Hepatitis B surface antigen and hepatitis B RNA changes in HIV/hepatitis B virus co-infected participants receiving hepatitis B virus-active antiretroviral therapy.

Introduction: With advances in hepatitis B virus (HBV) therapies, there is a need to identify serum biomarkers that assess the HBV covalently closed circular DNA (cccDNA) reservoir and predict functional cure in HIV/HBV co-infection.

Methods: In this retrospective study, combining samples from HIV/HBV co-infected participants enrolled in two ACTG interventional trials, proportions achieving HBsAg less than 0.05 log10 IU/ml and HBV RNA less than log10 1.

IMPAACT 2016: Operationalizing HIV Intervention Adaptations to Inform the Science and Outcomes of Implementation.

Uptake of evidence-based interventions for adolescents and young adults living with HIV (AYA-LWH) in sub-Saharan Africa (SSA) is complex, and cultural differences necessitate local adaptations to enhance effective implementation. Few models exist to guide intervention tailoring, yet operationalizing strategies is critical to inform science and implementation outcomes, namely acceptability, appropriateness, feasibility, fidelity, and sustainability. This paper describes operationalizing the ADAPT-ITT framework applied to a manualized trauma-informed cognitive behavioral therapy (TI-CBT) intervention addressing mental and sexual health for AYA-LWH in SSA in preparation for a randomized controlled trial (RCT).

Voluntary Medical Male Circumcision and Perceived Sexual Functioning, Satisfaction, and Risk Behavior: A Qualitative Study in Botswana.

This article examines perceptions of sexual functioning, satisfaction, and risk-taking related to voluntary medical male circumcision (VMMC) in Botswana. Twenty-seven focus group discussions were conducted in four purposively selected communities with community leaders, men, and women. Discussions were analyzed using an inductive content analytic approach.

Triggering the decision to undergo medical male circumcision: a qualitative study of adult men in Botswana.

In 2007, the World Health Organization endorsed voluntary medical male circumcision (VMMC) as part of comprehensive HIV-prevention strategies. A major challenge facing VMMC programs in sub-Saharan Africa remains demand creation; there is urgent need for data on key elements needed to trigger the decision among eligible men to seek VMMC. Using qualitative methods, we sought to better understand the circumcision decision-making process in Botswana related to VMMC.

Plasma Cytokine Levels in Chronic Asymptomatic HIV-1 Subtype C Infection as an Indicator of Disease Progression in Botswana: A Retrospective Case Control Study.

HIV infects cells of the immune system causing immune activation and proliferation of immune cells, leading to alteration of production and activity of a number of cytokines. These changes in cytokine levels can affect the immune function, and have the potential to directly impact the course of HIV disease. We characterized plasma cytokine concentration profiles in HIV-1 subtype C chronically infected, antiretroviral therapy (ART)-naive participants to establish their influence on disease progression and viremia.

Importance of Viral Sequence Length and Number of Variable and Informative Sites in Analysis of HIV Clustering.

To improve the methodology of HIV cluster analysis, we addressed how analysis of HIV clustering is associated with parameters that can affect the outcome of viral clustering. The extent of HIV clustering and tree certainty was compared between 401 HIV-1C near full-length genome sequences and subgenomic regions retrieved from the LANL HIV Database. Sliding window analysis was based on 99 windows of 1,000 bp and 45 windows of 2,000 bp.

Impact of sampling density on the extent of HIV clustering.

Identifying and monitoring HIV clusters could be useful in tracking the leading edge of HIV transmission in epidemics. Currently, greater specificity in the definition of HIV clusters is needed to reduce confusion in the interpretation of HIV clustering results. We address sampling density as one of the key aspects of HIV cluster analysis.

Nef-mediated down-regulation of CD4 and HLA class I in HIV-1 subtype C infection: association with disease progression and influence of immune pressure.

Nef plays a major role in HIV-1 pathogenicity. We studied HIV-1 subtype C infected individuals in acute/early (n = 120) or chronic (n = 207) infection to investigate the relationship between Nef-mediated CD4/HLA-I down-regulation activities and disease progression, and the influence of immune-driven sequence variation on these Nef functions. A single Nef sequence per individual was cloned into an expression plasmid, followed by transfection of a T cell line and measurement of CD4 and HLA-I expression.

