Duration of Antiretroviral Therapy Adherence Interruption Is Associated With Risk of Virologic Rebound as Determined by Real-Time Adherence Monitoring in Rural Uganda

Abstract

Background: Antiretroviral therapy (ART) adherence interruptions have been associated with viral rebound; however, the true risk is unknown because HIV RNA has never been measured during ongoing interruptions.

Methods: The Uganda AIDS Rural Treatment Outcomes Study is an observational longitudinal cohort of adults initiating ART. We monitored adherence with the device that wirelessly transmits records of device openings, and routinely assessed HIV RNA quarterly. When lapses of 48+ hours between device openings were detected, we made unannounced visits to participants to investigate the cause and assess HIV RNA. Generalized estimating equation logistic regressions were used to assess factors associated with viral rebound.

Results: We followed 479 participants (median: 25 months per participant). Most were women (72%), median age was 36 years, median pre-ART CD4 count was 198 cells per microliter, median pre-ART HIV RNA level was 5.0 log10 copies per milliliter, and median duration of prior viral suppression was 13 months. A total of 587 adherence interruptions followed confirmed prior viral suppression, of which 13 (2%) had detectable viral rebound. Viral rebound was associated with duration of adherence interruption (odds ratio: 1.25 for each day beyond 48 hours; P = 0.007) and 30-day adherence before the interruption (odds ratio: 0.73; P = 0.02).

Discussion: This article is the first demonstration of HIV RNA rebound during adherence interruptions objectively measured in real time. Odds of viral rebound increased by 25% with each day beyond 48 hours. Real-time adherence monitoring was feasible in a sub-Saharan African setting. Further research should assess the potential for real-time adherence interventions to sustain adherence to affordable first-line regimens.

Conflict of interest statement

Conflicts of interest : The authors have no conflicts of interest to disclose.

Figures

Figure 1

Identification of adherence interruptions for the analysis of the relationship between duration of interruption and viral rebound.

Figure 2

Association between detectable routine HIV RNA (collected quarterly) and overall adherence for participants in their first year of ART (N= 237; OR for

Figure 3

Association between duration of adherence interruption and viral rebound. A total of 587 interruptions were seen among 261 of the total 479 participants (54%). Viremia exceeded 5% of interruptions lasting longer than seven days. Twenty-one interruptions (3%) were longer than 14 days, none of which had detectable HIV RNA during the interruption or at the subsequent routine quarterly assessment.