Laboratory Surrogate Markers of Residual HIV Replication among Distinct Groups of Individuals under Antiretroviral Therapy

Background: Residual HIV-1 replication among individuals under antiretroviral therapy (ART) relates to HIV micro-inflammation. Objectives: To determine levels of residual HIV replication markers among distinct subgroups of antiretroviral-treated individuals. Methods: 116 patients were distributed into 5 treatment groups: first-line suppressive ART with non-nucleoside reverse-transcriptase inhibitor (NNRTI) (n=26), first-line suppressive ART with boosted protease inhibitors (PI-r) (n=25), salvage therapy using PI-r (n=27), salvage therapy with PI-r and raltegravir (n=22) and virologic failure (n=16). Episomal and total DNA quantitation was evaluated. ELISA was used for HIV antibody and LPS quantitation. Results: Episomal DNA was positive in 26% to 38% of individuals under suppressive ART, being higher among individuals experiencing virologic failure (p=0.04). HIV proviral load was higher among patients with detectable episomal DNA (p=0.01). Individuals receiving initial PI-r treatment presented lower HIV antibodies (p=0.027) and LPS (p=0.029) than individuals receiving NNRTI. There was a negative correlation between episomal DNA quantitation and suppressive ART duration (p=0.04), CD4+ T-cell count (p=0.08), and CD8+ T-cell count (p=0.07). Conclusions: Residual HIV replication has been inferred among individuals under suppressive ART according to episomal DNA detection. Residual replication may decrease with longer periods of suppressive ART and higher levels of CD4+ and CD8+ T cells. The relationship between episomal DNA and total DNA suggests a replenishment of the proviral reservoir with impacts on HIV persistence. Lower antibody and LPS levels among patients with initial PI-r ART suggest these regimens may more effectively suppress HIV with higher capacity to decrease the HIV antigenic component.