Association of Fcγ receptor IIIa genotype with the rate of HIV infection after gp120 vaccination.
We determined whether polymorphisms in Fcγ receptor (FcγR) IIa or FcγRIIIa genes were associated with outcomes in Vax004, a trial testing recombinant gp120 vaccination in preventing sexually acquired HIV infection. Male subjects (n = 1725), including infected and uninfected vaccinees and placebo recipients, were genotyped. We observed no association between FcγRIIa genotype and infection rate in vaccinees or placebo recipients. However, FcγRIIIa genotype was associated with infection rate among vaccinees (P = .035). Exploratory analyses revealed that vaccinees homozygous for the FcγRIIIa V allele in the lowest behavioral risk group had a greater rate of infection than low risk vaccinees with at least 1 F allele (hazard ratio [HR] = 3.52; P = .002). No such association was seen among vaccinees with high-risk behaviors or among placebo recipients in either risk stratum. Vaccinated low-risk VV subjects had a greater infection rate than low-risk VV placebo recipients (HR = 4.51; P = .17) or low-risk placebo recipients with any genotype (HR = 4.72; P = .002). Moreover, low-risk VV vaccinees had infection rates similar to individuals with high behavioral risk, irrespective of genotype. Our results generate the hypothesis that recombinant gp120 vaccine may have increased the likelihood of acquiring HIV infection in individuals with the VV genotype (present in ~ 10% of the population) at low behavioral risk of infection.
Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, CA 92697, USA. dnfortha@uci.edu
Donald N
DN
Forthal
Erin E
EE
Gabriel
Angela
A
Wang
Gary
G
Landucci
Tran B
TB
Phan
D000328:Adult; D016022:Case-Control Studies; D004311:Double-Blind Method; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006678:HIV / Q000472:pathogenicity*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000235:genetics / Q000628:therapy* / Q000821:virology; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D017452:Receptors, IgG / Q000235:genetics*; D012307:Risk Factors; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000627:therapeutic use*
C496124:FCGR3A protein, human; D015699:HIV Envelope Protein gp120; D017452:Receptors, IgG; D014614:Vaccines, Synthetic