1. Ian McGowan MD DPhil FRCP University of Pittsburgh Pittsburgh, PA, USA
Why We Need More than PrEP Expanding the HIV Prevention Toolbox in Africa
Ian McGowan MD DPhil FRCP
University of Pittsburgh
Pittsburgh, PA, USA

2. Disclosure
I have no financial relationships with a commercial entity producing, marketing, reselling or distributing healthcare related products and/or services.

3. Prevention Options for MSM & TGW
Proven interventions
Oral PrEP
(Diagnosis and treatment of STIs)
(Condoms)
(Circumcision)
Interventions under evaluation
Long-acting antiretroviral agents
Broadly neutralizing antibodies
Rectal microbicides
Vaccines

4. What Do People Want?
“With a lack of understanding of their social and sexual lives and HIV risks, and with MSM being a hidden and stigmatized group in the region, optimized HIV prevention packages for southern African MSM are an urgent public health and research priority.”
McNaghten A et al. 2014

6. The State of the Science

7. Rectal Microbicides

8. How Are They Applied?

9. Could a Rectal Microbicide Work?
“HIV” (99mTc-SC) in Ejaculate
“Microbicide”(111In-DTPA)
CHARM-02 Study (Hiruy H et al. AIDS Res Hum Retroviruses 2015)

10. Rectal Microbicide Animal Models
Humanized mouse
Rhesus macaque

11. Rectal Microbicide Studies
Completed studies
Nonoxynol-9
HIVNET-008
UC781
RMP-01
Tenofovir 1% gel
RMP-02/MTN-006
MTN-007
Project Gel
CHARM-01 & CHARM-02
Maraviroc
CHARM-03
Phase 2
MTN-017
Planned Phase 1 Studies
MTN-026
MTN-033
MTN-037
MTN-039
DREAM-01
PREVENT-01

12. Questions to Consider Do we need rectal microbicides?
Is tenofovir 1% gel the best candidate to move into later stage development?
Is a vaginal applicator the best way to deliver a microbicide?
What is the best dosing regimen?
What is the best study design?

13. Priorities in Rectal Microbicide Research
Pericoital use
Extended efficacy (72 hours)
Lubricant rather than applicator delivery
Multipurpose products
HIV, HPV, HSV, HCV
Novel delivery systems
Rectal douches
Rectal inserts
THSY08
The future of chemoprophylaxis: new concepts
Abstract: THSY08
14:30 – 16:00
Session Room 6

14. Long Acting Antiretroviral PrEP

15. Requirements for LA ARV
Potency and PK profile allowing infrequent dosing (~ 2-3 months)
Practical injection volume (~ 4mL)
Stable formulation ideally without cold chain requirements
Potential products
TMC278 LA (Rilpivirine)
GSK 744 (Cabotegravir)

16. Rilpivirine Levels in Plasma
Persistence of rilpivirine following
single dose of long-acting injection
Abstract: TUAC0103
11:00 – 12:30
Session Room 11
1200 mg
600 mg
300 mg
Jackson A et al. Clinical Pharmacology & Therapeutics 2014

17. HPTN-083 Study of Cabotegravir
One month
oral run in phase
Exposure to
LA PrEP every
2-3 months
Two IM injections
HPTN 083 is a study being done to evaluate the efficacy of the long-acting injectable agent, cabotegravir (CAB LA), for pre-exposure prophylaxis (PrEP) in HIV-uninfected men and transgender women who have sex with men (MSM and TGW).
HPTN 083 will enroll approximately 4500 HIV-uninfected MSM and TGW at risk for acquiring HIV infection, ages 18 or older at sites in the Americas, Asia and South Africa.
Status: Pending
PrEP
Cessation
12 months of
Oral PrEP

18. Implantable Formulations
Tenofovir alafenamide (TAF) implant
Gunawardana M et al.
Antimicrob Agents Chemother 2015
TAF biodegradable implant
Van der Straten A
USAID Grant
In Progress

19. Broadly Neutralizing Antibodies

20. Broadly Neutralizing Antibodies
HVTN 704 / HPTN-085 (The AMP Study)
N = 2,700
This study will evaluate the safety and efficacy of the human monoclonal antibody (mAb) VRC-HIVMAB AB (VRC01) in preventing HIV-1 infection among men and transgender (TG) persons who have sex with men, in North and South America
Timeline: March 2016 – September 2020
Participants will receive an intravenous (IV) infusion of 10 mg/kg of VRC01 over about 30 to 60 minutes at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72.
Companion study HVTN 703 in women in Africa

21. Vaccines

22. Vaccine Development HVTN 702 Phase 3 study in South Africa
ALVAC-HIV (Clade C)
Bivalent gp120 protein subunit vaccine (Clade C)
MF59 adjuvant
Phase 3 study in South Africa
Men and women
N= 5,400
Duration 3 years
Timeline: Starting in November 2016
The HVTN 702 vaccine regimen consists of two experimental vaccines: a canarypox-based vaccine called ALVAC-HIV and a bivalent gp120 protein subunit vaccine with an adjuvant that enhances the body's immune response to the vaccine. Both ALVAC-HIV (supplied by Sanofi Pasteur) and the protein subunit vaccine (supplied by GSK) have been modified from RV144 to be specific to HIV subtype C, the predominant HIV subtype in southern Africa. In addition, the protein subunit vaccine in HVTN 702 is combined with MF59 (also supplied by GSK), a different adjuvant than the one used in RV144, in the hope of generating a more robust immune response. Finally, the HVTN 702 vaccine regimen will include booster shots at the one-year mark in an effort to prolong the early protective effect observed in RV144

23. Product Access Timelines
Development Phase
Potential Access
Oral PrEP
Licensed
Kenya
South Africa
Vaccines
Phase 3
2021?
Broadly neutralizing antibodies
Phase 2
N/A
Rectal microbicides
2022?
LA PrEP
Phase 2B/3

24. Summary
In the short term oral PrEP will be the most accessible HIV prevention product for African MSM and TGW
Financial constraints may limit access to oral PrEP
A safe and effective HIV vaccine would have the biggest public health benefit
The future of LA PrEP and BNabs is uncertain due to costs and complexity of delivery
Pericoital products including rectal microbicides could provide a more cost effective PrEP product