Prognostic value of peripheral blood mononuclear cell-associated HIV-1 DNA for virological outcome in asymptomatic HIV-1 chronic infection

Abstract

Background: Studies in primary HIV-1 infection and advanced HIV-1 disease have demonstrated that HIV-1 DNA associated with peripheral blood mononuclear cells (PBMC HIV-1 DNA) has predictive value for disease progression.

Objectives: To analyse in asymptomatic HIV-1 chronic infection the predictive value of PBMC HIV-1 DNA for virological failure.

Study design: In 115 individuals who had previously participated in study STIR-2102, we retrospectively analysed the PBMC HIV-1 DNA by quantitative real-time PCR. Antiretroviral naïve patients (baseline pre-ART) received 6 weeks of ART prior to randomisation (baseline post-ART). The predictive value of PBMC HIV-1 DNA, HIV-1 RNA in plasma and CD4+ T cells, at baselines pre-ART and post-ART, was determined by Kaplan-Meier and Proportional Hazards Regression analyses.

Results: At baseline post-ART, 82% of patients showed suppression of HIV-1 RNA, however they maintained significant amounts of HIV-1 DNA (geometric mean: 690 copies/10(6) PBMC). Pre-ART and post-ART levels of HIV-1 DNA and pre-ART levels of HIV-1 RNA showed predictive value (Log-Rank test: p<0.001, p<0.001, p=0.003, respectively). In a multivariate model post-ART PBMC HIV-1 DNA was the stronger predictive variable (adjusted HR, 2.51 [95% CI, 1.33-4.73, p=0.004]) independently of HIV-1 RNA (HR 1.74 [95% CI, 1.16-2.61, p=0.007]).

Conclusions: PBMC HIV-1 DNA is an effective prognostic marker for virological outcome in individuals with asymptomatic HIV-1 chronic infection.