Second-line protease inhibitor-based antiretroviral therapy after non-nucleoside reverse transcriptase inhibitor failure: the effect of a nucleoside backbone.

TitleSecond-line protease inhibitor-based antiretroviral therapy after non-nucleoside reverse transcriptase inhibitor failure: the effect of a nucleoside backbone.
Publication TypeJournal Article
Year of Publication2013
AuthorsWaters L, Bansi L, Asboe D, Pozniak A, Smit E, Orkin C, Fearnhill E, Dunn D and Phillips A
Corporate AuthorsUK CHIC Study and UK HIV Drug Resustance Database
JournalAntivir Ther
Volume18
Issue2
Pagination213-9
Date Published2013
ISSN2040-2058
KeywordsAnti-HIV Agents, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Drug Resistance, Viral, Female, HIV Infections, HIV Protease Inhibitors, Humans, Longitudinal Studies, Male, Reverse Transcriptase Inhibitors, Risk Factors, Treatment Failure, Treatment Outcome, Viral Load
Abstract

BACKGROUND: Virological failures on combined antiretroviral therapy still occur. Boosted protease inhibitor ( Pl/r)- based therapy is a commonly used option after non-nucleoside reverse transcriptase inhibitor ( NNRTI) failure, but whether two fully active nucleoside reverse transciptase inhibitors (NRTIs) are required is unknown. We investigated the effect of an NRTI backbone in individuals receiving Pl/r after failing NNRTI-based combined antiretroviral therapy.

METHODS: A longitudinal analysis of the UK Collaborative HIV Cohort (CHIC) and the UK HIV Drug Resistance Database to identify individuals who failed first-line NNRTI and two NRTIs, and switched to Pl/r-based therapy between January 1999 and December 2008 was conducted. We investigated the effect of NRTI on suppression.

RESULTS: In total, 470 individuals met study criteria: 19.6%, 34.5% and 46.0% started 0, 1 or ≥ 2 NRTIs, respectively. Median CD4+ T-cell count was 223 cells/mm3 and HIV-RNA was 4.3 log10 copies/ml; 246 (52.3%) underwent genotyping before switch. virological failure occurred in 10.9% and 13% after 48 and 96 weeks, respectively. In multivariable analysis, heterosexual risk group and HIV RNA were independently associated with virological failure; higher CD4+ T-cell count was protective (HR= 0.92). Number of new NRTIs or genotypic sensitivity score of backbone had no effect on treatment success rates when modelled as categorical or continuous variables.

CONCLUSIONS: Successful treatment with a second-line Pl/r may not require two active NRTIs. If replicated in clinincal trials, these findings could guide future recommendations.

Alternate JournalAntivir. Ther. (Lond.)
PubMed ID23653911
Grant ListG0900274 / / Medical Research Council / United Kingdom
MC_UU_12023/15 / / Medical Research Council / United Kingdom