ABSTRACT: Background: The current recommendation that patients infected with HIV-1 be treated early is based on little evidence. We examined whether early initiation of highly active antiretroviral therapy (HAART) affects residual viraemia.
Methods: Viraemia was measured using an assay with a detection limit (DL) of 3 RNA copies/mL in three groups of patients. HAART was initiated in drug-naïve patients at the time of primary HIV-1 infection (PHI) (n=10) and after immune suppression developed (CD4 cell counts <500 cells/mm3; median, 113) (n=21). Peripheral blood mononuclear cell(PBMC)-associated RNA and DNA (DL, 5 copies/106 cells) were assessed in patients with persistent undetectable viraemia.
Results: In 249 samples collected 24 to 120 weeks after treatment initiation, the mean proportion of samples with viraemia <3 copies/mL was 75% for PHI patients compared to 32% and 8% for immunocompetent and immunosuppressed patients, respectively. 50% of PHI patients, but none of chronically infected patients, had persistently <3 copies/mL. PHI patients had lower residual viraemia than immunosuppressed patients (all pairwise, P<0.001). Mean residual viraemia was independently associated with the initiation of therapy during PHI and baseline CD4 cell counts (P<0.001 for both associations). PBMC-associated RNA and DNA were assessed in the five PHI patients with persistent undetectable viraemia. Four of them had a progressive decrease in PBMC-associated RNA resulting in levels lower than 5 copies/106 cells. After 18 months, whereas there was no clear tendency for a decrease over time of PBMC-associated DNA (mean at 18 months, 22 copies/106 PBMC; range, 1/74).
Conclusion: Initiation of antiretroviral therapy at time of PHI and while CD4 cells counts are high leads to stronger suppression of residual viral replication. In PHI patients, decrease of PBMC-associated RNA parallels viraemia.
