Showing papers by "Robert M. Grant published in 2013"

No Evidence of sexual risk compensation in the iPrEx trial of daily oral HIV preexposure prophylaxis

Abstract: Objective Preexposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) reduced HIV acquisition in the iPrEx trial among men who have sex with men and transgender women. Self-reported sexual risk behavior decreased overall, but may be affected by reporting bias. We evaluated potential risk compensation using biomarkers of sexual risk behavior. Design and methods Sexual practices were assessed at baseline and quarterly thereafter; perceived treatment assignment and PrEP efficacy beliefs were assessed at 12 weeks. Among participants with ≥1 follow-up behavioral assessment, sexual behavior, syphilis, and HIV infection were compared by perceived treatment assignment, actual treatment assignment, and perceived PrEP efficacy. Results Overall, acute HIV infection and syphilis decreased during follow-up. Compared with participants believing they were receiving placebo, participants believing they were receiving FTC/TDF reported more receptive anal intercourse partners prior to initiating drug (12.8 vs. 7.7, P = 0.04). Belief in receiving FTC/TDF was not associated with an increase in receptive anal intercourse with no condom (ncRAI) from baseline through follow-up (risk ratio [RR] 0.9, 95% confidence interval [CI]: 0.6–1.4; P = 0.75), nor with a decrease after stopping study drug (RR 0.8, 95% CI: 0.5–1.3; P = 0.46). In the placebo arm, there were trends toward lower HIV incidence among participants believing they were receiving FTC/TDF (incidence rate ratio [IRR] 0.8, 95% CI: 0.4–1.8; P = 0.26) and also believing it was highly effective (IRR 0.5, 95% CI: 0.1–1.7; P = 0.12). Conclusions There was no evidence of sexual risk compensation in iPrEx. Participants believing they were receiving FTC/TDF had more partners prior to initiating drug, suggesting that risk behavior was not a consequence of PrEP use.

Randomized trial of clinical safety of daily oral tenofovir disoproxil fumarate among HIV-uninfected men who have sex with men in the United States.

Abstract: Objectives To evaluate the clinical safety of daily tenofovir disoproxil fumarate (TDF) among HIV-negative men who have sex with men. Design Randomized, double-blind, placebo-controlled trial. Participants were randomized 1:1:1:1 to immediate or delayed study drug (TDF, 300 mg orally per day, or placebo). Methods Four hundred healthy HIV-uninfected men who have sex with men reporting anal sex with another man within the previous 12 months enrolled in Atlanta, Boston, and San Francisco. HIV serostatus, clinical and laboratory adverse events (AEs), adherence (pill count, Medication Event Monitoring System, and self-report), and sexual and other sociobehavioral data were assessed at 3-month intervals for 24 months. Primary outcomes were clinical safety, assessed by incidence of AEs and laboratory abnormalities. Results Study drug was initiated by 373 (93%) participants (186 TDF and 187 placebo), of whom 325 (87%) completed the final study visit. Of 2428 AEs reported among 334 (90%) participants, 2366 (97%) were mild or moderate in severity. Frequencies of commonly reported AEs did not differ significantly between TDF and placebo arms. In multivariable analyses, back pain was more likely among TDF recipients (P = 0.04); these reports were not associated with documented fractures or other objective findings. There were no grade ≥3 creatinine elevations; grades 1 and 2 creatinine increases were not associated with TDF receipt. Estimated percentage of study drug doses taken was 92% by pill count and 77% by Medication Event Monitoring System. Seven seroconversions occurred: 4 on placebo and 3 among delayed arm participants not yet on study drug. Conclusions Daily oral TDF was well tolerated, with reasonable adherence. No significant renal concerns were identified.

Facilitators and barriers to medication adherence in an HIV prevention study among men who have sex with men in the iPrEx study in Chiang Mai, Thailand

