| Liu et al. 3131. Liu AY, Vittinghoff E, Sellmeyer DE, Irvin R, Mulligan K, Mayer K, et al. Bone mineral density in HIV-negative men participating in a tenofovir pre-exposure prophylaxis randomized clinical trial in San Francisco. PLoS One 2011; 6:e23688. (2011) |
US CDC PrEP |
February 2005 to July 2007/January 2005 to July 2007 |
Yes |
Yes |
Cockroft-Gault creatinine clearance; spot urine calcium/creatinine ratio |
Each quarterly visit |
None |
| Grohskopf et al. 3434. Grohskopf LA, Chillag KL, Gvetadze R, Liu AY, Thompson M, Mayer KH, et al. Randomized trial of clinical safety of daily oral tenofovir disoproxil fumarate among HIV-uninfected men who have sex with men in the United States. J Acquir Immune Defic Syndr 2013; 64:79-86. (2013) |
US CDC PrEP |
February 2005 to July 2007/January 2005 to July 2007 |
Yes |
Yes |
Cockcroft-Gault creatinine clearance; serum creatinine; phosphorus |
Weeks 1, 3, 6, 9, 12, 15, 18, 21, and 24 |
DAIDS toxicity tables (January 2004) |
| Grant et al. 1010. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010; 363:2587-99. (2010) |
iPrEx |
July 2007 to December 2009 |
Yes |
Yes |
Serum creatinine; Cockcroft-Gault creatinine clearance; urine dipstick testing for protein and glucose; leukocyte esterase testing; urine phosphorus, calcium, creatinine, uric acid, protein, and glucose |
Weeks 4, 8, 12, 16, and 24 and then every 12 weeks |
Grade 1 or higher creatinine toxicity; grade 3 or higher phosphorous toxicity; grade 2, 3, or 4 laboratory; DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (2004) |
| Solomon et al. 3030. Solomon MM, Lama JR, Glidden DV, Mulligan K, McMahan V, Liu AY, et al. Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis. AIDS 2014; 28:851-9. (2014) |
iPrEx |
July 2007 to December 2009 |
Yes |
Yes |
Serum creatinine; Cockcroft-Gault creatinine clearance; urine dipstick testing for protein and glucose; leukocyte esterase testing; urine phosphorus, calcium, creatinine, uric acid, protein, and glucose |
Weeks 4, 8, 12, 16, and 24 and then every 12 weeks |
Grade 1 or higher creatinine toxicity; grade 3 or higher phosphorous toxicity; grade 2, 3, or 4 laboratory; DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (2004) |
| Deutsch et al. 2727. Deutsch MB, Glidden DV, Sevelius J, Keatley J, McMahan V, Guanira J, et al. HIV pre-exposure prophylaxis in transgender women: a subgroup analysis of the iPrEx trial. Lancet HIV 2015; 2:e512-9. (2015) |
iPrEx |
July 2007 to December 2009 |
Yes |
Yes |
Serum creatinine; Cockcroft-Gault creatinine clearance; urine dipstick testing for protein and glucose; leukocyte esterase testing; urine phosphorus, calcium, creatinine, uric acid, protein, and glucose |
Weeks 4, 8, 12, 16, and 24 and then every 12 weeks |
Grade 1 or higher creatinine toxicity; grade 3 or higher phosphorous toxicity; grade 2, 3, or 4 laboratory; DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (2004) |
| Liu et al. 3939. Liu AY, Cohen SE, Vittinghoff E, Anderson PL, Doblecki-Lewis S, Bacon O, et al. Preexposure prophylaxis for HIV infection integrated with municipal- and community-based sexual health services. JAMA Intern Med 2016; 176:75-84. (2016) |
US PrEP Demonstration Project |
October 1, 2012, to January 23,2014 |
Yes |
|
Cockcroft-Gault creatinine clearance and eGFR (CKD-EPI); urine protein dipstick test |
Weeks 4, 12, 24, 36, and 48 |
DAIDS adverse event grading table version 1.0, December 2004, and the DAIDS Male Genital Grading Table |
| Tang et al. 4040. Tang EC, Vittinghoff E, Anderson PL, Cohen SE, Doblecki-Lewis S, Bacon O, et al. Changes in kidney function associated with daily tenofovir disoproxil fumarate/emtricitabine for HIV preexposure prophylaxis use in the United States Demonstration Project. J Acquir Immune Defic Syndr 2018; 77:193-8. (2018) |
US PrEP Demonstration Project |
October 1, 2012, to January 23,2014 |
Yes |
|
Cockcroft-Gault creatinine clearance and eGFR (CKD-EPI) Urine protein dipstick test |
Weeks 4, 12, 24, 36, and 48 |
DAIDS adverse event grading table version 1.0, December 2004, and the DAIDS Male Genital Grading Table |
| McCormack et al. 2828. McCormack S, Dunn DT, Desai M, Dolling DI, Gafos M, Gilson R, et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet 2016; 387:53-60. (2016) |
PROUD |
November 2012 to October 2016 |
Yes |
|
Serum creatinine; urine protein dipstick test |
Annualy and every 3 months |
None |
| Hosek et al. 3838. Hosek SG, Siberry G, Bell M, Lally M, Kapogiannis B, Green K, et al. The acceptability and feasibility of an HIV preexposure prophylaxis (PrEP) trial with young men who have sex with men. JAIDS J Acquir Immune Defic Syndr 2013; 62:447-56. (2013) |
PrEPare ATN 08 3MV |
August 2005 to November 2006 |
Yes |
Yes |
Hepatic and pancreatic function tests; urine dipstick testing for protein and glucose |
Every 4 weeks for 24 weeks |
Expedited Adverse Event Reporting (grade 2 and higher) |
