Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand.

BACKGROUND In Thailand, phase 1/2 trials of monovalent subtype B and bivalent subtype B/E (CRF01_AE) recombinant glycoprotein 120 human immunodeficiency virus type 1 (HIV-1) vaccines were successfully conducted from 1995 to 1998, prompting the first HIV-1 vaccine efficacy trial in Asia. METHODS This randomized, double-blind, placebo-controlled efficacy trial of AIDSVAX B/E (VaxGen), which included 36-months of follow-up, was conducted among injection drug users (IDUs) in Bangkok, Thailand. The primary end point was HIV-1 infection; secondary end points included plasma HIV-1 load, CD4 cell count, onset of acquired immunodeficiency syndrome-defining conditions, and initiation of antiretroviral therapy. RESULTS A total of 2546 IDUs were enrolled between March 1999 and August 2000; the median age was 26 years, and 93.4% were men. The overall HIV-1 incidence was 3.4 infections/100 person-years (95% confidence interval [CI], 3.0-3.9 infections/100 person-years), and the cumulative incidence was 8.4%. There were no differences between the vaccine and placebo arms. HIV-1 subtype E (83 vaccine and 81 placebo recipients) accounted for 77% of infections. Vaccine efficacy was estimated at 0.1% (95% CI, -30.8% to 23.8%; P=.99, log-rank test). No statistically significant effects of the vaccine on secondary end points were observed. CONCLUSION Despite the successful completion of this efficacy trial, the vaccine did not prevent HIV-1 infection or delay HIV-1 disease progression.

[1]  J. Tappero,et al.  HIV type 1 incidence estimates by detection of recent infection from a cross-sectional sampling of injection drug users in Bangkok: use of the IgG capture BED enzyme immunoassay. , 2003, AIDS research and human retroviruses.

[2]  J. Tappero,et al.  Recruitment, screening and characteristics of injection drug users participating in the AIDSVAX®B/E HIV vaccine trial, Bangkok, Thailand , 2004, AIDS.

[3]  J. Tappero,et al.  Frequency of HIV-1 dual subtype infections, including intersubtype superinfections, among injection drug users in Bangkok, Thailand , 2005, AIDS.

[4]  R. Belshe,et al.  Neutralizing antibodies to HIV-1 in seronegative volunteers immunized with recombinant gp120 from the MN strain of HIV-1. NIAID AIDS Vaccine Clinical Trials Network. , 1994, JAMA.

[5]  F. Newman,et al.  Antibody to native human immunodeficiency virus type 1 envelope glycoproteins induced by IIIB and MN recombinant gp120 vaccines. The NIAID AIDS Vaccine Evaluation Group , 1996, Clinical and diagnostic laboratory immunology.

[6]  T. Brown,et al.  Thailand: lessons from a strong national response to HIV/AIDS. , 1998, AIDS.

[7]  T. Mastro,et al.  Genetic characterization of incident HIV type 1 subtype E and B strains from a prospective cohort of injecting drug users in Bangkok, Thailand. , 2000, AIDS research and human retroviruses.

[8]  Jon Cohen.  AIDS Vaccine Still Alive as Booster After Second Failure in Thailand , 2003, Science.

[9]  Bryan Langholz,et al.  Exposure Stratified Case-Cohort Designs , 2000, Lifetime data analysis.

[10]  D. Morens,et al.  Antibody-dependent enhancement of infection and the pathogenesis of viral disease. , 1994, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[11]  J. Tappero,et al.  Lack of increased HIV risk behavior among injection drug users participating in the AIDSVAX®B/E HIV vaccine trial in Bangkok, Thailand , 2004, AIDS.

[12]  D. Montefiori,et al.  ANTIBODY-DEPENDENT ENHANCEMENT OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 INFECTION , 1988, The Lancet.

[13]  P. Pitisuttithum,et al.  AIDSVAX (MN) in Bangkok injecting drug users: a report on safety and immunogenicity, including macrophage-tropic virus neutralization. , 2000, AIDS research and human retroviruses.

[14]  H. Sheppard,et al.  Phase I/II Study of a Candidate Vaccine Designed Against the B and E Subtypes of HIV-1 , 2004, Journal of acquired immune deficiency syndromes.

[15]  F. van Griensven,et al.  Genetic analysis of incident HIV-1 strains among injection drug users in Bangkok: evidence for multiple transmission clusters during a period of high incidence. , 2002, Journal of acquired immune deficiency syndromes.

[16]  Barney S. Graham,et al.  Neutralizing Antibodies to HIV-1 in Seronegative Volunteers Immunized With Recombinant gp 120 From the MN Strain of HIV-1 , 1994 .

