Pooled week 48 safety and efficacy results from the ECHO and THRIVE phase III trials comparing TMC278 vs EFV in treatment-naive, HIV-1-infected patients
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SUBMITTER: Cohen C
PROVIDER: S-EPMC3112863 | biostudies-literature | 2010 Jan
REPOSITORIES: biostudies-literature
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| S-EPMC3112967 | biostudies-literature
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| S-EPMC3112995 | biostudies-literature
Project description:The once daily, single-tablet regimen (STR) combining rilpivirine (RPV), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) provides a simplified treatment option for antiretroviral therapy (ART)-naïve patients with baseline HIV-1 RNA (BLVL) of ≤100,000 copies/mL. The aim of this analysis is to compare long-term efficacy, safety, and tolerability of RPV+FTC/TDF vs. efavirenz (EFV)+FTC/TDF as individual components in subjects with BLVL ≤100,000 copies/mL. Week 96 efficacy and safety data from subjects with BLVL ≤100,000 copies/mL, who received daily RPV 25 mg or EFV 600 mg with FTC/TDF in the phase 3, randomized, double-blind, double-dummy, active-controlled, registrational trials ECHO and THRIVE, were analyzed. Virologic response was evaluated by intent-to-treat, time to loss of virological response (ITT-TLOVR), and Snapshot algorithms. Through Week 96, RPV+FTC/TDF demonstrated non-inferior efficacy to EFV+FTC/TDF (84% vs. 81%, respectively; ITT-TLOVR) in 543 subjects with BLVL ≤100,000 copies/mL, and overall rates of virologic failure (VF) were 5.9% vs. 2.4%, respectively. Resistance development was lower in Year 2 than Year 1. Subjects in both arms with suboptimal adherence (≤95%) had lower virologic responses (63% vs. 62%, respectively). Treatment with RPV+FTC/TDF was associated with significantly fewer treatment-related adverse events (AEs), grade 2-4 AEs, neurological and psychiatric AEs (including dizziness and abnormal dreams/nightmares), and rash. Additionally, grade 2-4 treatment-emergent laboratory abnormalities and grade 1-3 lipid abnormalities were significantly less common with RPV+FTC/TDF than EFV+FTC/TDF. RPV+FTC/TDF demonstrated non-inferior efficacy to EFV+FTC/TDF in ART-naïve subjects with BLVL ≤100,000 copies/mL and was associated with a higher rate of VF but a more favorable safety and tolerability profile through Week 96.
| S-EPMC3985528 | biostudies-literature
Project description:BackgroundEtravirine (ETR), a non-nucleoside reverse transcriptase inhibitor approved for 200 mg twice-daily dosing in conjunction with other antiretrovirals (ARVs), has pharmacokinetic properties which support once-daily dosing.MethodsIn this single-arm, open-label study, 79 treatment-naive HIV-infected adults were assigned to receive ETR 400 mg plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300/200 mg once daily to assess antiviral activity, safety and tolerability. ARV activity at 48 weeks was determined by proportion of subjects with HIV-1 RNA<50 copies/ml (intention-to-treat, missing = failure).ResultsOf 79 eligible subjects, 90% were men, 62% African-American and 29% Caucasian. At baseline, median (Q1, Q3) age was 29 years (23, 44) and HIV-1 RNA 4.52 log10 copies/ml (4.07, 5.04). A total of 69 (87%) completed a week 48 visit and 61 (77%, 95% CI 66%, 86%) achieved HIV-1 RNA<50 copies/ml at week 48. At time of virological failure, genotypic resistance-associated mutations were detected in three participants, two with E138K (one alone and one with additional mutations). Median (95% CI) CD4(+) cell count increase was 163 (136, 203) cells/µl. Fifteen (19.0%) participants reported a new sign/symptom or lab abnormality ≥ Grade 3 and three participants (3.8%) permanently discontinued ETR due to toxicity. Two participants had psychiatric symptoms of any grade. There were no deaths.ConclusionsIn this study of ARV-naive HIV-positive adults, once-daily ETR with TDF/FTC had acceptable antiviral activity and was well-tolerated. Once-daily ETR may be a plausible option as part of a combination ARV regimen for treatment-naive individuals. ClinicalTrials.gov NCT00959894.
