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

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

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.

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.

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)

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 www.aidsinfo.nih.gov Adapted from: ”HIV Pre-Exposure Prophylasis (PrEP) 2011. Roy M. Gulick, MD,MPH. Weill Cornell Medical College.

HPTN 052: Treatment as Prevention in HIV+ Persons 1,763 discordant couples (97% heterosexual) in Africa, Asia, Americas. Those HIV+ had CD4 rage of 350-550 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) 2011. Roy M. Gulick, MD,MPH. Weill Cornell Medical College. years probability New HIV infections (all) 28 cases 1 case

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) 2011. Roy M. Gulick, MD,MPH. Weill Cornell Medical College.

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

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) 2011. Roy M. Gulick, MD,MPH. Weill Cornell Medical College.

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) 2011. Roy M. Gulick, MD,MPH. Weill Cornell Medical College.

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) 2011. Roy M. Gulick, MD,MPH. Weill Cornell Medical College. Peterson, PLoS One 2007;e27:1-9

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) 2011. Roy M. Gulick, MD,MPH. Weill Cornell Medical College. Grant NEJM 2010;363:2587; IAS 2011 #WELBC04

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 http://www.cdc.gov/hiv/prep/index.htm Adapted from: ”HIV Pre-Exposure Prophylasis (PrEP) 2011. Roy M. Gulick, MD,MPH. Weill Cornell Medical College.

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) 2011. Roy M. GulicMD,MPH.Weill Cornell Medical College. FHI Press Release 4/18/11

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. http://www.cdc.gov/hiv/prep/index.htm Adapted from: ”HIV Pre-Exposure Prophylasis (PrEP) 2011. Roy M. GulicMD,MPH.Weill Cornell Medical College.

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) 2011. Roy M. GulicMD,MPH.Weill Cornell Medical College. Baeten IAS 2011 #MOAX0106

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) 2011. Roy M. GulicMD,MPH.Weill Cornell Medical College. Thigpen IAS 2011 #WELBC01

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) 2011. Roy M. GulicMD,MPH.Weill Cornell Medical College.

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.

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

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;52:793-800 © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

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

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.

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.

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.

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.