title: Key toxicity issues with the WHO-recommended first-line antiretroviral therapy regimen.
abstract: WHO recommends tenofovir, efavirenz, and lamivudine or emtricitabine for first-line antiretroviral therapy (ART) in adults, which replaced more toxic regimens using stavudine, zidovudine or nevirapine. Areas covered: We searched Pubmed to identify observational studies and randomized controlled trials reporting toxicity of these antiretrovirals published between 2011 and 2016, and hand-searched abstracts presented at major HIV conferences in 2015 and 2016, focusing on data from sub-Saharan Africa. Tenofovir's nephrotoxicity manifests as mild renal tubular dysfunction (common and of uncertain clinical significance), acute kidney injury (rare), and chronic declining glomerular filtration rate (common). African studies, which include high proportions of patients with renal dysfunction from opportunistic diseases, report population improvement in renal function after starting tenofovir-based ART. Tenofovir modestly decreases bone mineral density, and there is emerging data that this increases fracture risk. Efavirenz commonly causes early self-limiting neuropsychiatric toxicity and hypersensitivity rashes. Recent studies have highlighted its long-term neuropsychiatric effects, notably suicidality and neurocognitive impairment, and metabolic toxicities (dyslipidemia, dysglycemia, and lipoatrophy). We point out the challenges clinicians face in the recognition and attribution of adverse drug reactions. Expert commentary: Tenofovir and efavirenz are generally well tolerated, but both are associated with potentially serious toxicities. Pharmacovigilance systems in resource-limited settings with high HIV burden should be strengthened.
authors: a Division of Clinical Pharmacology, Department of Medicine , University of Cape Town , Cape Town , South Africa.
authors: Johannes P
authors: http://orcid.org/0000-0002-3511-1259
authors: JP
authors: Mouton
authors: a Division of Clinical Pharmacology, Department of Medicine , University of Cape Town , Cape Town , South Africa.
authors: Karen
authors: K
authors: Cohen
authors: a Division of Clinical Pharmacology, Department of Medicine , University of Cape Town , Cape Town , South Africa.
authors: Gary
authors: http://orcid.org/0000-0003-3080-6606
authors: G
authors: Maartens
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects; D003521:Cyclopropanes; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D000068698:Tenofovir / Q000008:administration & dosage / Q000009:adverse effects; D014944:World Health Organization
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D000068698:Tenofovir; C098320:efavirenz
keywords: Antiretroviral therapy; adverse drug reactions; cumulative toxicity; efavirenz; emtricitabine; lamivudine; overlapping toxicity; tenofovir; toxicity