| S-EPMC5546302 | biostudies-literature
Project description:OBJECTIVES:To investigate efficacy and safety of a single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg vs. darunavir/cobicistat plus emtricitabine/tenofovir disoproxyl fumarate (TDF) (control) in antiretroviral-treatment-naive, HIV-1-infected adults. DESIGN:Phase-3, randomized, active-controlled, double-blind, international, multicenter, noninferiority study (NCT02431247). METHODS:Seven hundred and twenty-five participants were randomized (1 : 1) to D/C/F/TAF (362) or control (363). The primary objective was to demonstrate noninferiority of D/C/F/TAF vs. control for percentage viral load less than 50 copies/ml (FDA-snapshot analysis) at 48 weeks (10% margin). RESULTS:At week 48, D/C/F/TAF was noninferior to control (91.4 vs. 88.4% achieved viral load <50 copies/ml, respectively; difference 2.7%; 95% CI -1.6 to 7.1; P < 0.0001), with 4.4 vs. 3.3% of patients, respectively, having viral load greater or equal to 50 copies/ml. No treatment-emergent mutations associated with darunavir or TAF/TDF resistance were observed in either group. One patient (D/C/F/TAF) was identified with M184I/V conferring resistance to emtricitabine. Incidences of grades 3 and 4 adverse events (5 vs. 6%), serious adverse events (5 vs. 6%) and adverse event-related discontinuations (2 vs. 4%) were low and similar between groups. Mean decrease in urine protein/creatinine ratio was greater with D/C/F/TAF than control (-22.42 vs. -10.34 mg/g, P = 0.033). Mean percentage change in bone mineral density with D/C/F/TAF vs. control was 0.21 vs. -2.73%, P < 0.0001 (hip), -0.68 vs. -2.38%, P = 0.004 (lumbar spine), and -0.26 vs. -2.97%, P < 0.0001 (femoral neck). Median change from baseline in total cholesterol/HDL-cholesterol ratio was 0.20 vs. 0.08, P = 0.036. CONCLUSION:D/C/F/TAF achieved a high virologic suppression rate (91.4%) and was noninferior to darunavir/cobicistat with F/TDF. D/C/F/TAF also demonstrated the bone and renal safety advantages of TAF in combination with darunavir/cobicistat.
| S-EPMC6039393 | biostudies-literature
Project description: Not available
| S-EPMC6255676 | biostudies-literature
Project description:BackgroundIn HIV clinical trials, proportions of Black and female participants achieving virologic suppression (VS) are often lower compared with White and male participants. As the antiretroviral therapy (ART) landscape continues to evolve, addressing existing challenges in clinical trial diversity will be critical to effectively translate results into clinical practice. Here, we pooled data to evaluate the efficacy and safety of dolutegravir (DTG)-containing regimens by race, sex, and regional subgroups.MethodsThree pooled analyses were conducted using 48-week results from phase 3/3b trials: DTG 3-drug vs non-DTG-containing 3- or 4-drug regimens in ART-naive participants (ARIA, FLAMINGO, SINGLE, SPRING-2), DTG-containing 2-drug vs 3-drug regimens in ART-naive participants (GEMINI-1, GEMINI-2), and DTG 3-drug vs non-DTG-containing 3- or 4-drug regimens in ART-experienced participants (SAILING, DAWNING). Proportions of participants with VS, safety, and change from baseline in CD4+ cell count were analyzed.ResultsProportions of participants achieving VS were high among those receiving DTG vs comparator regimens. Proportions of participants achieving VS were generally lower in Black (vs non-Black), female (vs male), and US (vs non-US) subgroups. No new safety signals emerged from any subgroup in pooled analyses.ConclusionsThese analyses confirm that, across subgroups, DTG has robust efficacy and a good safety profile at week 48 relative to comparator regimens. Achieving VS may vary by participant characteristics, highlighting the urgent need for enrollment to reflect the demographics of global HIV populations more accurately. Future studies should strive to support participants throughout the trial to ensure optimal representation, inclusion, and retention.
