Meeting Minutes - November 10, 2011

Office of AIDS Research Advisory Council
Thirty-third Meeting
November 10, 2011

National Institutes of Health
U.S. Department of Health and Human Services
5635 Fishers Lane Conference Center
Rockville, MD

Members Present: Dr. Judith Auerbach (Acting Chair), Dr. Jack Whitescarver (Executive Secretary), Dr. David B. Clifford, Dr. Steven G. Deeks, Dr. Carrie E. Foote, Dr. Igor Grant, Dr. Lisa Jacobson, Ms. Catalina Sol, Dr. Ronald Swanstrom, Dr. Rochelle Walensky, Mr. Mitchell J. Warren, Dr. Judith N. Wasserheit, and Dr. Craig M. Wilson

Ex Officio Members Present: Dr. John G. Bartlett, Dr. Victoria Davey, Dr. Carl W. Dieffenbach, Dr. H. Kim Lyerly, Dr. Christel H. Uittenbogaart, Dr. Richard Wolitski for Dr. Kevin Fenton, and Dr. Steven M. Wolinsky

Invited Speakers and Guests: Dr. Stefan Baral, Dr. Cynthia I. Grossman, Dr. Roy M. Gulick, Dr. Albert Liu, Dr. David J. Malebranche, Dr. Ian McGowan, Mr. Jim Pickett, Dr. Magdalena Sobieszczyk, Dr. Ronald D. Stall, and Dr. Darrell P. Wheeler

Welcome and Meeting Overview

The National Institutes of Health (NIH) Office of AIDS Research Advisory Council (OARAC) convened its thirty-third meeting at 8:30 a.m. at the Fishers Lane Conference Center in Rockville, Maryland. Dr. Judith Auerbach served as Acting Chair due to the absence of Dr. Sharon Hillier. She welcomed the OARAC members, invited speakers, and guests.

The topic of the meeting was AIDS research in men who have sex with men (MSM): opportunities and challenges. Dr. Auerbach noted that AIDS research in this population, which comprises gay and other men who have sex with men, is a key priority in the President’s National HIV/AIDS Strategy. The specific issues to be addressed at this OARAC meeting were the evolving HIV/AIDS epidemic among MSM; the epidemiology of HIV infection among MSM in low- and middle-income countries; clinical and behavioral aspects of HIV infection; and recent prevention research related to MSM.

Dr. Auerbach referred participants to the meeting folder for additional information about the next two upcoming OARAC meetings.

The minutes of the March 24, 2011, OARAC meeting were approved as submitted.

Director’s Report

Dr. Jack Whitescarver, Director, OAR, welcomed everyone to this meeting of the OARAC. He introduced five new members of the OARAC: Dr. Rochelle Walensky, Harvard Medical School; Mr. Mitchell J. Warren, AIDS Vaccine Advocacy Coalition; Dr. Craig M. Wilson, University of Alabama at Birmingham; Dr. Steven Deeks, University of California, San Francisco; and Dr. Igor Grant, University of California, San Diego. He noted that they are world-renowned leaders in their fields and bring a wealth and breadth of knowledge and expertise to OARAC.

NIH Personnel Changes
Dr. Whitescarver reported on several recent personnel changes at NIH: Dr. Martha Somerman was appointed the new Director of the National Institute of Dental and Craniofacial Research; Dr. Vivian Pinn retired from the NIH after 20 years as Director of the Office of Research on Women’s Health (ORWH), and Dr. Janice Clayton is now Acting ORWH Director; Dr. Barbara Alving retired as Director of the National Center for Research Resources, and Dr. Louise Ramm became the Acting Director; Dr. Judith Greenberg was named as Acting Director of the National Institute of General Medical Sciences until Spring 2012 when Dr. Chris Kaiser, Professor and Chair of the Department of Biology, Massachusetts Institute of Technology, will become the new Director; and Dr. Mahendra Rao has been appointed Director of the new NIH Intramural Center for Regenerative Medicine.

Office of National AIDS Policy Personnel Change
Dr. Whitescarver reported that Mr. Jeffrey Crowley, Director of the Office of National AIDS Policy (ONAP) at the White House recently announced he will be leaving at the end of 2011. Dr. Whitescarver noted that the OAR has worked closely with Mr. Crowley and his colleagues over the past 2 years to develop and implement the President’s National HIV/AIDS Strategy.

Dr. Whitescarver introduced Mr. Gregory Millett, CDC liaison to ONAP, who has worked with Mr. Crowley, and was attending the OARAC meeting.

Budget Update
Dr. Whitescarver reported that NIH does not have a budget for Fiscal Year (FY) 2012 yet, and it is operating under a Continuing Resolution at the FY 2011 budget level, which is less than the budget for FY 2010. He stated that the OAR is proceeding to develop the trans-NIH FY 2013 AIDS budget, which the President will present to Congress in early February, and OAR is identifying the highest research priorities to support under these budget constraints. He noted that the discussions at OARAC meetings and OAR-sponsored workshops help guide the OAR in making these critical decisions that help frame the budget.

International AIDS Conference
Dr. Whitescarver mentioned that the XIX International AIDS Conference will be held on July 22–27, 2012, in Washington, D.C. He serves on the Conference Coordinating Committee for this important meeting, which will bring more than 20,000 participants and 2,000 media to Washington, D.C.

CONFLICT OF INTEREST STATEMENTS

Dr. Whitescarver asked Council members to review and sign the conflict of interest statement provided to them.  He reminded the Council members of the importance of this process.

