title: Choice of antiretroviral drugs for continued treatment scale-up in a public health approach: what more do we need to know?
abstract: BACKGROUND
  There have been several important developments in antiretroviral treatment in the past two years. Randomized clinical trials have been conducted to evaluate a lower dose of efavirenz (400 mg once daily). Integrase inhibitors such as dolutegravir have been approved for first-line treatment. A new formulation of tenofovir (alafenamide) has been developed and has shown equivalent efficacy to tenofovir in randomized trials. Two-drug combination treatments have been evaluated in treatment-naïve and -experienced patients. The novel pharmacokinetic booster cobicistat has been compared to ritonavir in terms of pharmacokinetics, efficacy and safety. The objective of this commentary is to assess recent developments in antiretroviral drug treatment to determine whether new treatments should be included in new international guidelines.
  
  
  CONCLUSIONS
  The use of first-line treatment with tenofovir and efavirenz at the standard 600 mg once-daily dose should remain the first-choice standard of care treatment. Evidence supporting a switch to efavirenz 400 mg once daily or integrase inhibitors is sufficient to consider these drugs as alternative first-line options, but more data are needed on their use in pregnant women and people with TB co-infection. The use of new formulations of tenofovir is currently too preliminary to justify immediate adoption and scale-up across HIV programmes in low- and middle-income countries. The evidence supporting use of two-drug combinations is not considered strong enough to justify changed recommendations from use of standard triple drug combinations. Cobicistat does not offer significant safety advantages over ritonavir as a pharmacokinetic booster.
  
  
  CONCLUSIONS
  For continued scale-up of antiretroviral treatment in low- and middle-income countries, use of first-line triple combinations including efavirenz 600 mg once daily is supported by the largest evidence base. Additional studies are underway to evaluate new treatments in key populations, and these results may justify changes to these recommendations.
authors: Department of HIV/AIDS, World Health Organization, Geneva, Switzerland; vitoriam@who.int.
authors: Marco
authors: M
authors: Vitoria
authors: Department of Pharmacology and Therapeutics, Liverpool University, Liverpool, UK.
authors: Andrew M
authors: AM
authors: Hill
authors: Department of HIV/AIDS, World Health Organization, Geneva, Switzerland.
authors: Nathan P
authors: NP
authors: Ford
authors: Department of HIV/AIDS, World Health Organization, Geneva, Switzerland.
authors: Meg
authors: M
authors: Doherty
authors: Department of Pharmacology and Therapeutics, Liverpool University, Liverpool, UK.
authors: Saye H
authors: SH
authors: Khoo
authors: St Stephens AIDS Trust, Chelsea and Westminster Hospital, London, UK.
authors: Anton L
authors: AL
authors: Pozniak
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D048588:Benzoxazines / Q000008:administration & dosage; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage; D006801:Humans; D010078:Oxazines; D010757:Phosphorous Acids / Q000008:administration & dosage; D010879:Piperazines; D011634:Public Health; D011728:Pyridones; D019438:Ritonavir / Q000008:administration & dosage; D000099226:Dolutegravir
chemical_list: D000225:Adenine; D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010757:Phosphorous Acids; D010879:Piperazines; D011728:Pyridones; D019438:Ritonavir; D000099226:Dolutegravir; C574165:9-(2-((bis(pivaloyloxymethoxy)phosphinoyl)methoxy)propyl)adenine; C098320:efavirenz
keywords: Universal Access; antiretroviral treatment; integrase inhibitors; non-nucleosides; nucleoside analogues; pregnancy; protease inhibitors; tuberculosis