalence and Incidence (%) 15 10 5 0 <20 20-29 30-39 40-49 >50 Age group (years) Source: Rehle T, et al. SAMJ 2007; 97: 194-199

  3. Young Women Have Increased Vulnerability in Many High Risk Areas 20 15 10 5 0 Mali 2001 Ghana 2003 Kenya 2003 Zambia 2002 Lesotho 2004 Tanzania 2003 Cameroon 2004 Uganda 2004/05 South Africa 2002 Burkina Faso 2003 Zimbabwe 2001/02 Women Men % HIV prevalence UNAIDS, WHO. AIDS epidemic update, December 2005

  4. How HIV-1 crosses mucosal barrier is still unknown but a model of SIV to rhesus macaques by intravaginal inoculations showed that VRNA+cells could be first detected in intraepithelial lymphocytes and CD4 + T cells in the sub mucosa underlying endocervix 72 hours after exposure.

  5. NSI HIV (M-tropic) SI HIV (T-tropic) semen lamina propria dendritic cell CD4+ CCR5+ DC-SIGN+ exposure at mucosal epithelium CD4 DC-SIGN CCR5 T cell migration to lymphoid organs

  6. HIV-1 Transmission Model Donor Mucosa Recipient Abortive Abortive Abortive Less fit or attenuated Time (days) 7 0 14 21 28 Summary: Phylogenetic analysis of HIV-1 in early infection in the context of a model of random viral evolution allows for the indentification of transmitted/early founder virus(es) responsible for productive clinical infection (Keele et al., PNAS 2008).

  7. HIV Transmission Efficiency??Powers, Poole, Pettifor and Cohen, IAS 2008 The “Dogma” 1/1000 “episodes” of vaginal intercourse leads to HIV transmission (11 studies) Can this be correct???

  8. Mucosal Transmission of HIV Infection Shattock and Moore 2003

  9. Translation of Evidence Based KnowledgeINTO HIV PREVENTION STRATEGIES • Voluntary counseling and testing • Education and behavioral modification • Drug abuse treatment • Condoms, clean syringes • PMTC • STI Treatment • ART • Microbicides, Circumcision, Vaccines

  10. Microbicides for HIV Prevention What is a microbicide? A substance that can be applied in the vagina or rectum in order to substantially reduce STIs/HIV acquisition.

  11. Microbicides Cream Suppository Gel Film

  12. The IPM Pipeline:

  13. Mechanism: Maintenance or mobilisation of normal vaginal defences Examples: * Buffergel * Engineered lactobacillus * Hydrogen peroxide/peroxidases Microbicides enhancing natural defences under development

  14. Mechanism: Kill or inactivate pathogens by disrupting membrane or envelope Examples: * Nonoxynol-9 / Octoxynol-9 * Benzalkonium chloride * C31G – Savvy * Chlorhexidine zinc gel 1st generation microbicides - surfactants Diagram source: Stone A. Nature Reviews 2002, 1: 977-85.

  15. Mechanism: Inhibits first steps of pathogen entry into mucosal cells Examples: * Carraguard / PC-515 * PRO 2000 gel * Cellulose Sulphate * Emmelle / Dextrin - 2 - Sulfate 2nd generation microbicides - polymers

  16. Mechanism: Inhibits post-fusion replication Examples: * Nucleoside reverse transcriptase inhibitors (Tenofovir) * NNRTIs (UC-781, TMC120) * Protease inhibitors (WHI-07) 3rd generation microbicides – Antiretroviral agents

  17. Progression in the product pipeline C31G, N9 BufferGel PRO2000, CS, Carraguard Tenofovir, TMC 120, UC781, MIV150

  18. Drug Discovery, Development and Review Process

  19. Effectiveness Trials 2007

  20. HPTN035 Study • Enrolled participants from Feb 2005 • Completely enrollment (3099 women) Jul 07 • Exited last participants Sept 2008 • Primary end point was HIV infection • HSV-2, BV, GC, syphilis, candidiasis and TV are all secondary study endpoints • At least once vaginal intercourse in three months prior to screening

  21. Survival Free of HIV Infection

  22. HIV Risk Reduction

  23. Prevention of HIV: PRO 2000 Gel • PRO 2000 Gel was 30% effective in preventing HIV infection. • One way to understand this result is to think about 10 women who might get HIV from having unprotected sex with an infected partner. Among these 10 women, using PRO 2000 Gel would be expected to prevent 3 of them from getting HIV.

  24. History of microbicide development 1st generation: Surfactants eg. N9, SAVVY 2nd generation: Polymers eg. PRO2000, Carraguard, Cellulose Sulfate (CS) 3rd generation: ARVs eg. Tenofovir gel, UC-781, TMC-120 4th generation: Co-receptor Blockers eg. CD4 blocker, CCR5 Blockers MTN trial Zena Stein publishes seminal article “HIV prevention: the need for methods women can use” COL-1492 trial IPM trial HPTN trial N-9 film trial Carraguard trial N-9 sponge trial MDP trial CAPRISA trial SAVVY trial CS trial ‘90 ‘92 ’98 ’00 ‘03 ‘04 ’04 ’05 ’05 ’07 ’08 08

More Related