Use of Non-Occupational Post-Exposure Prophylaxis does not Lead to an Increase in High Risk Sex Behaviors in Men Who have Sex with Men Participating in the EXPLORE Trial

Non-occupational post-exposure prophylaxis (nPEP) use is an HIV prevention strategy that has been recommended by the CDC to prevent HIV infection after a high risk sexual exposure since 1997. In a behavioral intervention trial of 4,295 MSM we assessed perceptions and use of nPEP over 4 years in six cities across the United States. Overall, 1.9% of MSM reported use of nPEP prior to enrollment, and 6.3% at least once during the trial. Awareness of nPEP was reported by 47.5%, with higher awareness in two sites with funded nPEP programs. Three seroconversions occurred in the 384 visits where nPEP courses were reported, with no effect of nPEP on risk of HIV acquisition in this cohort (hazard ratio = 0.91, 95% confidence interval [0.29, 2.86]). NPEP users were a riskier group: increased odds of nPEP use were observed in association with multiple partners and unprotected receptive and insertive anal sex with HIV infected partners and partners with unknown HIV status. NPEP use was also associated with use of illicit drugs (injection drugs, crack cocaine, hallucinogens, and amphetamines). Importantly, willingness to use nPEP after high risk sex was associated with lower odds of high risk sex. After an episode of nPEP use, nPEP users remained more likely to report high risk sex than those in this cohort who had not previously used nPEP. However, within the subset of people who had previously reported high risk sex, previous nPEP use was not associated with higher odds of high risk sex, thus allaying fears that availability of nPEP would lead to an increase in high risk sex

Serosorting Is Associated with a Decreased Risk of HIV Seroconversion in the EXPLORE Study Cohort

Background: Seroadaptation strategies such as serosorting and seropositioning originated within communities of men who have sex with men (MSM), but there are limited data about their effectiveness in preventing HIV transmission when utilized by HIV-negative men. Methodology/Principal Findings: Data from the EXPLORE cohort of HIV-negative MSM who reported both seroconcordant and serodiscordant partners were used to evaluate serosorting and seropositioning. The association of serosorting and seropositioning with HIV seroconversion was evaluated in this cohort of high risk MSM from six U.S. cities. Serosorting was independently associated with a small decrease in risk of HIV seroconversion (OR = 0.88; 95%CI, 0.81–0.95), even among participants reporting $10 partners. Those who more consistently practiced serosorting were more likely to be white (p = 0.01), have completed college (p =,0.0002) and to have had 10 or more partners in the six months before the baseline visit (p = 0.01) but did not differ in age, reporting HIV-infected partners, or drug use. There was no evidence of a seroconversion effect with seropositioning (OR 1.02, 95%CI, 0.92–1.14). Significance: In high risk HIV uninfected MSM who report unprotected anal intercourse with both seroconcordant and serodiscordant partners, serosorting was associated with a modest decreased risk of HIV infection. To maximize any potential benefit, it will be important to increase accurate knowledge of HIV status, through increased testing frequency

Willingness to participate in future HIV prevention studies among gay and bisexual men in Scotland, UK: a challenge for intervention trials

This article examines willingness to participate in future HIV prevention research among gay and bisexual men in Scotland, UK. Anonymous, self-complete questionnaires and Orasure Gäó oral fluid samples were collected in commercial gay venues. 1,320 men were eligible for inclusion. 78.2% reported willingness to participate in future HIV prevention research; 64.6% for an HIV vaccine, 57.4% for a behaviour change study, and 53.0% for a rectal microbicide. In multivariate analysis, for HIV vaccine research, greater age, minority ethnicity, and not providing an oral fluid sample were associated with lower willingness; heterosexual orientation and not providing an oral fluid sample were for microbicides; higher education and greater HIV treatment optimism were for behaviour change. STI testing remained associated with being more willing to participate in microbicide research and frequent gay scene use remained associated with being more willing to participate in behaviour change research. Having an STI in the past 12 months remained significantly associated with being willing to participate in all three study types. There were no associations between sexual risk behaviour and willingness. Although most men expressed willingness to participate in future research, recruitment of high-risk men, who have the potential to benefit most, is likely to be more challenging

