17 log10 copies/mL (95% CI 2.39–4.65 log10copies/mL) in those who started HAART in the early period; P for trend=0.03]. Sixty-two drug discontinuations (5.2%) were because of simplification. The Kaplan–Meier estimates by 1 year were 0.1% (95% CI 0–0.3%) among those who started HAART in 1997–1999,
2.0% (95% CI 1.1–3.0%) among those who started HAART in 2000–2002 and 7.6% (95% CI 5.4–9.9%) among those who started HAART in 2003–2007 (log rank P<0.0001) (Fig. 1). HAART initiation in 2000–2002 and in 2003–2007 was independently associated with a substantial increase in the risk of discontinuation because of simplification (ARH 15.26, 95% CI 3.21–74.45, P=0.0006 and ARH 37.97, 95% CI 7.56–190.64, P<0.0001 vs. 1997–1999, respectively). Two patients (1.5%) LDK378 who started HAART with three NRTIs and 15% of those who started HAART with a boosted PI discontinued ≥1 drugs included in the initial therapy because of simplification. Patients who started HAART with a single PI-based regimen (ARH 5.32, 95% CI 1.49–19.02, P=0.01) or a boosted PI-based regimen (ARH 13.07, 95% CI 4.48–32.12, P<0.0001) had a higher risk of discontinuing because of simplification
compared with those who started HAART with NNRTI-based regimens. Results were similar when all the analyses were repeated using the competing-risk approach (data not shown), suggesting that the informative censoring mechanism did not substantially influence the estimates of the Kinase Inhibitor Library high throughput rate of drug discontinuation. In the first ALK inhibitor year after HAART initiation, 36% of the patients discontinued at least one drug in the initial regimen,
most frequently because of intolerance/toxicity: this result is consistent with previous findings in the literature [7,9,11]. The incidence of discontinuation of first-line HAART for any reason did not change over time in our cohort. Time trends towards shorter times to treatment change in recent years have been described for other cohorts [4,5] and have been ascribed to an increase in the number of available drugs. However, the interpretation of time trends for the incidence of modification of initial HAART for any reason is difficult because the impact of the increasing number of treatment options may vary according to the reason for discontinuation. As previously reported [15], women were more likely to have treatment discontinuation than men; this is likely to be related to the higher relative hazards of initial HAART change because of intolerance/toxicity and poorer adherence. Furthermore, in our cohort, the higher rate of treatment interruption could be partly explained by the fact that pregnant women were not excluded from the study population. The significant decline in the rate of discontinuations because of intolerance/toxicity could reflect patients’ greater tolerability for the newly available regimens.
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