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Clin Infect Dis. 2019 May 18. pii: ciz417. doi: 10.1093/cid/ciz417. [Epub ahead of print]

Systematic Review And Meta-Analysis of Treatment Interruptions in HIV-1 Infected Patients Receiving Antiretroviral Therapy: Implications for Future HIV Cure Trials.

Author information

1
Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
2
German Center for Infection Research (DZIF), partner site Bonn-Cologne, Germany.
3
Laboratory of Experimental Immunology, Institute of Virology, University Hospital Cologne, Cologne, Germany.
4
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
5
Labor Dr. Wisplinghoff, Cologne, Germany.
6
Praxis am Ebertplatz, Cologne, Germany.
7
Hannover Medical School, Hannover, Germany.
8
German Center for Infection Research (DZIF), partner site Hannover, Germany.
9
Medical Department II, University Hospital of Frankfurt, Frankfurt, Germany.

Abstract

BACKGROUND:

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

METHODS:

Our analysis included studies reporting on AEs in HIV-1 infected patients undergoing TIs (including ATIs and structured TIs). All interventional and observational studies were reviewed and results extracted based on predefined criteria. Proportion of total AEs were pooled using random-effect models. A meta-regression model was calculated to explore the influence of baseline CD4+ T-cell count, viral load, study type, previous time on combined antiretroviral therapy (cART), and follow-up interval during TIs.

RESULTS:

We identified 1,048 studies, of which 22 studies including 7,104 individuals fulfilled the defined selection criteria. Included studies showed sample sizes between six and 5,472 subjects, with durations of TI cycles ranging from seven days to 27 months. Intervals of HIV-1-RNA testing varied from two days up to three months during TIs. The overall proportion of AEs during TIs >4 weeks was 3% (95% 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=0.01).

CONCLUSION:

We found moderate quality evidence indicating that studies with narrow follow-up intervals did not show a substantial increase of 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 during follow-up.

KEYWORDS:

Analytical treatment interruption; Cure; HIV; Meta-analysis; Systematic Review; Treatment interruption

PMID:
31102444
DOI:
10.1093/cid/ciz417

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