Schaefer, Robin and Amparo da Costa Leite, Pedro Henrique and Silva, Ronaido and Karim, Quarraisha Abdool and Akolo, Christopher and Caceres, Carlos F. and Dourado, Ines and Green, Kimberly and Hettema, Anita and Hoornenborg, Elske and Jana, Smarajit and Kerschberger, Bernhard and Mahler, Holly and Matse, Sindy and McManus, Hamish and Molina, Jean-Michel and Reza-Paul, Sushena and Raja Azwa, Raja Iskandar Shah and Shahmanesh, Maryam and Taylor, Doug and Vega-Ramirez, Hamid and Veloso, Valdilea G. and Baggaley, Rachel and Dalal, Shona (2022) Kidney function in tenofovir disoproxil fumarate-based oral pre-exposure prophylaxis users: a systematic review and meta-analysis of published literature and a multi-country meta-analysis of individual participant data. The Lancet HIV, 9 (4). E242-E253. ISSN 2352-3018, DOI https://doi.org/10.1016/S2352-3018(22)00004-2.
Full text not available from this repository.Abstract
Background Previous WHO guidance on tenofovir disoproxil fumarate-based oral pre-exposure prophylaxis (PrEP) suggests measuring creatinine levels at PrEP initiation and regularly afterwards, which might represent barriers to PrEP implementation and uptake. We aimed to systematically review published literature on kidney toxicity among tenofovir disoproxil fumarate-based oral PrEP users and conducted an individual participant data meta-analysis (IPDMA) on kidney function among PrEP users in a global implementation project dataset. Methods In this systematic review and meta-analysis we searched PubMed up to June 30, 2021, for randomised controlled trials (RCTs) or cohort studies that reported on graded kidney-related adverse events among oral PrEP users (tenofovir disoproxil fumarate-based PrEP alone or in combination with emtricitabine or lamivudine). We extracted summary data and conducted meta-analyses with random-effects models to estimate relative risks of grade 1 and higher and grade 2 and higher kidney-related adverse events, measured by elevated serum creatinine or decline in estimated creatinine clearance or estimated glomerular filtration rate. The IPDMA included (largely unpublished) individual participant data from 17 PrEP implementation projects and two RCTs. Estimated baseline creatinine clearance and creatinine clearance change after initiation were described by age, gender, and comorbidities. We used random-effects regressions to estimate the risk in decline of creatinine clearance to less than 60 mL/min. Findings We identified 62 unique records and included 17 articles reporting on 11 RCTs with 13 523 participants in meta-analyses. PrEP use was associated with increased risk of grade 1 and higher kidney adverse events (pooled odds ratio OR] 1 center dot 49, 95% CI 1 center dot 22-1 center dot 81; I-2=25%) and grade 2 and higher events (OR 1 center dot 75, 0 center dot 68-4 center dot 49; I-2=0%), although the grade 2 and higher association was not statistically significant and events were rare (13 out of 6764 in the intervention group vs six out of 6782 in the control group). The IPDMA included 18 676 individuals from 15 countries (1453 7 center dot 8%] from RCTs) and 79 (0 center dot 42%) had a baseline estimated creatinine clearance of less than 60 mL/min (increasing proportions with increasing age). Longitudinal analyses included 14 368 PrEP users and 349 (2 center dot 43%) individuals had a decline to less than 60 mL/min creatinine clearance, with higher risks associated with increasing age and baseline creatinine clearance of 60 center dot 00-89 center dot 99 mL/min (adjusted hazard ratio aHR] 8 center dot 49, 95% CI 6 center dot 44-11 center dot 20) and less than 60 mL/min (aHR 20 center dot 83, 12 center dot 83-33 center dot 82). Interpretation RCTs suggest that risks of kidney-related adverse events among tenofovir disoproxil fumarate-based oral PrEP users are increased but generally mild and small. Our global PrEP user analysis found varying risks by age and baseline creatinine clearance. Kidney function screening and monitoring might focus on older individuals, those with baseline creatinine clearance of less than 90 mL/min, and those with kidney-related comorbidities. Less frequent or optional screening among younger individuals without kidney-related comorbidities may reduce barriers to PrEP implementation and use. Copyright (c) 2022 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products, or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.
| Item Type: | Article |
|---|---|
| Funders: | Unitaid, Bill & Melinda Gates Foundation CGIAR, United States Department of Health & Human Services National Institutes of Health (NIH) - USA, United States Agency for International Development (USAID) |
| Uncontrolled Keywords: | Renal-function; Declinecreatinine clearance; HIV-infection; Antiretroviral prophylaxis; Bangkok tenofovir; Men; Risk; Dysfunction; Prevention; Exretion |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 13 Oct 2023 07:30 |
| Last Modified: | 13 Oct 2023 07:30 |
| URI: | http://eprints.um.edu.my/id/eprint/42020 |
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