RANDOMIZED TRIAL OF MNRGP120 HIV-1 VACCINE IN SYMPTOMLESS HIV-1 INFECTION

Background Most individuals infected with HIV-1 show disease progressi on 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 res ponse can slow progression of HIV-1 disease. Methods In a randomised, double-blind, placebo-controlled trial, carried out in university infe ctious 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 intr amuscular injection monthly for 6 months then every alternate month th roughout the study. The primary endpoint was the rate of decline in CD 4 count; secondary endpoints were HIV-1 RNA concentrations in plasma a nd minor clinical events associated with HIV. Analysis was by intentio n to treat. Findings At baseline, the study participants had a mean CD 4 count of 775 cells/mu L (SD 172) and 89% of participants had detecta ble HIV RNA (>200 copies/mL). These RNA-positive individuals had a med ian 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 mea n gradients 1.27 [95% CI 0.63-2.55]) or in plasma HIV-1 RNA concentrat ions (p greater than or equal to 0.63). The study was designed with po wer to detect a vaccine-induced reduction in rate of decline in CD4 co unt of 60%; these results exclude with 95% confidence a reduction of 4 0% or more. More vaccine-treated patients than placebo recipients show ed 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 event s were similar in the two groups. Pain at the injection site was the o nly adverse event that occurred more frequently in vaccine-treated gro up. Interpretation Postinfection immunisation of symptom-free HIV-infe cted patients with MNrgp120 vaccine did not alter HIV-1 disease progre ssion as measured by immunological, virological, and clinical endpoint s over a 15-month period.