A5087165714- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- HIV/AIDS drug development and treatment
- HIV, Drug Use, Sexual Risk
- HIV-related health complications and treatments
- vaccines and immunoinformatics approaches
- Immune Cell Function and Interaction
- Bacteriophages and microbial interactions
- Hepatitis C virus research
- SARS-CoV-2 and COVID-19 Research
- Adolescent Sexual and Reproductive Health
- SARS-CoV-2 detection and testing
- T-cell and B-cell Immunology
- Herpesvirus Infections and Treatments
- Genomics and Phylogenetic Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Glycosylation and Glycoproteins Research
- Chromosomal and Genetic Variations
- Blood groups and transfusion
- Plant Virus Research Studies
- HIV, TB, and STIs Epidemiology
- Tuberculosis Research and Epidemiology
- COVID-19 Clinical Research Studies
- Evolution and Genetic Dynamics
- Respiratory viral infections research
Brown University
2019-2025
John Brown University
2023
Botswana Harvard AIDS Institute Partnership
2013-2022
Harvard University
2013-2022
Development Fund
2022
Weatherford College
2022
Miriam Hospital
2021
Providence College
2021
Tygerberg Hospital
2017
National Health Laboratory Service
2017
Postnatal transmission of human immunodeficiency virus-1 (HIV) via breastfeeding reverses gains achieved by perinatal antiretroviral interventions.To compare the efficacy and safety 2 infant feeding strategies for prevention postnatal mother-to-child HIV transmission.A x factorial randomized clinical trial with peripartum (single-dose nevirapine vs placebo) postpartum (formula zidovudine prophylaxis) interventions. In Botswana between March 27, 2001, October 29, 2003, 1200 HIV-positive...
A single dose of nevirapine during labor reduces perinatal transmission human immunodeficiency virus type 1 (HIV-1) but often leads to viral resistance mutations in mothers and infants.
BackgroundInternational and global organisations advocate targeting interventions to areas of high HIV prevalence (ie, hotspots). To better understand the potential benefits geo-targeted control, we assessed extent which hotspots along Lake Victoria sustain transmission in neighbouring populations south-central Uganda.MethodsWe did a population-based survey Rakai, Uganda, using data from Rakai Community Cohort Study. The study surveyed all individuals aged 15–49 years four high-prevalence...
The current AIDS pandemic represents the uneven spread of multiple genetically related subtypes (A to J) human immunodeficiency virus type 1 (HIV-1). Notably, HIV-1 E in southeast Asia and C sub-Saharan Africa are expanding faster likely greater global significance than B subtype prevalent United States Europe. While many studies have focused on genetic variation among structural genes, we chose conduct a comparative analysis long terminal repeats isolates report subtype-specific differences...
ABSTRACT An evolving dominance of human immunodeficiency virus type 1 subtype C (HIV-1C) in the AIDS epidemic has been associated with a high prevalence HIV-1C infection southern African countries and an expanding India China. Understanding molecular phylogeny genetic diversity viruses may be important for design evaluation HIV vaccine ultimate use developing world. In this study we analyzed phylogenetic relationships (i) between 73 nonrecombinant near-full-length genome sequences, including...
ABSTRACT Routine monitoring of HIV-1 RNA or viral load (VL) in patients on antiretroviral therapy (ART) is important, but there are multiple impediments to VL testing resource-constrained settings. An accurate point-of-care (POC) test could alleviate many these challenges. We compared the performance Cepheid Xpert assay against laboratory-based Abbott m 2000sp/ 2000rt (Abbott assay). ART-naive individuals participating Botswana Combination Prevention Project 20 communities provided...
Abstract To prevent new infections with human immunodeficiency virus type 1 (HIV-1) in sub-Saharan Africa, UNAIDS recommends targeting interventions to populations that are at high risk of acquiring and passing on the virus. Yet it is often unclear who where these ‘source’ are. Here we demonstrate how viral deep-sequencing can be used reconstruct HIV-1 transmission networks infer direction networks. We able deep-sequence from a large population-based sample infected individuals Rakai...
ABSTRACT To better understand the virological aspect of expanding AIDS epidemic in southern Africa, a set 23 near-full-length clones human immunodeficiency virus type 1 (HIV-1) representing eight patients from Botswana were sequenced and analyzed phylogenetically. All study viruses belonged to HIV-1 subtype C. The interpatient diversity was higher than among full-length isolates B or genomes C India (mean value 9.1% versus 6.5 4.3%, respectively; P < 0.0001 for both comparisons). Similar...
A systematic analysis of immune responses on a population level is critical for human immunodeficiency virus type 1 (HIV-1) vaccine design. Our studies in Botswana (i) molecular the HIV-1 subtype C (HIV-1C) epidemic, (ii) frequencies major histocompatibility complex class I HLA types, and (iii) cytotoxic T-lymphocyte (CTL) course natural infection allowed us to address HIV-1C-specific level. We analyzed magnitude frequency gamma interferon ELISPOT-based CTL translated them into normalized...
