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HIV-1 Genetic Diversity Among Incident Infections in Mbeya, Tanzania
Billings, Erik,Sanders-Buell, Eric,Bose, Meera,Kijak, Gustavo H.,Bradfield, Andrea,Crossler, Jacqueline,Arroyo, Miguel A.,Maboko, Leonard,Hoffmann, Oliver,Geis, Steffen,Birx, Deborah L.,Kim, Jerome H. MARY ANN LIEBERT INC PUBL 2017 AIDS RESEARCH AND HUMAN RETROVIRUSES Vol.33 No.4
<P><B>Abstract</B></P><P>In preparation for vaccine trials, HIV-1 genetic diversity was surveyed between 2002 and 2006 through the Cohort Development study in the form of a retrospective and prospective observational study in and around the town of Mbeya in Tanzania's Southwest Highlands. This study describes the molecular epidemiology of HIV-1 strains obtained from 97 out of 106 incident HIV-1 infections identified in three subpopulations of participants (one rural, two urban) from the Mbeya area. Near full-genome or half-genome sequencing showed a subtype distribution of 40% C, 17% A1, 1% D, and 42% inter-subtype recombinants. Compared to viral subtyping results previously obtained from the retrospective phase of this study, the overall proportion of incident viral strains did not change greatly during the study course, suggesting maturity of the epidemic. A comparison to a current Phase I-II vaccine being tested in Africa shows ∼17% amino acid sequence difference between the gp120 of the vaccine and subtype C incident strains. Phylogenetic and recombinant breakpoint analysis of the incident strains revealed the emergence of CRF41_CD and many unique recombinants, as well as the presence of six local transmission networks most of which were confined to the rural subpopulation. In the context of vaccine cohort selection, these results suggest distinct infection transmission dynamics within these three geographically close subpopulations. The diversity and genetic sequences of the HIV-1 strains obtained during this study will greatly contribute to the planning, immunogen selection, and analysis of vaccine-induced immune responses observed during HIV-1 vaccine trials in Tanzania and neighboring countries.</P>
Neutralization Sensitivity of a Novel HIV-1 CRF01_AE Panel of Infectious Molecular Clones
Chenine, Agnes-Laurence,Merbah, Melanie,Wieczorek, Lindsay,Molnar, Sebastian,Mann, Brendan,Lee, Jenica,O’Sullivan, Anne-Marie,Bose, Meera,Sanders-Buell, Eric,Kijak, Gustavo H.,Herrera, Carolina,McLind Wolters Kluwer Health, Inc. All rights reserved. 2018 Journal of acquired immune deficiency syndromes Vol.78 No.3
<P>Conclusions: This novel panel of CRFOl_AE reporter IMC is useful for assessing vaccine-induced neutralizing antibodies in multiple assays, including those using primary cell targets. The significant differences in TZM-bl and A3R5 neutralization sensitivity, as well as the poor association when using polyclonal sera indicates the need for caution in choosing one specific platform.</P>
Kroon, Eugè,ne,Pham, Phuc T.,Sirivichayakul, Sunee,Trichavaroj, Rapee,Colby, Donn J.,Pinyakorn, Suteeraporn,Phanuphak, Nittaya,Sanders-Buell, Eric,van Griensven, Frits,Kijak, Gustavo H.,Kim, Jer Wolters Kluwer Health, Inc. 2018 AIDS Vol.32 No.16
OBJECTIVE:: To assess transmission characteristics in a predominantly MSM cohort initiating antiretroviral therapy (ART) immediately following diagnosis of acute HIV-1infection (AHI). METHODS:: A longitudinal study (2009–2017) was performed in participants with AHI (n = 439) attending a single clinic in Bangkok. Plasma samples obtained prior to ART were used to obtain HIV-1 pol sequences and combined with clinical and epidemiologic data to assess transmission dynamics (cluster formation and size) using phylogenetic analysis. Clusters were estimated using maximum likelihood, genetic distance of 1.5% and visual inspection. The potential transmitter(s) in a cluster was determined using time to viral suppression and interview data. RESULTS:: The cohort was predominantly MSM (93%) and infected with HIV-1 CRF01_AE (87%). Medians (ranges) for age and viral load prior to ART were 26 (18–70) years and 5.9 (2.5–8.2) log10 HIV-1 RNA copies/ml. Median time from history of HIV-1 exposure to diagnosis was 19 (3–61) days. Viral suppression was observed in 388 of 412 (94%) participants at a median time of 12 weeks following ART. Twenty-six clusters with median cluster size of 2 (2–5) representing 62 of 439 (14%) participants were observed. Younger age was associated with cluster formation: median 28 versus 30 years for unique infections (P = 0.01). A potential transmitter was identified in 11 of 26 (42%) clusters. CONCLUSION:: Despite high rates of viral suppression following diagnosis and treatment of AHI within a cohort of young Thai MSM, HIV-1 transmission continued, reflecting the need to expand awareness and treatment access to the entire MSM population.