10 results on '"Gray, Glenda E."'
Search Results
2. The HVTN503/Phambili HIV vaccine trial: a comparison of younger and older participants
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Volk, Jonathan E, Hessol, Nancy A, Gray, Glenda E, Kublin, James G, Churchyard, Gavin J, Mlisana, Koleka, Nchabeleng, Maphoshane, Buchbinder, Susan P, and Bekker, Linda-Gail
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Vaccine Related ,Aging ,Sexually Transmitted Infections ,HIV/AIDS ,Infectious Diseases ,Prevention ,Immunization ,Clinical Research ,Patient Safety ,Good Health and Well Being ,AIDS Vaccines ,Adolescent ,Adult ,Age Distribution ,Clinical Trials as Topic ,Female ,HIV Infections ,Humans ,Male ,Motivation ,Patient Participation ,Patient Selection ,South Africa ,Young Adult ,HIV ,AIDS ,prevention ,vaccination ,vaccine trials ,clinical trials ,youth ,Medical Microbiology ,Public Health and Health Services ,Public Health ,Clinical sciences ,Immunology - Abstract
By comparing younger to older participants enrolled in a HIV vaccine efficacy trial, we aimed to gain insights into the inclusion of adolescents in future trials. This was a sub-analysis of a multisite HIV vaccine randomized clinical trial in South Africa, conducted January-September 2007. Motivations for trial enrolment, social harms, adverse events and loss to follow-up were compared between younger (18-20 years old) and older participants (21-35 years old). Both younger (n = 238) and older participants (n = 563) were equally likely to report enrolling for altruistic reasons. Younger females were less likely than older participants to join for trial reimbursement (p = 0.005), while younger males were more likely to enrol because the vaccine may provide protection from HIV-acquisition (p < 0.001). There were no significant differences in the number of social harms reported. Compared to males over 20 years old, 18-20-year-old females were less likely to experience adverse events (OR = 0.1, CI 0.01-0.80) and no more likely to be lost to follow-up (OR = 0.7, CI 0.39-1.25), while 18-20-year-old males were no more likely to experience adverse events (OR = 1.3, CI 0.58-2.83) or loss to follow-up (OR = 0.8, CI 0.51-1.41). Our data support the inclusion of younger participants who are at risk for HIV in future HIV vaccine efficacy trials.
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- 2014
3. Antibody and cellular responses to HIV vaccine regimens with DNA plasmid as compared with ALVAC priming: An analysis of two randomized controlled trials
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Moodie, Zoe, Walsh, Stephen R., Laher, Fatima, Maganga, Lucas, Herce, Michael E., Naidoo, Sarita, Hosseinipour, Mina C., Innes, Craig, Bekker, Linda-Gail, Grunenberg, Nicole, Mann, Philipp, Yu, Chenchen, deCamp, Allan C., Miner, Maurine D., Yates, Nicole L., Heptinstall, Jack, Mkhize, Nonhlanhla N., Dintwe, One, Frahm, Nicole, Cohen, Kristen W., Allen, Mary, Hutter, Julia, Wagner, Ralf, Pantaleo, Giuseppe, McElrath, M. Juliana, Tomaras, Georgia D., Morris, Lynn, Montefiori, David C., Andersen-Nissen, Erica, Gray, Glenda E., Gilbert, Peter B., and Kublin, James G.