UPDATE ON OARAC WORKING GROUPS FOR TREATMENT AND PREVENTION GUIDELINES

Dr. John G. Bartlett, Professor of Medicine, Johns Hopkins University School of Medicine, and Co-Chair, OARAC Antiretroviral Treatment Guidelines for Adults and Adolescents Working Group, provided an overview of recent updates of the five treatment and prevention guidelines that are developed and updated by OARAC Working Groups and posted and disseminated by AIDSinfo.nih.gov. He noted that the five OARAC working groups jointly issued on August 26, 2011, the Guidance for Non-HIV-Specialized Providers Caring for HIV-Infected Residents Displaced from Disaster Areas. These guidelines were first issued in September 2005 and they are updated periodically based on clinical advances.

Dr. Bartlett reported that the updated Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection were issued in August 2011. These guidelines expand the criteria for therapy in children older than 5 years and allow for treatment at all CD4 counts in children older than 1 year. The preferred initial therapy for all infants and children ages ≥14 days to <3 years is lopinavir/ritonavir (LPV/r) plus two nucleoside reverse transcriptase inhibitors (NRTIs), with nevirapine-based regimens now considered an alternative regimen for initial therapy in this age group. For initial therapy for children age ≥6 years, atazanavir with low-dose ritonavir boosting has been added as a second preferred protease inhibitor choice, joining lopinavir/ritonavir. The guidelines include expanded use of tenofovir disoproxil fumarate (TDF) in combination with emtricitabine (FTC)/lamivudine (3TC) in children. The guidelines include four new sections on toxicity and specifically do not recommend the use of LPV/r in infants younger than 14 days old.

Dr. Bartlett noted that the revised Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States were issued in September 2011. He reported that the guidelines include new sections on management of acute HIV infection during pregnancy and diagnosis and management of HIV-2 infection in pregnancy. The guidelines now recommend TDF as an alternative nucleoside reverse transcriptase inhibitor (NRTI) for pregnant women and as a preferred NRTI for pregnant women with chronic hepatitis B virus (HBV). The guidelines also recommend a two-drug combination prophylaxis for neonates whose HIV-infected mothers did not receive antepartum antiretroviral therapy (ART).

Dr. Bartlett reported that the updated Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents were issued in October 2011. He summarized the key changes including the use of: rilpivirine was added as an alternative non-nucleoside reverse transcriptase inhibitor (NNRTI) option for initial therapy in treatment-naive patients; zidovudine + lamivudine was reclassified to an acceptable dual-NRTI option; ritonavir-boosted darunavir + abacavir/lamivudine was reclassified as an alternative regimen; and unboosted fosamprenavir (FPV) was removed from the recommended list.

Dr. Bartlett stated that the Guidelines for Prevention and Treatment of Opportunistic Infections among HIV-Exposed and HIV-Infected Children are currently being revised and will be issued in early 2012. He noted that all of the sections have been updated and are currently being reviewed by the Centers for Disease Control and Prevention (CDC) and several professional pediatric societies. The final version will be published in the Pediatric Infectious Disease Journal.

Dr. Bartlett reported that the most recent Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents were published in 2009. The next revision is expected to be released in early 2012 as an online document with changes in the format including harmonization of style, content, and the rating system. The revised guidelines will include major changes in the recommendations for HIV-associated OIs and coinfections, including tuberculosis (TB), human papillomavirus (HPV), and HBV and hepatitis C virus (HCV).

INTRODUCTION TO MEETING TOPIC 

Dr. William C. Grace, Coordinator, Behavioral and Social Science Research, OAR, introduced the meeting topic by noting that the purpose of the meeting was to focus on the evolving HIV/AIDS epidemic among MSM in the United States and internationally. He stated that the NIH has recognized the disproportionate impact of HIV/AIDS on MSM since the beginning of the epidemic and continues to focus its HIV/AIDS research agenda on at risk populations including MSM. Dr. Grace commented that representatives from the MSM community have participated in the development of the annual trans-NIH AIDS strategic plan and identification of AIDS research priorities. They also have actively participated in the design and conduct of NIH-sponsored AIDS research, including the Multicenter AIDS Cohort Study (MACS) that continues to provide critical information on the natural history of HIV infection among MSM in the United States.

Dr. Grace noted that more than one-half of HIV infections in the United States occur among MSM. Young MSM are particularly affected, especially African American and Hispanic MSM. From 2006 to 2009, the incidence of HIV infection increased 34 percent in young MSM and 48 percent in young black MSM. Dr. Grace stated that young MSM accounted for more than 25 percent of new HIV infections and that more black MSM who are HIV-infected are unaware of their HIV serostatus compared with their white counterparts.

Dr. Grace said that many countries show similar disproportionate patterns with a resurgence of HIV infection among MSM being reported in several high-income countries. He noted that recent studies show an increase of HIV among MSM, even in regions where HIV transmission has been highest among heterosexuals or injection drug users (IDUs). The purpose of the meeting is to ensure that NIH research priorities continue to address the highest needs in this area. 

THE EVOLVING HIV/AIDS EPIDEMIC AMONG MSM

Dr. Ronald D. Stall, Professor and Chair, Department of Community Health Sciences and Department of Infectious Diseases and Microbiology, University of Pittsburgh, discussed the epidemiology and prevention of HIV/AIDS among MSM in the United States. He noted that MSM is the dominant risk group for HIV/AIDS in the United States, accounting for 61 percent of newly diagnosed HIV infections in 2009. He emphasized that MSM, especially young black MSM, will continue to be the dominant risk group for HIV transmission in the foreseeable future. He suggested that, although the mean incidence rates of HIV infection currently reported for young MSM (2.39 percent to 3.84 percent) may seem low, they could yield a high proportion of HIV-infected MSM over the next decades.

Dr. Stall emphasized that halting the AIDS epidemic depends on prevention of new HIV infections among MSM. He described the history of prevention efforts in the United States, beginning with the successful behavioral risk reduction interventions in the 1980s. From these studies, an initial consensus emerged that reductions in sexual risk behaviors among MSM would be relatively easy to achieve and that behavioral risk reduction was the best tool to use. A number of subsequent randomized clinical studies testing behavioral interventions in at-risk populations showed the success of early efforts was not well understood and that the context and maintenance of risk reductions over time are important areas for behavioral research.