Predictors of suboptimal CD4 response among women achieving virologic suppression in a randomized antiretroviral treatment trial, Africa.

Background: A subset of HIV-1 infected patients starting highly active antiretroviral treatment (HAART) experience suboptimal CD4 response (SCR) despite virologic suppression. We studied the rate of and risk factors for SCR among women starting HAART in the ACTG A5208 study conducted in 7 African countries. 741 HAART-naive women with screening CD4 count <200 cells/μL were randomized to start HAART with Tenofovir/Emtricitabine plus either Nevirapine or Lopinavir/Ritonavir.

Single-arm evaluation of the AccuCirc device for early infant male circumcision in Botswana.

: Existing devices for early infant male circumcision (EIMC) have inherent limitations. We evaluated the newly developed AccuCirc device by circumcising 151 clinically well, full-term male infants with birth weight ≥2.5 kg within the first 10 days of life from a convenience sample in 2 hospitals in Botswana.

Cardiovascular disease risk factors in HIV-infected women after initiation of lopinavir/ritonavir- and nevirapine-based antiretroviral therapy in Sub-Saharan Africa: A5208 (OCTANE).

Background: Limited comparative, prospective data exist regarding cardiovascular risk factors in HIV-infected women starting antiretroviral therapy in Africa.

Methods: In 7 African countries, 741 women with CD4 <200 cells/mm were randomized to tenofovir/emtricitabine (TDF/FTC) plus either nevirapine (NVP, n = 370) or lopinavir/ritonavir (LPV/r, n = 371). Lipids and blood pressure (BP) were evaluated at entry, 48, 96, and 144 weeks.

Persistently elevated serum interleukin-6 predicts mortality among adults receiving combination antiretroviral therapy in Botswana: results from a clinical trial.

Elevated serum levels of inflammatory biomarkers have been associated with increased mortality and morbidity among HIV-infected individuals receiving combination antiretroviral therapy (cART) in European and U.S. cohorts.

Intra-host evolutionary rates in HIV-1C env and gag during primary infection.

Background: HIV-1 nucleotide substitution rates are central for understanding the evolution of HIV-1. Their accurate estimation is critical for analysis of viral dynamics, identification of divergence time of HIV variants, inference of HIV transmission clusters, and modeling of viral evolution.

Methods: Intra-patient nucleotide substitution rates in HIV-1C gag and env gp120 V1C5 were analyzed in a longitudinal cohort of 32 individuals infected with a single viral variant.

Estimating the prevalence of transmitted HIV drug resistance using pooled samples.

In many resource-poor countries, hiv-infected patients receive a standardized antiretroviral cocktail. In these settings, population-level surveillance of drug resistance is needed to characterize the prevalence of resistance mutations and to enable antiretroviral therapy programs to select the optimal regimen for their local population. The surveillance strategy currently recommended by the World Health Organization is prohibitively expensive in some settings and may not provide a sufficiently precise rendering of the emergence of drug resistance.

Abacavir alters the transcription of inflammatory cytokines in virologically suppressed, HIV-infected women.

Background: Abacavir (ABC) may be associated with a small, increased risk of myocardial infarction in HIV-infected adults, possibly related to cytokine-mediated inflammation.

Methods: To evaluate the induction of inflammatory cytokine transcription by ABC, we used samples from women randomized to receive zidovudine/lamivudine/ABC (Trizivir) or lopinavir/ritonavir and zidovudine/lamividine (Kaletra/Combivir) from the third trimester through six-months postpartum for the prevention of mother-to-child transmission (PMTCT). Women were matched by CD4 count and baseline HIV RNA.

Evolutionary gamut of in vivo Gag substitutions during early HIV-1 subtype C infection.

Two analyses of HIV-1 subtype C Gag quasispecies were performed in a prospective cohort of 42 acutely and recently infected individuals by SGA on viral RNA/proviral DNA templates. First, in vivo Gag substitutions were assessed in relation to the HIV-1C consensus sequence, which revealed that 29.3% of detected amino acid substitutions can be classified as reversions to subtype consensus, 61.

Prevalence of human papillomavirus genotypes and associated cervical squamous intraepithelial lesions in HIV-infected women in Botswana.