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Clinical trials ,AIDS vaccines ,Genetic research ,HIV antigens ,HIV -- Drug therapy ,DNA ,Vaccination ,T cells ,Biological sciences - Abstract
Background DNA plasmids promise a pragmatic alternative to viral vectors for prime-boost HIV-1 vaccines. We evaluated DNA plasmid versus canarypox virus (ALVAC) primes in 2 randomized, double-blind, placebo-controlled trials in southern Africa with harmonized trial designs. HIV Vaccine Trials Network (HVTN) 111 tested DNA plasmid prime by needle or needleless injection device (Biojector) and DNA plasmid plus gp120 protein plus MF59 adjuvant boost. HVTN 100 tested ALVAC prime and ALVAC plus gp120 protein plus MF59 adjuvant boost (same protein/adjuvant as HVTN 111) by needle. Methods and findings The primary endpoints for this analysis were binding antibody (bAb) responses to HIV antigens (gp120 from strains ZM96, 1086, and TV1; variable 1 and 2 [V1V2] regions of gp120 from strains TV1, 1086, and B.CaseA, as 1086 V1V2 and B.CaseA were correlates of risk in the RV144 efficacy trial), neutralizing antibody (nAb) responses to pseudoviruses TV1c8.2 and MW925.26, and cellular responses to vaccine-matched antigens (envelope [Env] from strains ZM96, 1086, and TV1; and Gag from strains LAI and ZM96) at month 6.5, two weeks after the fourth vaccination. Per-protocol cohorts included vaccine recipients from HVTN 100 (n = 186, 60% male, median age 23 years) enrolled between February 9, 2015, and May 26, 2015 and from HVTN 111 (n = 56, 48% male, median age 24 years) enrolled between June 21, 2016, and July 13, 2017. IgG bAb response rates were 100% to 3 Env gp120 antigens in both trials. Response rates to V1V2 were lower and similar in both trials except to vaccine-matched 1086 V1V2, with rates significantly higher for the DNA-primed regimen than the ALVAC-primed regimen: 96.6% versus 72.7% (difference = 23.9%, 95% CI 15.6%-32.2%, p < 0.001). Among positive responders, bAb net mean fluorescence intensity (MFI) was significantly higher with the DNA-primed regimen than ALVAC-primed for 1086 V1V2 (geometric mean [GM] 2,833.3 versus 1,200.9; ratio = 2.36, 95% CI 1.42-3.92, p 98% in both trials, with significantly higher 50% inhibitory dilution (ID.sub.50) among DNA-primed positive responders (n = 53) versus ALVAC-primed (n = 182) to tier 1A MW965.26 (GM 577.7 versus 265.7, ratio = 2.17, 95% CI 1.67-2.83, p < 0.001) and to TV1c8.2 (GM 187.3 versus 100.4, ratio = 1.87, 95% CI 1.48-2.35, p < 0.001). CD4+ T-cell response rates were significantly higher with DNA plasmid prime via Biojector than ALVAC prime (91.4% versus 52.8%, difference = 38.6%, 95% CI 20.5%-56.6%, p < 0.001 for ZM96.C; 88.0% versus 43.1%, difference = 44.9%, 95% CI 26.7%-63.1%, p < 0.001 for 1086.C; 55.5% versus 2.2%, difference = 53.3%, 95% CI 23.9%-82.7%, p < 0.001 for Gag LAI/ZM96). The study's main limitations include the nonrandomized comparison of vaccines from 2 different trials, the lack of data on immune responses to other non-vaccine-matched antigens, and the uncertain clinical significance of the observed immunological effects. Conclusions In this study, we found that further investigation of DNA/protein regimens is warranted given enhanced immunogenicity to the V1V2 correlates of decreased HIV-1 acquisition risk identified in RV144, the only HIV vaccine trial to date to show any efficacy., Author(s): Zoe Moodie 1,*, Stephen R. Walsh 2,3,4, Fatima Laher 5, Lucas Maganga 6, Michael E. Herce 7, Sarita Naidoo 8, Mina C. Hosseinipour 9, Craig Innes 10, Linda-Gail Bekker [...]
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- 2020
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4. Review of preventative HIV vaccine clinical trials in South Africa.
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Laher, Fatima, Bekker, Linda-Gail, Garrett, Nigel, Lazarus, Erica M., and Gray, Glenda E.
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AIDS vaccines ,VACCINE trials ,GENETIC vectors ,VACCINES ,CLINICAL trials ,MONOCLONAL antibodies ,HIV - Abstract
New HIV infections continue relentlessly in southern Africa, demonstrating the need for a vaccine to prevent HIV subtype C. In South Africa, the country with the highest number of new infections annually, HIV vaccine research has been ongoing since 2003 with collaborative public-private-philanthropic partnerships. So far, 21 clinical trials have been conducted in South Africa, investigating seven viral vectors, three DNA plasmids, four envelope proteins, five adjuvants and three monoclonal antibodies. Active vaccine candidates have spanned subtypes A, B, C, E and multi-subtype mosaic sequences. All were well tolerated. Four concepts were investigated for efficacy: rAd5-gag/pol/nef showed increased HIV acquisition in males, subtype C ALVAC/gp120/MF59 showed no preventative efficacy, and the trials for the VRC01 monoclonal antibody and Ad26.Mos4.HIV/subtype C gp140/ aluminum phosphate are ongoing. Future trials are planned with DNA/viral vector plus protein combinations in concert with pre-exposure prophylaxis, and sequential immunization studies with transmitted/founder HIV envelope to induce broadly neutralizing antibodies. Finally, passive immunization trials are underway to build on the experience with VRC01, including single and combination antibody trials with an antibody derived from a subtype-C-infected South African donor. Future consideration should be given to the evaluation of novel strategies, for example, inactivated-whole-virus vaccines. [ABSTRACT FROM AUTHOR]
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- 2020
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5. The path to find an HIV vaccine.