Dr. Stall noted that behavioral researchers have developed a number of evidence-based interventions (EBIs) to prevent HIV/AIDS, but most are not applicable to MSM and that EBIs for MSM at the highest risk are largely unavailable. He cautioned that no single intervention fits all contexts and that translation of EBIs into the field has been difficult, with very low uptake of and access to EBIs among MSM. He stated that behavioral interventions for prevention of HIV can reduce risk if they are well supported and carefully fielded.

Dr. Stall further cautioned that attempts to control the AIDS epidemic by intervening solely in individual-level risk behaviors may not be effective in real-world settings. He noted that HIV infection is often intertwined with other psychosocial issues that are predictive of HIV prevalence and high-risk sexual behaviors. He proposed that multiple levels of prevention—individual, interpersonal and community, and structural - are needed.

Dr. Stall stated that prevention tools are needed that can be used for decades and can be diffused widely without dependence on public health bureaucracies and community-based organizations (CBOs). He commented that CBOs are needed to translate research findings into practice. He noted that combination prevention approaches of biomedical and behavioral and social science, hold significant promise. He emphasized that biomedical approaches to stopping HIV transmission among MSM must incorporate behavioral components in order to be effective. He also cited the need for additional research to better understand the effects of interventions at structural levels.

THE EPIDEMIOLOGY OF HIV AMONG MSM IN LOW- AND MIDDLE-INCOME COUNTRIES

Dr. Stefan Baral, Assistant Scientist, Department of Epidemiology, Johns Hopkins School of Public Health, described the epidemiology of HIV infection among MSM and the interplay among human rights, HIV, and MSM in low- and middle-income countries (LMIC). He stated that HIV infection disproportionately affects MSM in these settings. He suggested several ways to advance the epidemiology, prevention, treatment, and health care research needed to address the epidemic internationally.

Dr. Baral noted that HIV epidemics are ongoing among MSM in multiple LMICs, have been newly identified in previously unstudied areas, and are resurging in high-income countries. 
He described four scenarios of HIV risk for MSM: (1) MSM as the predominant exposure group for HIV infection (e.g., in Latin America and the Caribbean); (2) MSM risk occurring within established epidemics driven by IDU (e.g., in countries of the former Soviet Union and Eastern Europe); (3) MSM risk occurring within mature, widespread epidemics among heterosexuals (e.g., in sub-Saharan Africa); and (4) MSM, heterosexuals, and IDUs all contributing significantly to the epidemic (e.g., in South Asia and Southeast Asia). He noted that countries within regions may have different scenarios.

Dr. Baral commented that the existence and quality of data on risk of HIV infection among MSM varies across LMICs. In more than 100 countries, including some in North Africa and the Middle East, there is no epidemiology data available. In other nations, the quality of the data is less than optimal since it is based on prevalence data that likely yields conservative estimates and may not be generalizable. He stated that there is limited data on HIV incidence in various populations. Dr. Baral noted that individual-level risk factors are the same across settings and that community- and structural-level factors affect risk in all settings.

Dr. Baral described several ongoing case studies from Africa to illustrate the interplay among human rights, HIV infection, and MSM. He noted that awareness of the rights of lesbian, gay, bisexual, and transgender (LGBT) individuals has increased internationally, as have community empowerment and activism. He noted that in some countries, structurally-created fear and discrimination, including criminalization of same-sex practices, have negatively affected HIV prevention, care, and treatment services, resulting in an increased HIV risk among MSM.

Dr. Baral noted that coverage for services is inadequate, and governments in most LMICs are not investing in them. The percentage of total HIV prevention expenditures supporting efforts for MSM varies from 3.3 percent in countries with concentrated epidemics (scenarios 1, 2, and 4) to 0.1 percent in countries with generalized epidemics (scenarios 3 and 4)—and to 0 percent in most sub-Saharan African countries other than South Africa.

Dr. Baral suggested that there is a need for further epidemiology and prevention research to obtain complete HIV prevalence and incidence data on MSM and to continue phylogenetic analyses to prepare for potential vaccine clinical trials. He emphasized that there is a need for additional prevention research combining biomedical, behavioral, and structural approaches such as targeted in the NIH-sponsored Methods for Prevention Packages Program (MP3) for MSM in Africa.

DISCUSSION

OARAC members, speakers, and guests commented on the concerns, knowledge, attitudes, and behaviors of HIV-infected MSM. They noted that current prevention tools (e.g., condom use) are insufficient and that MSM need evidence-based prevention and harm-reduction strategies for the long term. They discussed the data on HIV incidence and prevalence among MSM, noting that the increases may differ locally and that they mirror those of other sexually transmitted infections (STIs) among MSM. OARAC members encouraged further research on prevention of HIV infection among young MSM especially young black MSM and young MSM under age 18 years old.

OARAC members and speakers encouraged additional research to better understand the drivers of the increasing incidence and prevalence of HIV infection among MSM. They noted that there is a need to relate any outcomes of behavioral change to reductions in HIV incidence. In addition, they emphasized the need for prevention strategies that combine structural and individual-level interventions that link behavioral, clinical, biomedical, psychosocial, contextual, and community-based approaches. It was suggested that community organizations could be mobilized to promote the use of prevention tools for MSM. It was noted that further studies are needed to clarify the entry points for MSM in the health care system and to train health care providers in screening HIV-infected MSM and retaining them in care.

OARAC members and speakers expressed concerns about using the acronym MSM to represent men having sex with men, who may be gay, transgender, bisexual, or heterosexual. They emphasized that differentiation of terms is critical for data collection and research on behavioral interventions. 

