Observational study of effects of HIV acquisition and antiretroviral treatment on biomarkers of systemic immune activation.

To assess whether biomarkers of systemic inflammation are associated with HIV acquisition or with the timing of ART initiation ("immediate", at diagnosis, versus "deferred", at 24 weeks post-diagnosis) in men-who-have-sex-with-men (MSM) and transgender women, we conducted a retrospective study comparing inflammatory biomarkers in participants' specimens collected before infection and after ≥2 years of effective ART. We measured biomarkers in four longitudinally collected plasma, including two specimens collected from each participant before and two after HIV acquisition and confirmed ART-suppression. Biomarkers were quantified by enzyme-linked immuno-assay or Meso Scale Discovery.

Observational study of effects of HIV Acquisition and Antiretroviral Treatment on Biomarkers of Systemic Immune Activation.

Objective: Assess whether biomarkers of systemic inflammation are associated with HIV acquisition or with the timing of ART initiation ("immediate", at diagnosis, versus "deferred", at 24 weeks post-diagnosis) in men-who-have-sex-with-men (MSM) and transgender women.

Design: A retrospective study comparing inflammatory biomarkers in participants' specimens collected before and after ≥2 years of effective ART.

Methods: Inflammatory biomarkers were measured in four longitudinally collected plasma specimens, including two plasma specimens collected from each participant before and two after HIV acquisition and confirmed ART-suppression.

Viral Suppression Levels in Men Who Have Sex With Men and Transgender Women With Newly Diagnosed HIV and Alcohol Use Disorder in Peru: Results From a Randomized, Double-Blind, Placebo-Controlled Trial Using Oral Naltrexone.

Background: Alcohol use disorders (AUDs) are common in men who have sex with men (MSM) and transgender women (TGW) in Peru and undermine antiretroviral therapy (ART) adherence. Oral naltrexone (NTX) is an evidence-based treatment for AUD that has not been assessed in cotreating AUD in MSM/TGW with HIV.

Setting And Design: A multi-site, randomized, double-blind, placebo-controlled trial among MSM/TGW with AUD and newly diagnosed with HIV in Lima, Peru.

Sexual Behavior and Sexually Transmitted Infection Outcomes Among Men Who Have Sex With Men and Transgender Women Participating in a Study of the Timing of Antiretroviral Therapy in Lima, Peru.

Background: We assessed sexual behavior and incidence of sexually transmitted infections (STIs) among men who have sex with men and transgender women participating in Sabes, a study of an expanded treatment as prevention strategy focused on early diagnosis and treatment of HIV infection in Lima, Peru (2013-2017).

Methods: Sabes participants were tested monthly for HIV to identify acute or early infections, and HIV-positive participants were randomized to receive antiretroviral therapy immediately (immediate arm) or after 24 weeks (deferred arm) during a 48-week follow-up period. Sexual behavior was assessed at randomization (baseline) and every 12 weeks thereafter.

Correlates of concurrent partnerships and patterns of condom use among men who have sex with men and transgender women in Peru.

Background: In Peru, there is an ongoing high-incidence HIV epidemic among men who have sex with men (MSM) and transgender women (TW). Sexual concurrency, or having sex with a partner in between two acts of sex with another partner, may be a key factor in onward HIV transmission. In this study, we quantify concurrency, evaluate factors associated with concurrency, and assess condom use with concurrent partners among MSM and TW in Peru.

Impact of pre-diagnosis awareness of HIV-related stigma and dispositional coping on linkage to HIV care among newly diagnosed HIV+ Peruvian patients.

A substantial body of literature has characterized how psychosocial factors, including HIV-related stigma and coping, are associated with HIV testing and HIV care utilization post-diagnosis. Less is known about if certain psychosocial characteristics pre-diagnosis may also predict linkage to care among individuals who receive an HIV-positive diagnosis. We examined if pre-diagnosis awareness/perception about HIV-related stigma and dispositional coping styles predicted linkage to HIV care within three months post-diagnosis with a secondary analysis of 604 patients from a randomized controlled trial (Sabes Study).

Computational analysis of antibody dynamics identifies recent HIV-1 infection.

Accurate HIV-1 incidence estimation is critical to the success of HIV-1 prevention strategies. Current assays are limited by high false recent rates (FRRs) in certain populations and a short mean duration of recent infection (MDRI). Dynamic early HIV-1 antibody response kinetics were harnessed to identify biomarkers for improved incidence assays.

A Qualitative Assessment of Alcohol Consumption and Sexual Risk Behaviors Among Men Who Have Sex With Men and Transgender Women in Peru.

