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Background:  Although several studies have explored long-term T-lymphocyte responses to HAART, patterns of immunologic recovery still remain unclear. We aim to address the long-term response of CD4⁺ T cell after initiation of HAART in the PISCIS cohort study and whether reaching and maintaining an undetectable viral load could be associated to this response.

Methods:  The PISCIS cohort (11 hospitals) has enrolled 5968 HIV⁺ patients since 1998 until 2003. We selected naïve patients who started HAART between January 1998 and December 2001, with at least 1 measure of CD4 within 6 months before initiation of HAART and > 2 years of follow-up. Quantitative characteristics were described through the median and interquatile ranges (IQR). CD4 cell counts measured over time were analyzed using linear mixed models for each stratum of baseline CD4 cell count, accounting for within individual variances. Longitudinal models were defined allowing different mean slopes of CD4 increase over 2 to 3, 3 to 4 and > 4 years after initiation of HAART and were adjusted by age.

Results:  We included 1452 patients (median age 36 years; 76% men) with a median of follow-up of 3.6 years (range 2 to 6). The median of CD4 T-cells increased from 267 (IQR, 83 to 375) to 497 (IQR, 310 to 718) cells/mm³. At the end of follow-up 49.5% of subjects reached CD4 > 500, and 11.6% had a CD4 < 200. We identified 787 (54.2%) patients with viral response that reached a RNA HIV-1 < 500 copies/mL within 6 months after initiation of HAART and maintained it for 2 years. Longitudinal models showed a significant increase of CD4 cell counts during 2 years and over 2 to 3 and 3 to 4 years after HAART for each CD4 baseline strata. A plateau was found during the 4- to 6-year period, except in patients with a baseline CD4 < 100, for which the increase remained significant even after 4 years from the initiation of HAART. Among the viral response patients, longitudinal models found similar patterns of CD4 increase, showing a plateau after 4 years. However, in viral response patients with baseline CD4 < 100 the mean slope after 4 years of HAART was no longer significant. Finally, in this group having > 40 years was associated with a lower immunological reconstitution.

Conclusions: Among patients with viral response on HAART during follow-up, there is a plateau in CD4 increase after 4 years of treatment, independently of baseline CD4. However, a longer follow-up would be necessary to determine the degree of immunological reconstitution in patients with lower CD4 baseline without virologic response.

Keywords: Antiretroviral therapy; CD4+ T cells recovery; Longitudinal studies