scholarly journals US Black Women and Human Immunodeficiency Virus Prevention: Time for New Approaches to Clinical Trials

2017 ◽  
Vol 65 (2) ◽  
pp. 324-327 ◽  
Author(s):  
Adaora A Adimora ◽  
Stephen R Cole ◽  
Joseph J Eron
Author(s):  
Sharana Mahomed ◽  
Nigel Garrett ◽  
Cheryl Baxter ◽  
Quarraisha Abdool Karim ◽  
Salim S Abdool Karim

Abstract Passive immunization with broadly neutralizing antibodies (bnAbs) is a promising approach to reduce the 1.7 million annual human immunodeficiency virus (HIV) infections globally. Early studies on bnAbs showed safety in humans, but short elimination half-lives and low potency and breadth. Since 2010, several new highly potent bnAbs have been assessed in clinical trials alone or in combination for HIV prevention. Published data indicate that these bnAbs are safe and have a half-life ranging from 15 to 71 days. Only intravenous VRC01 has advanced to an efficacy trial, with results expected in late 2020. If bnAbs are shown to be effective in preventing HIV infection, they could fast-track vaccine development as correlates of protection, and contribute as passive immunization to achieving the goal of epidemic control. The purpose of the current review is to describe the current status and provide a synopsis of the available data on bnAbs in clinical trials for HIV prevention.


2008 ◽  
Vol 35 (1) ◽  
pp. 28-35 ◽  
Author(s):  
Allison V. Schlosser ◽  
Arbi Ben Abdallah ◽  
Catina L. Callahan ◽  
Susan Bradford ◽  
Linda B. Cottler

2018 ◽  
Vol 69 (2) ◽  
pp. 207-214 ◽  
Author(s):  
Anne Derache ◽  
Collins C Iwuji ◽  
Kathy Baisley ◽  
Siva Danaviah ◽  
Anne-Geneviève Marcelin ◽  
...  

Abstract Background Previous studies in human immunodeficiency virus (HIV)-positive individuals on thymidine analogue backbone antiretroviral therapy (ART) with either nevirapine or efavirenz have suggested poorer virological outcomes in the presence of pretreatment drug resistance (PDR). We assessed the impact of PDR on virological suppression (VS; <50 copies/mL) in individuals prescribed primarily tenofovir/emtricitabine/efavirenz in rural KwaZulu-Natal within a treatment-as-prevention trial. Methods Among 1557 HIV-positive individuals who reported no prior ART at study entry and provided plasma samples, 1328 individuals with entry viral load (VL) >1000 copies/mL had next-generation sequencing (NGS) of the HIV pol gene with MiSeq technology. Results were obtained for 1148 individuals, and the presence of PDR was assessed at 5% and 20% detection thresholds. Virological outcome was assessed using Cox regression in 837 of 920 ART initiators with at least 1 follow-up VL after ART initiation. Results PDR prevalence was 9.5% (109/1148) and 12.8% (147/1148) at 20% and 5% thresholds, respectively. After a median of 1.36 years (interquartile range, 0.91–2.13), mostly on fixed-dose combination tenofovir/emtricitabine/efavirenz, presence of both nonnucleoside reverse transcriptase inhibitor (NNRTI)/nucleoside reverse transcriptase inhibitor PDR vs no PDR was associated with longer time to VS (adjusted hazard ratio [aHR], 0.32; 95% confidence interval [CI], 0.12–0.86), while there was no difference between those with only NNRTI PDR vs no PDR (aHR, 1.05; 95% CI, 0.82–1.34) at the 5% threshold. Similar differences were observed for mutations detected at the 20% threshold, although without statistical significance. Conclusions NGS uncovered a high prevalence of PDR among participants enrolled in trial clinics in rural KwaZulu-Natal. Dual-class PDR to a mainly tenofovir/emtricitabine/efavirenz regimen was associated with poorer VS. However, there was no impact of NNRTI PDR alone. Clinical Trials Tegistration NCT01509508; South African National Clinical Trials Register: DOH-27-0512-3974.


2004 ◽  
Vol 85 (4) ◽  
pp. 911-919 ◽  
Author(s):  
Matilu Mwau ◽  
Inese Cebere ◽  
Julian Sutton ◽  
Priscilla Chikoti ◽  
Nicola Winstone ◽  
...  

The immunogenicities of candidate DNA- and modified vaccinia virus Ankara (MVA)-vectored human immunodeficiency virus (HIV) vaccines were evaluated on their own and in a prime–boost regimen in phase I clinical trials in healthy uninfected individuals in the United Kingdom. Given the current lack of approaches capable of inducing broad HIV-neutralizing antibodies, the pTHr.HIVA DNA and MVA.HIVA vaccines focus solely on the induction of cell-mediated immunity. The vaccines expressed a common immunogen, HIVA, which consists of consensus HIV-1 clade A Gag p24/p17 proteins fused to a string of clade A-derived epitopes recognized by cytotoxic T lymphocytes (CTLs). Volunteers' fresh peripheral blood mononuclear cells were tested for HIV-specific responses in a validated gamma interferon enzyme-linked immunospot (ELISPOT) assay using four overlapping peptide pools across the Gag domain and three pools of known CTL epitopes present in all of the HIVA protein. Both the DNA and the MVA vaccines alone and in a DNA prime–MVA boost combination were safe and induced HIV-specific responses in 14 out of 18, seven out of eight and eight out of nine volunteers, respectively. These results are very encouraging and justify further vaccine development.


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