Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

Abstract

IntroductionWithin the first weeks of human immunodeficiency virus (HIV) infection, virus replication reaches systemic circulation. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of disease progression, there is limited understanding of the conditions required to transform a small localized transmitted founder population into a large and heterogeneous systemic infection.MethodsCynomolgus and rhesus macaques were infected with simian immunodeficiency virus (SIV) and followed longitudinally. Plasma levels of SIV were monitored using qRT-PCR. Bacterial genomic DNA in plasma was characterized and quantified longitudinally using 16S ribosomal deep sequencing and qPCR. ELISA-based assays were used to monitor intestinal permeability (IFABP) and perturbation of bacteria-specific host factors (sCD14 and EndoCab). Flow cytometry was used to track peripheral blood lymphocyte populations. In vitro assays were performed by exposing freshly isolated peripheral blood mononuclear cells to bacterial lysate prepared from major translocators. Effects of bacterial lysate on CD4+ T cell activation and CD8+ T cell cytotoxicity were measured using flow cytometry. Statistical significance was calculated using ANOVA or Wilcoxon signed-rank testing.ResultsPrior to the peak of viremia, we observed a transient high-level influx of microbial genomic DNA into peripheral blood. This microbial translocation was accompanied by perturbation of bacteria-specific host factors in plasma, as well as expansion of the CD4+CCR5+ T cell compartment. Exposure of freshly isolated peripheral blood mononuclear cells to lysate prepared from major translocating taxa revealed differential taxa-specific effects on the CD4+CCR5+ T cell compartment and cytotoxic granule expression within CD8+ T cells.ConclusionsAltogether, our data identify the influx of microbial products into blood during hyperacute SIV infection as a candidate modifier of early interactions between the antiviral host response and nascent HIV infection. Over the next few months, we will explore the effect of inducing microbial translocation during SIV infection, with particular interest on microbial reactivity within the CD4+CCR5+ target cell compartment.

Relationship Between Time to Initiation of Antiretroviral Therapy and Treatment Outcomes: A Cohort Analysis of ART Eligible Adolescents in Zimbabwe

“…Our findings are supported by another routine programme evaluation from South Africa, which found high ART uptake, good adherence, and no evidence for increased post-initiation LTFU after introducing a comprised preparation schedule for accelerated treatment start within one week 58. Similarly encouraging evidence is emerging from a randomized trial in Haiti, where preliminary results suggest better retention and lower mortality among patients initiated at the same day of establishing ART eligibility compared to patients who initiated after three weekly preparatory visits 59. Another recently completed cluster-randomized trial in Uganda using a multi-component intervention primarily targeting health care workers to accelerate ART initiation, including the option to start ART at the same day of HIV diagnosis, found better adherence among rapidly initiated patients, and no difference in LTFU and mortality compared to standard of care 60.…”

“…High mortality and LTFU around the time of becoming ART eligible has also been found elsewhere across different settings and patient groups, in particular among patients not initiated on ART 6,33,54–57. Considering that many of those coded as LTFU are like to have actually died,59,60 mortality among our patients is probably even higher than reported in the data. We attribute the slightly increased mortality among patients initiated at 0-7 days in our analysis to selection bias caused by health care workers prioritizing sicker patients, who had a higher probability of dying despite fast ART initiation, over less sick patients.…”

Family planning providers' role in offering PrEP to women

“…While multiple modalities of PrEP are in development ranging from vaginal rings to injectables and implants, only PrEP with oral tenofovir/emtricitabine is currently FDA-approved. The Centers for Disease Control and Prevention (CDC) estimates 468,000 women in the United States (U.S.) are eligible for PrEP, defined as having condomless sex in the prior 6 months with a man living with HIV, a man who has sex with men, or a man who injects drugs [2]. However, to date, only approximately 19,000 women have ever been prescribed PrEP, and that number appears to have stabilized [3, 4]. Moreover, while Black women in the U.S. are twenty times more likely to acquire HIV than White women and have 1 in 54 lifetime risk of acquiring HIV [5], disproportionately fewer Black women have been prescribed PrEP or know about PrEP [4, 6].…”

Forming and implementing community advisory boards in low- and middle-income countries: a scoping review

“…It is worth noting that researchers may also have lacked the skills necessary to communicate scientific knowledge in understandable and meaningful ways to participating communities. CAB training helped to build capacity and knowledge among members and researchers [113, 114]. This also suggests the need for further CAB member and researcher training [16].…”