Increasing the Effectiveness of Vaginal Microbicides: A Biophysical Framework to Rethink Behavioral Acceptability

Microbicide candidates delivered via gel vehicles are intended to coat the vaginal epithelium after application. The coating process depends on intrinsic biophysical properties of the gel texture, which restricts the potential choices for an effective product: the gel first must be physically synthesizable, then acceptable to the user, and finally applied in a manner promoting timely adequate coating, so that the user adherence is optimized. We present a conceptual framework anchoring microbicide behavioral acceptability within the fulfillment of the product biophysical requirements.We conducted a semi-qualitative/quantitative study targeting women aged 18-55 in Northern California to assess user preferences for microbicide gel attributes. Attributes included: (i) the wait time between application and intercourse, (ii) the gel texture and (iii) the trade-off between wait time and gel texture. Wait times were assessed using a mathematical model determining coating rates depending upon the gel's physical attributes.71 women participated. Results suggest that women would independently prefer a gel spreading rapidly, in 2 to 15 minutes (P<0.0001), as well as one that is thick or slippery (P<0.02). Clearly, thick gels do not spread rapidly; hence the motivation to study the trade-off. When asked the same question 'constrained' by the biophysical reality, women indicated no significant preference for a particular gel thickness (and therefore waiting time) (P>0.10) for use with a steady partner, a preference for a watery gel spreading rapidly rather than one having intermediate properties for use with a casual partner (P = 0.024).Biophysical constraints alter women's preferences regarding acceptable microbicide attributes. Product developers should offer a range of formulations in order to address all preferences. We designed a conceptual framework to rethink behavioral acceptability in terms of biophysical requirements that can help improve adherence in microbicide use ultimately enhancing microbicide effectiveness

First Phase 1 Double-Blind, Placebo-Controlled, Randomized Rectal Microbicide Trial Using UC781 Gel with a Novel Index of Ex Vivo Efficacy

Objectives: Successful control of the HIV/AIDS pandemic requires reduction of HIV-1 transmission at sexually-exposed mucosae. No prevention studies of the higher-risk rectal compartment exist. We report the first-in-field Phase 1 trial of a rectally-applied, vaginally-formulated microbicide gel with the RT-inhibitor UC781 measuring clinical and mucosal safety, acceptability and plasma drug levels. A first-in-Phase 1 assessment of preliminary pharmacodynamics was included by measuring changes in ex vivo HIV-1 suppression in rectal biopsy tissue after exposure to product in vivo. Methods: HIV-1 seronegative, sexually-abstinent men and women (N = 36) were randomized in a double-blind, placebo-controlled trial comparing UC781 gel at two concentrations (0.1%, 0.25%) with placebo gel (1:1:1). Baseline, single-dose exposure and a separate, 7-day at-home dosing were assessed. Safety and acceptability were primary endpoints. Changes in colorectal mucosal markers and UC781 plasma drug levels were secondary endpoints; ex vivo biopsy infectibility was an ancillary endpoint. Results: All 36 subjects enrolled completed the 7-14 week trial (100% retention) including 3 flexible sigmoidoscopies, each with 28 biopsies (14 at 10 cm; 14 at 30 cm). There were 81 Grade 1 adverse events (AEs) and 8 Grade 2; no Grade 3, 4 or procedure-related AEs were reported. Acceptability was high, including likelihood of future use. No changes in mucosal immunoinflammatory markers were identified. Plasma levels of UC781 were not detected. Ex vivo infection of biopsies using two titers of HIV-1 BaL showed marked suppression of p24 in tissues exposed in vivo to 0.25% UC781; strong trends of suppression were seen with the lower 0.1% UC781 concentration. Conclusions: Single and 7-day topical rectal exposure to both concentrations of UC781 were safe with no significant AEs, high acceptability, no detected plasma drug levels and no significant mucosal changes. Ex vivo biopsy infections demonstrated marked suppression of HIV infectibility, identifying a potential early biomarker of efficacy. (Registered at ClinicalTrials.gov; #NCT00408538). © 2011 Anton et al