HIV-INFECTED MSM: COMORBIDITIES AND CLINICAL COMPLICATIONS

Dr. Roy M. Gulick, Professor of Medicine, and Chief, Division of Infectious Diseases, Weill Medical College of Cornell University, presented recent data on the comorbidities and clinical complications of HIV infection in MSM.  He noted that this data is incomplete and that additional research is needed to improve the collection and analyses of clinical information on HIV-associated comorbidities among MSM. 

Dr. Gulick focused on the risks of mortality and causes of death in HIV-infected MSM.  He cited CDC data for 1985–2008 that showed a dramatic decrease in AIDS diagnoses and deaths among MSM beginning in 1995 after the introduction and wide-spread dissemination of ART.  He noted that data on the life expectancy of HIV-infected MSM who are effectively managed with ART are controversial.  Dr. Gulick noted that comorbidities contribute to the heterogeneous risks for mortality among HIV-infected persons, including MSM, and that those with comorbidities (e.g., HCV, alcohol and drug abuse) have significantly decreased life expectancies.  

Dr. Gulick cited the causes of death among HIV-infected MSM including:  non-AIDS defining malignancies; cardiovascular, liver, and pulmonary diseases; violence; and substance use.  He noted that deaths from AIDS-defining cancers including Kaposi’s sarcoma or non-Hodgkin’s lymphoma have decreased dramatically, while there have been increasing rates of prostate cancer; anal and oral pharyngeal cancer, related to co-infection with HPV; liver cancer, related to co-infection with HBV or HCV; and lung cancer, related to cigarette smoking.  He commented that cardiovascular diseases account for significant morbidity and mortality among HIV-infected individuals, including MSM.  There are multiple factors contributing to these comorbidities including HIV disease, ART, and other host factors. 

Dr. Gulick noted that changes in body fat are a particular concern for HIV-infected individuals starting treatment.  Patients on different ART regimens show variable lipoatrophy and lipohypertrophy, as well as bone changes in the spine or hip.  He stated that aging related complications, as well as neurologic and neurocognitive disorders are other comorbidities for HIV-infected MSM. 

Dr. Gulick cited several recent reports that show increasing rates of STIs, including syphilis, gonorrhea, and chlamydia, among MSM, especially Black MSM, in major U.S. cities.  He also noted HCV as a newly recognized STI associated with risky behaviors among MSM.

Dr. Gulick proposed that additional research is needed on the comorbidities affecting HIV-infected MSM including:  the contributory factors associated with cardiovascular disease and aging; ART-related lipohypertrophy and bone loss; HCV, HPV, and other STIs; mental health disorders; and the role of substance use.  He emphasized the need for improved prevention, screening, diagnosis, clinical evaluation, and treatment for HIV-associated comorbidities in MSM.

EMERGING THEMES AND LESSONS FROM HPTN 061 – THE BROTHERS STUDY

Dr. Darrell P. Wheeler, Dean, School of Social Work, Loyola University of Chicago, presented an update on the HIV Prevention Trials Network protocol designated HPTN 061, entitled “Feasibility Study of a Community-level Intervention for Black MSM (The Brothers Study)”. He noted preliminary findings from this study may guide future HIV prevention interventions among black MSM.

The primary objectives of HPTN 061 are to establish the feasibility of: (1) recruiting black MSM and their sexual/social networks into intervention studies; (2) HIV testing of index cases and network members; and (3) peer navigation for prevention and care. This clinical study is being conducted in six U.S. cities (Atlanta, Boston, Los Angeles, New York, San Francisco, and Washington, D.C.). Dr. Wheeler noted that the study results will provide an estimate of the number of participants newly diagnosed with HIV at enrollment and over 52 weeks, as well as the use of condoms, changes in viral load among HIV-infected participants after initiation of ART, and incidence of STIs. The study uses qualitative research methods to examine the influences on enrollment and participation in the study and the effects of stigma and discrimination on HIV testing and access to care.

Dr. Wheeler reported that more than 1,500 individuals have been enrolled since July 2009 with an expected goal of 2,400 study participants. Of the enrolled participants, 69 percent are HIV sero-negative, 8 percent are newly diagnosed with HIV infection, approximately one-third are less than 30 years old, and more than 50 percent are unemployed. Approximately 60 percent of the study participants have health coverage and more than half are receiving health care at public health or free clinics, while others go to emergency rooms or private physicians. He commented that access to different venues for health care services may influence the information MSM receive and use, as well as their ability to establish alliances with health care providers for treatment.

Dr. Wheeler noted two challenges in the study—the difficulty of identifying “naïve” study participants (i.e., many participants “cycle” through studies) and of generalizing findings from diverse sites. He stated that preliminary findings are variable within the study population and across the sites. He noted that enrollees have pre-existing traumas from living in socially impoverished communities, which may affect their HIV risk and the preventive strategies that they use. He emphasized that it is critical that community-based studies incorporate the specific needs of the communities in how the study is designed and conducted.

Dr. Wheeler described the HPTN Scholars Program that is one of the outcomes of HPTN 061. He noted that the program is helping to foster a new cadre of scientists from racial and ethnic populations to reduce HIV infection in U.S. communities that bear a disproportionate HIV risk. This program has supported six scholars in 2010–2011 and five scholars in 2011–2012.

FACTORS INFLUENCING HIV PREVENTION AND TREATMENT AMONG BLACK MSM

Dr. David J. Malebranche, Associate Professor, Department of Medicine, Emory University School of Medicine, described the racial disparity in HIV prevention and treatment and the various factors that contribute to this disparity. He summarized findings from several studies on black MSM and described a pilot project that explored the medical experiences of black MSM.

