Background
Viral reservoir is established early during primary HIV infection (PHI). Early antiretroviral therapy (ART) is essential to limit reservoir development. The aim of this work was to evaluate the impact of rapid bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) treatment on intact and defective proviral HIV-1 DNA in people with PHI.
Methods
Multicenter, single-arm clinical trial in confirmed PHI individuals (<3 months) starting BIC/FTC/TAF. Reservoir was quantified at baseline (w0) and 48 weeks (w48) after ART initiation. Intact Proviral DNA Assay was used to measure intact and defective HIV-1 proviral DNA in patients’ CD4+ T cells. Fiebig stages were categorized in 2 groups, II-IV and V-VI, respectively. Changes over time in DNA reservoir and comparisons between baseline characteristics were estimated using a mixed-effects linear regression model considering as covariates calendar visit (w0 and w48), Fiebig stage, baseline HIV-1 RNA viral load (VL), subtype (B/non-B) and the interaction between visit and each of the other three variables, and with random effects at participant level.
Results
48/66 (73%) participants with paired samples were included, 92% male, median (IQR) 31.5 (26-41) y.o.; 88% MSM; 62% subtype B and median (IQR) VL was 503500 (155000-1385000) cp/mL. At ART initiation, 13 patients were at Fiebig stages II-IV (27%) and 25 at V-VI (73%). Intact and defective proviral DNA significantly decreased (p<0.001) after 48 weeks of treatment in Fiebig II-IV (from 7376 to 95 and from 13497 to 157 cp/106 CD4+ T cells respectively) and in Fiebig V-VI (from 8899 to 458 and from 2119 to 233 cp/106 CD4+ T cells respectively) (figure-1). Decay between w0 and w48 was higher in Fiebig II-IV (98.71% in intact and 98.83% in defective viruses) than in Fiebig V-VI (94.86% in intact and 89.01% in defective viruses). Intact/defective ratio in Fiebig II-IV is lower than in Fiebig V-VI both in w0 (0.54 and 4.2 respectively) and in w48 (0.60 and 1.9 respectively). Total proviral DNA decrease was more pronounced in participants with higher VL at w0 (p=0.014), subtype B (p=0.049) and Fiebig stages II-IV (p=0.002); however, these differences were not statistically significant for intact proviral DNA.
Conclusions
Reservoir, including intact DNA, significantly decreases at w48, after controlling for Fiebig stage, viral subtype or baseline VL. Starting ART at Fiebig II-IV results in a more pronounced reservoir decay and a lower intact/defective ratio at both timepoints than at Fiebig V-VI.
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