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Gray, Glenda E and Corey, Lawrence
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NEUTRALIZATION tests , *AIDS vaccines , *AIDS - Abstract
This strategy was broken into two frameworks: I the first i to determine whether broadly protective antibodies could reduce HIV acquisition, that is could a vaccine regimen that elicited high levels of non-neutralizing antibodies be developed that would enhance the protective efficacy beyond that seen in RV144; I and second i , to discern whether neutralizing antibodies could actually prevent acquisition. HIV vaccine development has become a process of stepwise learning of how to make a vaccine that induces an immune response that is markedly better than the human immune response to HIV. Keywords: HIV vaccine; clinical trials; broadly neutralizing antibodies EN HIV vaccine clinical trials broadly neutralizing antibodies 1 3 3 06/05/21 20210501 NES 210501 Since the discovery that a retrovirus, human immunodeficiency virus type one (HIV-1), causes the acquired immune deficiency syndrome (AIDS), more than 77 million people have become infected with HIV and 37 million have died over the last 40 years [1]. Essentially the inability to elicit broadly neutralizing antibodies to HIV to cover its strain diversity has been a major flaw in the HIV vaccine field for the first 30 years of vaccine development. [Extracted from the article]
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- 2021
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6. Effect of rAd5-Vector HIV-1 Preventive Vaccines on HIV-1 Acquisition: A Participant- Level Meta-Analysis of Randomized Trial
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Huang, Yunda, Follmann, Dean, Nason, Martha, Zhang, Lily, Huang, Ying, Mehrotra, Devan V., Moodie, Zoe, Metch, Barbara, Janes, Holly, Keefer, Michael C., Churchyard, Gavin, Robb, Merlin L., Fast, Patricia E., Duerr, Ann, McElrath, M. Juliana, Corey, Lawrence, Mascola, John R., Graham, Barney S., Sobieszczyk, Magdalena E., Kublin, James G., Hammer, Scott M., Robertson, Michael, Gray, Glenda E., Buchbinder, Susan P., and Gilbert, Peter B.
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Public health ,Clinical trials ,Epidemiology ,Medicine ,HIV infections--Epidemiology ,Medical policy ,HIV-positive persons ,AIDS vaccines - Abstract
Background Three phase 2b, double-blind, placebo-controlled, randomized efficacy trials have tested recombinant Adenovirus serotype-5 (rAd5)-vector preventive HIV-1 vaccines: MRKAd5 HIV-1 gag/pol/nef in Step and Phambili, and DNA/rAd5 HIV-1 env/gag/pol in HVTN505. Due to efficacy futility observed at the first interim analysis in Step and HVTN505, participants of all three studies were unblinded to their vaccination assignments during the study but continued follow–up. Rigorous meta-analysis can provide crucial information to advise the future utility of rAd5-vector vaccines. Methods We included participant-level data from all three efficacy trials, and three Phase 1–2 trials evaluating the HVTN505 vaccine regimen. We predefined two co-primary analysis cohorts for assessing the vaccine effect on HIV-1 acquisition. The modified-intention-to-treat (MITT) cohort included all randomly assigned participants HIV-1 uninfected at study entry, who received at least the first vaccine/placebo, and the Ad5 cohort included MITT participants who received at least one dose of rAd5-HIV vaccine or rAd5-placebo. Multivariable Cox regression models were used to estimate hazard ratios (HRs) of HIV-1 infection (vaccine vs. placebo) and evaluate HR variation across vaccine regimens, time since vaccination, and subgroups using interaction tests. Findings Results are similar for the MITT and Ad5 cohorts; we summarize MITT cohort results. Pooled across the efficacy trials, over all follow-up time 403 (n = 224 vaccine; n = 179 placebo) of 6266 MITT participants acquired HIV-1, with a non-significantly higher incidence in vaccine recipients (HR 1.21, 95% CI 0.99–1.48, P = 0.06). The HRs significantly differed by vaccine regimen (interaction P = 0.03; MRKAd5 HR 1.41, 95% CI 1.11–1.78, P = 0.005 vs. DNA/rAd5 HR 0.88, 95% CI 0.61–1.26, P = 0.48). Results were similar when including the Phase 1–2 trials. Exploratory analyses based on the efficacy trials supported that the MRKAd5 vaccine-increased risk was concentrated in Ad5-positive or uncircumcised men early in follow-up, and in Ad5-negative or circumcised men later. Overall, MRKAd5 vaccine-increased risk was evident across subgroups except in circumcised Ad5-negative men (HR 0.97, 95% CI 0.58−1.63, P = 0.91); there was little evidence that the DNA/rAd5 vaccine, that was tested in this subgroup, increased risk (HR 0.88, 95% CI 0.61–1.26, P = 0.48). When restricting the analysis of Step and Phambili to follow-up time before unblinding, 114 (n = 65 vaccine; n = 49 placebo) of 3770 MITT participants acquired HIV-1, with a non-significantly higher incidence in MRKAd5 vaccine recipients (HR 1.30, 95% CI 0.89–1.14, P = 0.18). Interpretation and Significance The data support increased risk of HIV-1 infection by MRKAd5 over all follow-up time, but do not support increased risk of HIV-1 infection by DNA/rAd5. This study provides a rationale for including monitoring plans enabling detection of increased susceptibility to infection in HIV-1 at-risk populations.
