Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study

TLDR: Findings confirm present treatment guidelines for HIV, which state that the initial treatment choice should be based on resistance testing in treatment-naive patients, that the effect of TDR on outcome in the first year of cART is confirmed.

Abstract: Summary Background The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration. Methods HIV-infected patients of any age were included if they started cART (at least three antiretroviral drugs) for the first time after Jan 1, 1998, and were antiretroviral naive and had at least one sample for a genotypic test taken before the start of cART. We used the WHO drug resistance list and the Stanford algorithm to classify patients into three resistance categories: no TDR, at least one mutation and fully-active cART, or at least one mutation and resistant to at least one prescribed drug. Virological failure was defined as time to the first of two consecutive viral load measurements over 500 copies per mL after 6 months of therapy. Findings Of 10 056 patients from 25 cohorts, 9102 (90·5%) had HIV without TDR, 475 (4·7%) had at least one mutation but received fully-active cART, and 479 (4·8%) had at least one mutation and resistance to at least one drug. Cumulative Kaplan-Meier estimates for virological failure at 12 months were 4·2% (95% CI 3·8–4·7) for patients in the no TDR group, 4·7% (2·9–7·5) for those in the TDR and fully-active cART group, and 15·1% (11·9–19·0) for those in the TDR and resistant group (log-rank p Interpretation These findings confirm present treatment guidelines for HIV, which state that the initial treatment choice should be based on resistance testing in treatment-naive patients. Funding European Community's Seventh Framework Programme FP7/2007-2013 and Gilead.