Abstract
Objective:To investigate the characteristics and outcomes of people who initiated different antiretroviral therapy (ART) regimens during the era of integrase strand transfer inhibitors (INSTIs).Design:UK-based observational cohort study.Methods:UK Collaborative HIV Cohort study participants were included if they had started ART between 1 January 2012 and 30 June 2017. Virological failure was defined as the first of two consecutive plasma HIV RNA more than 50 copies/ml, at least 6 months after starting ART. Follow-up was censored at ART discontinuation, class switch or death. The risk of virological failure among those on INSTI, protease inhibitor or nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens was compared using Kaplan–Meier and Cox regression methods.Results:Of 12 585 participants, 45.6% started a NNRTI, 29.0% a protease inhibitor and 25.4% an INSTI regimen. Over a median follow-up of 20.3 months (interquartile range 7.9–38.9), 7.5% of participants experienced virological failure. Compared with those starting an NNRTI regimen, people receiving INSTIs or protease inhibitors were more likely to experience virological failure: INSTI group adjusted hazard ratio 1.52, 95% confidence interval 1.19–1.95, P = 0.0009; protease inhibitor group adjusted hazard ratio 2.70, 95% confidence interval 2.27–3.21, P less than 0.0001, likelihood ratio test P less than 0.0001.Conclusion:First-line INSTI regimens were associated with a lower risk of virological failure than protease inhibitor regimens but both groups were more likely to experience virological failure than those initiating treatment with a NNRTI. There is likely to be residual channelling bias resulting from selected use of INSTIs and protease inhibitors in specific clinical contexts, including in those with a perceived risk of poor adherence.
Highlights
Integrase strand transfer inhibitors (INSTIs) form the newest class of antiretroviral agents to be incorporated into the standard of care for treatment-naive people living with HIV in the United Kingdom
The remaining 12 585 participants were eligible for inclusion in the study, of whom 5744 (45.6%) received a regimen containing a nonnucleoside reverse transcriptase inhibitor (NNRTI), 3648 (29.0%) received a protease inhibitor and 3193 (25.4%) received an INSTI
INSTI regimens had a lower risk of virological failure than protease inhibitors with about 12% experiencing virological failure, though this was higher than the NNRTI group at about 8%
Summary
Integrase strand transfer inhibitors (INSTIs) form the newest class of antiretroviral agents to be incorporated into the standard of care for treatment-naive people living with HIV in the United Kingdom. The INSTI class has performed well when compared with other third agents in randomized controlled trials (RCTs) of first-line antiretroviral therapy (ART). The STARTMRK trial randomized ART-naive participants to receive either raltegravir or the nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz, with a nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbone of tenofovir and emtricitabine. Raltegravir was compared with the boosted protease inhibitors darunavir and atazanavir, with a tenofovir-emtricitabine backbone in the phase III open label study ACTG A5257 [4]. Dolutegravir, a next-generation INSTI, was found to be superior to efavirenz in ART-naive participants in two RCTs: SPRING-1, a phase IIb dose-ranging study in which the dolutegravir 50 mg once daily arm had 88% viral suppression at 96 weeks compared with 72% of the efavirenz arm, and SINGLE, a phase III study in which viral suppression was achieved in 88 and 81% at 48 weeks, respectively [8,9]. Dolutegravir was shown to be noninferior to atazanavir in the ARIA study [13] and to darunavir in the FLAMINGO study [14]
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