Dr. Malebranche noted that black MSM face two overlapping disparities -- being black and being MSM (or LGBT). He commented that black MSM exist at a “fluid intersection” of multiple social identities that may ebb and flow in relation to their social or geographic situation. He emphasized that sexuality among MSM cannot be separated from race and culture and that these factors contribute to variability among MSM. He elaborated on this intersectionality and the contribution of race and culture in intra-racial sexual networks, selection of partners, role expectations, perceptions of masculinity, perception of HIV risk, and use of condoms.

Dr. Malebranche presented qualitative data on medical experiences of black MSM from his study of eight focus groups in New York and Atlanta that was conducted in 2001. The study included 81 men; 68 percent of them were between the ages of 30–44 years, and 53 percent were gay. Approximately 47 percent were HIV sero-positive. During the focus groups, the men noted several external factors (lack of money or insurance to pay for care), institutional factors (perceiving the medical system as impersonal), and interpersonal factors (dissatisfaction with health care providers’ communications and judgment and the medical “culture”) affecting their medical experience. The study participants also expressed several internalized factors (e.g., perceived stereotyping by medical providers) and distrust of medical practices. In addition, he commented that the study participants emphasized their need for successful medical experiences including positive interactions with health care providers, a feeling that someone cares, and encouragement to invest in themselves.

Dr. Malebranche noted that these health care experiences influence access to and quality of care, trust in the health care system, HIV and STI testing and treatment, adherence, and willingness to attend follow-up appointments. He emphasized that simply assuring access to care is not sufficient because of the intersectionality in medical venues, where personal experiences of racism and sexual prejudice play out, medical miscommunication is common, and not all medical staff are culturally competent.

Dr. Malebranche stated that biomedical research and prevention interventions to reduce HIV infection cannot move forward without addressing social and structural inequities of black MSM. He noted the importance of acknowledging that race and culture influence sexuality (not vice versa) and to assess the fluidity of “healthy” and “risky” behaviors. He suggested that priority should be given to: conducting social science research along with biomedical research; incorporating African-centered theory; shifting from a deficit model to one of resiliency; and examining the intra-racial diversity of black MSM in studies on HIV infection.

Dr. Malebranche stated that black MSM are “exhausted” by being defined solely by HIV and that, in black communities, broader life experiences are the main concern, not HIV infection. He proposed the following specific topic areas for further research: (1) prospective studies to assess how structural factors and stress influence behavior and genetic susceptibility; (2) evaluating the impact of structural health interventions on sexual health and HIV-related outcomes; and (3) assessing the quality of health care, not just access to it.

DISCUSSION

OARAC members and speakers commented that prevention and treatment of HIV/AIDS among young black MSM is a top priority. They noted that there is a critical need to better understand and approach the intersectionality of black MSM and their distrust of the medical system and health care providers. They encouraged support for more qualitative research in all studies of MSM.

OARAC members and speakers discussed the role of networks as an important issue for MSM. They noted that there is a need to define and study the most important issues linked to the high-risk status of MSM. They commented that individual and structural factors complement biology as a “driver” of HIV risk and complicate the implementation of interventions. They identified the need for combination prevention approaches that incorporate this understanding and will further require additional investments in drug and vaccine development for HIV prevention.

OARAC members and speakers viewed the engagement of communities as essential to research — to foster trust, recruitment into clinical studies, implementation of strategies, and dissemination of public health information. This engagement includes participation in the origination and planning of clinical studies, training of community leaders, and organization of community advisory boards. They noted that having more providers of color interacting with MSM and communities at risk could help foster trust.

OARAC members and speakers suggested that there is a need for research to better understand the resilience that some gay men have to HIV infection, as well as a need for studies on the unique issues of HIVsero-positive MSM who have survived from the early years of the epidemic.

NIMH MSM RESEARCH:  CURRENT PORTFOLIO AND PRIORITY DIRECTIONS

Dr. Cynthia I. Grossman, Center for Mental Health Research on AIDS, Division of AIDS Research, National Institute of Mental Health (NIMH), provided an overview of the NIMH research agenda on HIV infection among MSM. She noted that NIMH is one of many NIH Institutes, Centers, and Offices (ICOs) supporting research on MSM, and NIMH is the lead IC sponsoring behavioral and social science research in this population.

Dr. Grossman stated that NIMH has issued several funding opportunity announcements (FOAs) since 2010 that address the needs of MSM in relation to HIV infection; specifically, targeting research on social and structural interventions and the barriers to HIV prevention, care, and treatment among MSM. She noted that NIMH recently developed a database of its research portfolio that permits NIMH to evaluate its portfolio and assure that research priorities align with the current HIV epidemic among MSM. She commented that NIMH plans to continue to stimulate behavioral research on MSM and to pursue new research priorities.

Dr. Grossman reported that NIMH currently supports 82 active studies specifically addressing MSM. This number represents approximately one-fifth of all NIMH-funded behavioral research grants. Approximately 55 percent of these active grants have a majority of participants from racial and ethnic populations with about one-fourth of that number focusing on African Americans. In addition, NIMH supports research on MSM in other studies not specifically focused on HIV. Dr. Grossman noted that NIMH recently awarded 8 new grants in response to an FOA targeted to reinvigorate HIV prevention research with MSM.

Dr. Grossman commented that 42 of the 82 active projects involving MSM are intervention studies. She stated that most of these studies have historically focused on the individual level, but approximately one-fourth currently address community and structural levels. She noted that the primary outcome in approximately two-thirds of the studies is sexual risk behaviors, and in a few studies the outcome is on STIs. While the primary mode for delivering an intervention is in a face-to-face setting, there is an increase in the number of studies using the Internet, social media, or cell telephones. Among these studies, the settings for delivering interventions are diverse and mostly community-based with peers, families, friends, lay persons, or outreach health workers delivering the intervention rather than specialized medical personnel.

