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Nucleoside reverse transcriptase inhibitor-reducing strategies in HIV treatment: assessing the evidence.
- Source :
-
HIV medicine [HIV Med] 2018 Jan; Vol. 19 (1), pp. 18-32. Date of Electronic Publication: 2017 Jul 24. - Publication Year :
- 2018
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Abstract
- Antiretroviral (ARV) therapy, comprising a backbone of two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) plus another ARV, is the recognized standard of care (SOC), which has helped extend life expectancy in people living with HIV. In a quest to reduce lifelong drug exposure and minimize or avoid the toxicity of NRTIs, "NRTI-reducing" regimens have been investigated. This descriptive review assessing the results of NRTI-reducing strategies from the largest randomized trials focuses on virological efficacy, resistance, regimen safety (in terms of bone mineral density, renal function, lipids and central nervous system function) and simplicity. The review considers efficacy across various NRTI-sparing strategies, for example an integrase strand transfer inhibitor (INSTI) plus a ritonavir-boosted protease inhibitor (PI/r) or PI/r + lamivudine (3TC), in both naïve and switch regimes. Of 10 key studies in treatment-naïve adults assessing five NRTI-reducing strategies, only four studies demonstrated noninferiority vs. SOC [GARDEL, NEAT 001, AIDS Clinical Trials Group 5142 and PROGRESS]. In switch settings, 17 studies (10 randomized) were reviewed that used four strategies, including three studies assessing an INSTI plus a nonnucleoside reverse transcriptase inhibitor . Noninferiority of the NRTI-reducing arm was shown in six of 10 studies (ATLAS-M, SALT, DUAL, OLE, LATTE-2 and SWORD). In general, NRTI-reducing therapy did not always result in an improvement in short- or long-term adverse events; however, in many cases, these endpoints were not reported. Some of these studies reported higher virological failure rates with more frequent emergence of resistance mutations. None of these NRTI-reducing strategies has been compared against a single-pill regimen, including those containing tenofovir alafenamide. Only strategies demonstrating noninferior efficacy, a benefit in safety/tolerability, and a favourable cost-efficacy ratio, preferably in a single pill, will eventually match the current SOC of triple ARV therapy.<br /> (© 2017 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)
- Subjects :
- Anti-HIV Agents adverse effects
Antiretroviral Therapy, Highly Active adverse effects
Drug Utilization
Humans
Nucleosides adverse effects
Randomized Controlled Trials as Topic
Reverse Transcriptase Inhibitors adverse effects
Treatment Outcome
Anti-HIV Agents administration & dosage
Antiretroviral Therapy, Highly Active methods
HIV Infections drug therapy
Nucleosides administration & dosage
Reverse Transcriptase Inhibitors administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1468-1293
- Volume :
- 19
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- HIV medicine
- Publication Type :
- Academic Journal
- Accession number :
- 28737291
- Full Text :
- https://doi.org/10.1111/hiv.12534