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Kidney Function in Oral Pre-Exposure Prophylaxis Users: A Systematic Literature Review and Individual Patient Data Meta-Analysis

17 Pages Posted: 19 Aug 2021

See all articles by Robin Schaefer

Robin Schaefer

World Health Organization (WHO) - Global HIV, Hepatitis and STI Programme

Pedro Amparo da Costa Leite

Oswaldo Cruz Foundation (FIOCRUZ) - Evandro Chagas National Institute of Infectious Diseases (INI)

Ronaldo Silva

Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) - Department of Infectious-Tropical Diseases and Microbiology

Quarraisha Abdool Karim

University of KwaZulu-Natal - Centre for the AIDS Programme of Research in South Africa (CAPRISA)

Christopher Akolo

FHI 360

Carlos F. Caceres

Universidad Peruana Cayetano Heredia; Universidad Peruana Cayetano Heredia - Center for Interdisciplinary Studies in Sexuality, AIDS and Society

Inês Dourado

Federal University of Bahia (UFBA) - Institute of Collective Health

Kimberly Green

Program for Appropriate Technology in Health(PATH) Vietnam

Anita Hettema

Clinton Health Access Initiative - Swaziland

Elske Hoornenborg

Public Health Service of Amsterdam, Department of Infectious Diseases

Smarajit Jana

Durbar Mahilla Samanwaya Committee (DMSC)

Bernhard Kerschberger

Médecins Sans Frontières - Swaziland

Hally Mahler

FHI 360

Sindy Matse

National AIDS Programme

Hamish McManus

University of New South Wales (UNSW) - Kirby Institute

Jean-Michel Molina

University of Paris - INSERM U944

Sushena Reza-Paul

University of Manitoba

Iskandar Azwa

University of Malaya (UM) - Infectious Diseases Unit

Maryam Shahmanesh

Africa Health Research Institute

Doug Taylor

FHI 360

Hamid Vega-Ramírez

Ramón de la Fuente Muñiz National Institute of Psychiatry

Valdiléa G. Veloso

Oswaldo Cruz Foundation (FIOCRUZ) - Evandro Chagas National Institute of Infectious Diseases (INI)

Rachel Baggaley

World Health Organization (WHO) - Global HIV, Hepatitis and STI Programme

Shona Dalal

World Health Organization (WHO) - Global HIV, Hepatitis and STI Programme

More...

Abstract

Background: Previous World Health Organization (WHO) guidance on tenofovir disoproxil fumarate (TDF)-based oral pre-exposure prophylaxis (PrEP) suggests measuring creatinine levels at PrEP initiation and regularly afterwards. Creatinine screening may represent barriers to PrEP implementation and uptake. We systematically reviewed published literature on renal toxicity among PrEP users and conducted an individual patient data meta-analysis (IPDMA) on kidney function among PrEP users in a global data set. 

Methods: Meta-analyses were conducted on published data to estimate pooled relative risks of grade 1+ and 2+ kidney-related adverse events among PrEP users. The IPDMA included data on PrEP users from 19 PrEP programmes. Estimated creatinine clearance at baseline and change in creatinine clearance after PrEP initiation were described by age, gender, and comorbidities. Random-effects regressions estimated risk in decline in creatinine clearance to <60ml/min. 

Findings: Eleven randomised controlled trials on oral PrEP were identified in the literature review. Pooled odds ratio (OR) for grade 1+ and grade 2+ renal adverse events was 1.51 (95% confidence interval [CI]=1.17-1.94) and 2.57 [0.97-6.77], respectively. The IPDMA included 18,676 individuals from 15 countries and 0.42% had abnormal baseline estimated creatinine clearance (<60ml/min) (increasing proportions with increasing age). Longitudinal analyses included 14,368 PrEP users and 2.43% experienced a decline to <60ml/min creatine clearance, with higher risk associated with increasing age and a baseline creatinine clearance of 60-89.99ml/min (adjusted hazard ratio [HR]=8.06 [6.44-11.2]) and <60ml/min (aHR=20.8 [12.8-33.8]). 

Interpretation: Few people screened for TDF-based oral PrEP had a <60ml/min creatinine clearance and renal adverse evets were rare. Older age and baseline creatinine clearance of <90ml/min were associated with clinically significant declines in creatinine clearance. Less frequent or optional screening among younger individuals without kidney-related comorbidities may be appropriate and may reduce barriers to PrEP implementation and use. 