Dr. Grossman reported that approximately 10 percent of NIMH’s portfolio on MSM includes a biomedical component, which is largely pre-exposure prophylaxis (PrEP) and treatment as prevention. She noted that NIMH issued an FOA in 2010 to foster integration of biomedical and behavioral approaches in prevention for MSM. Several grants awarded under this FOA are focused on enhancing PrEP for MSM using community settings. She outlined NIMH’s plans to enhance integrative science by collaborating with the NIH-sponsored HIV/AIDS clinical trials networks and cohort studies, other ICs, and CDC.

ORAL PrEP FOR MSM: BUILDING ON RESULTS FROM THE GLOBAL iPrEx STUDY

Dr. Albert Liu, Director, HIV Prevention Intervention Studies, San Francisco Department of Public Health, presented findings from the Pre-Exposure Prophylaxis Initiative (iPrEx) and outlined the next steps to build on these results. He suggested the inclusion of oral PrEP as a component of combination prevention approaches for HIV infection among MSM.

Dr. Liu noted that iPrEx is an NIH-sponsored international clinical trial to evaluate oral PrEP to prevent HIV infection among gay and other MSM. The study also addressed drug resistance, safety and tolerability, adherence, and risk behaviors. It included about 2,500 MSM at 11 sites in Asia (Thailand), South Africa, South America, and the United States. He commented that almost three-fourths of the study participants were Latinos, reflecting the project’s origination in Andean countries. At some of the clinical trial sites, this was the first time that MSM were participating in biomedical prevention research. The cohort was young (50 percent were younger than 25 years old) and had significant risk factors for HIV infection. One half of the study enrollees were randomly assigned to receive oral Truvada (FTC/TDF), while the other half received a placebo. He noted that all of the study participants received comprehensive prevention services.

Dr. Liu noted that the study results showed a mean efficacy for Truvada of 42 percent and that 35 infections were averted with the drug. He stated this study and several others testing oral Truvada in Africa have now demonstrated that oral PrEP is moderately efficacious in at-risk MSM and may be highly efficacious in those who take it consistently. He noted that adherence to treatment regimens is a significant challenge, particularly at sites outside the United States. Truvada was shown to be safe and well tolerated in HIV sero-negative individuals in this study. 
Dr. Liu outlined the next steps that have been taken since the findings from the iPrEx study were released. In January 2011, the CDC issued interim guidance for U.S. health care providers on the use of PrEP to prevent HIV infection in MSM. He noted that CDC is collaborating with other agencies in developing more comprehensive, formal guidelines and that, currently, there is no label indication for using Truvada to prevent HIV infection.

Dr. Liu highlighted several questions that need to be answered including: how to prioritize PrEP for those who need it most; how to encourage interest in using PrEP; how to engage health care providers in risk assessments; whether MSM will be interested in taking PrEP; and how best to frame and communicate messages about PrEP. He noted that several feasibility studies have recently reported the acceptability of PrEP including the Prevention Umbrella for MSM in the Americas (PUMA) and the Sigma Panel in the United Kingdom. These studies showed that a relatively small proportion of the MSM surveyed had heard of the iPrEx results and approximately half expressed interest in using PrEP.

Dr. Liu noted other important scientific questions that need to be explored related to: how monitoring of adherence in real-world settings will be performed; the minimal anti-HIV drug levels needed to provide protection from HIV acquisition/transmission; the effects of the availability of PrEP on sexual practices; and the long-term safety of PrEP. He described several studies that are ongoing or planned to evaluate these factors in MSM including the iPrEx Open-Label Extension (OPE) and the PrEP Demonstration Project.

Dr. Liu highlighted the need for further research on PrEP to: (1) expand demonstration projects, coordinate across projects, and measure costs; (2) learn more about the pharmacological kinetics of PrEP drugs and levels of exposure needed for protection; (3) determine how to prioritize PrEP for at-risk populations; and (4) integrate sociobehavioral research into demonstration projects.

KEY CONSIDERATIONS IN ENGAGING MSM IN HIV VACCINE TRIALS

Dr. Magdalena Sobieszczyk, Assistant Professor, Department of Medicine, Infectious Diseases Division, Columbia University College of Physicians and Surgeons, addressed the key factors that should be considered in order to engage MSM in HIV vaccine clinical trials. These are the result of experiences learned from the HIV Vaccine Trials Network protocol designated HVTN 505. She emphasized the need to enroll individuals at high risk of HIV infection, such as MSM, to participate in biomedical prevention studies such as vaccine clinical trials.

Dr. Sobieszczyk noted that some of the key HIV vaccine efficacy trials conducted since 1997 have advanced research even though they failed to show a protective efficacy of the vaccine candidate tested. She focused on HVTN 505, which started in 2009 and was expanded recently to evaluate the effect of a vaccine candidate, comprised of a multiclade DNA prime and a multiclade rAdenovirus (Ad)5 boost, on HIV acquisition and viral load in HIVsero-negative MSM. This NIH-sponsored clinical trial is being conducted at numerous U.S. sites. The primary objectives are to evaluate the effects of the vaccine regimen on the rate of HIV-1 acquisition, HIV-1 viral load set point, and safety parameters, in comparison with a placebo. The aim of HVTN 505 is to enroll 2,200 MSM and transgender individuals who are circumcised and Ad5 seronegative. To date, approximately 1,400 study participants have been enrolled.

Dr. Sobieszczyk highlighted four key considerations emerging from HVTN 505, including the need for: (1) a multi-dimensional approach to community engagement and recruitment; (2) incorporation of social and behavioral science into HIV vaccine and biomedical prevention studies; (3) commitment to and transparency with study volunteers; and (4) sustained commitment and partnership. She described the value of community education, partnerships with community and national stakeholders, and outreach to ethnic and racial populations in laying the groundwork for the study and raising awareness of HIV vaccine research.

