1. HIV Prevention Biomedical A New Landmark in the Field of HIV Treatment
Moisés Agosto-Rosario
November 20th , 2011

2. TREATMENT IS PREVENTION: A CLINICAL SUMMARY.
A New Landmark in the Field of HIV Treatment
TREATMENT IS PREVENTION: A CLINICAL SUMMARY.

3. Game changers in the treatment of HIV
Discovery of the virus as the cause of AIDS.
Monitoring of immune damage and CD4 counts.
Prophylaxis for opportunistic infections.
The discovery of the first antiretroviral: AZT.
The introduction of new classes of HIV drugs and their use in combination therapy.
New diagnostics tests. The viral load test, Genotype and Phenotype tests.
Biomedical clinical modalities to prevent HIV infection.

4. The new landmark and the science behind it
ACTG 076 and the prevention of mother to child transmission using antiretroviral medications works.
CAPRISA 004. Effectiveness & safety of vaginal microbicide 1% tenofovir gel for prevention of HIV infection in women.
Needle Exchange. Clean needles works.
Male circumcision.
British Columbia Community Viral load cohort study.

5. The new landmark and the science behind it
Undetectable levels of HIV viral load in the blood may reflect undetectable levels in the seminal fluids.
HPTN 052 study. Use ARVs in sero-discordant couples
Pre-Exposure Prophylaxis (PrEP)
Post-Exposure Prophylaxis (PEP)

6. Prevention and Antiretroviral Therapy (ART) Treatment = Prevention
Prevention of Mother to Child Transmission
AZT alone reduced transmission from 25% to 8% Connor NEJM 1994
Current ART reduces transmission to <0.5%
Post-exposure prophylaxis (PEP)
AZT reduced risk in health care workers by 81%
Cardo NEJM 1997
Current CDC Guidelines recommend 2- or 3-drug antiretroviral treatment for 4 weeks following exposure
Adapted from: ”HIV Pre-Exposure Prophylasis (PrEP) Roy M. Gulick, MD,MPH. Weill Cornell Medical College.

7. HPTN 052: Treatment as Prevention in HIV+ Persons
1,763 discordant couples (97% heterosexual) in Africa, Asia, Americas. Those HIV+ had CD4 rage of
HIV+ partner randomized to start HIV treatment immediately or deferred until CD4 <250
DSMB Interim analysis:
90% on ART had HIV RNA <400
40 incident cases of HIV
29 linked genetically to partner
96% reduction in transmission!
Cohen IAS 2011 #MOAX0102 and NEJM 2011;365:493
Adapted from: ”HIV Pre-Exposure Prophylasis (PrEP) Roy M. Gulick, MD,MPH. Weill Cornell
Medical College.
years
probability
New HIV infections (all)
28 cases
1 case

8. Definitions: Treatment as Prevention in HIV- Persons
Microbicides
Gels, creams, films, or suppositories that can be applied inside the vagina or rectum to protect against sexually transmitted infections, including HIV
Post-exposure prophylaxis
Strategy of administering HIV drugs to uninfected individuals who are at-risk for HIV infection
Pre-exposure prophylaxis
Having HIV drugs present at the site of exposure should reduce the risk of infection
Adapted from: ”HIV Pre-Exposure Prophylasis (PrEP) Roy M. Gulick, MD,MPH. Weill
Cornell Medical College.

9. CAPRISA 04: Treatment as Prevention in HIV- (Microbicide Gel)
Safety
No substantive safety concerns
No tenofovir resistance identified
Safe in Hepatitis B infected women
No evidence of risk compensation/behavioral disinhibition
Proof of concept that tenofovir gel can prevent HSV-2 infection in women
51% reduction in HSV-2
Proof of concept that tenofovir gel can prevent HIV infection in women
39%protection against HIV overall
50%reduction in HIV after 1 year often of ovirgel use
54%effective in women with high adherence
Adapted from: “Quarraisha & Salim S Abdool Karim” on behalf of the CAPRISA 004 Trial Group

10. PrEP NIH Drug Criteria: Treatment as Prevention in HIV-
Safe
Penetrates target tissues
Protects against HIV infection in tissues
Long-lasting activity for convenient dosing
Unique resistance profile or high barrier to resistance
No significant drug-drug interactions
Affordable, easy to use and implement
NIH/DAIDS Working Group Report 4/09
Adapted from: ”HIV Pre-Exposure Prophylasis (PrEP) Roy M. Gulick, MD,MPH. Weill
Cornell Medical College.

