Impact of 5 years of maximally successful highly active antiretroviral therapy on CD4 cell count and HIV-1 DNA level

Objectives: To evaluate the impact on CD4 cell count and HIV-1 DNA level in peripheral blood mononuclear cells (PBMC) of long-term highly active antiretroviral therapy (HAART) in the setting of maximal success, i.e., constant plasma HIV-1 RNA load suppression. Design: Retrospective analysis of patients selected for a constantly undetectable plasma HIV-1 RNA load since HAART initiation. Methods: HIV-1 DNA was measured in PBMC using a real-time polymerase chain reaction assay. Loess estimates and regression analysis were used for modelling the variations of the CD4 cell count and HIV DNA level over time. Results: The study included 41 patients chronically infected with HIV-1 who had been taking HAART for a median duration of 60.4 months and had an undetectable plasma HIV RNA load ever since the first 6 months of HAART, 25 were tested for HIV-1 DNA. The mean CD4 cell count increase was high during the first 18 months on therapy (168x10(6) cells/l per year), much lower afterwards (38x10(6) cells/l per year), independently of the baseline CD4 cell count. Most of the patients (73.2%) reached a CD4 cell count constantly greater than or equal to400x10(6)/l during follow-up. HIV-1 DNA showed a mean decrease of 0.48 log(10) copies/10(6) PBMC during the first year, of 0.18 log(10) copies/10(6) PBMC per year during the 2nd and 3rd years, but no significant decrease afterwards. Conclusions: These results question the benefit of very long-term maintenance of HAART in terms of CD4 gain and HIV-1 DNA reduction. (C) 2004 Lippincott Williams Wilkins.