To assess whether the benefit of highly active antiretroviral therapies (HAART) is continuing, a longitudinal retrospective study of CD4 counts and viral load (VL) in a large group of human immunodeficiency virus (HIV)-infected subjects was undertaken in Madrid.

Consecutive plasma VL values and CD4⁺ T-lymphocyte counts were collected during a 3-month period yearly from 1996 to 2000 in one HIV/acquired immune deficiency syndrome (AIDS) reference institution, where currently around 1500 HIV-infected individuals are on regular follow-up.

VL values and CD4⁺ counts were collected at each time-point from an average of 375 and 391 patients, respectively. The proportion of subjects receiving HAART among those on any kind of antiretroviral treatment increased between 1996 (61%) and 2000 (95.1%) (P < 0.01). The number of subjects with undetectable VL (<500 HIV-RNA copies/mL) increased from 12% in 1996 to 64% in 2000 (P < 0.01). Accordingly, the proportion of individuals with CD4⁺ counts >500 cells/μL increased from 16% in 1997 to 54% in 2000 (P < 0.01). Notably, the number of subjects with VL values >10 000 copies/mL has declined over time, and currently represents only 17% of the population. Despite this favorable trend, the proportion of subjects with low CD4⁺ counts (<200 cells/μL) seems to have reached a plateau, in the range of 10%.

A dramatic virological and immunological benefit has followed the introduction of HAART in HIV-infected patients since 1996. This favorable trend seems to be maintained over time, despite the negative impact of drug-related toxicity and/or adherence issues. However, a subgroup of subjects seems to persist with low CD4 counts despite having good virological control. They should be managed with alternative treatment strategies, including immune stimulatory agents.