Once-daily darunavir/ritonavir vs. lopinavir/ritonavir in treatment-naive, HIV-1-infected patients: 96-week analysis.
ABSTRACT Present 96-week data from ongoing ARTEMIS (AntiRetroviral Therapy with TMC114 ExaMined In Naive Subjects) trial.
Randomized, open-label, phase III trial of antiretroviral-naive patients with HIV-1 RNA at least 5000 copies/ml (stratified by HIV-1 RNA and CD4 cell count) receiving darunavir/ritonavir (DRV/r) 800/100 mg once daily or lopinavir/ritonavir (LPV/r) 800/200 mg total daily dose (twice daily or once daily) and fixed-dose tenofovir/emtricitabine. Primary outcome measure was noninferiority of DRV/r vs. LPV/r in virologic response (<50 copies/ml, time-to-loss of virologic response) at 96 weeks (secondary outcome: superiority).
Six hundred eighty-nine patients were enrolled. At week 96, significantly more DRV/r (79%) than LPV/r patients (71%) had viral load less than 50 copies/ml, confirming statistical noninferiority (estimated difference: 8.4%; 95% confidence interval 1.9-14.8; P < 0.001; per-protocol) and superiority (P = 0.012; intent-to-treat) in virologic response. Median CD4 cell count increases from baseline were 171 and 188 cells/microl for DRV/r and LPV/r, respectively (P = 0.57; noncompleter=failure). Overall, 4% of DRV/r patients and 9% of LPV/r patients discontinued treatment due to adverse events. Lower rates of grade 2-4 treatment-related diarrhea were seen with DRV/r (4%) vs. LPV/r (11%; P < 0.001), whereas grade 2-4 treatment-related rash occurred infrequently in both arms (3 vs. 1%, respectively; P = 0.273). DRV/r patients had smaller median increases in triglycerides (0.1 and 0.6 mmol/l, respectively, P < 0.0001) and total cholesterol (0.6 and 0.9 mmol/l, respectively; P < 0.0001) than LPV/r patients; levels remained below National Cholesterol Education Program cut-offs for DRV/r.
At week 96, once-daily DRV/r was both statistically noninferior and superior in virologic response to LPV/r, with a more favorable gastrointestinal and lipid profile, confirming DRV/r as an effective, well tolerated, and durable option for antiretroviral-naive patients.
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ABSTRACT: Objectives: To investigate differences in liver enzyme elevation (LEE) between HIV-infected patients with and without HCV coinfection who start a darunavir/ritonavir-containing regimen. Methods: HIV-infected patients enrolled in the Italian Cohort of Naive to Antiretrovirals (ICONA) Foundation Study were included if they started darunavir/ritonavir for the first time. Patients were classified as not HCV coinfected, HCV active coinfected (HCV RNA positive), and HCV nonactive coinfected (HCV-Ab positive/HCV RNA negative). Time to LEE endpoint was defined using the ACTG toxicity scale, based on changes relative to baseline. Kaplan-Meier was used to estimate 1-year and 2-year probability of LEE. The incidence rate ratios (IRRs) of LEEs were estimated until the last follow-up (intention-to-treat analysis [ITT]) and up to darunavir/ritonavir discontinuation (on-treatment analysis [OT]). Results: Overall, 703 patients were included. Ninety-one were HCV-Ab positive; of those, 68 (9.7%) had active HCV coinfection. In 879 person-years of follow-up, 101 LEEs occurred (ITT). No severe hepatotoxicity event was registered in active HCV coinfected patients. HCV active coinfection was predictive of LEE in the overall population (OT: adjusted incidence rate ratio (IRR), 2.25; 95% CI, 0.70-7.24; P = .17; ITT: adjusted IRR, 3.62; 95% CI, 1.67-7.83; P < .001) and in naive patients (OT: adjusted IRR, 6.29; 95% CI, 2.54-15.55; P = .00; ITT: adjusted IRR, 3.87; 95% CI, 0.99-15.16; P = .05). Conclusions: No grade 3-4 LEEs occurred in HCV active coinfected patients. HCV active coinfected patients experienced low grade LEEs more frequently than HCV-Ab negative patients. Darunavir/ritonavir seems to be safe whatever the HCV status, when liver enzymes are carefully monitored.HIV Clinical Trials 07/2014; 15(4):151-60. DOI:10.1310/hct1504-151 · 2.14 Impact Factor
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ABSTRACT: Second line antiretroviral therapy (ART) regimen is used when patients fail their first line regimen. There are many factors such as non-adherence, drug resistance as well as virological and immunological failure that lead to second line highly active antiretroviral therapy (HAART) regimen treatment failure. This study was aimed at determining predictor factors to treatment failure with second line HAART and analyzing median survival time. An observational, retrospective study was conducted in Sungai Buloh Hospital (HSB) to assess current status of HIV patients treated with second line HAART regimen. Convenience sampling was used and 104 patients were included based on the study's inclusion and exclusion criteria. Data was collected for six months i.e. from July until December 2013. Data was then analysed using SPSS version 18. Kaplan-Meier and Cox regression analyses were used to measure median survival times and predictor factors for treatment failure. The study population consisted mainly of male subjects, aged 30-45 years, who were heterosexual, and had HIV infection for less than 6 years. The most common second line HAART regimen given was lopinavir/ritonavir (LPV/r)-based combination. Kaplan-Meier analysis showed that patients on LPV/r demonstrated longer median survival times than patients on indinavir/ritonavir (IDV/r) based combination (p<0.001). The commonest reason for a treatment to fail with second line HAART was non-adherence. Based on Cox regression analysis, other predictor factors for treatment failure with second line HAART regimen were age and mode of HIV transmission.Journal of Medical, Health, Pharmaceutical and Biomedical Engineering; 10/2014