Funding Information: Unitaid, Bill & Melinda Gates Foundation, WHO

Declaration of Interests: The authors declare no conflict of interests.

Suggested Citation

Schaefer, Robin and da Costa Leite, Pedro Amparo and Silva, Ronaldo and Karim, Quarraisha Abdool and Akolo, Christopher and Caceres, Carlos F. and Dourado, Inês and Green, Kimberly and Hettema, Anita and Hoornenborg, Elske and Jana, Smarajit and Kerschberger, Bernhard and Mahler, Hally and Matse, Sindy and McManus, Hamish and Molina, Jean-Michel and Reza-Paul, Sushena and Azwa, Iskandar and Shahmanesh, Maryam and Taylor, Doug and Vega-Ramírez, Hamid and Veloso, Valdiléa G. and Baggaley, Rachel and Dalal, Shona, Kidney Function in Oral Pre-Exposure Prophylaxis Users: A Systematic Literature Review and Individual Patient Data Meta-Analysis. Available at SSRN: https://ssrn.com/abstract=3899107 or http://dx.doi.org/10.2139/ssrn.3899107

Robin Schaefer (Contact Author)

World Health Organization (WHO) - Global HIV, Hepatitis and STI Programme ( email )

Geneva
Switzerland

Pedro Amparo Da Costa Leite

Oswaldo Cruz Foundation (FIOCRUZ) - Evandro Chagas National Institute of Infectious Diseases (INI) ( email )

Av. Brasil 4365
Rio de Janeiro, 21040-360
Brazil

Ronaldo Silva

Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) - Department of Infectious-Tropical Diseases and Microbiology

Negrar
Italy

Quarraisha Abdool Karim

University of KwaZulu-Natal - Centre for the AIDS Programme of Research in South Africa (CAPRISA) ( email )

2nd Floor, Doris Duke Medical Research Institute
719 Umbilo Road
Durban, 4041
South Africa

Christopher Akolo

FHI 360 ( email )

Washington, DC
United States

Carlos F. Caceres

Universidad Peruana Cayetano Heredia

Lima
Peru

Universidad Peruana Cayetano Heredia - Center for Interdisciplinary Studies in Sexuality, AIDS and Society

Inês Dourado

Federal University of Bahia (UFBA) - Institute of Collective Health ( email )

Kimberly Green

Program for Appropriate Technology in Health(PATH) Vietnam

Vietnam

Anita Hettema

Clinton Health Access Initiative - Swaziland ( email )

Mbabane
Swaziland

Elske Hoornenborg

Public Health Service of Amsterdam, Department of Infectious Diseases ( email )

Smarajit Jana

Durbar Mahilla Samanwaya Committee (DMSC)

India

Bernhard Kerschberger

Médecins Sans Frontières - Swaziland ( email )

Mbabane
Swaziland

Hally Mahler

FHI 360

Washington, DC
United States

Sindy Matse

National AIDS Programme ( email )

Swaziland

Hamish McManus

University of New South Wales (UNSW) - Kirby Institute ( email )

Sydney
Australia

Jean-Michel Molina

University of Paris - INSERM U944 ( email )

Paris
France

Sushena Reza-Paul

University of Manitoba

501 F.A. Bldg
Winnipeg R3T 5V4, R3T 5V5
Canada

Iskandar Azwa

University of Malaya (UM) - Infectious Diseases Unit ( email )

Kuala Lumpur
Malaysia

Maryam Shahmanesh

Africa Health Research Institute ( email )

719 Umbilo Road
K-RITH Tower Building, level 3
Durban, KwaZulu-Natal 4001
South Africa

Doug Taylor

FHI 360

Durham, NC
United States

Hamid Vega-Ramírez

Ramón de la Fuente Muñiz National Institute of Psychiatry ( email )

Mexico City
Mexico

Valdiléa G. Veloso

Oswaldo Cruz Foundation (FIOCRUZ) - Evandro Chagas National Institute of Infectious Diseases (INI) ( email )

Av. Brasil 4365
Rio de Janeiro, 21040-360
Brazil

Rachel Baggaley

World Health Organization (WHO) - Global HIV, Hepatitis and STI Programme

Geneva
Switzerland

Shona Dalal

World Health Organization (WHO) - Global HIV, Hepatitis and STI Programme ( email )

Geneva
Switzerland

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