Dr. Sobieszczyk noted the importance of combining centrally coordinated strategies with local, site-specific campaigns that use culturally appropriate and diverse recruitment images and messages. She noted the value of social media and Internet sites (e.g., to disseminate information messages and engage MSM) and the need to regularly collect data on this outreach to evaluate the strategies used and to modify information messages as needed. She commented that face-to-face interactions and the use of Internet sites have been the most successful outreach strategies for the HVTN 505 protocol.

Dr. Sobieszczyk noted that social and behavioral science is being integrated into the HVTN by an NIMH supplemental grant supporting surveys and focus groups among MSM at six HVTN sites. The goals are to enhance recruitment and to assess barriers and facilitators to MSM participation in HIV vaccine clinical trials. She noted that the results so far indicate that most MSM agree that an HIV vaccine is needed and that more information about this research should be disseminated.

Dr. Sobieszczyk emphasized the importance of keeping study participants apprised of results from other clinical studies. She noted that HVTN 505 researchers communicated through a series of consultations with study participants about the impact of iPrEx as soon as the results were released. This led to important modifications to the HVTN 505 protocol.

Dr. Sobieszczyk commented that as prevention technologies intersect there may be opportunities that will emerge to evaluate combination strategies for reducing the incidence of HIV infection. She stated that the vaccine field welcomes and has incorporated new developments in prevention research. She also noted that as studies become more complex, they will become more relevant and applicable to diverse populations in the greatest need for prevention interventions.

RECTAL MICROBICIDES – CAN WE MAKE THEM AND WILL PEOPLE USE THEM?

Dr. Ian McGowan, Professor, Department of Medicine, University of Pittsburgh School of Medicine and Co-Principal Investigator of the Microbicide Trials Network (MTN), presented an overview of research on rectal microbicides. He noted that rectal microbicides are needed for men and women across the world who are at risk of HIV infection associated with unprotected receptive anal intercourse (RAI).

Dr. McGowan stated that the development of rectal microbicides is a rapidly evolving and exciting research field that has gained significant momentum over the past decade. He defined microbicides as products that can be applied to vaginal or rectal mucosa to prevent or significantly reduce the risk of acquiring STIs, including HIV infection. Microbicide candidates have various mechanisms of action and can provide lubrication to reduce trauma and potential infection, or deliver antiretrovirals to inhibit viral replication. He noted that the rationale for their use is that unprotected RAI is the highest-risk sexual activity for HIV transmission and it is practiced by men and women everywhere. He commented that mouse and nonhuman primate studies have proven the concept that rectal application of microbicide candidates containing ARVs can prevent SIV and HIV infection. He suggested that delivery of an ARV in the form of a lubricant could circumvent the adherence problems associated with other prevention strategies.

Dr. McGowan noted that the clinical development of rectal microbicides has evolved from early Phase 1 studies with nonoxynol-9 (N-9) gels in the 1990s to the onset of Phase 2 studies in 2012. He noted that the earliest Phase 1 studies of N-9 delivered rectally, yielded discordant results and observations of histological abnormalities. Following these studies, the HPTN funded research to establish biomarkers of safety for rectal microbicides. He noted that the HPTN 056 study yielded a number of assays and normative ranges that set the stage for future studies. One of these studies, the UC-781 Phase 1 trial, addressed the efficacy of a single dose versus repeated doses and used explant data to establish efficacy.

Dr. McGowan summarized results from other Phase 1 studies that focused on the safety, acceptability, and pharmacokinetics and pharmacodynamics (pK/pD) of microbicide candidates taken orally versus applied topically to mucosal tissue. He noted one pK/pD study conducted by the MTN showed that vaginal tenofovir gel, when used as a rectal microbicide, was not tolerated well in the rectum; however, repeated rectal dosing was associated with significant viral inhibition. He reported that an ongoing MTN study (designated MTN 007) is testing whether a new formulation of tenofovir gel is harmful to rectal mucosa when it is applied repeatedly.

Dr. McGowan noted that additional Phase 1 studies of rectal microbicide candidates have been conducted or are under way in the NIAID-sponsored Integrated Preclinical/Clinical Program for HIV Topical Microbicides. This innovative program has been funded for almost nine years and has supported rectal microbicide research including the Microbicide Development Program and the Combination HIV Antiretroviral Rectal Microbicide (CHARM) program. He also cited another study, Project Gel, which is funded by the Eunice K. Shriver National Institute of Child Health and Human Development (NICHD) and NIMH. This study is assessing the safety and acceptability of tenofovir 1% gel in young MSM from racial and ethnic populations who are at risk of HIV infection.

Dr. McGowan described several Phase 2 studies including MTN 017. He noted that this study will evaluate the safety, adherence, acceptability, and pK/pD of two microbicide candidates (tenofovir gel and Truvada) in 200 MSM and transgender individuals at sites in four countries (Peru, South Africa, Thailand, and United States). He anticipated that the results of the study may provide the necessary data to design a Phase 2 clinical trial of a rectal microbicide.

Dr. McGowan proposed that the landscape of PrEP efforts is constantly changing and that an eventual Phase 2B or 3 trial will probably utilize a combination of prevention approaches. He suggested that the timeline for planning an effectiveness study of a rectal microbicide candidate should begin now. He proposed the completion of Phase 2 studies in 2012–2013, Phase 2B/3 studies in 2014–2016, and the availability of a potential product in 2018 or earlier.

