Cynthia I. Grossman

Tenofovir-Based Preexposure Prophylaxis for HIV Infection among African Women

BACKGROUND Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection. METHODS We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir-emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly. RESULTS Of 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 person-years. In the modified intention-to-treat analysis, the effectiveness was -49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), -4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P=0.004). We observed no significant differences in the frequencies of other adverse events. CONCLUSIONS None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low. (Funded by the National Institutes of Health; VOICE ClinicalTrials.gov number, NCT00705679.).

International AIDS Society global scientific strategy: towards an HIV cure 2016

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the groups strategy.

The impact of mental health and substance abuse factors on HIV prevention and treatment.

The convergence of HIV, substance abuse (SA), and mental illness (MI) represents a distinctive challenge to health care providers, policy makers, and researchers. Previous research with the mentally ill and substance-abusing populations has demonstrated high rates of psychiatric and general medical comorbidity. Additionally, persons living with HIV/AIDS have dramatically elevated rates of MI and other physical comorbidities. This pattern of co-occurring conditions has been described as a syndemic. Syndemic health problems occur when linked health problems involving 2 or more afflictions interact synergistically and contribute to the excess burden of disease in a population. Evidence for syndemics arises when health-related problems cluster by person, place, or time. This article describes a research agenda for beginning to understand the complex relations among MI, SA, and HIV and outlines a research agenda for the Social and Behavioral Science Research Network in these areas.

Challenges in Addressing Depression in HIV Research: Assessment, Cultural Context, and Methods

Depression is one of the most common co-morbidities of HIV infection. It negatively impacts self-care, quality of life, and biomedical outcomes among people living with HIV (PLWH) and may interfere with their ability to benefit from health promotion interventions. State-of-the-science research among PLWH, therefore, must address depression. To guide researchers, we describe the main diagnostic, screening, and symptom-rating measures of depression, offering suggestions for selecting the most appropriate instrument. We also address cultural considerations in the assessment of depression among PLWH, emphasizing the need to consider measurement equivalence and offering strategies for developing measures that are valid cross-culturally. Finally, acknowledging the high prevalence of depression among PLWH, we provide guidance to researchers on incorporating depression into the theoretical framework of their studies and employing procedures that account for participants with depression.

Adolescent Sexual Risk: Factors Predicting Condom Use Across the Stages of Change

This study examined factors associated with high-risk adolescents’ movement toward or away from adopting consistent condom use behavior using the Transtheoretical Model Stages of Change. Participants drawn from the inactive comparison condition of a randomized HIV prevention trial (Project SHIELD) responded to items assessing pros and cons of condom use, peer norms, condom communication, and perceived invulnerability to HIV. Participants were categorized based on their condom use behavior using the Transtheoretical Model. Multiple logistic regressions found that progression to consistent condom use was predicted by continuing to perceive more advantages to condom use, reporting greater condom use communication with partners, and less perceived invulnerability to HIV. Movement away from adopting consistent condom use was predicted by a decrease in perceived advantages to condom use, increased perceived condom disadvantages, and fewer condom discussions. Future interventions may be tailored to enhance these factors that were found to change over time.

Advancing novel HIV prevention intervention research with MSM--meeting report.

HIV continues to exact an enormous toll on society and to disproportionately affect gay and bisexual men and other men who have sex with men (MSM). Innovative prevention interventions are needed to reverse this trend. In August 2009, the U.S. National Institute of Mental Health and the Centers for Disease Control and Prevention convened a meeting of scientists, community representatives, advocates, and federal partners to discuss innovative prevention-intervention science. The meeting was structured to maximize discussion of (7) healthy sex interventions, (2) community and structural interventions, (3) integrated biomedical and behavioral interventions, and (4) interventions to improve uptake of HIV testing. Presentations and discussion focused on research gaps in designing risk-reducing and sexual health-promoting interventions for MSM, including interventions to address mental health, substance use, disclosure, and stigma. This article summarizes the meeting proceedings, highlights key points, and outlines future directions.

Disclosure of pharmacokinetic drug results to understand nonadherence.

