|Title||Second-line protease inhibitor-based antiretroviral therapy after non-nucleoside reverse transcriptase inhibitor failure: the effect of a nucleoside backbone|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Waters L., Bansi L, Asboe D, Pozniak A, Smit E, Orkin C, Fearnhill E, Dunn DT, Phillips AN|
|Keywords||Anti-HIV Agents/*therapeutic use, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Drug Resistance, Viral, Female, HIV Infections/drug therapy/virology, HIV Protease Inhibitors/*therapeutic use, Humans, Longitudinal Studies, Male, Reverse Transcriptase Inhibitors/*therapeutic use, Risk Factors, Treatment Failure, Treatment Outcome, Viral Load|
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.
|Short Title||Antiviral therapy|
|Alternate Journal||Antiviral therapy|