ABSTRACT The most severe human immunodeficiency virus type 1 (HIV-1) epidemic is occurring in southern Africa. It caused by HIV-1 subtype C (HIV-1C). In this study we present the identification and analysis of cumulative cytotoxic T-lymphocyte (CTL) responses African country Botswana. CTLs were shown to be an important component immune response control infection. definition optimal dominant epitopes across HIV-1C genome that are targeted CTL critical for vaccine design. characteristics...
Background: Single-dose nevirapine given to women and infants reduces mother-to-child HIV transmission, but resistance develops in a large percentage of women. Objective: To determine whether the maternal dose could be eliminated setting zidovudine prophylaxis. Design, setting, participants: A 2 × factorial, randomized, clinical trial, with double-blinded peripartum factor designed assess equivalence single-dose versus placebo respect transmission. total 709 HIV-infected pregnant were...
Background: The ability of nucleoside reverse transcriptase inhibitors (NRTIs) to inhibit human mitochondrial polymerase-γ results in impaired synthesis enzymes that generate adenosine triphosphate (ATP) by oxidative phosphorylation. This has been associated with several long-term toxicities, which include lactic acidosis and pancreatitis, peripheral neuropathy, lipoatrophy. Methods: Enrolled highly active antiretroviral therapy (HAART)-treated adults have completed nearly 2 years follow-up...
Objective: The present study addressed two questions: what fraction of individuals maintain a sustained high HIV-1 RNA load after the acute HIV-1C infection peak and how long is maintained in this subpopulation? Design/methods: Plasma dynamics were studied 77 participants with primary from African cohorts Gaborone, Botswana, Durban, South Africa. HIV-infected who mean viral at least 100 000 (5.0 log10) copies/ml days postseroconversion (p/s) termed extended viremics. Individuals followed...
Background: Mathematical models predict that community-wide access to HIV testing-and-treatment can rapidly and substantially reduce new infections. Yet several large universal test-and-treat prevention trials in high-prevalence epidemics demonstrated variable reduction population-level incidence. Methods: To elucidate patterns of spread trials, we quantified the contribution geographic-location, gender, age, randomized-HIV-intervention transmissions 30-community Ya Tsie trial Botswana. We...
Abstract Background Due to the high prevalence of resistance NNRTI-based ART since 2018, consolidated recommendations from WHO have indicated dolutegravir as preferred drug choice for HIV treatment globally. There is a paucity outcome data HIV-1 non-B subtypes circulating across West Africa. Aims We characterized mutational profiles persons living with cross-sectional cohort in North-East Nigeria failing dolutegravir-based regimen. Methods WGS plasma samples collected 61 HIV-1-infected...
Abstract Background The use of antiretroviral therapy (ART) has surged globally, heralding an era life-saving treatment for millions. However, with this widespread adoption ART, a concerning trend emerged: the escalation resistance. Within confines La Hispaniola, encompassing Dominican Republic (DO) and Haiti(HT), prevalence HIV stands among highest in Caribbean region. Our main objective is to identify characterize extent transmitted drug resistance (TDR) naïve participants, its demographic...
The human immunodeficiency virus type 1 (HIV-1) epidemic within southern Africa is predominantly associated with the HIV-1C subtype. Functional analysis of enhancer region long terminal repeat (LTR) indicates that isolates have ⩾3 NF-κB binding sites, unlike other subtypes, which only or 2 sites. A correlation was shown between configuration and responsiveness to proinflammatory cytokine tumor necrosis factor (TNF)-α context naturally occurring subtype LTRs, subtype-specific regions cloned...
ABSTRACT HLA class I-mediated selection of immune escape mutations in functionally important Gag epitopes may partly explain slower disease progression HIV-1-infected individuals with protective alleles. To investigate the impact function on progression, replication capacities viruses encoding Gag-protease from 60 early HIV-1 subtype C infection were assayed an HIV-1-inducible green fluorescent protein reporter cell line and correlated subsequent progression. Replication did not correlate...
The first aim of the study is to assess distribution HIV-1 RNA levels in subtype C infection. Among 4,348 drug-naïve HIV-positive individuals participating clinical studies Botswana, median baseline plasma differed between general population cohorts (4.1–4.2 log10) and cART-initiating (5.1–5.3 by about one log10. proportion with high (≥50,000 (4.7 copies/ml) ranged from 24%–28% 65%–83% cohorts. second estimate who maintain for an extended time duration this period. For analysis, we could be...
Background: Numerous national antiretroviral (ARV) treatment initiatives offering protease inhibitor-sparing combination therapy (cART) have recently commenced in southern Africa, the first of which began Botswana January 2002. Evaluation efficacy and tolerability various cART regimens requires intensive study region, as does investigation development drug resistance optimal means sustaining adherence. The "Tshepo" Study is large-scale, randomized, clinical trial that addresses these...
To address whether sequences of viral gag and env quasispecies collected during the early post-acute period can be utilized to determine multiplicity transmitted HIV's, recently developed approaches for analysis evolution in acute HIV-1 infection [1], [2] were applied. Specifically, phylogenetic reconstruction, inter- intra-patient distribution maximum mean genetic distances, Poisson fitness, shape highlighter plots, recombination analysis, estimation time most recent common ancestor (tMRCA)...