Interventions for families affected by HIV

Family-based interventions are efficacious for human immunodeficiency virus (HIV) detection, prevention, and care, but they are not broadly diffused. Understanding intervention adaptation and translation processes can support evidence-based intervention (EBI) diffusion processes. This paper provides a narrative review of a series of EBI for families affected by HIV (FAH) that were adapted across five randomized controlled trials in the US, Thailand, and South Africa over 15 years. The FAH interventions targeted parents living with HIV and their children or caregiver supports. Parents with HIV were primarily mothers infected through sexual transmission. The EBIs for FAH are reviewed with attention to commonalities and variations in risk environments and intervention features. Frameworks for common and robust intervention functions, principles, practice elements, and delivery processes are utilized to highlight commonalities and adaptations for each location, time period, and intervention delivery settings. Health care, housing, food, and financial security vary dramatically in each risk environment. Yet, all FAH face common health, mental health, transmission, and relationship challenges. The EBIs efficaciously addressed these common challenges and were adapted across contexts with fidelity to robust intervention principles, processes, factors, and practices. Intervention adaptation teams have a series of structural decision points: mainstreaming HIV with other local health priorities or not; selecting an optimal delivery site (clinics, homes, community centers); and how to translate intervention protocols to local contexts and cultures. Replication of interventions with fidelity must occur at the level of standardized functions and robust principles, processes, and practices, not manualized protocols. Adopting a continuous quality improvement paradigm will enhance rapid and global diffusion of EBI for FAH

Assessing Motivations to Engage in Intentional Condomless Anal Intercourse in HIV Risk Contexts (Bareback Sex) Among Men Who Have Sex with Men

Although condom use is an effective barrier against HIV transmission, some men who have sex with men (MSM) engage in bareback sex (unprotected anal sex in risky contexts) and increase their risk for HIV (re)infection. Understanding MSM's decision to bareback (vis-à-vis condom use) is essential to develop effective HIV/AIDS prevention programs for this population. An ethnically diverse sample of men who bareback (n = 120) was recruited exclusively on the Internet and stratified to include two thirds who reported both unprotected receptive anal intercourse (URAI) and being HIV uninfected. We used exploratory factor analysis to explore the domains within the Decisional Balance to Bareback (DBB) scale, and test the association between DBB and risky sexual behaviors. HIV-positive MSM (n = 31) reported higher costs/losses associated with condom use than HIV-negative men (n = 89). We found two underlying factors in the DBB scale: a Coping with Social Vulnerabilities subscale (eight items; alpha = .89) and a Pleasure and Emotional Connection subscale (five items; alpha = .92). We found a positive association between DBB (i.e. greater gains associated with bareback sex) and URAI occasions, number of partners, and having one or more sero-discordant partners in the past 3 months. We conclude that because MSM may avoid using condoms in order to cope with psychosocial vulnerabilities and create intimacy with other MSM, this population could benefit from alternatives to condoms such as pre/post exposure prophylaxis and rectal microbicides.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85205/1/Bauermeister_AEP_09.pd

Preference for gel over suppository as delivery vehicle for a rectal microbicide: results of a randomised, crossover acceptability trial among men who have sex with men.

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85186/1/CarballoDieguez_STI-08.pd

Use of a Rapid HIV Home Test to Screen Sexual Partners: An Evaluation of its Possible Use and Relative Risk

We estimated the HIV risk reduction that could be attained by using a rapid HIV home test (HT) to screen sexual partners versus using condoms in different proportions of anal intercourse (AI) occasions among men who have sex with men (MSM). Special attention was paid to the role of the window period during which infected cases go undetected. Our results show that if MSM engage in AI without condoms following a non-reactive HT result, they have lower chances of becoming infected by someone still in the window period than by following heuristics and using condoms inconsistently. For MSM who do not use condoms, use of HT as a screening device may be a useful risk reduction strategy. This advantage increases with higher HIV population prevalence. With higher HIV incidence, this strategy will not provide any advantage if condoms are used in as little as one out of four occasions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85197/1/Ventuneacetal_09.pd