| Hosek et al. 3636. Hosek SG, Landovitz RJ, Kapogiannis B, Siberry GK, Rudy B, Rutledge B, et al. Safety and feasibility of antiretroviral preexposure prophylaxis for adolescent men who have sex with men aged 15 to 17 years in the United States. JAMA Pediatr 2017; 171:1063-71. (2017) |
PrEPare |
January to September 2013 |
Yes |
Yes |
Renal function: phosphate, blood urea nitrogen, creatinine, and urine dipstick testing for protein and glucose; pancreatic function: amylase; hepatic function: AST, ALT, alcaline phosphatase, total bilirubin, and direct bilirubin |
Monthly in the first quarter (weeks 4, 8, and 12) and then quarterly until 48 weeks |
ATN adverse event severity grading table for adolescents (October 2006 to March 2011)/Manual for Expedited Reporting of Adverse Events to DAIDS (version 2.0, March 2011) |
| Hosek et al. 3737. Hosek SG, Rudy B, Landovitz R, Kapogiannis B, Siberry G, Rutledge B, et al. An HIV preexposure prophylaxis demonstration project and safety study for young MSM. J Acquir Immune Defic Syndr 2017; 74:21-9. (2017) |
PrEPare |
August 2013 to September 2014 |
Yes |
Yes |
Renal function: phosphate, blood urea nitrogen, creatinine, and urine dipstick testing for protein and glucose; pancreatic function: amylase; hepatic function: AST, ALT, alcaline phosphatase, total bilirubin, and direct bilirubin |
Monthly in the first quarter (weeks 4, 8, and 12) and then quarterly until 48 weeks |
ATN adverse event severity grading table for adolescents (October 2006 to March 2011)/Manual for Expedited Reporting of Adverse Events to DAIDS (version 2.0, March 2011) |
| Havens et al. 3535. Havens PL, Stephensen CB, Van Loan MD, Schuster GU, Woodhouse LR, Flynn PM, et al. Decline in bone mass with tenofovir disoproxil fumarate/emtricitabine is associated with hormonal changes in the absence of renal impairment when used by HIV-uninfected adolescent boys and young men for HIV preexposure prophylaxis. Clin Infect Dis 2017; 64:317-25. (2017) |
ATN 117 |
December 2012 to October 2014 |
Yes |
Yes |
Serum creatinine, albumin, calcium, phosphate, glucose, protein, and retinol binding protein |
Weeks 4, 8, 12, 24, 36, and 48 |
None |
| Grant et al. 2929. Grant RM, Mannheimer S, Hughes JP, Hirsch-Moverman Y, Loquere A, Chitwarakorn A, et al. Daily and nondaily oral preexposure prophylaxis in men and transgender women who have sex with men: the human immunodeficiency virus prevention trials network 067/ADAPT Study. Clin Infect Dis 2018; 66:1712-21. (2018) |
067/ADAPT Study |
July 4, 2012, to May 6, 2014 |
Yes |
Yes |
Renal function: estimated creatinine clearance, phosphate; hepatic function: AST and ALT |
Weeks 4, 10, 18, and 30 |
None |
| Wheeler et al. 3333. Wheeler DP, Fields SD, Beauchamp G, Chen YQ, Emel LM, Hightow-Weidman L, et al. Pre-exposure prophylaxis initiation and adherence among black men who have sex with men (MSM) in three US cities: results from the HPTN 073 study. J Int AIDS Soc 2019; 22:e25223. (2019) |
HPTN 073 |
February 2013 to September 2014 |
Yes |
|
Cockcroft-Gault creatinine clearance; urine dipstick testing for protein and glucose |
At screening, 4 and 13 weeks after inclusion, and then quarterly; at screening and quarterly after inclusion |
None |
| Mayer et al. 3232. Mayer KH, Molina J-M, Thompson MA, Anderson PL, Mounzer KC, De Wet JJ, et al. Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet 2020; 396:239-54. (2020) |
DISCOVER |
September 13, 2016, to June 30, 2017 |
Yers |
|
Cockcroft-Gault creatinine clearance; urinary RBP; lipids and fasting glucose; urine protein and urine protein to creatinine ratio |
Weeks 4 and 12 and then every 12 weeks |
None |
| Ogbuagu et al. 4141. Ogbuagu O, Ruane PJ, Podzamczer D, Salazar LC, Henry K, Asmuth DM, et al. Long-term safety and efficacy of emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV-1 pre-exposure prophylaxis: week 96 results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet HIV 2021; 8:e397-407. (2021) |
DISCOVER |
September 13, 2016, to June 30, 2017 |
Yes |
|
Cockcroft-Gault creatinine clearance ; urinary RBP; lipids and fasting glucose; urine protein and urine protein to creatinine ratio |
Weeks 4 and 12 and then every 12 weeks |
None |
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PrEP: pre-exposure prophylaxis. Note: the reasons for excluding publications can be accessed in the Supplementary Material 3 (
Domains: D1 - bias due to confounding; D2 - bias in selection of participants into the study; D3 - bias in classification of interventions; D4 - bias due to deviations from intended interventions; D5 - bias due to missing data; D6 - bias in measurement of outcomes; D7 - bias in selection of the reported result.
95%CI: 95% confidence interval; RR: relative risk. * The weights are from the random effects model; ** The weights are from the random effects model; continuity correction applied to studies with zero cells; *** The weights and the test for heterogeneity between subgroups are from the random effects model.