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- 2015
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7. Continued Follow-Up of Phambili Phase 2b Randomized HIV-1 Vaccine Trial Participants Supports Increased HIV-1 Acquisition among Vaccinated Men.
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Moodie, Zoe, Metch, Barbara, Bekker, Linda-Gail, Churchyard, Gavin, Nchabeleng, Maphoshane, Mlisana, Koleka, Laher, Fatima, Roux, Surita, Mngadi, Kathryn, Innes, Craig, Mathebula, Matsontso, Allen, Mary, Bentley, Carter, Gilbert, Peter B., Robertson, Michael, Kublin, James, Corey, Lawrence, and Gray, Glenda E.
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FOLLOW-up studies (Medicine) ,CLINICAL trials ,HIV infections ,VIRAL vaccines ,PERIODIC health examinations - Abstract
Background: The Phase 2b double-blinded, randomized Phambili/HVTN 503 trial evaluated safety and efficacy of the MRK Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine vs placebo in sexually active HIV-1 seronegative participants in South Africa. Enrollment and vaccinations stopped and participants were unblinded but continued follow-up when the Step study evaluating the same vaccine in the Americas, Caribbean, and Australia was unblinded for non-efficacy. Final Phambili analyses found more HIV-1 infections amongst vaccine than placebo recipients, impelling the HVTN 503-S recall study. Methods: HVTN 503-S sought to enroll all 695 HIV-1 uninfected Phambili participants, provide HIV testing, risk reduction counseling, physical examination, risk behavior assessment and treatment assignment recall. After adding HVTN 503-S data, HIV-1 infection hazard ratios (HR vaccine vs. placebo) were estimated by Cox models. Results: Of the 695 eligible, 465 (67%) enrolled with 230 from the vaccine group and 235 from the placebo group. 38% of the 184 Phambili dropouts were enrolled. Enrollment did not differ by treatment group, gender, or baseline HSV-2. With the additional 1286 person years of 503-S follow-up, the estimated HR over Phambili and HVTN 503-S follow-up was 1.52 (95% CI 1.08–2.15, p = 0.02, 82 vaccine/54 placebo infections). The HR was significant for men (HR = 2.75, 95% CI 1.49, 5.06, p = 0.001) but not for women (HR = 1.12, 95% CI 0.73, 1.72, p = 0.62). Conclusion: The additional follow-up from HVTN 503-S supported the Phambili finding of increased HIV-1 acquisition among vaccinated men and strengthened the evidence of lack of vaccine effect among women. Trial Registration: clinicaltrials.gov SA National Health Research Database DOH-27-0207-1539 [ABSTRACT FROM AUTHOR]
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- 2015
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8. Recombinant adenovirus type 5 HIV gag/pol/nef vaccine in South Africa: unblinded, long-term follow-up of the phase 2b HVTN 503/Phambili study.
