Background:
Nonsuppressible viremia (NSV) on antiretroviral therapy (ART) has been shown to originate from infected T-cell clones rather than viral replication. The variation and longitudinal persistence of NSV have not been well defined. To address this knowledge gap, we enrolled a longitudinal cohort of persons with NSV on stable ART.
Methods:
We enrolled individuals living with HIV into a longitudinal ACTG cohort study of NSV who met the following inclusion criteria: At least 2 HIV-1 RNA values ≥20 and ≤1500 copies (c)/mL within 24 months prior to entry, at least 1 documented HIV-1 RNA value ≥20 and ≤1500 c/mL within 12 months prior to entry and on uninterrupted ART for at least 12 months. Persistence of NSV was categorized into three groups among those without ART changes or interruptions using RNAs at week 0 (entry), week 24, 48 (all 3 required): 1) all RNAs <40 c/mL, 2) mix of RNAs <40 and ≥40 c/mL, and 3) all RNAs ≥40 c/mL. Analyses of participant characteristics at study entry compared the 3 groups by age, sex, gender, pre-ART plasma HIV-1 RNA (log10 c/mL), pre-ART and entry CD4+ T-cell count (cells/mm3), entry CD8+ T-cell count (cells/mm3), entry CD4:CD8 ratio, years on ART at entry, and the proportion of RNAs ≥40 c/mL during 24 months on ART prior to entry
Results:
22 participants were analyzed: 1 (5%) female; median age 58 (range 24-75); median years on ART 9.5 (range, 2.9-26.8). The reported pre-study duration of NSV ranged to 10+ years. At week 48, 8 of 22 (36%) still had quantifiable viremia (≥40 c/mL). Only 3 (14%) participants had RNA ≥40 c/mL at weeks 0, 24 and 48; 10 (45%) had RNA <40 c/mL at all three weeks and 9 (41%) had mix of <40 and ≥40 c/mL. The median pre-ART CD4 T-cell count for groups 1, 2 and 3 were 98, 121 and 164 cells/mm…3, respectively. The only factor significantly associated with persistence of NSV ≥40 c/mL was the proportion of plasma HIV RNA measurements that were ≥40 c/mL during the 24 months on ART prior to entry (p=0.001, Kruskal-Wallis Test) (Figure).
Conclusions:
NSV was dynamic and consistently ≥40 c/mL at 0-48 weeks in only 14% of participants. Persistence of NSV over 48 weeks was only associated with the proportion of RNAs ≥40 c/mL prior to entry. These results are consistent with variable persistence of clones producing virus with the minority being stable, and the majority declining in size and/or producing less virus.
