Impact of analytical treatment interruptions on sexual behaviors: a mixed-methods longitudinal study of women enrolled in an HIV cure-related trial in Durban, South Africa.

BACKGROUND

Analytical treatment interruptions (ATIs) are increasingly used in HIV cure-related trials to assess intervention efficacy.

OBJECTIVE

To assess the impact of participation in ATI-inclusive trials on sexual behaviors and transmission risks among women in Durban, South Africa, and to develop recommendations for safer trial design.

METHODS

From 2022-2025, we conducted a mixed-methods socio-behavioral study embedded within a Phase 2A ATI-inclusive HIV cure-related trial. Nineteen participants completed surveys at four trial timepoints, baseline (T1), pre-ATI (T2), post-ATI (T3), and end of trial (T4), and in-depth interviews at the first three (T1-T3). We summarized quantitative data using medians and percentages and used the Theory of Planned Behavior to analyze the qualitative data.

RESULTS

Participants had strong intentions toward HIV prevention; however, behaviors were inconsistently enacted during the trial. Condom use was highest during the ATI; however, 40% of participants reported never using condoms. Abstinence was not considered an acceptable option within relationships. Disclosure of HIV and ATI participation facilitated prevention behavior but was undermined by HIV-related stigma, while non-disclosure and new sexual behaviors created relationship instability. Prevention was supported by trial staff's responsiveness and close monitoring, which helped build participants' trust.

CONCLUSIONS

For ATI-inclusive trials to reduce HIV transmission risk and social harms, investigators must understand contextual barriers perceived by participants who are expected to enact protective behaviors. Adaptive trial designs that incorporate participant-centered behavioral support, monitor and address emergent harms and facilitate prevention through access to HIV testing and PrEP for partners, must align with participants' evolving realities.