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Gray, Glenda E, Moodie, Zoe, Metch, Barbara, Gilbert, Peter B, Bekker, Linda-Gail, Churchyard, Gavin, Nchabeleng, Maphoshane, Mlisana, Koleka, Laher, Fatima, Roux, Surita, Mngadi, Kathryn, Innes, Craig, Mathebula, Matsontso, Allen, Mary, McElrath, M Julie, Robertson, Michael, Kublin, James, and Corey, Lawrence
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RECOMBINANT viruses , *ADENOVIRUSES , *VIRAL vaccines , *ANTI-HIV agents , *FOLLOW-up studies (Medicine) , *CLINICAL trials , *HIV , *BLIND experiment , *PLACEBOS - Abstract
Summary: Background: The HVTN 503/Phambili study, which assessed the efficacy of the Merck Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine in South Africa, was stopped when futility criteria in the Step study (assessing the same vaccine in the Americas, Caribbean, and Australia) were met. Here we report long-term follow-up data. Methods: HVTN 503/Phambili was a double-blind, placebo-controlled, randomised trial that recruited HIV-1 uninfected, sexually active adults aged 18–35 years from five sites in South Africa. Eligible participants were randomly assigned (1:1) by computer-generated random numbers to either vaccine or placebo, stratified by site and sex. Cox proportional hazards models were used to estimate HIV-1 infection in the modified intention-to-treat cohort, all of whom were unmasked early in follow-up. The trial is registered with ClinicalTrials.gov, number NCT00413725 and the South African National Health Research Database, number DOH-27-0207-1539. Findings: Between Jan 24, 2007, and Sept 19, 2007, 801 participants (26·7%) of a planned 3000 were randomly assigned (400 to vaccine, 401 to placebo); 216 (27%) received only one injection, 529 (66%) received only two injections, and 56 (7%) received three injections. At a median follow-up of 42 months (IQR 31–42), 63 vaccine recipients (16%) had HIV-1 infection compared with 37 placebo recipients (9%; adjusted HR 1·70, 95% CI 1·13–2·55; p=0·01). Risk for HIV-1 infection did not differ according to the number of vaccinations received, sex, circumcision, or adenovirus type 5 (Ad5) serostatus. Differences in risk behaviour at baseline or during the study, or annualised dropout rate (7·7% [95% CI 6·2–9·5] for vaccine recipients vs 8·8% [7·1–10·7] for placebo recipients; p=0·40) are unlikely explanations for the increased rate of HIV-1 infections seen in vaccine recipients. Interpretation: The increased risk of HIV-1 acquisition in vaccine recipients, irrespective of number of doses received, warrants further investigation to understand the biological mechanism. We caution against further use of the Ad5 vector for HIV vaccines. Funding: National Institute of Allergy and Infectious Diseases, Merck, and South African Medical Research Council. [ABSTRACT FROM AUTHOR]
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- 2014
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9. HIV disclosure and other factors that impact on adherence to antiretroviral therapy: the case of Soweto, South Africa.
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Skhosana, Nokuthula L., Struthers, Helen, Gray, Glenda E., and McIntyre, James A.
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CLINICAL trials ,PATIENT compliance ,ANTIRETROVIRAL agents ,SOCIAL stigma ,LIFESTYLES - Abstract
Some authors argue that there are no predictors of adherence to medication, while others proffer indicators of likely adherence. These contextual factors are wide-ranging and may be Interdependent. There are few studies of adherence in resource-poor settings. Of these, many were linked to particular trials whose conditions were highly controlled. For instance, the number of participants in the trial was small, the participants were strictly selected and they were offered much adherence support. These conditions will largely fall away with wider access to antiretroviral drugs (ARVs) such as South Africa is undertaking. Poor adherence remains one of the challenges to scaling-up access to ARVs, and, as such, the likely barriers to adherence need to be understood and countered. This study explores contextual factors -- such as disclosure, preparation for treatment, treatment meaning and treatment acceptance -- as aspects of lifestyle that can bear on adherence. Those who had disclosed were largely supported at household level, and after initial problems with adherence, participants adjusted and were able to include ARM treatment in their daily repertoire. Although the anticipation of stigma remains an obstacle to wide disclosure, antiretroviral therapy offers new hope and has the potential to impact on stigma. [ABSTRACT FROM AUTHOR]
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- 2006
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10. The NEAT Study: A 48-Week Open-Label Study to Compare the Antiviral Efficacy and Safety of GW433908 Versus Nelfinavir in Antiretroviral Therapy-Naive HIV-1-Infected Patients.
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Rodrigeuz-French, Amalia, Boghossian, Jack, Gray, Glenda E., Nadler, Jeffrey P., Quinones, Arnaldo R., Sepulveda, Gladys E., Millard, Judith M., and Wannamaker, Paul G.
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ANTIRETROVIRAL agents , *HIV-positive persons , *DRUG efficacy , *CLINICAL trials , *THERAPEUTICS - Abstract
Compares the antiviral efficacy and safety between GW433908 and Nelfinavir in antiretroviral therapy-naive HIV-1-infected patients. Performance of an international, multi-center, randomized, open-label study in antiretroviral therapy-naive HIV-infected adults; Clinical developments for the treatment of HIV; Background of abacavir and lamivudine.
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- 2004
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