11. Drugs studied for PrEP: TDF and FTC/TDF for PrEP
Optimal PrEP candidates:
potency, tolerability, and convenience
TDF = tenofovir
FTC/TDF = co-formulated emtricitabine+tenofovir
Potential concerns:
Used widely; preferred first-line treatment
Drug resistance
Toxicities: renal, ?bone
Cost
Adapted from: ”HIV Pre-Exposure Prophylasis (PrEP) Roy M. Gulick, MD,MPH. Weill
Cornell Medical College.

12. Clinical Trial of Tenofovir PrEP
West Africa Phase II PrEP Trial
RCT: TDF 300mg or matching placebo daily
Women in Ghana, Cameroon, Nigeria (N=936)
Conducted 6/04 - 3/06
No evidence of increased clinical or laboratory adverse effects
No evidence of behavioral risk compensation
Numbers too small to assess efficacy
8 new HIV infections: 2 TDF, 6 placebo
RR = 0.35, p=0.24
Adapted from: ”HIV Pre-Exposure Prophylasis (PrEP) Roy M. Gulick, MD,MPH.
Weill Cornell Medical College.
Peterson, PLoS One 2007;e27:1-9

13. iPrEx: PrEP in Gay Men
Study population: HIV-uninfected MSM or transgendered women from South America, South Africa, Thailand and U.S. (N=2499)
Ten were acutely HIV-infected at enrollment
44% reduction
64 infections
% HIV+
44% reduction
36 infections
If drug levels measurable, 92% reduction in risk
Adapted from: ”HIV Pre-Exposure Prophylasis (PrEP) Roy M. Gulick, MD,MPH. Weill Cornell Medical College.
Grant NEJM 2010;363:2587; IAS 2011 #WELBC04

14. CDC Guidance for PrEP for MSM: (Interim; 1/27/11)
Before starting:
document HIV status and r/o acute infection
Check kidney function, screen for sexually transmitted infections (STI) and hepatitis B
Rx TDF/FTC one pill a day X 90 days
provide risk reduction, adherence counseling, condoms
On treatment:
check HIV status every 2-3 months
check kidney function at 3 months and yearly
risk reduction, condoms, treat STIs
Adapted from: ”HIV Pre-Exposure Prophylasis (PrEP) Roy M. Gulick, MD,MPH. Weill
Cornell Medical College.

15. FEM-PrEP Study
Double-blind randomized study of PREP with TDF/FTC (vs. placebo) in HIV-uninfected heterosexual African women (N=1951)
Study stopped early by DSMB: “highly unlikely” to demonstrate benefit.
New HIV infections ~5%/yr in both groups
10% lost, 95% self-reported adherence
Why no difference?
True lack of effect?
Suboptimal PK in vagina/secretions?
Low adherence?
Adapted from: ”HIV Pre-Exposure Prophylasis (PrEP) Roy M. GulicMD,MPH.Weill
Cornell Medical College.
FHI Press Release 4/18/11

16. CDC Statement for PrEP for women: (4/18/11)
CDC cautions against women using PrEP for HIV prevention at this time. 
We will not know if PrEP is effective for women, couples, or injection drug users until the conclusive results of this and other trials are reported.
Adapted from: ”HIV Pre-Exposure Prophylasis (PrEP) Roy M. GulicMD,MPH.Weill
Cornell Medical College.

