Background:
As HIV cure remains a high priority for HIV research, analytical treatment interruption (ATI) in clinical studies remain vital to understand mechanisms for ART-free HIV remission. However, the impact of short-term treatment interruption on the intact HIV reservoir remains unclear.
Methods:
We evaluated participants who underwent treatment interruption as part of the ACTG A5345 trial. Participants had been on suppressive ART ≥2 years and comprised two groups: individuals who initiated ART during chronic infection (n=33) and during early infection (n=12). HIV reservoir levels were measured at three time points: pre-ATI, during the ATI and ~ 24 weeks of viral resuppression on ART (Step 3). We quantified levels of unspliced cell-associated RNA (CA-RNA), intact, defective, and total proviruses by the intact proviral DNA assay (IPDA). Residual viremia was measured by the integrase single-copy assay (iSCA). Wilcoxon rank-sum test was used for between-group comparison and Wilcoxon signed-ranks test for within-person comparison.
Results:
The median duration of ATI was 4 weeks in the study. Compared to the pre-ATI time point, levels of intact, defective, and total HIV DNA levels were significantly increased during the ATI for both the early and chronic-treated groups. Approximately 24 weeks after viral resuppression on ART, almost all levels of proviral measures (including intact and total HIV DNA) had returned to their baseline levels with no significant differences compared to the pre-ATI time point for both early and chronic-treated participants (Figure). Compared to pre-ATI, there was also no significant increase in CA-RNA levels 24 weeks after viral resuppression on ART. At all time points, levels of CA-RNA, intact, defective, and total HIV DNA levels were higher in chronic-treated compared to early-treated individuals. Early after ATI (median 1 week), higher levels of residual viremia by the iSCA was significantly associated with a shorter time to viral rebound ≥1000 HIV-1 RNA copies/mL amongst all participants (Spearman r = -0.60, p<0.01).
Conclusions:
Short-term ATI does not irreversibly change the reservoir size as reflected by stable levels of CA-RNA, or intact and total HIV DNA after viral resuppression. High-level viral rebound can be predicted by early signals of very low viremia.
