Suchergebnisse

IntroductionIn HIV+ patients exhibiting multidrug resistance (MDR), NRTIs often have little activity, increased toxicity, drug interactions and add unnecessary treatment costs. The 48 week VERITAS study demonstrated that these patients can have a safe and effective simplification of salvage regimen by removing inactive NRTIs as determined by genotypic data. Virological, immunological, clinical and financial outcomes were evaluated at an additional 96 weeks of follow‐up.Materials and MethodsMDR patients with an undetectable viral load (VL) on a stable regimen containing at least four ARVs (including one inactive NRTI) were enrolled in an open‐label, prospective simplification trial, where one inactive NRTI was removed at baseline (BL). A second NRTI could be removed at week 24 if the regimen contained at least five ARVs at enrolment.Results31 male patients participated. The mean length of treatment was 14 years, with a median CD4 count of 525. The BL regimen consisted of 4 ARVs in 22 patients (71%) and 5 ARVs in 9 patients (29%). 3TC or FTC was removed in 29 patients (94%), and either AZT or TDF was interrupted in 2 others. Four patients had a second NRTI stopped. One patient was removed at W26 as an active NRTI was removed for creatinine elevation. 30 well‐controlled patients continued follow‐up after W48. At W144, six patients had additional changes in their ARV regimen. Half were due to toxicity (jaundice, neuropathy and nephrotoxicity) while the other half were the result of treatment simplification. None of the patients exhibited virologic failure at the time of treatment change and maintained undetectable VLs throughout the entire follow‐up. These six patients had a mean gain of 79 CD4 (p=0.17) compared to baseline. 22 of the 24 patients (92%) with no changes in ARV therapy after W48 had undetectable VLs. The other two had confirmed virologic failure, one with genotypic resistance. All 24 had elevated CD4 counts (mean +118 CD4, p<0.0001). No deaths or serious adverse events were observed. One or two ARV removals translated to a mean annual saving of $3319 CDN (11%) and $8630 (24%) respectively.ConclusionsFinal results indicate that removing one or two inactive NRTIs from a regimen in patients taking four or more ARVs with controlled VL appears to be safe, maintains virological suppression through 144 weeks and significantly reduces treatment costs.

IntroductionMany studies have shown the superiority of single tablet regimens (STRs) of antiretrovirals for the treatment of HIV in terms of efficacy, adherence and rate of hospitalisation as they offer a low pill burden and once daily dosing. Our objective was to compare the duration of first‐line STRs to multi‐tablet regimens.MethodsFrom our clinical database, we selected patients initiating any of the major first‐line regimens between 2007 and 2013. Two STRs, Atripla (ATP) and Complera (CPLR), were compared to three non‐STRs: two NRTIs and raltegravir (RAL), atazanavir/ritonavir (ATV/r) or darunavir/ritonavir (DRV/r). The primary outcome was time to discontinuation of the first‐line regimen. The association between regimen type and duration was estimated using Cox proportional hazards models adjusted for age, gender, baseline CD4, baseline viral load, risk factor, site and year of treatment initiation.ResultsA total of 743 patients (281 on STRs and 462 on non‐STRs) were included. 693 (93%) were male and median age was 43 years. Median length of follow‐up was 3.2 years. 56% of patients were MSM, 6% IDU and 6% from endemic countries. Patients on an STR were less likely to be IDU (p<0.024) and have a baseline HIV‐RNA ≥100,000 copies/mL (p<0.011). Overall, 321 (43%) patients discontinued their regimen during the study period. The rate of discontinuation one year after starting ARV depends on the regimen: 29% for patients on 2NRTIs+DRV/r, 26% on ATP, 25% on 2NRTIs+ATV/r, 17% on 2NRTIs+RAL and 10% on CPLR (p<0.001). In the adjusted model, durability for STR and non‐STR was equivalent (aHR=0.83, p=0.108). Compared to patients on ATP, patients on CPLR were less likely to discontinue (HR=0.58, p=0.070). No difference between ATP and the other regimens was observed: HR for 2NRTIs+RAL=0.92 (p=0.66), 2NRTIs+ DRV/r=1.16 (p=0.36), 2NRTIs+ATV/r=1.11 (p=0.46).ConclusionsOur findings suggest that STRs do not necessarily result in a more durable treatment. Even with a higher pill burden and/or twice daily dosing, patients initiating therapy with RAL or boosted‐PI based regimens were not more likely to discontinue the first‐line regimen compared to patients on an STR. Among the STR subgroups, the regimen with better known tolerability conferred more durable treatment. Limitations included our inability to adjust for the patient's adherence to a given regimen.

IntroductionCombination antiretroviral therapy (ART) significantly decreases morbidity, mortality and HIV transmission. We aimed to characterize the timing of ART initiation based on CD4 cell count from 2000 to 2012 and identify factors associated with late initiation of treatment.MethodsParticipants from the Canadian Observational Cohort (CANOC), a multi‐site cohort of HIV‐positive adults initiating ART naively after 1 January 2000, in three Canadian provinces (British Columbia, Ontario and Québec) were included. Late initiation was defined as a CD4 count <200 cells/mm3 or an AIDS‐defining illness before ART initiation (baseline). Temporal trends were assessed using the Cochran–Armitage test, and independent correlates of late initiation were identified using logistic regression.ResultsIn total, 8942 participants (18% female) of median age 40 years (Q1–Q3 33–47) were included. The median baseline CD4 count increased from 190 cells/mm3 (Q1–Q3 80–320) in 2000 to 360 cells/mm3 (Q1–Q3 220–490) in 2012 (p<0.001). Overall, 4274 participants (48%) initiated ART with a CD4 count <200 cells/mm3 or AIDS‐defining illness. Late initiation was more common among women, non‐MSM, older individuals, participants from Ontario and BC (vs. Québec), persons with injection drug use (IDU) history and individuals starting ART in earlier calendar years. In sub‐analysis exploring recent (2008 to 2012) predictors using an updated CD4 criterion (<350 cells/mm3), IDU and residence in BC (vs. Québec) were no longer significant correlates of late initiation.ConclusionsThis analysis documents increasing baseline CD4 counts over time among Canadians initiating ART. However, CD4 counts at ART initiation remain below contemporary treatment guidelines, highlighting the need for strategies to improve earlier engagement in HIV care.