17. Partners PrEP 4758 serodiscordant couples in Kenya and Uganda
HIV- partners 38% women, 62% men; 98% married
95% retention; 97% adherence
unprotected sex 27% at baseline and ↓ during study
No difference in side effects, lab abnormalities, deaths
Adapted from: ”HIV Pre-Exposure Prophylasis (PrEP) Roy M. GulicMD,MPH.Weill
Cornell Medical College.
Baeten IAS 2011 #MOAX0106

18. CDC – TDF-2 Double blind, placebo-controlled study in Botswana
18-39 years old, heterosexual, sexually active
1200 followed over time (45% women)
No safety differences
No differences by sex
Adapted from: ”HIV Pre-Exposure Prophylasis (PrEP) Roy M. GulicMD,MPH.Weill
Cornell Medical College.
Thigpen IAS 2011 #WELBC01

19. What do we know thanks to biomedical research?
Taking HIV treatment (ART) reduces transmission from HIV+ to HIV- people (mother/child; sexual partners).
PrEP works by providing HIV drugs prophylactically to HIV-negative people.
PrEP, when used consistently, reduces the HIV transmission risk among HIV-negative gay men.
New biomedical prevention modalities are new tools that add to existing proven behavioral modalities.
Adapted from: ”HIV Pre-Exposure Prophylasis (PrEP) Roy M. GulicMD,MPH.Weill
Cornell Medical College.

20. What do these science advances mean for the HIV Epidemic?
They mean:
The ability to decrease HIV transmission, morbidity and possibly contain the epidemic.
By giving PWA early access to HIV treatment and reducing viral loads to undetectable levels, we may prevent transmission to HIV-negative partners by 96%.
By using PrEP, Microbocides, and PEP to the HIV - adding it to the prevention arsenal we may reduce HIV incidence among sexually active adults.

21. Operationalization and Implementation
From Clinical to Public Health
Controlled settings VS Real Life
Adapted from: HIV Care in a Shifting Landscape.

22. and achievement of complete viral suppression.
The spectrum of engagement in HIV care in the United States spanning from
HIV acquisition to full engagement in care, receipt of antiretroviral therapy,
and achievement of complete viral suppression.
The spectrum of engagement in HIV care in the United States spanning from HIV acquisition to full engagement in care, receipt of antiretroviral therapy, and achievement of complete viral suppression. We estimate that only 19% of HIV-infected individuals in the United States have an undetectable HIV load.
Gardner E M et al. Clin Infect Dis. 2011;52:
© The Author Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please

23. Global & Caribbean
About 40% of people living with HIV know their status.
Caribbean: ? % of people living with HIV know their status.

24. HIV Prevention Biomedical
Treatment is Prevention: What do we do and how do we do it?
HIV Prevention Biomedical

25. ART for Prevention: A Multi-Component Strategy: Obstacles and Challenges
Strengthen Community Mobilization
Leadership development
Community and evidence based approaches will allow high risk groups to have universal access.
Buy-in by PLWH and start the conversation. Removal of HIV Stigma.
A WHO evaluation of 186 community –based service delivery projects in Europe, South-East Asia and Latin America found that local CBOs led by PLWH are best in reaching populations at higher risk.

26. ART for Prevention: A Multi-Component Strategy: Obstacles and Challenges
We must have political will, guidance and public policies at all government levels to make ARV for prevention an essential component of universal access to HIV care.
Make second line treatment in low and middle income countries available.
The cost of the pills and complex monitoring systems and supply management are needed. With access to only first line treatment we will not be able to reach universal access.
We need new formulations, better pills and simpler diagnostics tools.

27. ART for Prevention: A Multi-Component Strategy: Obstacles and Challenges
We need to improve increase and uptake of HIV testing and linkage to care.
Evidence based programs around the world show that individual engagement with CBOs has a positive impact and increase HIV testing rates, use of prevention and treatment services, adherence, prevention practices and stigma reduction.

28. Conclusions:
We have strong scientific evidence that prove that the AIDS epidemic could be contained in our lifetime.
We need to remove socio-economic and political obstacles to make it a reality: An AIDS free generation.