Objectives:In VOICE, a phase IIB trial of daily oral and vaginal tenofovir for HIV prevention, at least 50% of women receiving active products had undetectable tenofovir in all plasma samples tested. MTN-003D, an ancillary study using in-depth interviews (IDIs) and focus group discussions (FGDs), together with retrospective disclosure of plasma tenofovir pharmacokinetic results, explored adherence challenges during VOICE. Methods:We systematically recruited participants with pharmacokinetic data (median six plasma samples), categorized as low (0%, N = 79), inconsistent (1–74%, N = 28) or high (≥75%; N = 20) on the basis of frequency of tenofovir detection. Following disclosure of pharmacokinetic results, reactions were captured and adherence challenges systematically elicited; IDIs and FGDs were audio-recorded, transcribed, coded and thematically analysed. Results:We interviewed 127 participants from South Africa, Uganda and Zimbabwe. The most common reactions to pharmacokinetic results included surprise (41%; low pharmacokinetic), acceptance (39%; inconsistent pharmacokinetic) and happiness (65%; high pharmacokinetic). On the basis of participants’ explanations, we developed a typology of adherence patterns: noninitiation, discontinuation, misimplementation (resulting from visit-driven use, variable taking, modified dosing or regimen) and adherence. Fear of product side effects/harm was a frequent concern, fuelled by stories shared among participants. Although women with high pharmacokinetic levels reported similar concerns, several described strategies to overcome challenges. Women at all pharmacokinetic levels suggested real-time drug monitoring and feedback to improve adherence and reporting. Conclusion:Retrospective provision of pharmacokinetic results seemingly promoted candid discussions around nonadherence and study participation. The effect of real-time drug monitoring and feedback on adherence and accuracy of reporting should be evaluated in trials.

Frequency of adolescent self-cutting as a predictor of HIV risk.

Objective: A wide range exists in the frequency of adolescent self-cutting behavior; however, the implications of this variability are relatively unexplored. Although evidence suggesting a relationship between self-harm and sexual risk behaviors has been identified, little is known regarding the relationship between frequency of self-cutting and sexual risk. The present study aimed to test the hypothesis that adolescents who repeatedly self-cut would report more HIV risk behaviors and riskier attitudes than those who had engaged in infrequent self-injury. Method: Adolescents (11–18 years; mean age, 15 years) from intensive psychiatric treatment programs with a history of self-cutting (N = 105, 53% female) completed measures of self-cutting, sexual risk behaviors, and risk attitudes. Results: Frequent self-cutting (more than three times, lifetime) was associated with being sexually active, using condoms inconsistently, and sharing cutting instruments. Frequent self-cutters were significantly more likely to be female and nonwhite, and report low self-restraint. They also showed a trend toward being more likely to have a history of sexual abuse. Conclusions: This study found important differences in self-cutters based on frequency of cutting. Adolescent self-cutting may be a spectrum of behavior that ranges from habitual, repeated behavior contrasted with infrequent, experimental, socially motivated cutting. The associations between frequent cutting, sexual risk, and low self-restraint suggest that common underlying mechanisms may determine these patterns.

Mental Health Considerations in Secondary HIV Prevention

Despite substantial attention in the past decade to the co-morbidity of mental health problems among people living with HIV/AIDS (PLWHA), these problems remain a significant barrier to maintaining health and secondary prevention. To address these issues, program staff from the Center for Mental Health Research on AIDS at the NIMH convened a meeting on 19th and 20th July 2007 to discuss the intersection of mental health and HIV. The conveners brought together leaders in the fields of mental illness and HIV to discuss current gaps in the research related to the prevention, diagnosis, and treatment of mental disorders among PLWHA, and how attention to mental health can affect a variety of health outcomes. Attendees were asked to discuss key questions that, if addressed through empirical investigation, could move the field toward the aim of reducing or alleviating the burden of mental illness for those living with HIV disease. The purpose of this brief report is to summarize this meeting’s proceedings, overview key points of discussion, and outline areas that may be useful to consider for clinical researchers in the field.

Opportunities for HIV combination prevention to reduce racial and ethnic health disparities.

Despite advances in HIV prevention and care, African Americans and Latino Americans remain at much higher risk of acquiring HIV, are more likely to be unaware of their HIV-positive status, are less likely to be linked to and retained in care, and are less likely to have suppressed viral load than are Whites. The first National HIV/AIDS Strategy (NHAS) has reducing these disparities as one of its three goals by encouraging the implementation of combination high-impact HIV intervention strategies. Federal agencies have expanded their collaborations in order to decrease HIV-related disparities through better implementation of data-driven decision making; integration and consolidation of the continuum of HIV care; and the reorganization of relationships among public health agencies, researchers, community-based organizations, and HIV advocates. Combination prevention, the integration of evidence-based and impactful behavioral, biomedical, and structural intervention strategies to reduce HIV incidence, provides the tools to address the HIV epidemic. Unfortunately, health disparities exist at every step along the HIV testing-to-care continuum. This provides an opportunity and a challenge to everyone involved in HIV prevention and care to understand and address health disparities as an integral part of ending the HIV epidemic in the United States. To further reduce health disparities, successful implementation of NHAS and combination prevention strategies will require multidisciplinary teams, including psychologists with diverse cultural backgrounds and experiences, to successfully engage groups at highest risk for HIV and those already infected with HIV. In order to utilize the comprehensive care continuum, psychologists and behavioral scientists have a role to play in reconceptualizing the continuum of care, conducting research to address health disparities, and creating community mobilization strategies.