Quantification of HIV-1 proviral DNA in patients with undetectable plasma viremia over long-term highly active antiretroviral therapy

Abstract

Objectives: To assess the prognostic role of proviral DNA in peripheral blood mononuclear cells (PBMC) of patients with undetectable viremia over long-term highly active antiretroviral therapy (HAART). Methods: Eighty-two human immunodeficiency virus (HIV)-1-infected patients, free of acquired immunodeficiency syndrome (AIDS), received zidovudine plus lamivudine plus indinavir. Levels of plasma HIV-RNA, and PBMC proviral DNA and RNA unspliced (US) transcripts were evaluated by using competitive polymerase chain reaction (cPCR) assays, every 3 months over 1 year. Results: Among patients with undetectable viremia at baseline, 13 of 18 with CD4 cell count 350/mm 3 or less and 12 of 16 with CD4 between 351 and 700/mm 3, constantly maintained undetectable RNA levels; in these patients, a mean proviral DNA decrease of 0.67 ± 0.7 and 1.03 ± 0.53 log (P < 0.001), respectively, a significant decrease of RNA-US transcripts (P < 0.001), and significant correlations between decreases of proviral DNA and RNA-US transcripts (P = 0.008 and P < 0.001, respectively) were observed. Conclusions: Proviral DNA quantitation permits the continued monitoring of HAART in patients with undetectable viremia.