Mucosal Application of gp140 Encoding DNA Polyplexes to Different Tissues Results in Altered Immunological Outcomes in Mice

Increasing evidence suggests that mucosally targeted vaccines will enhance local humoral and cellular responses whilst still eliciting systemic immunity. We therefore investigated the capacity of nasal, sublingual or vaginal delivery of DNA-PEI polyplexes to prime immune responses prior to mucosal protein boost vaccination. Using a plasmid expressing the model antigen HIV CN54gp140 we show that each of these mucosal surfaces were permissive for DNA priming and production of antigen-specific antibody responses. The elicitation of systemic immune responses using nasally delivered polyplexed DNA followed by recombinant protein boost vaccination was equivalent to a systemic prime-boost regimen, but the mucosally applied modality had the advantage in that significant levels of antigen-specific IgA were detected in vaginal mucosal secretions. Moreover, mucosal vaccination elicited both local and systemic antigen-specific IgG(+) and IgA(+) antibody secreting cells. Finally, using an Influenza challenge model we found that a nasal or sublingual, but not vaginal, DNA prime/protein boost regimen protected against infectious challenge. These data demonstrate that mucosally applied plasmid DNA complexed to PEI followed by a mucosal protein boost generates sufficient antigen-specific humoral antibody production to protect from mucosal viral challenge

Association of sex, hygiene and drug equipment sharing with hepatitis C virus infection among non-injecting drug users in New York City

Background: Hepatitis C virus (HCV) rates are higher in non-injecting drug users (NIDUs) than general population estimates. Whether this elevated HCV rate is due to drug use or other putative risk behaviors remains unclear. Methods: Recent non-injection drug users of heroin, crack and/or cocaine were street-recruited from 2000 to 2003 and underwent an interview and venipuncture for HCV antibody assays. Multiple logistic regression analyses were used to assess correlates for HCV infection. Results: Of 740 enrollees, 3.9% were HCV positive. The median age (intraquartile range) was 30 (35–24) years, 70% were male and 90% were Black or Hispanic. After adjustment, HCV seropositives were significantly more likely than seronegatives to be older than 30 [adjusted odds ratio (AOR) = 5.71], tattooed by a friend/relative/acquaintance [AOR= 3.61] and know someone with HCV [AOR= 4.29], but were less likely to have shared nail or hair clippers, razors or a toothbrush [AOR= 0.32]. Conclusions: Non-commercial tattooing may be a mode of HCV transmission among NIDUs and education on the potential risk in using non-sterile tattooing equipment should be targeted toward this population. While no evidence was found for HCV transmission through NIDU equipment sharing or sexual risk behavior, further research is still warranted.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/40317/2/Howe_Association of Sex, Hygiene and Drug Equipment_2005.pd

Neighborhood-Level Correlates of Consistent Condom Use among Men Who have Sex with Men: A Multi-Level Analysis

http://deepblue.lib.umich.edu/bitstream/2027.42/61277/1/Frye.et.al.Neighborhood-LevelCorrelatesofConsistantCondomUse.pd

An Intervention to Reduce HIV Risk Behavior of Substance-Using Men Who Have Sex with Men: A Two-Group Randomized Trial with a Nonrandomized Third Group

In a randomized trial of a behavioral intervention among substance-using men who have sex with men, aimed at reducing sexual risk behavior, Mansergh and colleagues fail to find evidence of a reduction in risk from the intervention

Capturing the Molecular Mechanism of Anesthetic Action by Simulation Methods

Significant computational efforts have been focused toward exposing the molecular mechanisms of anesthesia in recent years. In the past decade, this has been aided considerably by a momentous increase in the number of high-resolution structures of ion channels, which are putative targets for the anesthetic agents, as well as advancements in high-performance computing technologies. In this review, typical simulation methods to investigate the behavior of model membranes and membrane-protein systems are briefly reviewed, and related computational studies are surveyed. Both lipid- and protein-mediated mechanisms of anesthetic action are scrutinized, focusing on the behavior of ion channels in the latter case

