Long-term clinical benefit after highly active antiretroviral therapy in advanced HIV-1 infection, even in patients without immune reconstitution

Our objective was to assess, in the clinical setting, the predictors of imm une reconstitution (IR) and its relation with long-term clinical benefit, i n HIV patients with advanced disease after highly active antiretroviral the rapy (HAART) through an observational study. A retrospective cohort study i n a clinical setting of 383 consecutive adult patients with advanced HIV in fection (CD4+ cells < 200/mm(3) at baseline), starting their first protease inhibitor (Pl)-containing regimen was observed. Immune reconstitution was defined as CD4 count > 200 cells/mm(3) and an increase greater than or equa l to 100 cells from baseline, anytime since starting HAART. Clinical benefi t was defined as decreased mortality nd reduction in AIDS-defining events, AIDS-related complex (ARC) events, major infections and hospitalization (da ys spent in hospital). During a mean follow-up of 808 days, 261 patients (6 8.1%) achieved IR. About 50% of these patients reached this result within o ne year after starting HAART. In multivariate analysis, predictors of immun e recovery were sex (female) and baseline CD4 count higher than 50 cells/mm (3). The group of patients with IR had greater clinical benefit with lower mortality, fewer AIDS-defining events, shorter lengths of stay in hospital, fewer ARC events and fewer major infections during all the follow-up (P < 0.0001, tests for trends). However, although they did less remarkably than the first group of patients, even those patients who did not achieve IR exp erienced a significant decrease in the incidence of all the above events, a s compared with the first and sometimes the second trimester after starting their HIV therapy. About 70% of HIV patients with advanced disease achieve d IR after starting HAART. Such a benefit is a time-dependent effect and ma y even take more than 2 years to occur. Predictors of IR were sex (female) and higher baseline CD4 count (> 50 cells/mm(3)). The patients who achieved immune recovery performed clinically better than patients who did not. Als o the patients who failed to gain such a strong immunological recovery expe rienced a long-term clinical benefit. This suggests that PI-containing regi mens, in advanced HIV disease, may produce a significant clinical benefit, at least temporary, even for patients who do not achieve a substantial immu ne response.