Laboratory surrogate markers of residual HIV replication among distinct groups of individuals under antiretroviral therapy

Abstract

15 Background: Residual HIV-1 replication among individuals under antiretroviral therapy 16 (ART) relates to HIV micro-inflammation. 17 Objectives: To determine levels of residual HIV replication markers among distinct 18 subgroups of antiretroviral-treated individuals.19Methods: 116 patients were distributed into 5 treatment groups: first-line suppressive ART 20 with non-nucleoside reverse-transcriptase inhibitor (NNRTI) (n=26), first-line suppressive 21 ART with boosted protease inhibitors (PI-r) (n=25), salvage therapy using PI-r (n=27), 22 salvage therapy with PI-r and raltegravir (n=22) and virologic failure (n=16). Episomal and 23 total DNA quantitation was evaluated. ELISA was used for HIV antibody and LPS 24 quantitation. 25 Results: Episomal DNA was positive in 26% to 38% of individuals under suppressive ART, 26 being higher among individuals experiencing virologic failure (p=0.04). HIV proviral load 27 was higher among patients with detectable episomal DNA (p=0.01). Individuals receiving 28 initial PI-r treatment presented lower HIV antibodies (p=0.027) and LPS (p=0.029) than 29 individuals receiving NNRTI. There was a negative correlation between episomal DNA 30 quantitation and suppressive ART duration (p=0.04), CD4+ T-cell count (p=0.08), and CD8+ 31 T-cell count (p=0.07).32 Conclusions: Residual HIV replication has been inferred among individuals under 33 suppressive ART according to episomal DNA detection. Residual replication may decrease 34 with longer periods of suppressive ART and higher levels of CD4+ and CD8+ T cells. The 35 relationship between episomal DNA and total DNA suggests a replenishment of the proviral 36 reservoir with impacts on HIV persistence. Lower antibody and LPS levels among patients 37with initial PI-r ART suggest these regimens may more effectively suppress HIV with higher 38 capacity to decrease the HIV antigenic component. 39 Patients 61Patients were chosen between 2011 to 2013 in São Paulo Brazil according to their 62 current antiretroviral treatment (see Supplementary Table 1). Individuals were under ART 63 with undetectable plasma viral loads for at least one year, except for the virologic failure 64 4 group. This study was approved by the Ethics Committee in Research at the Federal 65 University of São Paulo (approval #0201/11), and informed consent was obtained from all 66 patients. 67One hundred sixteen patients were allocated to five treatment subgroups as follows: 68(1) patients treated with two nucleoside-analogue reverse-transcriptase inhibitors (NRTI) 69 associated with the non-nucleoside analog reverse-transcriptase inhibitors (NNRTI) Efavirenz 70 or Nevirapine as the first ART regimen; (2) patients treated with two NRTIs and a protease 71 inhibitor boosted with ritonavir (PI-r) as the first ART regimen; (3) patients on salvage 72 therapy with two NRTIs and a PI-r; (4) patients under salvage therapy containing two NRTIs, 73 PI-r and the integrase inhibitor raltegravir; and (5) patients under antiretroviral virologic 74 failure with the confirmed presence o...