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

## TL;DR

This study shows that higher HIV levels and longer interruptions in treatment do not harm CD4+ T cell recovery when treatment is restarted.

## Contribution

The study demonstrates the safety of flexible treatment interruptions in HIV cure trials regarding CD4+ T cell recovery.

## Key findings

- High peak viral loads did not affect CD4+ T cell counts after ART resumption.
- Duration of viremia did not impair CD4+ T cell recovery following ART restart.
- CD4+ T cell counts remained stable from pre-ATI to post-ATI viral re-suppression.

## Abstract

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.

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.

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).

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.

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.

Summary: The levels and duration of plasma HIV-1 RNA during ATI do not impact CD4+ T cell recovery after ART resumption.