Lamivudine/Tenofovir Disoproxil Fumarate is an Appropriate PrEP Regimen.

Oral pre-exposure prophylaxis (PrEP) containing tenofovir disoproxil fumarate (TDF) co-formulated with emtricitabine (FTC) or lamivudine (3TC) is recommended as an additional prevention option for persons at substantial risk of HIV infection by both the World Health Organization (WHO) and the US President's Emergency Plan for AIDS Relief (PEPFAR). The WHO and PEPFAR consider 3TC clinically interchangeable with FTC for PrEP given comparable pharmacologic equivalence, resistance and toxicity patterns, and indirect clinical trial evidence from TDF-containing studies. Globally, FTC/TDF has been widely used in clinical trials, open-label extension studies and demonstration projects. Thus, most PrEP efficacy and safety data are based on FTC/TDF use in heterosexual women and men, men who have sex with men, and people who inject drugs. However, generic 3TC/TDF is less expensive than FTC/TDF, is already available in supply chains for HIV drugs, and has 60-70% of the global adult market share, making it particularly appealing in settings with limited availability or affordability of FTC/TDF. Compelling indirect evidence suggests that scaling up use of 3TC/TDF is potentially cost saving for HIV programs in settings where restricting drug choice to FTC/TDF would delay PrEP implementation. Guideline committees and public health decision-makers in countries should encourage flexibility in PrEP drug selection, support off-label use of 3TC/TDF, and approve use of generic formulations to decrease the cost of PrEP medications and accelerate PrEP delivery through the public and private sectors.

Validation of publicly-available software used in analyzing NGS data for HIV-1 drug resistance mutations and transmission networks in a Washington, DC, Cohort.

The DC Cohort is an ongoing longitudinal observational study of persons living with HIV. To better understand HIV-1 drug resistance and potential transmission clusters among these participants, we performed targeted, paired-end next-generation sequencing (NGS) of protease, reverse transcriptase and integrase amplicons. We elected to use free, publicly-available software (HyDRA Web, Stanford HIVdb and HIV-TRACE) for data analyses so that laboratory personnel without extensive bioinformatics expertise could use it; making the approach accessible and affordable for labs worldwide. With more laboratories transitioning away from Sanger-based chemistries to NGS platforms, lower frequency drug resistance mutations (DRMs) can be detected, yet their clinical relevance is uncertain. We looked at the impact choice in cutoff percentage had on number of DRMs detected and found an inverse correlation between the two. Longitudinal studies will be needed to determine whether low frequency DRMs are an early indicator of emerging resistance. We successfully validated this pipeline against a commercial pipeline, and another free, publicly-available pipeline. RT DRM results from HyDRA Web were compared to both SmartGene and PASeq Web; using the Mantel test, R2 values were 0.9332 (p<0.0001) and 0.9097 (p<0.0001), respectively. PR and IN DRM results from HyDRA Web were then compared with PASeq Web only; using the Mantel test, R2 values were 0.9993 (p<0.0001) and 0.9765 (p<0.0001), respectively. Drug resistance was highest for the NRTI drug class and lowest for the PI drug class in this cohort. RT DRM interpretation reports from this pipeline were also highly correlative compared to SmartGene pipeline; using the Spearman's Correlation, rs value was 0.97757 (p<0.0001). HIV-TRACE was used to identify potential transmission clusters to better understand potential linkages among an urban cohort of persons living with HIV; more individuals were male, of black race, with an HIV risk factor of either MSM or High-risk Heterosexual. Common DRMs existed among individuals within a cluster. In summary, we validated a comprehensive, easy-to-use and affordable NGS approach for tracking HIV-1 drug resistance and identifying potential transmission clusters within the community.

Oxytocin's impact on social face processing is stronger in homosexual than heterosexual men.

Oxytocin is an evolutionarily highly preserved neuropeptide that contributes to the regulation of social interactions including the processing of facial stimuli. We hypothesized that its improving effect on social approach behavior depends on perceived sexual features and, consequently, on sexual orientation. In 19 homosexual and 18 heterosexual healthy young men, we investigated the acute effect of intranasal oxytocin (24IU) and placebo, respectively, on the processing of social stimuli as assessed by ratings of trustworthiness, attractiveness and approachability for male and female faces. Faces were each presented with a neutral, a happy, and an angry expression, respectively. In heterosexual subjects, the effect of oxytocin administration was restricted to a decrease in ratings of trustworthiness for angry female faces (p<0.02). In contrast, in homosexual men oxytocin administration robustly increased ratings of attractiveness and approachability for male faces regardless of the facial expression (all p ≤ 0.05), as well as ratings of approachability for happy female faces (p<0.01). Results indicate that homosexual in comparison to heterosexual men display higher sensitivity to oxytocin's enhancing impact on social approach tendencies, suggesting that differences in sexual orientation imply differential oxytocinergic signaling.

Differential processing of social chemosignals obtained from potential partners in regards to gender and sexual orientation.

