The impact of magnitude and duration of plasma viremia during analytical treatment interruptions on CD4+ T cell recovery after ART resumption

Objective

Analytical treatment interruption (ATI) is crucial for assessing the efficacy of HIV-1 cure strategies. Recent cure studies have implemented more flexible ART restart criteria, permitting higher plasma viral loads (pVLs) for longer periods, which could potentially impair CD4⁺ T cell recovery even following ART resumption.

Design

We conducted a pooled analysis of six clinical HIV cure trials that included an ATI to evaluate the impact of magnitude and duration of plasma viremia during ATI on CD4⁺ T cell dynamics.

Methods

Wilcoxon signed-rank or rank-sum test was used to analyze differences in CD4⁺ T cell counts from 3 time points: 1) pre-ATI, 2) ART resumption, and 3) ART-induced viral re-suppression, with analyses stratified by peak pVL (≤10,000 or >10,000 copies/mL) or by duration of viremia (0–14, 15–28, or >28 days).

Results

Among 114 participants, we found no change in CD4⁺ T cell counts from pre-ATI to post-ATI (at viral re-suppression, P = 0.80). We also found no impact of low (≤10,000 copies/mL) versus high (>10,000 copies/mL) peak viremia on CD4⁺ T cell counts at the time of ART resumption or viral re-suppression (P = 0.48, P = 0.88, respectively). Similarly, the change in CD4⁺ T cell count from pre-ATI to viral re-suppression did not differ significantly between individuals with viremia lasting 0–14 days versus those with >28 days.

Conclusion

In our pooled analysis, high peak rebound pVLs and longer duration of viremia did not impair CD4⁺ T cell recovery following the resumption of ART, supporting the safety of more flexible ATIs in HIV-1 cure trials.