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

Background The eff ect of transmitted drug resistance (TDR) on fi rst-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the eff ect of TDR on outcome in the fi rst 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 fi rst 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 defi ned as time to the fi rst 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<0·0001). The hazard ratio for the diff erence in virological failure between patients with TDR and resistance to at least one drug and those without TDR was 3·13 (95% CI 2·33 4·20, p<0·0001). The hazard ratio for the diff erence between patients with TDR receiving fully-active cART and patients without TDR was 1·47 (95% CI 0·19 2·38, p=0·12). In stratifi ed analysis, the hazard ratio for the risk of virological failure in patients with TDR who received fully-active cART that included a non-nucleoside reverse transcriptase inhibitor (NNRTI) compared with those without TDR was 2·0 (95% CI 0·9 4·7, p=0·093). Interpretation These fi ndings confi rm present treatment guidelines for HIV, which state that the initial treatment choice should be based on resistance testing in treatment-naive patients.