RESUMEN
OBJECTIVES: To assess the dynamics of neutralizing antibodies (NAb) in long-term AIDS-free HIV-1-infected subjects and establish correlations with known markers of disease progression. DESIGN: Cross-sectional study using sera collected from long-term non-progressors (LTNP) 8 years after seroconversion or study entry. Longitudinal study using sera collected from LTNP at 0, 0.5, 1, 2, 4, 6, 8 and 10 years after seroconversion and, as controls, from rapid progressors. METHODS: Individuals with documented AIDS-free HIV-1 infection for at least 8 years were evaluated for NAb against five heterologous HIV-1 primary isolates. In the cross-sectional study, serum viral RNA levels, CD4+ T-cell numbers and T-cell function were determined on samples collected during the eighth year of follow-up. For the longitudinal study, NAb were assessed in sequential sera taken from LTNP and rapid progressors. RESULTS: Serum neutralization titres found in individual sera differed from one HIV-1 isolate to another, were detected in 49-76% of LTNP, without correlation with the coreceptor usage of the isolate, and were positively associated with CD4+ T-lymphocyte counts (P = 0.0041) and T-cell function (P = 0.04). No correlation was found between NAb and the level of viral RNA in serum or the rate of CD4+ T-cell decline. Longitudinal analysis of sera from LTNP and rapid progressors showed that although several subjects in both groups had neutralizing activity at seroconversion, it thereafter became lower or no longer detectable. NAb were again found 1-4 years later and stably persisted in LTNP, but remained undetectable or at low levels in rapid progressors. CONCLUSIONS: NAb were preferentially found in subjects with relatively preserved T-cell function and CD4+ T-cell numbers. In these individuals, neutralizing activity against heterologous isolates increased with time. These data suggest that the capacity to produce broadly NAb is a function of the integrity of the immune system.