# Long-term immune recovery under continuous antiretroviral therapy (ART) among ART-naive people living with HIV in two cohorts in Germany

## TL;DR

This study shows that most HIV patients on long-term treatment see improved immune function, but only about a third reach optimal recovery levels after ten years.

## Contribution

The study provides new insights into long-term immune recovery patterns in ART-naive HIV patients over a decade of treatment.

## Key findings

- After ten years of ART, median CD4 counts increased to 630 cells/µl and CD4/CD8 ratio to 0.84.
- Only 32% of patients achieved both CD4 ≥ 800 cells/µl and CD4/CD8 ratio ≥ 1 after ten years.
- Higher baseline CD4 counts predicted better immune recovery outcomes.

## Abstract

Immune recovery among people living with HIV (PWHIV) receiving antiretroviral therapy (ART) is determined analysing CD4 cell counts and the CD4/CD8 ratio. Recovery to ≥ 800 CD4 cells/µl and CD4/CD8 ratio ≥ 1 was associated with favourable outcomes. We investigated immune recovery over 10 years among ART-naive PWHIV on ART.

Data were obtained from two German HIV cohorts, the HIV-1 Seroconverter study and the ClinSurv-HIV study, between 2003 and 2018. We included ART-naïve PWHIV starting with continuous ART and analysed CD4 cell counts and the CD4/CD8 ratio. The time to reaching immune thresholds was investigated using Kaplan–Meier analyses with inverse probability censoring weights.

Overall, 8,927 participants were included. At baseline, PWHIV had a median CD4 cell count of 257 (interquartile range [IQR] 124–393) cells/µl and CD4/CD8 ratio of 0.26 (IQR 0.14–0.43). After ten years, median CD4 counts increased to 630 (IQR 474–811) cells/µl and CD4/CD8 ratio to 0.84 (IQR 0.61–1.11). PWHIV with higher baseline CD4 values and without viral failure had higher median CD4 counts and CD4/CD8 ratios. The cumulative probability of achieving a CD4 count ≥ 800 cells/µl and/or CD4/CD8 ratio ≥ 1 over 10 years of ART were 54% for the CD4 threshold, 53% for the CD4/CD8 ratio threshold, and 32% for both thresholds. CD4 at baseline was identified as a predictor to achieve immune recovery in all models.

Early diagnosis and treatment, as well as effective antiviral therapy without viral failure, should be considered to achieve long-term immune recovery among PWHIV.

The online version contains supplementary material available at 10.1007/s15010-026-02740-y.