ENGAGING THE GAY “COMMUNITY” IN HIV PREVENTION RESEARCH

Mr. Jim Pickett, Director, Prevention Advocacy and Gay Men’s Health, AIDS Foundation of Chicago, described ways to engage gay communities in HIV prevention research based on his perspective as a leading advocate for research on new HIV prevention strategies for gay men. 
He emphasized that there is a multiplicity of gay communities and that one community is not representative of others. He noted that the public “narrative” about gay men and their health is overwhelmingly negative and that public health campaigns directed to gay men need to be developed that encourage young gay black men at high risk of HIV infection to be tested for HIV.

Mr. Pickett outlined six key features that have characterized the gay men’s health movement since the 1990s. He emphasized the need to adopt messaging that is: holistic (not HIV-centric); relationally focused (friends and families); asset-driven (i.e., focused on resilience and strength); empowering and celebratory; multicultural; and informative (not directive). He cited the need to strategically confront structural forces that challenge the well-being of gay men and to engender respect for diverse ways of organizing sexual relationships. He noted that shame and guilt are the real health hazards for gay men.

Mr. Pickett described several examples of healthy, positive campaigns available for gay men and cited several Internet venues that provide this information. He noted that these websites can disseminate information on clinical studies and help to overcome stigmatization. He emphasized that disease prevention campaign designers need to ask questions of and listen to the communities that they are trying to reach.

Mr. Pickett described the activities of the International Rectal Microbicide Advocates (IRMA), which targets media outreach to U.S. and international communities. Mr. Pickett noted that further research is needed on the safety of lubricants, use of female condoms for anal sex, and the effects of seroadaptation/serosorting on sexual behaviors.

REPORT FROM THE OFFICE OF AIDS RESEARCH BLACK MSM THINK TANK

Dr. Victoria Cargill, Director of Minority Research and Clinical Studies, OAR, reported on the Black MSM Think Tank meeting that OAR convened on October 20, 2011. She noted that approximately 35 government and non-government researchers, academicians, and public health officials including those from NIH, CDC, and other Federal agencies attended the meeting, which focused on identifying emerging research needs, priorities, and gaps related to HIV research on black MSM. She noted that 10 major themes were identified by the meeting participants.

Dr. Cargill stated that three of the 10 themes related to the natural history of HIV infection among black MSM compared with white MSM including: the effects of chronic stressors (e.g., social determinants of health, stigma, racism, and internalized self-hatred) on the immune system and physiology of black MSM; the contributors to resilience (e.g., social networks, communities) among black MSM; and the contexts of life (i.e., needs, issues, challenges) for black MSM over the lifespan. She noted that a fourth theme was the disconnect between health care providers and black MSM that involves the effects of culture and context on health care access and outcomes. The fifth theme focused on the impact of macrostructural issues, such as poverty, homelessness, and incarceration, on black MSM over time.

Dr. Cargill provided a summary of the second set of five themes that focused on research and training issues. She commented that the Think Tank participants specifically emphasized the need to develop and test HIV interventions targeting MSM and to assess these and existing interventions for their applicability to diverse populations. The meeting participants also identified the critical need for increased focus on training and capacity building, collaborative interdisciplinary work, and the development of initiatives that would expand the understanding of life and health experiences of black MSM.

DISCUSSION

OARAC members and speakers discussed the additional “tools” that are needed in the toolbox of prevention strategies for MSM. They noted that the potential of PrEP interventions and combination prevention strategies is impressive and needs further research. They suggested that more attention should be focused on structural interventions that could complement and enhance individual- and community-level efforts.

OARAC members suggested a need for creative implementation of interventions for HIV-infected MSM. This could include a variety of different approaches such as venue-based care that incorporates recruitment into clinical studies and primary care. OARAC members noted that issues of acceptability and buy-in of interventions by MSM patients and communities are complex and need to be better understood. They also commented that interactions between health care providers and patients are particularly difficult for MSM and need to be improved. They noted that interventions should be community-based, cost-effective, feasible, targeted, and able to be scaled up in order to ensure their effective delivery.

OARAC members commented that young MSM, particularly young black MSM, are at significant risk of HIV infection and have a critical need for interventions to prevent HIV infection. They noted several other MSM subgroups that also are at high risk of HIV infection and need targeted interventions. These subgroups include: small networks of HIV-infected MSM who are in the acute stage of disease and have serious coinfections (e.g., from cancer-associated viruses, such as HPV); Latino MSMs and other disproportionately affected and underserved groups in the United States; older HIV-infected MSM who have unique complications associated with aging; and the new population of veterans, especially young veterans, who are returning from Iraq and Afghanistan and engage in at risk behaviors.

OARAC members noted that more research is needed on the comorbidities and coinfections associated with HIV infection among MSM. They commented that international, as well as domestic, research would be informative and complementary.

OARAC members discussed the need for more research to better understand the natural history of MSM with and without HIV infection and the complexity of factors contributing to the health and health care of MSM. They suggested the addition of studies on MSM to existing cohort studies of older HIV-infected populations.

OARAC members noted that researchers should continue to collaborate with and engage MSM communities in designing and conducting AIDS studies. They suggested that this will be critical to halting the AIDS epidemic among MSM.

PUBLIC COMMENTS

No members of the public requested time to comment.

CLOSING COMMENTS

Dr. Auerbach thanked the OARAC members, speakers, and guests for their participation and comments. Dr. Whitescarver thanked Dr. Auerbach for chairing the meeting. He also thanked the speakers for their stimulating presentations and the OARAC members for their thoughtful comments. Dr. Whitescarver commented that OAR will continue to work closely with the NIH Institutes, Centers, and Offices and other Federal agencies to advance HIV prevention and treatment research in MSM, as a critical component to ending the AIDS epidemic.  

ADJORN

The meeting was adjourned at 4:30 p.m. on November 10, 2011.

/Jack Whitescarver, Ph.D./

Jack Whitescarver, Ph.D., Executive Secretary

/Judith D. Auerbach, Ph.D./ 

Judith D. Auerbach, Ph.D., Acting Chair