Lubricant Use Among Men Who Have Sex with Men Reporting Receptive Anal Intercourse in Peru: Implications for Rectal Microbicides as an HIV Prevention Strategy

This study assessed lubricant use during receptive anal intercourse (RAI) among Peruvian men who have sex with men (MSM) and willingness to use a hypothetical rectal microbicide (RM) formulated as a lubricant to prevent HIV infection. Data were collected from 843 Peruvian MSM for the 2008 HIV Sentinel Surveillance using a computerized self-interview. Half of the participants reported using a lubricant with their last sex partner during RAI, while 77% were willing to use a lubricant to prevent HIV transmission. Lubricant use with last sex partner was significantly associated with unprotected RAI (odds ratio [OR] 1.59, 95% confidence interval [CI], 1.23, 2.05; P \u3c 0.001) and willingness to use a future lubricant RM (OR 1.56, 95% CI: 1.24, 1.95; P \u3c 0.001). This study provides information on the behaviours associated with lubricant use and non-use among MSM practicing RAI in Peru that should inform future RM studies in Peru and other Latin American countries

A mobile health intervention in HIV primary care: supporting patients at risk for ART non-adherence

Mobile health (mHealth) interventions that are integrated in HIV clinical settings to facilitate ongoing patient-provider communication between primary care visits are garnering evidence for their potential in improving HIV outcomes. Rango is an mHealth intervention to support engagement in HIV care and treatment adherence. This study used a single-arm prospective design with baseline and 6-month assessments for pre-post comparisons, as well as a matched patient sample for between-group comparisons to test Rango’s preliminary efficacy in increasing viral suppression. The Rango sample (n = 406) was predominantly 50 years of age or older (63%; M = 50.67; SD = 10.97, 23–82), Black/African-American (44%) or Hispanic/Latinx (38%), and male (59%). At baseline, 18% reported missing at least one dose of ART in the prior three days and chart reviews of recent VL showed that nearly 82% of participants were virally suppressed. Overall 95% of the patients enrolled in Rango returned for a medical follow-up visit. Of the 65 unsuppressed patients at baseline who returned for a medical visit, 38 (59%) achieved viral suppression and only 5% of the suppressed group at baseline had an increase in viral load at 6 months despite being at risk for ART non-adherence. While viral suppression was similar between Rango participants and patients receiving treatment as usual over the same time period, it is unknown whether those patients were similarly at risk for non-adherence. Our findings support efforts to formally test this innovative approach in addressing ART non-adherence and viral suppression particularly to reach HIV treatment goals

Perceived Risks and Protective Strategies Employed by Young Men Who Have Sex with Men (YMSM) When Seeking Online Sexual Partners

This study examined the perceptions of risk by young men who have sex with men (YMSM) regarding meeting sexual partners through the Internet. Fifty-four YMSM ages 18-29 who reported engaging in bareback sex (intentional unprotected anal intercourse in high-risk contexts) completed a structured assessment and a face-to-face interview. Participants reported using the Internet to meet sexual partners at least once per week, having had multiple sexual partners in the past 2 months (M = 10.50, SD = 9.25), and engaging in occasions of unprotected receptive (M = 5.35, SD = 6.76) and insertive (M = 5.06, SD = 10.11) anal intercourse. A third of the sample reported having had unprotected sex with a partner who was serodiscordant or of unknown serostatus. Despite the obvious HIV risks, the most commonly perceived risks included threats to physical safety and difficulties trusting a stranger. Risk reduction strategies included leaving information about partner and whereabouts with a friend, meeting in a public place, and screening partner through online chatting. Those YMSM who meet partners online may be at risk for physical violence in addition to HIV or sexually transmitted infections (STIs). Public health campaigns should increase awareness of safety concerns when meeting sexual partners online and support YMSM's self-protective actions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85184/1/Bauermeister2010_HealthComm.pd