Browsing by Author "Goodier, Sarah A."

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CAPRISA 004 tenofovir microbicide trial: no impact of tenofovir gel on the HIV transmission bottleneck.
(Oxford University Press., 2011) Valley-Omar, Ziyaad.; Sibeko, Sengeziwe.; Anderson, Jeffrey A.; Goodier, Sarah A.; Werner, Lise.; Arney, Leslie.; Naranbhai, Vivek.; Treurnicht, Florette K.; Abrahams, Melissa-Rose.; Bandawe, Gama P.; Swanstrom, Ronald.; Abdool Karim, Salim Safurdeen.; Abdool Karim, Quarraisha.; Williamson, Carolyn.
Alterations of the genital mucosal barrier may influence the number of viruses transmitted from a human immunodeficiency virus–infected source host to the newly infected individual. We used heteroduplex tracking assay and single-genome sequencing to investigate the effect of a tenofovir-based microbicide gel on the transmission bottleneck in women who seroconverted during the CAPRISA 004 microbicide trial. Seventy-seven percent (17 of 22; 95% confidence interval [CI], 56%–90%) of women in the tenofovir gel arm were infected with a single virus compared with 92% (13 of 14; 95% CI, 67%–>99%) in the placebo arm (P = .37). Tenofovir gel had no discernable impact on the transmission bottleneck.
No evidence for selection of HIV-1 with enhanced gag-protease or nef function among breakthrough infections in the CAPRISA 004 tenofovir microbicide trial.
(2013) Chopera, Denis Rutendo.; Mann, Jaclyn Kelly.; Mwimanzi, Philip.; Omarjee, Saleha.; Kuang, Xiaomei T.; Ndabambi, Nonkululeko.; Goodier, Sarah A.; Martin, Eric.; Naranbhai, Vivek.; Abdool Karim, Salim Safurdeen.; Abdool Karim, Quarraisha.; Brumme, Zabrina L.; Ndung'u, Peter Thumbi.; Williamson, Carolyn.; Brockman, Mark A.
Background: Use of antiretroviral-based microbicides for HIV-1 prophylaxis could introduce a transmission barrier that inadvertently facilitates the selection of fitter viral variants among incident infections. To investigate this, we assessed the in vitro function of gag-protease and nef sequences from participants who acquired HIV-1 during the CAPRISA 004 1% tenofovir microbicide gel trial. Methods and Results: We isolated the earliest available gag-protease and nef gene sequences from 83 individuals and examined their in vitro function using recombinant viral replication capacity assays and surface protein down regulation assays, respectively. No major phylogenetic clustering and no significant differences in gag-protease or nef function were observed in participants who received tenofovir gel versus placebo gel prophylaxis. Conclusion: Results indicate that the partial protective effects of 1% tenofovir gel use in the CAPRISA 004 trial were not offset by selection of transmitted/early HIV-1 variants with enhanced Gag-Protease or Nef fitness.
Rapid, complex adaption of transmitted HIV-1 full-length genomes in subtype C-infected individuals with differing disease progression.
(Wolters Kluwer Health., 2013) Abrahams, Melissa-Rose.; Treurnicht, Florette K.; Ngandu, Nobubelo K.; Goodier, Sarah A.; Marais, Jinny C.; Bredell, Helba.; Thebus, Ruwayhida.; de Assis Rosa, Debra.; Seoighe, Cathal.; Abdool Karim, Salim Safurdeen.; Gray, Clive M.; Williamson, Carolyn.; Mlisana, Koleka Patience.
Objective(s): There is limited information on full-length genome sequences and the early evolution of transmitted HIV-1 subtype C viruses, which constitute the majority of viruses spread in Africa. The purpose of this study was to characterize the earliest changes across the genome of subtype C viruses following transmission, to better understand early control of viremia. Design: We derived the near full-length genome sequence responsible for clinical infection from five HIV subtype C-infected individuals with different disease progression profiles and tracked adaptation to immune responses in the first 6 months of infection. Methods: Near full-length genomes were generated by single genome amplification and direct sequencing. Sequences were analyzed for amino acid mutations associated with cytotoxic T lymphocyte (CTL) or antibody-mediated immune pressure, and for reversion. Results: Fifty-five sequence changes associated with adaptation to the new host were identified, with 38% attributed to CTL pressure, 35% to antibody pressure, 16% to reversions and the remainder were unclassified. Mutations in CTL epitopes were most frequent in the first 5 weeks of infection, with the frequency declining over time with the decline in viral load. CTL escape predominantly occurred in nef, followed by pol and env. Shuffling/toggling of mutations was identified in 81% of CTL epitopes, with only 7% reaching fixation within the 6-month period. Conclusion: There was rapid virus adaptation following transmission, predominantly driven by CTL pressure, with most changes occurring during high viremia. Rapid escape and complex escape pathways provide further challenges for vaccine protection.