Background: Peruvian men who have sex with men (MSM) and transgender women (TGW) experience the double burden of a highly concentrated HIV epidemic with a high prevalence of alcohol use disorders (AUDs). Recent research has associated both with risky sexual behaviors, including unprotected sex, having multiple sexual partners, engaging in sex work, having recent sexually transmitted infections, and having HIV-infected partners. AUDs have also been associated in MSM/TGW with being unaware of HIV+ status.

Men Who Have Sex With Men in Peru: Acceptability of Medication-Assisted Therapy for Treating Alcohol Use Disorders.

In Peru, the HIV epidemic is concentrated in men who have sex with men (MSM) and transgender women (TGW). Multiple studies correlate alcohol use disorders (AUDs) with risky sexual behaviors among Peruvian MSM. Qualitative research was used to inform a clinical trial on the acceptability of medication-assisted therapies to assist management of AUDs and improve antiretroviral therapy (ART) adherence among MSM/TGW in Peru.

Merck Ad5/HIV induces broad innate immune activation that predicts CD8⁺ T-cell responses but is attenuated by preexisting Ad5 immunity.

To better understand how innate immune responses to vaccination can lead to lasting protective immunity, we used a systems approach to define immune signatures in humans over 1 wk following MRKAd5/HIV vaccination that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases in peripheral blood mononuclear cell gene expression associated with inflammation, IFN response, and myeloid cell trafficking occurred, and lymphocyte-specific transcripts decreased. These alterations were corroborated by marked serum inflammatory cytokine elevations and egress of circulating lymphocytes.

Differential specificity and immunogenicity of adenovirus type 5 neutralizing antibodies elicited by natural infection or immunization.

A recent clinical trial of a T-cell-based AIDS vaccine delivered with recombinant adenovirus type 5 (rAd5) vectors showed no efficacy in lowering viral load and was associated with increased risk of human immunodeficiency virus type 1 (HIV-1) infection. Preexisting immunity to Ad5 in humans could therefore affect both immunogenicity and vaccine efficacy. We hypothesized that vaccine-induced immunity is differentially affected, depending on whether subjects were exposed to Ad5 by natural infection or by vaccination.

Safety analysis of the diaphragm in combination with lubricant or acidifying microbicide gels: effects on markers of inflammation and innate immunity in cervicovaginal fluid.

Objective: Diaphragms are being considered for use with vaginal microbicide gels to provide enhanced protection against sexually transmitted pathogens. The purpose of this study was to determine whether use of a diaphragm with microbicide or placebo gel causes cervicovaginal inflammation or perturbations in cervicovaginal immune defense.

Method Of Study: Eighty-one non-pregnant women were randomized into three groups and instructed to use Milex (CooperSurgical, Inc.

Peptide selection for human immunodeficiency virus type 1 CTL-based vaccine evaluation.

Dozens of human immunodeficiency virus-type 1 (HIV-1) vaccine candidates specifically designed to elicit cytotoxic T-lymphocyte (CTL) responses have entered the pipeline of clinical trials. Evaluating the immunogenicity and potential efficacy of these HIV-1 vaccine candidates is challenging in the face of the extensive viral genetic diversity of circulating strains. Standardized peptide reagents to define the magnitude and potential breadth of the T-cell response, especially to circulating strains of HIV-1, are needed.

Participant retention in clinical trials of candidate HIV vaccines.

Objective: : To determine predictors of loss to follow-up (LTFU) in trials of candidate HIV vaccines.

Methods: : Data were obtained from trials of candidate preventive HIV vaccines conducted by the AIDS Vaccine Evaluation Group (AVEG) and HIV Network for Prevention Trials (HIVNET) that enrolled HIV-negative volunteers. Analytic models included multiple logistic regression and generalized estimating equations.

Influence of sex hormones, HIV status, and concomitant sexually transmitted infection on cervicovaginal inflammation.

The impact of demographic characteristics, phase of the menstrual cycle, use of hormonal contraceptives, and concomitant lower genital-tract infections on cervicovaginal inflammatory cells was assessed in 967 women, 654 of whom were infected with human immunodeficiency virus type 1 (HIV-1). Cervicovaginal lavage (CVL) fluid was evaluated for total white blood cell (WBC), polymorphonuclear leukocyte, and monocyte counts. HIV-1 infection was not associated with statistically significant differences in numbers of inflammatory cells in CVL fluid except in 1 group--HIV-1-infected women with Chlamydia trachomatis infection had a 0.

Resistance to HIV-1 infection: lessons learned from studies of highly exposed persistently seronegative (HEPS) individuals.

The medical, social, and economic impact of the human immunodeficiency virus (HIV) epidemic has underscored the need to quickly develop effective control strategies. Vigorous efforts to develop a vaccine and therapeutic agents have not yet succeeded in containing the spread of the virus. Studies of persons who remain uninfected despite extensive exposure to HIV continue to provide valuable information on mechanisms of natural protection, which can then be applied to vaccine design.