Systematic review of renal and bone safety of the antiretroviral regimen efavirenz, emtricitabine, and tenofovir disoproxil fumarate in patients with HIV infection.
Tenofovir disoproxil fumarate (TDF) is a component of many combinations of antiretroviral treatment (ART) regimens. Although potent and generally well tolerated, TDF may cause renal and bone toxicity. The magnitude of off-target side effects is proposed to be related to tenofovir plasma concentrations, which are affected by food and drug-drug interactions with concomitant antiretrovirals.



To perform a systematic literature review and qualitatively report on renal and bone safety outcomes associated with efavirenz (EFV), emtricitabine (FTC), and TDF (EFV+FTC+TDF) ART.



Embase and PubMed databases were searched for randomized clinical trials and observational cohort studies reporting on HIV treatment with EFV+FTC+TDF. Relevant articles were hand-searched for renal (Grade 3-4 serum creatinine/estimated glomerular filtration rate elevations, renal adverse events [AEs], discontinuation due to renal AEs, and urinary biomarkers) and bone outcomes (bone mineral density [BMD] reductions, bone turnover markers, and fracture), and results compiled qualitatively.



Of 337 retrieved articles, 29 reporting renal and 11 reporting bone outcomes met the review criteria. EFV+FTC+TDF was associated with a low frequency of renal AEs and treatment discontinuations due to renal AEs. Renal AEs were more frequent when TDF was taken with protease inhibitor (PI)- or cobicistat-containing ART. EFV+FTC+TDF was associated with reduced BMD and increased bone turnover markers, but BMD reductions were less than with PI-containing ART. No treatment-related bone fractures were identified.



EFV+FTC+TDF appeared to have a more favorable renal safety profile than TDF administered with a PI or cobicistat. BMD decreased with EFV+FTC+TDF, but no treatment-related fractures were identified.
a Department of Medicine , VA North Texas Health Care System, University of Texas Southwestern Medical Center , Dallas , TX , USA.
Roger
R
Bedimo
b Bristol-Myers Squibb , Plainsboro , NJ , USA.
Lisa
L
Rosenblatt
b Bristol-Myers Squibb , Plainsboro , NJ , USA.
Joel
J
Myers
D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D048588:Benzoxazines / Q000008:administration & dosage; D001847:Bone Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D002986:Clinical Trials as Topic; D003521:Cyclopropanes; D004347:Drug Interactions; D000068679:Emtricitabine / Q000008:administration & dosage; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D015994:Incidence; D007674:Kidney Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D000068698:Tenofovir / Q000008:administration & dosage; D016896:Treatment Outcome
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D000068698:Tenofovir; D000068679:Emtricitabine; C098320:efavirenz
Atripla; Bone disease; Efavirenz; Emtricitabine; Protease inhibitor; Renal disease; Tenofovir