Systematic Review and Meta-analysis of Treatment Interruptions in Human Immunodeficiency Virus (HIV) Type 1-infected Patients Receiving Antiretroviral Therapy: Implications for Future HIV Cure Trials

Abstract

Background: Safety and tolerability of analytical treatment interruptions (ATIs) as a vital part of human immunodeficiency virus type 1 (HIV-1) cure studies are discussed. We analyzed current evidence for the occurrence of adverse events (AEs) during TIs.

Methods: Our analysis included studies that reported on AEs in HIV-1-infected patients undergoing TIs. All interventional and observational studies were reviewed, and results were extracted based on predefined criteria. The proportion of AEs was pooled using random-effects models. Metaregression was used to explore the influence of baseline CD4+ T-cell count, viral load, study type, previous time on combined antiretroviral therapy, and follow-up interval during TIs.

Results: We identified 1048 studies, of which 22 studies including 7104 individuals fulfilled the defined selection criteria. Included studies had sample sizes between 6 and 5472 participants, with durations of TI cycles ranging from 7 days to 27 months. The intervals of HIV-1-RNA testing varied from 2 days to 3 months during TIs. The overall proportion of AEs during TIs >4 weeks was 3% (95% confidence interval [CI], 0%-7%) and was lower in studies with follow-up intervals ≤14 days (0%; 95% CI, 0%-1%) than in studies with wider follow-up intervals (6%; 95% CI, 2%-13%; P value for interaction = .01).

Conclusions: We found moderate-quality evidence indicating that studies with narrow follow-up intervals did not show a substantial increase in AEs during TIs. Our findings indicate that ATI may be a safe strategy as part of HIV-1 cure trials by closely monitoring for HIV-1 rebound.

Keywords: HIV; analytical treatment interruption; meta-analysis.