Cellular HIV-1 DNA quantification and short-term and long-term response to antiretroviral therapy

Abstract

BACKGROUND: The aim of our study was to determine whether HIV-1 DNA level before antiretroviral therapy (ART) was associated with short- and long-term virological and immunological responses. METHODS: Patients starting first-line protease inhibitor-containing regimens were enrolled in a prospective multicentre cohort in 1998-99. HIV-1 DNA was quantified using real-time PCR at baseline and after 1 year of ART. The association between HIV-1 DNA and virological and immunological responses after 1 and 7 years on ART was studied in multivariate regression models along with other biological and clinical variables. Virological failure (VF) at month 12 (M12) was defined as a plasma HIV-1 RNA >500 copies/mL. Time to death or two plasma HIV-1 RNA >500 copies/mL between M12 and M84 was studied for long-term VF. RESULTS: HIV-1 DNA levels were measured in 148 patients. The median baseline peripheral blood mononuclear cell (PBMC) HIV-1 DNA was 3.7 log(10) copies/10(6) PBMCs. At M12, the median PBMC HIV-1 DNA was 2.99 log(10) copies/10(6) PBMCs. The median decrease in PBMC HIV-1 DNA between M0 and M12 was -0.7 log(10) copies/10(6) PBMCs. Higher baseline PBMC HIV-1 DNA and plasma HIV-1 RNA were independently associated with a higher risk of VF at M12. Only the baseline plasma HIV-1 RNA was independently associated with long-term virological response. The baseline CD4 cell count was the only parameter associated with short- and long-term immunological responses. CONCLUSIONS: HIV-1 DNA impacted the virological response in our cohort. Further research is warranted to study the impact of HIV-1 DNA with currently recommended first-line cART.