Browsing by Author "Allen, Susan"
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- ItemOpen AccessBroadly neutralizing antibody responses in a large longitudinal sub-Saharan HIV primary infection cohort(Public Library of Science, 2016) Landais, Elise; Huang, Xiayu; Havenar-Daughton, Colin; Murrell, Ben; Price, Matt A; Wickramasinghe, Lalinda; Ramos, Alejandra; Bian, Charoan B; Simek, Melissa; Allen, Susan; Karita, Etienne; Kilembe, William; Lakhi, Shabir; Inambao, Mubiana; Kamali, Anatoli; Sanders, Eduard J; Anzala, Omu; Edward, Vinodh; Bekker, Linda-Gail; Tang, Jianming; Gilmour, Jill; Kosakovsky-Pond, Sergei L; Phung, Pham; Wrin, Terri; Crotty, Shane; Godzik, Adam; Poignard, PascalAuthor Summary Understanding how HIV-1-broadly neutralizing antibodies (bnAbs) develop during natural infection is essential to the design of an efficient HIV vaccine. We studied kinetics and correlates of neutralization breadth in a large sub-Saharan African longitudinal cohort of 439 participants with primary HIV-1 infection. Broadly nAb responses developed in 15% of individuals, on average three years after infection. Broad neutralization was associated with high viral load, low CD4+ T cell counts, virus subtype C infection and HLA*A3(-) genotype. A correlation with high overall plasma IgG levels and anti-Env binding titers was also found. Specificity mapping of the bnAb responses showed that glycan-dependent epitopes, in particular the N332 region, were most commonly targeted, in contrast to other bnAb epitopes, suggesting that the HIV Env N332-glycan epitope region may be a favorable target for vaccine design.
- ItemOpen AccessRegional differences in prevalence of HIV-1 discordance in Africa and enrollment of HIV-1 discordant couples into an HIV-1 prevention trial(Public Library of Science, 2008) Lingappa, Jairam R; Lambdin, Barrot; Bukusi, Elizabeth Ann; Ngure, Kenneth; Kavuma, Linda; Inambao, Mubiana; Kanweka, William; Allen, Susan; Kiarie, James N; Makhema, JosephBACKGROUND: Most HIV-1 transmission in Africa occurs among HIV-1-discordant couples (one partner HIV-1 infected and one uninfected) who are unaware of their discordant HIV-1 serostatus. Given the high HIV-1 incidence among HIV-1 discordant couples and to assess efficacy of interventions for reducing HIV-1 transmission, HIV-1 discordant couples represent a critical target population for HIV-1 prevention interventions and prevention trials. Substantial regional differences exist in HIV-1 prevalence in Africa, but regional differences in HIV-1 discordance among African couples, has not previously been reported. METHODOLOGY/PRINCIPAL FINDINGS: The Partners in Prevention HSV-2/HIV-1 Transmission Trial ("Partners HSV-2 Study"), the first large HIV-1 prevention trial in Africa involving HIV-1 discordant couples, completed enrollment in May 2007. Partners HSV-2 Study recruitment data from 12 sites from East and Southern Africa were used to assess HIV-1 discordance among couples accessing couples HIV-1 counseling and testing, and to correlate with enrollment of HIV-1 discordant couples. HIV-1 discordance at Partners HSV-2 Study sites ranged from 8-31% of couples tested from the community. Across all study sites and, among all couples with one HIV-1 infected partner, almost half (49%) of couples were HIV-1 discordant. Site-specific monthly enrollment of HIV-1 discordant couples into the clinical trial was not directly associated with prevalence of HIV-1 discordance, but was modestly correlated with national HIV-1 counseling and testing rates and access to palliative care/basic health care (r = 0.74, p = 0.09). Conclusions/Significance HIV-1 discordant couples are a critical target for HIV-1 prevention in Africa. In addition to community prevalence of HIV-1 discordance, national infrastructure for HIV-1 testing and healthcare delivery and effective community outreach strategies impact recruitment of HIV-1 discordant couples into HIV-1 prevention trials.