Adherence and HIV Protection Thresholds for Emtricitabine and Tenofovir Disoproxil Fumarate Preexposure Prophylaxis among Cisgender Women: A Systematic Review.

Autor: Wu L; Department of Global Health, University of Washington, 908 Jefferson Street, Seattle, WA, 98104, USA.; Department of Epidemiology, University of Washington, 3980 15th Ave NE, Seattle, WA, 98195, USA., Niu X; Department of Global Health, University of Washington, 908 Jefferson Street, Seattle, WA, 98104, USA.; Department of Epidemiology, University of Washington, 3980 15th Ave NE, Seattle, WA, 98195, USA., Brunelli MK; School of Public Health, University of Washington, Seattle, WA, USA., Mugwanya KK; Department of Global Health, University of Washington, 908 Jefferson Street, Seattle, WA, 98104, USA. mugwanya@uw.edu.; Department of Epidemiology, University of Washington, 3980 15th Ave NE, Seattle, WA, 98195, USA. mugwanya@uw.edu.
Jazyk: angličtina
Zdroj: Current HIV/AIDS reports [Curr HIV/AIDS Rep] 2024 Oct; Vol. 21 (5), pp. 264-281. Date of Electronic Publication: 2024 Aug 09.
DOI: 10.1007/s11904-024-00705-0
Abstrakt: Purpose of Review: Adherence-concentration-efficacy benchmarks have not been fully characterized for cisgender women using emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) oral daily pre-exposure prophylaxis (PrEP) for HIV prevention.
Recent Findings: We conducted a systematic review to investigate current evidence on the adherence-concentration-efficacy relationship of tenofovir-diphosphate (TFV-DP) derived from FTC/TDF PrEP in dried blood spots (DBS) and peripheral mononuclear cells (PBMC) in cisgender women without HIV, including during pregnancy. We searched for completed and ongoing studies published before May 2024 in PubMed, Embase, Cochrane Library, CINAHL, and clinicaltrial.gov.  Overall, 11 studies assessing adherence benchmarks focusing on (n = 5) or involving (n = 6) cisgender women were included. Women-specific median steady-state TFV-DP concentration for daily dosing ranged from 17 to 51 fmol/10 6 in PBMC and 1389 to 1685 fmol/punch in DBS in non-pregnant women; 50 to 71 fmol/10 6 in PBMC and 583 to 965 fmol/punch in DBS in pregnant women; and 618 to 1406 fmol/punch in DBS in postpartum women. DBS TFV-DP levels were 14-43% lower in pregnancy versus postpartum or non-pregnant periods, but PBMC TFV-DP levels appear to be comparable. Clinical and modeling studies demonstrate effective HIV protection for women taking at least four doses/week of oral TDF-based PrEP, and emerging evidence suggests that systemic drug levels are more likely to be predictive of efficacy than local tissue levels at the site of exposure. The preponderance of emerging evidence points to comparable efficacy and similar adherence requirement for women as men among those with detectable drug levels, although there was an indication that the highest achievable efficacy may be reached at a lower adherence level in men than women. In this review, we found evidence that women-specific TFV-DP adherence benchmarks in DBS and PBMC are within range of US-based historical thresholds derived from healthy men and women. Emerging evidence suggests that imperfect but adequate adherence to oral FTC/TDF PrEP with at least four doses/week provides sufficient HIV protection in cisgender women as it does in MSM, but more data are still needed to refine intrinsic achievable efficacy estimates for cisgender women.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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