The prognostic value of several immunologic markers were compared in Los Angeles Multicenter AIDS Cohort Study (MACS) participants, most of whom had been infected with HIV for >8 years. Markers studied included CD4+ cell number, flow cytometric measurements of CD8+ cell expression of CD38 and HLA-DR antigens, and serum markers of immune activation including neopterin, beta2-microglobulin, soluble interleukin-2 receptor, soluble CD8, and soluble tumor necrosis factor receptor-alpha (TNF-alpha) type II. Cox proportional hazards models indicated that elevated CD38 on CD8, a flow cytometric measurement of CD8+ T-lymphocyte activation, was the most predictive marker of those studied for development of a clinical AIDS diagnosis and death. As compared with the reference group, who had CD38 on CD8 <2470 molecules per CD8+ cell and in whom 4 of 99 developed clinical AIDS within 3 years, participants with CD38 on CD8 between 2470 and 3899, 3900 and 7250, and >7250 had relative risks (and numbers developing AIDS within 3 years) of 5.0 (15 of 81), 12.3 (24 of 60), and 41.4 (36 of 49), respectively. The strong prognostic value of CD38 on CD8 measurements and the fundamental importance of chronic immune activation in the pathogenesis of HIV disease suggests that this marker might have utility in the clinical management of HIV-infected persons.

Background Social networking technologies are an emerging tool for HIV prevention. Objective To determine whether social networking communities can increase HIV testing among African American and Latino men who have sex with men (MSM). Design Randomized; controlled trial with concealed allocation (ClinicalTrials.gov: NCT01701206). Setting Online. Patients 112 MSM based in Los Angeles, more than 85% of whom were African American or Latino. Intervention Sixteen peer leaders were randomly assigned to deliver information about HIV or general health to participants via Facebook groups over 12 weeks. After participants accepted a request to join the group, participation was voluntary. Group participation and engagement was monitored. Participants could request a free home-based HIV testing kit and completed questionnaires at baseline and 12-week follow-up. Measurements Participant acceptance of and engagement in the intervention and social network participation, rates of home-based HIV testing, and sexual risk behaviors. Results Almost 95% of intervention participants and 73% of control participants voluntarily communicated using the social platform. Twenty-five of the 57 intervention participants (44%) requested home-based HIV testing kits compared with 11 of 55 control participants (20%) (difference, 24 percentage points [95% CI, 8 to 41 percentage points]). Nine of the 25 intervention participants (36%) who requested the test took it and mailed it back compared with 2 of the 11 control participants (18%) who requested the test. Retention at study follow-up was more 93%. Limitations Only 2 Facebook communities were included for each group. Conclusions Social networking communities are acceptable and effective tools to increase home-based HIV testing among at-risk populations. Primary funding source National Institute of Mental Health ClinicalTrials.gov Identifier (NCT01701206)

Background Social media technologies are newly emerging tools that can be used for HIV prevention and testing in low- and middle-income countries, such as Peru. This study examined the efficacy of using the Harnessing Online Peer Education (HOPE) social media intervention to increase HIV testing among men who have sex with men (MSM) in Peru. Methods In a cluster randomized controlled trial with concealed allocation, Peruvian MSM from Greater Lima/Callao (N = 556) were randomly assigned to join private intervention or control groups on Facebook for 12 weeks. In the intervention condition, forty-nine Peruvian MSM were trained and randomly assigned to be HIV prevention mentors to participants via Facebook groups over 12 weeks. Control participants received an enhanced standard of care, including standard offline HIV prevention available in Peru as well as participation in Facebook groups (without peer leaders) that provided study updates and HIV testing information. After accepting a request to join the groups, continued participation was voluntary. Participants could request a free HIV test at a local community clinic, and completed questionnaires on HIV risk behaviors and social media use at baseline and 12-week follow-up. Findings Between March 19, 2012, and June 11, 2012, and Sept 26, 2012, and Dec 19, 2012, 556 participants were randomly assigned to intervention groups (N=278) or control groups (N=278); we analyse data for 252 and 246. 43 participants (17%) in the intervention group and 16 (7%) in the control groups got tested for HIV (adjusted odds ratio 2.61, 95% CI 1.55–4.38). No adverse events were reported. Retention at 12-week follow-up was 90%. Across conditions, 7 (87.5%) of the 8 participants who tested positive were linked to care at a local clinic. Interpretation Development of peer-mentored social media communities seemed to be an effective method to increase HIV testing among high-risk populations in Peru.: Results suggest that the HOPE social media HIV intervention may improve HIV testing rates among MSM in Peru. Funding National Institute of Mental Health (NIMH MH090844)

This study was designed to assess the safety, acceptability, pharmacokinetic (PK), and pharmacodynamic (PD) responses to rectal administration of tenofovir (TFV) 1% vaginally formulated gel and oral tenofovir disoproxil fumarate (TDF). This study was designed as a phase 1, randomized, two-site (United States), double-blind, placebo-controlled study of sexually abstinent men and women. Eighteen participants received a single 300-mg exposure of oral TDF and were then randomized 2:1 to receive a single and then seven daily exposures of rectal TFV or hydroxyethyl cellulose (HEC) placebo gel. Safety endpoints included clinical adverse events (AEs) and mucosal safety parameters. Blood and colonic biopsies were collected for PK analyses and ex vivo HIV-1 challenge. No serious AEs were reported. However, AEs were significantly increased with 7-day TFV gel use, most prominently with gastrointestinal AEs ( p = 0.002). Only 25% of participants liked the TFV gel. Likelihood of use ''if somewhat protective'' was *75% in both groups. Indices of mucosal damage showed minimal changes. Tissue TFV diphosphate (TFV-DP) C max 30 min after single rectal exposure was 6-10 times greater than single oral exposure; tissue TFV-DP was 5.7 times greater following 7-day versus single rectal exposure. In vivo exposure correlated with significant ex vivo tissue infectibility suppression [single-rectal: p = 0.12, analysis of covariance (ANCOVA) p = 0.006; 7-day rectal: p = 0.02, ANCOVA p = 0.005]. Tissue PK-PD was significantly correlated ( p = 0.002). We conclude that rectal dosing with TFV 1% gel resulted in greater TFV-DP tissue detection than oral dosing with reduced ex vivo biopsy infectibility, enabling PK-PD correlations. On the basis of increased gastrointestinal AEs, rectally applied, vaginally formulated TFV was not entirely safe or acceptable, suggesting the need for alternative rectal-specific formulations.

The CD8+ T-cell response is central to control and eventual elimination of persistent viral infections. Although it might be expected that CD8+ T-cell activation would be associated with a better clinical outcome during viral infections, in long-term HIV-1 infection, high levels of CD8+ T-cell activation are instead associated with faster disease progression. In this study, cell surface expression of CD38, a flow cytometric marker of T-cell activation of CD8+ T cells, had predictive value for HIV-1 disease progression that was in part independent of the predictive value of plasma viral burden and CD4+ T-cell number. Measurements of CD38 antigen expression on CD8+ T cells in HIV-1-infected patients may be of value for assessing prognosis and the impact of therapeutic interventions. The pathogenetic reason why CD8+ T-cell activation is associated with poor outcome in HIV-1 disease remains unknown. Possibly CD8+ T-cell activation contributes to immunologic exhaustion, hyporesponsiveness of T cells to their cognate antigens, or perturbations in the T-cell receptor repertoire.