2. Advances in Biomedical HIV Prevention Interventions
Z Mike Chirenje MD FRCOG
University of Zimbabwe, College of Health Sciences,
Dept. of Obstetrics and Gynaecology
Avondale, Harare, Zimbabwe

3. Controlling HIV Epidemic
UNAIDS recent data that shows 35% decline in new HIV infections and dramatic (42%) fall in AIDS related deaths brings us hope towards a future AIDS free generation.
These remarkable achievements are a result of interventions such as condom use, VMMC, knowledge of partner status, all of which require male partner cooperation thus inadequate for many women
Development of new biomedical interventions that women can use remains a high priority as critical step towards ending the epidemic in 2030
Adapted from
Lets look at burden of new HIV infections in 2013, clearly SSA is epicenter of new infections

4. Annual New HIV Infections in 2013
Women have higher burden of disease because of biological, socio-behavioural and structural differences.
Now lets look at new HIV infections in ESA 2013
Of the million Worldwide infections in 2013, SSA had 1.5million (68.8%) infections majority (57 %) were women. Most of these infections were in ESA

5. Eastern and Southern Africa:
Eastern and Southern Africa: New HIV infections among young people aged years
Again we are pleased to see a decline, but burden of disease is almost twice heavier in the girl child than boy child, a huge justification for urgent biomedical intervention methods which are suitable for young women.
What data for HIV prevention has accumulated from biomedical research in the past 15 years by chronology of study results?
Pleased to notice a decline but burden of disease twice as high in F than M

6. Randomised controlled trials of voluntary medical male circumcision to reduce HIV infection
Rakai, Uganda
Gray et. al. (2007) Lancet; 657 – 66%
Kisumu, Kenya
Bailey et. al. (2007) Lancet; 643 – 56%
We are please to see current accelerated efforts to see MMC across Africa in massive scale.
Orange Farm, South Africa
Auvert et. al. (2005) PLoS Med; e298 – 61%

7. VMMC is essential to maintain decline in HIV incidence
For high HIV prevalence and low rates circumcision communities, VMMC remains a critical priority towards control new HIV infections
Every 10% increase in circumcision coverage is associated with 12% reduction HIV incidence
UNAIDS fast track target of 27 million men circumcised in next 5 yrs if implemented will result in significant impact reduction new HIV infections

8. PrEP for HIV Prevention in Men Who Have Sex with Men. Grant et al, 2010
Truvada had a 44% protection against HIV infection of MSM and transgender women who sex with men
ARV Prophylaxis for HIV Prevention in Heterosexual Men and Women. Beaten et al, 2012
Truvada had a 75% protection against HIV infection

9. TDF/FTC was FDA Approved for use for Prevention on July 16, 2012
Approval was based on iPrEx and Partner’s Study
PrEP uptake has been limited to mainly
demonstration programs thus inadequate to give us
wide population level impact

10. Prevention of HIV -1 Infection with Early Antiretroviral Therapy
Prevention of HIV -1 Infection with Early Antiretroviral Therapy. Cohen MS et al, 2011
Early initiation of antiretroviral therapy reduced the rate of sexual transmission of HIV-1 in discordant couples by 96%
No index-to-partner (linked) HIV transmissions were observed when the index participant was stably suppressed on ART (After 5 year extended follow up, data presented at IAS Vancouver, 2015)(after 5yr extended follow-up): (after 5yr):

11. HPTN 052 Enrollment (Total: 1763 couples)
54% of HPTN 052 participants were from 5 African participating sites including Zimbabwe!

12. Biomedical Interventions: Focusing on HIV prevention options for women
Development of a microbicide since 1992 has been long, tortuous, with at least 41,000 women from ESA volunteering in these trials
Microbicides are compounds that can be applied topically(vaginally or rectally), have no systemic(blood) exposure
For a product to be effective, it must get to right place, right time, right dose, high barrier to develop resistance
Available & affordable
Lets now look at different options tested in biomedical intervention studies.

13. A Model of HIV Entry Into Female Genital Tract
Epithelial Disruption that allows viral entry
Entry of HIV infection into female genital tract is accelerated by disruption (“cracks”) in the lining of vagina or cervix. Development of microbicides products are designed to prevent HIV from arriving at illustrated target cells
Hassey,Nature 2010

14. Progression in the product pipeline
C31G, N9 BufferGel
PRO2000, CS, Carraguard
Tenofovir, TMC 120, UC781, MIV150
THREE generations of microbicides have been tested in clinical trials, mechanism of action follows HIV entry into female genital tract. ARV based formulations are the most promising to enter registration and market.

