During a median patient follow-up period of 45 weeks, 22 of 130 patients stopped taking darunavir after a median exposure of 20 weeks, although later 12 patients restarted darunavir. None of these patients stopped taking darunavir because of ‘treatment failure’. Three patients were lost to follow-up, 13 patients stopped for unspecified reasons (10 later restarted darunavir) and the remaining six patients stopped because of adverse events – abnormal fat distribution (two patients), liver toxicity (two patients), gastrointestinal tract toxicity (one patient), and an unspecified toxicity (one patient), although these
last two patients later restarted darunavir. Of the two patients who stopped because of liver toxicity, neither tested positive for hepatitis ALK inhibitor B or C. Changes to therapy were common: 53 patients made a change of some sort on a median of two occasions. Among the 37 patients receiving enfuvirtide when starting darunavir, 22 were no longer receiving enfuvirtide at the end of follow-up and, of these, 11 had switched to raltegravir (all in combination with darunavir). One of the patients restarting darunavir then stopped taking darunavir again and died 1 month
later. The main cause of death was recorded as ‘HIV disease resulting in other bacterial infections’ [International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) code B20.1]. The patient had a history of virological failure on PI-based regimens (lopinavir, atazanavir and tipranavir) and never achieved viral suppression on darunavir. Of the 130 patients,
selleck chemicals llc four were diagnosed with either a new AIDS-defining disease or a relapse of such a disease after starting darunavir. During a median patient follow-up period of 51 weeks, 115 patients had a median of four viral load measurements with a median interval between measurements of 9.4 weeks. Of the 571 viral load measurements, 88% were made using a Cobas-TaqMan 96 assay (Roche Molecular Diagnostics, Rotkreuz, Switzerland), 11% were made using an Amplicor ultra-sensitive assay (Roche Molecular Diagnostics) and only five measurements (<1%) were made using an Amplicor standard assay. Under the three variants of the FDA's algorithm, virological failure was seen in 20, 18 and Nabilone 29 patients for the first, second and third variants, respectively (Table 2). Many of the patients who failed started darunavir with HIV mutations associated with resistance to darunavir: 11, 10 and 14 patients among those who failed (55, 56 and 48%, respectively) had at least one relevant mutation and a median of 3, 2 and 1.5 relevant mutations under the three variants, respectively. We present full results of time to event analyses for the third variant (Table 3) because this variant leads to the greatest number of failures, increasing the information available for analysis.