[17]  S. Halstead,et al.  Summary report: workshop on the potential risks of antibody-dependent enhancement in human HIV vaccine trials. , 1993, AIDS research and human retroviruses.

[18]  J. Tappero,et al.  CCR5 promoter human haplogroups associated with HIV-1 disease progression in Thai injection drug users , 2004, AIDS.

[19]  T. Mastro,et al.  Estimating the number of HIV-infected injection drug users in Bangkok: a capture--recapture method. , 1994, American journal of public health.

[20]  Jerome H. Kim,et al.  Safety and immunogenicity of combinations of recombinant subtype E and B human immunodeficiency virus type 1 envelope glycoprotein 120 vaccines in healthy Thai adults. , 2003, The Journal of infectious diseases.

[21]  P. Gilbert,et al.  HIV-1 virologic and immunologic progression and initiation of antiretroviral therapy among HIV-1-infected subjects in a trial of the efficacy of recombinant glycoprotein 120 vaccine. , 2005, The Journal of infectious diseases.

[22]  J. Mullins,et al.  The evolving molecular epidemiology of HIV‐1 envelope subtypes in injecting drug users in Bangkok, Thailand: implications for HIV vaccine trials , 1995, AIDS.

[23]  Michael R Kosorok,et al.  Simultaneous Inferences on the Contrast of Two Hazard Functions with Censored Observations , 2002, Biometrics.

[24]  J. Tappero,et al.  Trends in the injection of midazolam and other drugs and needle sharing among injection drug users enrolled in the AIDSVAX B/E HIV-1 vaccine trial in Bangkok, Thailand , 2005 .

[25]  C. Latkin,et al.  The influence of Thailand's 2003 ‘war on drugs’ policy on self-reported drug use among injection drug users in Chiang Mai, Thailand , 2005 .

[26]  R. Belshe,et al.  Advancing AIDSVAX to phase 3. Safety, immunogenicity, and plans for phase 3. , 1998, AIDS research and human retroviruses.

[27]  K. Buchacz,et al.  Early Markers of HIV-1 Disease Progression in a Prospective Cohort of Seroconverters in Bangkok, Thailand: Implications for Vaccine Trials , 2004, Journal of acquired immune deficiency syndromes.

[28]  J. Klotter.  War on Drugs , 2001 .

[29]  J. Mullins,et al.  Determination of HIV‐1 subtypes in injecting drug users in Bangkok, Thailand, using peptide‐binding enzyme immunoassay, and heteroduplex mobility assay: evidence of increasing infection with HIV‐1 subtype E , 1995, AIDS.

[30]  Michael G Hudgens,et al.  Correlation between immunologic responses to a recombinant glycoprotein 120 vaccine and incidence of HIV-1 infection in a phase 3 HIV-1 preventive vaccine trial. , 2005, The Journal of infectious diseases.

[31]  P. Akarasewi,et al.  Was the 1988 HIV epidemic among Bangkok's injecting drug users a common source outbreak? , 1994, AIDS.

[32]  P. Berman.  Development of bivalent rgp120 vaccines to prevent HIV type 1 infection. , 1998, AIDS research and human retroviruses.

[33]  D. D. Des Jarlais,et al.  Higher viral loads and other risk factors associated with HIV-1 seroconversion during a period of high incidence among injection drug users in Bangkok. , 2002, Journal of acquired immune deficiency syndromes.

[34]  W. Heneine,et al.  Viral load differences in early infection with two HIV-1 subtypes , 2001, AIDS.

[35]  D. Burke,et al.  Genetic variants of HIV-1 in Thailand. , 1992, AIDS research and human retroviruses.

[36]  P Mock,et al.  Willingness of injection drug users to participate in an HIV vaccine efficacy trial in Bangkok, Thailand. , 1999, Journal of acquired immune deficiency syndromes.

[37]  J. Esparza,et al.  Continued high HIV-1 incidence in a vaccine trial preparatory cohort of injection drug users in Bangkok, Thailand , 2001, AIDS.

[38]  M. Kieny,et al.  Vaccine protection of chimpanzees against challenge with HIV-1-infected peripheral blood mononuclear cells. , 1992, Science.

[39]  T. Wrin,et al.  Development of bivalent (B/E) vaccines able to neutralize CCR5-dependent viruses from the United States and Thailand. , 1999, Virology.

[40]  D. D. Des Jarlais,et al.  Infection with HIV-1 subtypes B and E in injecting drug users screened for enrollment into a prospective cohort in Bangkok, Thailand. , 1998, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[41]  Kenneth H Mayer,et al.  Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. , 2005, The Journal of infectious diseases.