Human papillomaviruses (HPV) constitute one of the most prevalent sexually transmitted infections and are the etiological agents for invasive cervical cancer, the predominant cancer among women in Botswana. However, the prevalence of HPV genotypes in Botswana has yet to be reported. One hundred thirty-nine endocervical swabs were taken at baseline from HIV-1 infected, HSV-2 seropositive women enrolled in a longitudinal cohort study designed to assess the influence of herpes simplex virus-2 (HSV-2) infection on genital tract shedding of HIV-1.

Acceptability of male circumcision among adolescent boys and their parents, Botswana.

Little is known of the acceptability of male circumcision (MC) to adolescent boys, a key target group for HIV prevention. We conducted a cluster design survey among adolescent boys and their parents/guardians in two villages in Botswana. Of 1300 households visited, 398 boys were eligible; 269 boys and 210 parents/guardians participated.

Transmission of single and multiple viral variants in primary HIV-1 subtype C infection.

To address whether sequences of viral gag and env quasispecies collected during the early post-acute period can be utilized to determine multiplicity of transmitted HIV's, recently developed approaches for analysis of viral evolution in acute HIV-1 infection [1,2] were applied. Specifically, phylogenetic reconstruction, inter- and intra-patient distribution of maximum and mean genetic distances, analysis of Poisson fitness, shape of highlighter plots, recombination analysis, and estimation of time to the most recent common ancestor (tMRCA) were utilized for resolving multiplicity of HIV-1 transmission in a set of viral quasispecies collected within 50 days post-seroconversion (p/s) in 25 HIV-infected individuals with estimated time of seroconversion. The decision on multiplicity of HIV infection was made based on the model's fit with, or failure to explain, the observed extent of viral sequence heterogeneity.

Replicative fitness costs of nonnucleoside reverse transcriptase inhibitor drug resistance mutations on HIV subtype C.

Single-dose nevirapine (NVP) is quite effective in preventing transmission of the human immunodeficiency virus (HIV) from mother to child; however, many women develop resistance to NVP in this setting. Comparing outcomes of clinical studies reveals an increased amount of resistance in subtype C relative to that in other subtypes. This study investigates how nonnucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutations of subtype C affect replication capacity.

Psychosocial factors affecting medication adherence among HIV-1 infected adults receiving combination antiretroviral therapy (cART) in Botswana.

As increasing numbers of persons are placed on potentially life-saving combination antiretroviral therapy (cART) in sub-Saharan Africa, it is imperative to identify the psychosocial and social factors that may influence antiretroviral (ARV) medication adherence. Using an 87 question survey, the following data were collected from patients on cART in Botswana: demographics, performance (Karnofsky) score, perceived stigma and level of HIV disclosure, attitudes and beliefs concerning HIV/AIDS, substance and/or drug use, depression, and pharmacy and healthcare provider-related factors. Overall adherence rates were determined by patient self-report, institutional adherence, and a culturally modified Morisky scale.

Dynamics and timing of in vivo mutations at Gag residue 242 during primary HIV-1 subtype C infection.

Viral mutations at Gag residue 242 and relevant viral polymorphisms were analyzed in a cohort of 42 individuals with primary HIV-1 subtype C infection using single-genome amplification/sequencing. In HLA-B*57/5801-negative subjects infected with 242N escape variant, reversion to Asn appeared at median (IQR) 103 days (97-213 days) post-seroconversion (p/s) and became dominant at 193 days (170-215 days) p/s. In subjects expressing HLA-B*57/5801 and infected with the wild-type virus, the T242N escape appeared at 203 days (196-231) p/s, reached dominance at 277 days (265-315 days) p/s, and became complete at 323 days (289-373 days) p/s.

HIV-1 subtype C-infected individuals maintaining high viral load as potential targets for the "test-and-treat" approach to reduce HIV transmission.

The first aim of the study is to assess the distribution of HIV-1 RNA levels in subtype C infection. Among 4,348 drug-naïve HIV-positive individuals participating in clinical studies in Botswana, the median baseline plasma HIV-1 RNA levels differed between the general population cohorts (4.1-4.

Adult combination antiretroviral therapy in sub-Saharan Africa: lessons from Botswana and future challenges.

Numerous national public initiatives offering first-line combination antiretroviral therapy (cART) for HIV infection have commenced in sub-Saharan Africa since 2002. Presently, 2.1 million of an estimated seven million Africans in need of cART are receiving treatment.