Browsing by Author "Metch, Barbara."

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Continued Follow-Up of Phambili Phase 2b Randomized HIV-1 Vaccine Trial Participants Supports Increased HIV-1 Acquisition among Vaccinated Men.
(Public Library of Science., 2015) Moodie, Zoe.; Metch, Barbara.; Bekker, Linda-Gail.; Churchyard, Gavin J.; Nchabeleng, Maphoshane.; Mlisana, Koleka Patience.; Laher, Faatima.; Roux, Surita.; Mngadi, Kathryn Therese.; Innes, Craig.; Mathebula, Matsontso.; Allen, Mary.; Bentley, Carter.; Gilbert, Peter B.; Robertson, Michael.; Kublin, James.; Corey, Lawrence.; Gray, Glenda Elizabeth.
Abstract available in pdf.
Does participation in an HIV vaccine efficacy trial affect risk behaviour in South Africa?
(Elsevier., 2012) Gray, Glenda Elizabeth.; Metch, Barbara.; Churchyard, Gavin J.; Mlisana, Koleka Patience.; Nchabeleng, Maphoshane.; Allen, Mary.; Moodie, Zoe.; Kublin, James.; Bekker, Linda-Gail.
Background: Increased sexual risk behaviour in participants enrolled in HIV prevention trials has been a concern. The HVTN 503/Phambili study, a phase 2B study of the Merck Ad-5 multiclade HIV vaccine in South Africa, suspended enrollment and vaccinations following the results of the Step study. Participants were notified of their treatment allocation and continue to be followed. We investigated changes in risk behaviour over time and assessed the impact of study unblinding. Methods: 801 participants were enrolled. Risk behaviours were assessed with an interviewer administered questionnaire at 6-month intervals. We assessed change from enrolment to the first 6-month assessment pre-unblinding and between enrolment and at least 6 months post-unblinding on all participants with comparable data. A one-time unblinding risk perception questionnaire was administered post-unblinding. Results: A decrease in participants reporting unprotected sex was observed in both measured time periods for men and women, with no differences by treatment arm. At 6 months (pre-unblinding), 29.6% of men and 35.8% of women reported changing from unprotected to protected sex (p < 0.0001 for each). Men (22%) were more likely than women (14%) to report behaviour change after unblinding (p = 0.009). Post-enrolment, 142 (45%) of 313 previously uncircumcised men underwent medical circumcision. 663 participants completed the unblinding questionnaire. More vaccine (24.6%) as compared to placebo recipients (12.0%) agreed that they were more likely to get HIV than most people (p < 0.0001), and attributed this to receiving the vaccine. Conclusion: We did not find evidence of risk compensation during this clinical trial. Some risk behaviour reductions including male circumcision were noted irrespective of treatment allocation.
Safety and efficacy of the HVTN 503/Phambili Study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-concept phase 2b study.
(Elsevier., 2011) Gray, Glenda Elizabeth.; Allen, Mary.; Moodie, Zoe.; Churchyard, Gavin J.; Bekker, Linda-Gail.; Nchabeleng, Maphoshane.; Mlisana, Koleka Patience.; Metch, Barbara.; De Bruyn, Guy.; Latka, Mary H.; Roux, Surita.; Mathebula, Matsontso.; Naicker, Nivashnee.; Ducar, Constance.; Carter, Donald K.; Puren, Adrian.; Eaton, Niles.; McElrath, Margaret Juliana.; Robertson, Michael.; Corey, Lawrence.; Kublin, James.
Background. The MRKAd5 HIV-1 gag/pol/nef subtype B vaccine was designed to elicit T-cell-mediated immune responses capable of providing complete or partial protection from HIV-1 infection or a decrease in viral load after acquisition. We aim to assess the safety and efficacy of the vaccine in South Africa, where the major circulating clade is subtype C. Methods. We did a phase 2b double-blind, randomised test-of-concept study in sexually active HIV-1 seronegative participants at five sites in South Africa. Randomisation was by a computer-generated random number sequence. The vaccine and placebo were given by intramuscular injection on a 0, 1, 6 month schedule. Our coprimary endpoints were a vaccine-induced reduction in HIV-1 acquisition and viral-load setpoint. These endpoints were assessed independently in the modified intention-to-treat (MITT) cohort with two-tailed significance tests stratified by sex. We assessed immunogenicity by interferon-γ ELISPOT in peripheral-blood mononuclear cells. After the lack of efficacy of the MRKAd5 HIV-1 vaccine in the Step study, enrolment and vaccination in our study was halted, treatment allocations were unmasked, and follow-up continued. This study is registered with the South Africa National Health Research Database, number DOH-27-0207-1539, and ClinicalTrials.gov, number NCT00413725. Findings. 801 of a scheduled 3000 participants, of whom 360 (45%) were women, were randomly assigned to receive either vaccine or placebo. 445 participants (56%) had adenovirus serotype 5 (Ad5) titres greater than 200, and 129 men (29%) were circumcised. 34 MITT participants in the vaccine group were diagnosed with HIV-1 (incidence rate 4·54 per 100 person-years) and 28 in the placebo group (3·70 per 100 person-years). There was no evidence of vaccine efficacy; the hazard ratio adjusted for sex was 1·25 (95% CI 0·76–2·05). Vaccine efficacy did not differ by Ad5 titre, sex, age, herpes simplex virus type 2 status, or circumcision. The geometric mean viral-load setpoint was 20 483 copies per mL (n=33) in the vaccine group and 34 032 copies per mL (n=28) in the placebo group (p=0·39). The vaccine elicited interferon-γ-secreting T cells that recognised both clade B (89%) and C (77%) antigens. Interpretation. The MRKAd5 HIV-1 vaccine did not prevent HIV-1 infection or lower viral-load setpoint; however, stopping our trial early probably compromised our ability to draw conclusions. The high incidence rates noted in South Africa highlight the crucial need for intensified efforts to develop an efficacious vaccine.