15. 2010 was a very good year for microbicide studies!
First study to provide proof of concept for ARV-based prevention
CAPRISA 004
1% tenofovir gel resulted in 39% (CI 6-60) reduction HIV infection among high-risk women
Women inserted the gel up to 12 hrs before sex and another insertion within 12 hrs after sex, less than 2 doses in 24 hrs

16. The end of TFV gel development for HIV prevention in women?
At CROI March 2013, VOICE study reported no protection of HIV infection among women using TFV gel as daily regimen
At CROI Feb 2015, FACTS 001 report no protection of HIV infection among women using TFV gel BAT regimen used in CAPRISA
Clearly tenofovir gel was not acceptable for these women as evidenced by low levels (<25%) of detectable tenofovir in swabs collected from genital tract

17. What was Impact of VOICE Study
VOICE was “Game-changer” – removed any reliance on self-reported adherence
Surprisingly, HIV risk perception was clearly not their greatest concern, particularly in young women < 25yrs
Objective measurements(PK) of adherence are now obtained during the trial and results discussed with participants as unblinded data across CRS

19. To overcome adherence challenges: longer acting products on the horizon
Vaginal ring containing ARV dapivirine replaced every 4 weeks
Women need safe and effective HIV prevention products that work within the context of their lives!
Women need safe and effective HIV prevention products that work within the context of their lives!
Even if women say they like it, will they actually be inclined to use it, as directed, once a month?
But the underlying reason we conducted ASPIRE is, of course, because women need options for preventing HIV that are safe and effective. And they need options that work for them - that are practical and make sense within the context of the lives. Efforts to promote abstinence, monogamy and the use of male condoms have not been enough to put a stop to the epidemic, nor are these methods practical for many women.

20. ASPIRE and its “Sister Study”
ASPIRE is one of two Phase III trials of the dapivirine ring
Both ASPIRE and The Ring Study are designed to support potential approval and licensure of the dapivirine ring
2,629 women in Malawi, South Africa, Uganda, Zimbabwe
Study was completed June 2015
Results early 2016
1,959 women in South Africa and Uganda
Study to be completed Dec. 2016
Results early 2017
ASPIRE and The Ring Study are the first large-scale trials of a vaginal ring for HIV prevention, and they are designed to gather the kind of information that regulators would need in order to decide whether or not to approve the ring for widespread use.

21. Long Acting ARV IM injection formulations: A new biomedical tool
New nanosuspension ARV based IM formulations given every 8 weeks are in early testing phases
LA form of oral Rilpivirine (TMC278 LA) an NNRTI is being tested for safety and acceptability in HPTN 076
GSK LA an Intergrase Inhibitor with low resistance threshold is being tested in HPTN 077
Concern of long tail of drug release at sub therapeutic levels with potential to development of resistance.

22. Neutralizing Antibody Epitopes on Native Trimer (since 2009)
A phase 2b study will test if pasive infusions of monochlonal Ab will prevent HIV infection
gp41 MPER:
2F5, 4E10 10e8
CD4 Binding Site:
VRC01, PG04, CH31 3BNC117, 12A12 CH103, VRC07
Trimer (gp120/41)
8ANC195 PGT
V1V2 Glycan:
PG6, PG16, CH01-04 PGT CAP256-VRC26
N332 Glycan Supersite:
PGT121, PGT
Highly selected donors

23. What are our current challenges towards UNAIDS 90/90/90 targets
Stigma of HIV continues unabated resulting: people from not getting tested, not taking medications, not disclosing their diagnosis to loved ones
 We need strong advocacy to implement PrEP: avoiding PrEP condemns some people to lifetime of HIV treatment at enormous cost
Advocacy for test linked to care to achieve high viral suppression, reduction in community viral load, reduction new infections

24. Combination HIV Prevention Vaccine Condoms Microbicides PrEP/PEP
Scientists need to test novel prevention modalities to fill the prevention gap
Vaccine
HIV Testing
and the Care
Continuum
Microbicides
Condoms
Combination
HIV
Prevention
PrEP/PEP
Education
Treatment as
Prevention
STI
Treatment
Circumcision
Drug/Alcohol
Interventions
Structural
Interventions
Adherence to
Prevention and
Treatment

25. Summary
Its an exciting time for HIV prevention research with biomedical tools as core to combination approach
We must urgently advocate for universal access to ART, scaling up VMMC, offering PrEP as prevention option to all at substantial risk populations
In 2016 the long journey for a microbicide may have fruitful end!

26. Acknowledgements Study Participants NIH (Grant Number U01AI069436)
UZ-UCSF
All our international Collaborators.
Put our current grant number