Mental distress in the general population in Zambia: Impact of HIV and social factors

<p>Abstract</p> <p>Background</p> <p>Population level data on mental health from Africa are limited, but available data indicate mental problems to represent a substantial public health problem. The negative impact of HIV on mental health suggests that this could particularly be the case in high prevalence populations. We examined the prevalence of mental distress, distribution patterns and the ways HIV might influence mental health among men and women in a general population.</p> <p>Methods</p> <p>The relationship between HIV infection and mental distress was explored using a sample of 4466 participants in a population-based HIV survey conducted in selected rural and urban communities in Zambia in 2003. The Self-reporting questionnaire-10 (SRQ-10) was used to assess global mental distress. Weights were assigned to the SRQ-10 responses based on DSM IV criteria for depression and a cut off point set at 7/20 for probable cases of mental distress. A structural equation modeling (SEM) was established to assess the structural relationship between HIV infection and mental distress in the model, with maximum likelihood ratio as the method of estimation.</p> <p>Results</p> <p>The HIV prevalence was 13.6% vs. 18% in the rural and urban populations, respectively. The prevalence of mental distress was substantially higher among women than men and among groups with low educational attainment vs. high. The results of the SEM showed a close fit with the data. The final model revealed that self-rated health and self perceived HIV risk and worry of being HIV infected were important mediators between underlying factors, HIV infection and mental distress. The effect of HIV infection on mental distress was both direct and indirect, but was particularly strong through the indirect effects of health ratings and self perceived risk and worry of HIV infection.</p> <p>Conclusion</p> <p>These findings suggest a strong effect of HIV infection on mental distress. In this population where few knew their HIV status, this effect was mediated through self-perceptions of health status, found to capture changes in health perceptions related to HIV, and self-perceived risk and worry of actually being HIV infected.</p

T- and B-cell responses to multivalent prime-boost DNA and viral vectored vaccine combinations against hepatitis C virus in non-human primates.

Immune responses against multiple epitopes are required for the prevention of hepatitis C virus (HCV) infection, and the progression to phase I trials of candidates may be guided by comparative immunogenicity studies in non-human primates. Four vectors, DNA, SFV, human serotype 5 adenovirus (HuAd5) and Modified Vaccinia Ankara (MVA) poxvirus, all expressing hepatitis C virus Core, E1, E2 and NS3, were combined in three prime-boost regimen, and their ability to elicit immune responses against HCV antigens in rhesus macaques was explored and compared. All combinations induced specific T-cell immune responses, including high IFN-γ production. The group immunized with the SFV+MVA regimen elicited higher E2-specific responses as compared with the two other modalities, while animals receiving HuAd5 injections elicited lower IL-4 responses as compared with those receiving MVA. The IFN-γ responses to NS3 were remarkably similar between groups. Only the adenovirus induced envelope-specific antibody responses, but these failed to show neutralizing activity. Therefore, the two novel regimens failed to induce superior responses as compared with already existing HCV vaccine candidates. Differences were found in response to envelope proteins, but the relevance of these remain uncertain given the surprisingly poor correlation with immunogenicity data in chimpanzees, underlining the difficulty to predict efficacy from immunology studies.This work was supported by European Union contract QLK2-CT-1999- 00356, by the Biomedical Primate Research Centre, The Netherlands, and by the Swedish Research Council. We are grateful to Alexander van den Berg for technical assistance with the ICS, to our colleagues from Animal Science Department for technical assistance and expert care of the macaques, to the participants of the European HCVacc Cluster who provided help and support, and to Thomas Darton (Oxford Vaccine Group, UK) for input and advice on the manuscript. Christine Rollier is an Oxford Martin fellow and a Jenner Insitute Investigator.This is the author accepted manuscript. The final version is available from Nature Publishing Group at https://doi.org/10.1038/gt.2016.55