Extended evaluation of the virologic, immunologic, and clinical course of volunteers who acquired HIV-1 infection in a phase III vaccine trial of ALVAC-HIV and AIDSVAX B/E.

Abstract

BACKGROUND:

The Thai Phase III Trial of ALVAC-HIV and AIDSVAX B/E showed an estimated vaccine efficacy (VE) of 31% to prevent acquisition of human immunodeficiency virus (HIV). Here we evaluated the effect of vaccination on disease progression after infection.

METHODS:

CD4(+) T-cell counts and HIV viral load (VL) were measured serially. The primary analysis evaluated vaccine efficacy (VEP) as the percent reduction (vaccine vs placebo) in cumulative probability of a primary composite endpoint of clinical and CD4(+) count components at prespecified time points after infection. Secondary analyses of biomarker-based endpoints were assessed using marginal mean and linear mixed models.

RESULTS:

There were 61 endpoints in the modified intent-to-treat cohort (mITT; n = 114). There was no evidence for efficacy at 30, 42, 54, and 60 months in the mITT and per protocol (n = 90) cohorts. Estimated VEP (mITT) was15.8% (-21.9, 41.8) at 60 months postinfection. There was weak evidence of lower VL and higher CD4(+) count at 60 and 66 months in the vaccine group. Lower mucosal VL was observed among vaccine recipients, primarily in semen (P = .04).

CONCLUSIONS:

Vaccination did not affect the clinical course of HIV disease after infection. A potential vaccine effect on the genital mucosa warrants further study.

• Authors: Supachai Rerks-Ngarm, Robert M Paris, Supamit Chunsutthiwat, Nakorn Premsri, Chawetsan Namwat, Chureeratana Bowonwatanuwong, Shuying S Li, Jaranit Kaewkungkal, Rapee Trichavaroj, Nampueng Churikanont, Mark S de Souza, Charla Andrews, Donald Francis, Elizabeth Adams, Jorge Flores, Sanjay Gurunathan, Jim Tartaglia, Robert J O'Connell, Chirapa Eamsila, Sorachai Nitayaphan, Viseth Ngauy, Prasert Thongcharoen, Prayura Kunasol, Nelson L Michael, Merlin L Robb, Peter B Gilbert, Jerome H Kim
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 207 Issue 8 Pg. 1195-205 (Apr 15 2013) ISSN: 1537-6613 [Electronic] United States
• PMID: 22837492 (Publication Type: Clinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• AIDS Vaccines
• AIDSVAX B-E
• ALVAC vaccine
• Viral Vaccines

Topics

• AIDS Vaccines (administration & dosage, immunology)
• Adult
• Antiretroviral Therapy, Highly Active (methods)
• CD4 Lymphocyte Count
• Disease Progression
• Female
• Follow-Up Studies
• HIV Infections (immunology, pathology, prevention & control, virology)
• HIV-1 (immunology, pathogenicity)
• Humans
• Linear Models
• Male
• Prospective Studies
• Risk-Taking
• Semen (virology)
• Thailand
• Time Factors
• Vaccination
• Vagina (virology)
• Viral Load
• Viral Vaccines (administration & dosage, immunology)
• Young Adult