On an individual level, human body odors carry information about whether a person is an eligible mate. The current studies investigate if body odors also transmit information about individuals being potential partners in more general terms, namely in regards to gender and sexual orientation. In study 1, 14 gay and 14 heterosexual men were presented with body odors obtained from potential partners (gay male and heterosexual female body odors, respectively) and heterosexual male body odor as a control. In study 2, 14 lesbian and 14 heterosexual women were presented with lesbian female and heterosexual male body odors representing body odors of potential partners, and heterosexual female body odor as a control. Central nervous processing was analyzed using chemosensory event-related potentials and current source density analysis (64-channel EEG recording). Gay and heterosexual men responded with shorter P2 latencies to the body odors of their preferred sexual partners, and lesbian women responded with shorter P2 latencies to body odors of their preferred gender. In response to heterosexual male body odors, lesbian women displayed the most pronounced P3 amplitude, and distinct neuronal activation in medial frontal and parietal neocortical areas. A similar pattern of neuronal activation was observed in gay men when presented with heterosexual male body odor. Both the early processing advantage (P2) for desirable partners' body odors as well as the enhanced evaluative processing (P3, CSD) of undesirable partners' body odors suggest that human body odors indeed carry information about individuals being potential partners in terms of gender and sexual orientation.

Factors associated with event-level stimulant use during sex in a sample of older, low-income men who have sex with men in Los Angeles.

Prior research shows that stimulant use is consistently associated with high-risk sexual behavior in samples of men who have sex with men (MSM), but few studies have explored factors associated with use of crack or methamphetamine during sex during specific sexual events among older, very low-income MSM. This study examined stimulant use during the most recent sexual episodes in a sample of primarily older, very low-income MSM (n=779). Although crack use was more prevalent than methamphetamine use (33% vs. 22%), findings suggest that methamphetamine users may be at greater risk for HIV transmission. HIV prevalence was higher among methamphetamine users (49%) than among crack users (24%). Having unprotected sex (OR 2.77, 95% CI 1.46-5.26), having sex in a public sex venue (OR 3.63, 95% CI 1.52-8.64), having sex with an HIV positive rather than with an HIV negative partner (OR 6.15, 95% CI 2.14-17.62), having exchanged sex for money or drugs (OR 4.16, 95% CI 1.78-9.72), and having a higher number of sexual partners (OR 1.67, 95% CI 1.17-2.38) all were associated with increased odds of methamphetamine use during sex. Fewer high-risk behaviors were associated with increased odds of using crack during sex. Having unprotected sex was associated with increased odds of crack use during sex only when sex partners were perceived to be HIV negative rather than to be HIV positive or of unknown status. Findings provide observations on associations between stimulant use during sex and risk behaviors that may be important to HIV prevention and drug treatment approaches for urban, older, very poor MSM.

In the shadows of a prevention campaign: sexual risk behavior in the absence of crystal methamphetamine.

Because of its ability to reduce inhibitions and increase sexual drive, an emerging body of research has repeatedly identified crystal methamphetamine as a key variable in explaining new HIV transmissions among men who have sex with men (MSM). The implications of which have included the development of HIV prevention policies and public health campaigns centered on curbing methamphetamine use in urban gay centers throughout the United States. Data collected from a diverse sample of gay and bisexual men attending large-scale gay, lesbian, and bisexual community events in New York City (n=738) indicated that 10.2% of men used methamphetamine recently (i.e., <90 days) and that 29.9% of the sample had experienced a recent episode of unprotected anal intercourse. The majority, 81.1%, of those men reporting unsafe sex had not used methamphetamine recently. This analysis identified a bivariate relationship between methamphetamine use and sexual risk, but also highlights other variables that were significantly related to risky sexual behavior. Logistic regression analyses indicated that recent GHB use, temptation for unsafe sex, being younger in age, and identification as a barebacker were better indicators of risky sexual behavior than methamphetamine use. Policies focused on methamphetamine prevention may help to curb risky sexual behavior among select groups of individuals; however, these will not adequately address the sexual health of the many gay and bisexual men who, in the shadows of anti-methamphetamine policies and prevention programs, continue to engage in unsafe sex but are nonusers of methamphetamine.

A glial amino-acid transporter controls synapse strength and courtship in Drosophila.

Mate choice is an evolutionarily critical decision that requires the detection of multiple sex-specific signals followed by central integration of these signals to direct appropriate behavior. The mechanisms controlling mate choice remain poorly understood. Here, we show that the glial amino-acid transporter genderblind controls whether Drosophila melanogaster males will attempt to mate with other males. Genderblind (gb) mutant males showed no alteration in heterosexual courtship or copulation, but were attracted to normally unappealing male species-specific chemosensory cues. As a result, genderblind mutant males courted and attempted to copulate with other Drosophila males. This homosexual behavior could be induced within hours using inducible RNAi, suggesting that genderblind controls nervous system function rather than its development. Consistent with this, and indicating that glial genderblind regulates ambient extracellular glutamate to suppress glutamatergic synapse strength in vivo, homosexual behavior could be turned on and off by altering glutamatergic transmission pharmacologically and/or genetically.