The causal relationship between HIVspecific CD4 ؉ T-cell responses and viral control and the effect of these responses on the natural history of HIV infection is unclear. In a detailed longitudinal study, functional HIV-1 Gag-specific CD4 ؉ T cells were analyzed in long-term asymptomatic individuals (LTA; n ‫؍‬ 6) and progressors to AIDS (n ‫؍‬ 7) with a median follow-up of, respectively, 118 and 57 months. Next, HIV-specific CD4 ؉ T-helper cell responses were measured in a prospective cohort study among 96 HIV seroconverters and were related to clinical endpoints using Cox proportional hazard analyses. In the detailed study, no difference for HIV-specific helper-cell responses between LTAs and progressors was observed early in infection, but Gagspecific CD4 ؉ T cells producing IL-2 or IFN␥ were lost in progressors late in infection. Multivariate proportional hazard analyses in the prospective cohort study showed that HIV-specific IL-2 ؉ , IFN␥ ؉ , or IL-2 ؉ IFN␥ ؉ CD4 ؉ T cells early after seroconversion had no prognostic value for the rate of progression to AIDS. Our results are compatible with viral load determining the nature and magnitude of HIV-specific CD4 ؉ T-cell responses, rather than HIV-specific CD4 ؉ T-cell responses controlling HIV plasma viral load. (Blood.

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Sequential serum samples from 13 homosexual men who seroconverted for antibodies to human immunodeficiency virus (HIV) were tested for HIV antigen. In one of these men, who developed the acquired immune deficiency syndrome (AIDS), HIV antigenaemia preceded the onset of AIDS by more than a year and persisted throughout the course of the disease. This antigenaemia was accompanied by the disappearance of IgG antibody reactivity to the major HIV core protein p24. In none of the 12 others, who all remained without serious disease, were serum concentrations of HIV antigen detected, except on one occasion in one man. All their serum samples showed strong IgG antibody reactivity to p24.Nine children who were infected with HIV in 1981 by plasma transfusion from a single donor were also followed up for HIV

To gain insight into determinants that define the duration of the asymptomatic period preceding AIDS, groups of long-term asymptomatic (LTA) person (> 7 years of follow-up) and slow and rapid progressors of human immunodeficiency virus infection were studied. LTAs had no clinical manifestations of AIDS or immunologic abnormalities in 7 years of follow-up. RNA copy numbers, gag- and env-specific, and neutralizing antibody titers in serum were determined 1 and 5 years after seroconversion or entry into the cohort. Early in infection, before immunologic markers or clinical manifestations allowed group discrimination, subjects who were later classified as LTAs had significantly less serum viral RNA than progressors. No significant increase in virus load was found in progressors, indicating that the initial load defines clinical outcome. In slow progressors, high virus load was associated with high p24-specific antibody titers, suggesting that delay of clinical manifestations of AIDS may be related to the presence of high levels of p24-specific but not V3-specific antibodies.

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.