Randomised trial of MNrgp120 HIV-1 vaccine in symptomless HIV-1 infection

Background Most individuals infected with HIV-1 show disease progression despite both cellular and humoral immune responses. We investigated whether immunisation of patients who had symptomless HIV-1 infection with an envelope subcomponent Vaccine (MNrgp120) to augment immune response can slow progression of HIV-1 disease. Methods In a randomised, double-blind, placebo-controlled trial, carried out in university infectious disease clinics and community infectious disease practices, we enrolled 573 HIV-infected patients with CD4 counts above 600 cells/mu L (0.6x10(9)/L). Patients received 600 mu g vaccine or placebo by intramuscular injection monthly for 6 months then every alternate month throughout the study. The primary endpoint was the rate of decline in CD4 count; secondary endpoints were HIV-1 RNA concentrations in plasma and minor clinical events associated with HIV. Analysis was by intention to treat. Findings At baseline, the study participants had a mean CD4 count of 775 cells/mu L (SD 172) and 89% of participants had detectable HIV RNA (>200 copies/mL). These RNA-positive individuals had a median viral load of 9250 copies/mL (IQR 2670-26 960). Analysis after 15 months of follow-up of the 568 subjects who had at least one CD4 count done after randomisation showed no difference between the 287 vaccine recipients and 281 placebo recipients in rate of decline of CD4 count (yearly decrease 53.8 [SE 7.6] vs 42.3 [7.6] cells/mu L; ratio of mean gradients 1.27 [95% CI 0.63-2.55]) or in plasma HIV-1 RNA concentrations (p greater than or equal to 0.63). The study was designed with power to detect a vaccine-induced reduction in rate of decline in CD4 count of 60%; these results exclude with 95% confidence a reduction of 40% or more. More vaccine-treated patients than placebo recipients showed a 50% decrease in CD4 count (11 vs 5; relative risk 2.15 [95% CI 0.76-6.12], p=0.13). The frequencies of HIV-related minor clinical events were similar in the two groups. Pain at the injection site was the only adverse event that occurred more frequently in vaccine-treated group. Interpretation Postinfection immunisation of symptom-free HIV-infected patients with MNrgp120 vaccine did not alter HIV-1 disease progression as measured by immunological, virological, and clinical endpoints over a 15-month period.