Statistical Interpretation of the RV144 HIV Vaccine Efficacy Trial in Thailand: A Case Study for Statistical Issues in Efficacy Trials

Gilbert, Peter B.; Berger, James O.; Stablein, Donald M.; Becker, Stephen; Essex, Max; Kim, Jerome H.; DeGruttola, Victor

doi:10.1093/infdis/jiq152

Cited by 89 publications

(59 citation statements)

References 25 publications

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“…112,113 The prime-boost vaccine regimen consisted of a recombinant canarypox vector, ALVAC-HIV (vCP1521) prime and AIDSVAX B/E boost. The vaccine regimen was safe and generally well tolerated.…”

Section: Hiv Vaccine Clinical Developmentmentioning

confidence: 99%

HIV Epidemic in Asia: Implications for HIV Vaccine and Other Prevention Trials

Phanuphak

Shao³

et al. 2015

AIDS Research and Human Retroviruses

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An overall decrease of HIV prevalence is now observed in several key Asian countries due to effective prevention programs. The decrease in HIV prevalence and incidence may further improve with the scale-up of combination prevention interventions. The implementation of future prevention trials then faces important challenges. The opportunity to identify heterosexual populations at high risk such as female sex workers may rapidly wane. With unabating HIV epidemics among men who have sex with men (MSM) and transgender (TG) populations, an effective vaccine would likely be the only option to turn the epidemic. It is more likely that efficacy trials will occur among MSM and TG because their higher HIV incidence permits smaller and less costly trials. The constantly evolving patterns of HIV-1 diversity in the region suggest close monitoring of the molecular HIV epidemic in potential target populations for HIV vaccine efficacy trials. CRF01_AE remains predominant in southeast Asian countries and MSM populations in China. This relatively steady pattern is conducive to regional efficacy trials, and as efficacy warrants, to regional licensure. While vaccines inducing nonneutralizing antibodies have promise against HIV acquisition, vaccines designed to induce broadly neutralizing antibodies and cell-mediated immune responses of greater breadth and depth in the mucosal compartments should be considered for testing in MSM and TG. The rationale and design of efficacy trials of combination prevention modalities such as HIV vaccine and preexposure prophylaxis (PrEP) remain hypothetical, require high adherence to PrEP, are more costly, and present new regulatory challenges. The prioritization of prevention interventions should be driven by the HIV epidemic and decided by the country-specific health and regulatory authorities. Modeling the impact and cost-benefit may help this decision process.

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Section: Hiv Vaccine Clinical Developmentmentioning

confidence: 99%

HIV Epidemic in Asia: Implications for HIV Vaccine and Other Prevention Trials

Phanuphak

Shao³

et al. 2015

AIDS Research and Human Retroviruses

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“…Of these four trials, only the RV144 trial, the largest HIV vaccine trial so far concluded in humans, showed a limited but significant protection (31.2%) from HIV acquisition (P ϭ 0.04) in the 16,395 participants (4,5). This result has engendered cautious optimism about the feasibility of a vaccine for HIV.…”

mentioning

confidence: 99%

Antibodies with High Avidity to the gp120 Envelope Protein in Protection from Simian Immunodeficiency Virus SIV _mac251 Acquisition in an Immunization Regimen That Mimics the RV-144 Thai Trial

Pegu

Vaccari

Gordon

et al. 2013

J Virol

129

141

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The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the limited ability of the vaccine components to induce CD8 ؉ T-cell responses or broadly neutralizing antibodies. We vaccinated macaques with an immunization regimen intended to mimic the RV144 trial and exposed them intrarectally to a dose of the simian immunodeficiency virus SIV mac251 that transmits few virus variants, similar to HIV transmission to humans. Vaccination induced anti-envelope antibodies in all vaccinees and CD4؉ and CD8 ؉ T-cell responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were protected from SIV mac251 acquisition, but the result was not significant. The remaining vaccinees were infected and progressed to disease. The magnitudes of vaccine-induced SIV mac251 -specific T-cell responses and binding antibodies were not significantly different between protected and infected animals. However, sera from protected animals had higher avidity antibodies to gp120, recognized the variable envelope regions V1/V2, and reduced SIV mac251 infectivity in cells that express high levels of ␣ 4 ␤ 7 integrins, suggesting a functional role of antibodies to V2. The current results emphasize the utility of determining the titer of repeated mucosal challenge in the preclinical evaluation of HIV vaccines.

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“…This study, known as RV144, conducted by the US military research program in collaboration with several Thai institutions in more than 16,000 Thai associate with any particular danger in advance of HIV [64][65][66]. The system consists of a canarypox vector Prime Minister recombinant vaccine (ALVAC HIV, and Sanofi Pasteur) and boost the protein gp120 (AIDSVAX B/E, Global Solutions for Infectious Diseases).…”

Section: Step Studymentioning

confidence: 99%

Efficacy Trials and Progress of HIV Vaccines

Asif¹,

Irshad²

2017

J Cell Sci Ther

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Discovery of HIV as causative agent of AIDS let to the belief that a vaccine for AIDS will be available shortly but was not that easy, and it took more than 30 years of hard laboratory and clinical work toward HIV vaccine development. Efficacy trials of RV144 and their results revealed that HIV vaccine is accomplishable. Clinical trials for developing bNAbs has monoclonal antibodies and to increase its half-life are also underway to achieve a proper HIV vaccine. In this review article, we see that how these efficacy trials are highlighting HIV vaccine concepts in clinical development. Therapeutic vaccines are proving to be a functional cure toward HIV treatment and progress is ongoing in such HIV vaccine development which will attack HIV before it fuses with cell and cause infection thus preventing AIDS. So, in near future it will be possible to cure HIV and bring an end to this epidemic.

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Statistical Interpretation of the RV144 HIV Vaccine Efficacy Trial in Thailand: A Case Study for Statistical Issues in Efficacy Trials

Cited by 89 publications

References 25 publications

HIV Epidemic in Asia: Implications for HIV Vaccine and Other Prevention Trials

HIV Epidemic in Asia: Implications for HIV Vaccine and Other Prevention Trials

Antibodies with High Avidity to the gp120 Envelope Protein in Protection from Simian Immunodeficiency Virus SIV _mac251 Acquisition in an Immunization Regimen That Mimics the RV-144 Thai Trial

Efficacy Trials and Progress of HIV Vaccines

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Statistical Interpretation of the RV144 HIV Vaccine Efficacy Trial in Thailand: A Case Study for Statistical Issues in Efficacy Trials

Cited by 89 publications

References 25 publications

HIV Epidemic in Asia: Implications for HIV Vaccine and Other Prevention Trials

HIV Epidemic in Asia: Implications for HIV Vaccine and Other Prevention Trials

Antibodies with High Avidity to the gp120 Envelope Protein in Protection from Simian Immunodeficiency Virus SIV mac251 Acquisition in an Immunization Regimen That Mimics the RV-144 Thai Trial

Efficacy Trials and Progress of HIV Vaccines

Contact Info

Product

Resources

About

Antibodies with High Avidity to the gp120 Envelope Protein in Protection from Simian Immunodeficiency Virus SIV _mac251 Acquisition in an Immunization Regimen That Mimics the RV-144 Thai Trial