Background: The rate of progression to AIDS in HIV-1 infected subjects is variable, and circumstances associated with more rapid or slow development of severe immunodeficiency might be grouped in three categories; environmental cofactors, host features, and particular virulence of the virus itself. Currently, it is not yet clear the the relative impact of each one.
Patients and methods: A cross-sectional study was done in a cohort of 1,783 IV-1 infected persons from three centers located in Madrid, mainly devoted to attend persons at risks for HIV infection. Long-term nonprogressors (LTNP) were defined as those with more than 8 years of confirmed HIV seropositivity, and CD4+ T-cell count above 500 x 10(6)/I in the absence of antiretroviral therapy or symptoms suggesting immunodeficiency. Rapid progressors (RP) were those with less than 5 years from seroconversion and repeatedly current CD4+ T-cell count below 200 x 10(6)/I. An analysis of different epidemiological, immunological and virological features was performed comparing LTNP and RP.
Results: Among 1,783 HIV (+) subjects studied, 100 (5.6%) fulfilled criteria for LTNP and 12 (0.7%) for RP. Among LTNP, stabilized CD4 slope was seen in 16 (33%) out of 48 after more than 8 years of infection. Variables statistically associated with LTNP were: past history of intravenous drug addiction (80% of them), male gender (79% of them), high alcohol intake (48% of them), HIV-1 non-syncitium inducing viral phenotype, and very low or undetectable HIV-1 plasma viremia. In contrast, variables associated with RP were: infection by sexual contact (75% of cases), female gender (50% of them), syncitium-inducing viral plenotype, and high titers of plasma viremia. The CD4/CD8 ratio below 1 was seen in all RP and in 88% of LTNP. However, a preferent depletion of CD4+ cell occurred in the first group, instead of an enhancement of the CD8 T-cell count in LTNP. The prevalence of serological markers for hepatotropic viruses and other potential infectious cofactors was not higher in RP.
Conclusions: Multiple factors seems to account for the different rate of disease progression observed in HIV-1 infected persons. The dynamic equilibrium between the immune system and the virulence of the virus seem to be influenced--but not determined--by environmental infectious or non infectious cofactors.