Abstract: In 2008, the Pre-exposure Prophylaxis Initiative (iPrEx) study expanded to include men who have sex with men (MSM) in Chiang Mai, Thailand. In full, 114 participants from Chiang Mai joined this international double-blinded trial of daily FTC-TDF (Truvada®) or placebo as a pre-exposure prophylaxis (PrEP) HIV prevention strategy. To better understand the characteristics of iPrEx participants specifically from this underserved population in Thailand, and gain insights into their experiences of trying to take a daily tablet as part of this blinded PrEP trial, we conducted a qualitative study. In 2010, 32 MSM iPrEx participants provided in-depth interviews and an additional 14 joined focus group discussions. Results of the qualitative analyzes suggested that participants held generally positive attitudes toward the iPrEx study and study medication and related this to high rates of adherence to the daily regimen. Participants also reflected on the provision of quality health care as part of participation in the trial, as well as support from clinical research staff, family and friends as helpful in supporting high rates of study medication adherence. Discourse concerning challenges to adherence included medication taking behavior, which was contextualized by lifestyle, living arrangement, social life, social stigma in terms of being mistakenly identified as HIV positive or unintentional disclosure of sexual identity to family and friends, and relationship conflicts with partners. The results provide broader perspectives of participant experiences of the study medication and daily adherence in the larger contexts of the MSM community, close relationships, and the study climate, and can be leveraged in constructing PrEP adherence support approaches within these communities.

Participant Experiences and Facilitators and Barriers to Pill Use Among Men Who Have Sex with Men in the iPrEx Pre-Exposure Prophylaxis Trial in San Francisco

Abstract: In 2010, the iPrEx study demonstrated efficacy of daily emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) pre-exposure prophylaxis (PrEP) in reducing HIV acquisition among men who have sex with men. Adherence to study product was critical for PrEP efficacy, and varied considerably, with FTC/TDF detection rates highest in the United States. We conducted a qualitative study to gain insights into the experiences of iPrEx participants in San Francisco (SF) where there was high confirmed adherence, to understand individual and contextual factors influencing study product use in this community. In 2009 and 2011, we conducted focus groups and in-depth interviews in 36 and 16 SF iPrEx participants, respectively. Qualitative analyses indicate that participants joined the study out of altruism. They had a clear understanding of study product use, and pill taking was facilitated by establishing or building on an existing routine. Participants valued healthcare provided by the study and relationships wit...

Use of Antiretrovirals for HIV Prevention: What Do We Know and What Don’t We Know?

Abstract: Pre-exposure prophylaxis (PrEP), in which HIV uninfected persons with ongoing HIV risk use antiretroviral medications as chemoprophylaxis against sexual HIV acquisition, is a promising new HIV prevention strategy. Proof-of-concept that PrEP, as oral or vaginal topical tenofovir-based products, protects against sexual HIV acquisition has been demonstrated in clinical trials conducted among men who have sex with men and heterosexual men and women. The degree of HIV protection in these trials was strongly related to the level of adherence to PrEP. Many questions are yet unanswered – including how to motivate uptake of and sustain adherence to PrEP for HIV prevention, how much PrEP use is enough to achieve HIV protection, and the potential of “next-generation” PrEP agents to improve on this effective technology.

External evaluation of Saving Mothers Giving Life. Final report.

Abstract: Saving Mothers Giving Life (SMGL) is a $200 million initiative that seeks to reduce maternal mortality through a public-private partnership between the governments of the United States Norway Uganda and Zambia Merck for Mothers Every Mother Counts the American College of Gynecology and Obstetrics and Project CURE. The first phase (2012-2013) focused on eight rural districts in Uganda and Zambia. The SMGL initiative encompasses a wide scope of activities that fall into four categories: generating demand improving access improving quality and health systems strengthening. These range from mobilizing community health workers to providing incentive kits for mothers who deliver in health facilities to training providers in obstetric and newborn care to equipping and upgrading facilities. This independent external implementation evaluation was commissioned by the SMGL Leadership Council and carried out by researchers at Columbia University and New York University. We assessed the reach extent fidelity and dynamic effects of SMGL in order to identify best practices and remaining barriers to reducing maternal mortality in Uganda and Zambia and to inform future efforts of SMGL. We also examined the functioning of the SMGL partnership and engagement of various stakeholders. This report covers SMGL’s Phase 1 the first 12-18 months of SMGL implementation. A separate internal evaluation done by the CDC and USAID will assess care utilization and mortality reduction. (Excerpts)

Changes in Seroadaptive Practices from before to after Diagnosis of Recent HIV Infection among Men Who Have Sex with Men

Abstract: Objective: We assessed changes in sexual behavior among men who have sex with men (MSM), before and for several years after HIV diagnosis, accounting for adoption of a variety of seroadaptive practices. Methods: We collected self-reported sexual behavior d