Quality of Life During HIV ATIs: An Unexpected Finding

Pausing antiretroviral therapy (ART) is central to HIV cure research. Analytical treatment interruptions (ATIs) let investigators observe viral rebound and test experimental strategies in the absence of suppressive therapy. For participants, however, an ATI carries real costs, like the prospect of rebound viremia, concern about transmission, and the temporary loss of viral suppression.

Little quantitative evidence exists on whether these burdens erode perceived health. A 2026 analysis in HIV Research & Clinical Practice offers a counterintuitive answer: health-related quality of life (HRQOL) rose modestly over the course of ATI-inclusive studies, and baseline depressive symptoms, anxiety, and resilience each shaped how participants fared.

Tracking Quality of Life Across Two ATI Studies
Investigators pooled data from 17 patients with HIV enrolled in two University of California, San Francisco studies: the UCSF SCOPE Analytic Treatment Interruption Study (n=11) and the UCSF-amfAR Combination Trial (n=6). SCOPE-ATI sought biomarkers predictive of viral rebound and involved no experimental intervention, and the amfAR trial tested whether a combination intervention could sustain viral control off of ART. Interruptions lasted an average of approximately 70 and 308 days, respectively. Participants averaged 51.2 years of age; 70.6% were White and 88.2% were cisgender men.

HRQOL was captured on the EuroQol visual analogue scale (0–100) at four points: baseline, immediately before ATI, at ART restart, and at study completion. Depressive symptoms, trait-based anxiety, and resilience were measured at baseline with validated instruments. Frequentist and Bayesian linear mixed-effects models assessed change over time and psychosocial associations.

Quality of Life Improved Despite Treatment Interruption
Investigators had hypothesized that interrupting therapy might erode perceived health. Instead, HRQOL actually increased modestly over time (β=0.63, p=0.016).

Mean scores moved from 78.9 at baseline to 80.9 before ATI and 85.1 at ART restart, then eased to 81.2 at study completion. The group average masked considerable heterogeneity: some participants improved, while others held steady or declined.

The finding stands out against the well-documented link between detectable viremia and lower quality of life. The authors propose that close clinical monitoring, regular contact with study staff, and a sense of purpose in advancing cure research may have offset part of the psychosocial burden of interruption. These mechanisms, however, were not directly tested.

Anxiety and Depression Linked to Lower Perceived Health
Participants entering with more depressive symptoms reported lower HRQOL across visits (β=−1.00, p=0.048), although depressive symptoms over time approached but didn’t reach significance (β=0.10, p=0.055). The relationship was stronger for anxiety: participants with higher baseline anxiety consistently reported poorer perceived health across study visits, with trait-based anxiety showing a more robust inverse association (β=−1.18, p=0.001). Bayesian analyses supported this finding (95% credible interval, −1.94 to −0.48), while the results for depressive symptoms were less conclusive because the credible interval included zero.

Higher Resilience, Steeper Improvement
Resilience behaved differently. Baseline scores were not independently associated with HRQOL, but they significantly moderated change over time (time x resilience β=0.36, p=.040). In the model that included this interaction, participants with higher resilience began with lower HRQOL yet improved more steeply, narrowing the gap as the study progressed. However, the Bayesian credible interval for the interaction narrowly included zero (95% credible interval, −0.01 to 0.71), so this finding should be interpreted as preliminary.

Weighing the Evidence from a Small Cohort
The analysis included only 17 participants, limiting both statistical power and generalizability. Plus, multiple exploratory models were run without correction for multiple comparisons, raising the risk of chance findings. The cohort was predominantly White and cisgender male and likely enriched for highly motivated research volunteers, further narrowing applicability.

Critically, the design cannot isolate the effect of ATIs themselves. The observed trajectories may reflect the broader research experience, including clinical monitoring and participant support, as much as the interruption.

Supporting Participant Well-Being in Cure Trials
The findings make a case for pairing psychosocial assessment with biomedical monitoring in ATI-inclusive protocols. Baseline screening for depressive symptoms and anxiety could flag participants who need added support. Resilience-oriented strategies, such as coping skills training and peer support, merit formal evaluation.

Larger, more diverse studies are needed to test whether targeted psychosocial interventions can improve HRQOL during treatment interruption. But for clinicians and cure researchers, the practical message is that participant well-being extends beyond viral load and safety monitoring. Accounting for both psychological vulnerability and adaptive capacity may help build research environments that better support people through an ATI.

Reference
Meanley S, Ahmed A, Lisha NE, et al. Health-related quality of life trajectories during analytical treatment interruptions in HIV cure-related studies and the influence of depression, anxiety, and resilience. HIV Res Clin Pract. 2026;27(1):2715800. doi:10.1080/25787489.2026.2715800