| S-EPMC9423381 | biostudies-literature
Project description:BackgroundIn studies of diabetic gastroparesis, patients with type 1 and type 2 diabetes mellitus (T1DM, T2DM) are often combined for analyses. We compared gastroparesis severity, healthcare utilization, psychological function, and quality of life in T1DM vs T2DM gastroparesis patients.MethodsQuestionnaire, laboratory, and scintigraphy data from patients with gastroparesis and T1DM and T2DM from seven centers of the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Registry were compared at enrollment and after 48 weeks. Multiple regression models assessed baseline and follow-up differences between diabetes subtypes.Key resultsAt baseline, T1DM patients (N = 78) had slower gastric emptying, more hospitalizations, more gastric stimulator implantations, higher hemoglobin A1c (HbA1c), and more anxiety vs T2DM patients (N = 59). Independent discriminators of patients with T1DM vs T2DM included worse gastroesophageal reflux disease, less bloating, more peripheral neuropathy, and fewer comorbidities (p ≤ 0.05). On follow-up, gastrointestinal (GI) symptom scores decreased only in T2DM (p < 0.05), but not in T1DM patients who reported greater prokinetic, proton pump inhibitor, anxiolytic, and gastric stimulator usage over 48 weeks (p ≤ 0.03). Gastrointestinal symptoms at baseline and 48 weeks with both subtypes were not associated with HbA1c, peripheral neuropathy, psychological factors, or quality of life.Conclusions & inferencesBaseline symptoms were similar in T1DM and T2DM patients, even though T1DM patients had worse gastric emptying delays and higher HbA1c suggesting other factors mediate symptom severity. Symptom scores at 48 weeks decreased in T2DM, but not T1DM patients, despite increased medical and surgical treatment utilization by T1DM patients. Defining causes of different outcomes in diabetic gastroparesis warrants further investigation.
| S-EPMC5319426 | biostudies-literature
Project description:A randomized controlled noninferiority trial was conducted in HIV-infected patients receiving tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV) with virological suppression in a resource-limited setting. Switching to TDF/FTC/rilpivirine was noninferior to continuing TDF/FTC/EFV in terms of maintaining compete viral suppression at 24 weeks and provided better lipid profiles and fewer central nervous system adverse effects.
| S-EPMC6641787 | biostudies-literature
Project description:BackgroundThe main international guidelines indicate DTG/3TC therapy as one of the preferred regimens for people living with HIV (PLWH), due to its observed efficacy in randomized clinical trials. However, information in real-life cohorts is relatively scarce for first-line use.MethodsA retrospective multicenter study of adult PLWH starting DTG+3TC as a first-line regimen before January 31st, 2020. Virological failure (VF) was defined as 2 consecutive HIV RNA viral load (VL) >50 copies/mL.Results135 participants were included. Treatment was started without knowing baseline drug resistance testing (bDRT) results in 71.9% of cases, with baseline resistance mutations being later confirmed in 17 patients (12.6%), two of them with presence of M184V mutation. Effectiveness at week 48 was 85.2% (CI95%: 78.1-90.7%) (ITT missing = failure [M = F]) and 96.6% (CI 95%: 91.6-99.1%) (per-protocol analysis). Six patients (4.4%) discontinued treatment. One developed not confirmed VF after discontinuing treatment due to poor adherence; no resistance-associated mutations emerged. Three discontinued treatments due to central nervous system side effects (2.2%), and two due to a medical decision after determining the M184V mutation in bDRT. Finally, 14 (10.4%) were lost to follow-up, most of them due to the COVID-19 pandemic.ConclusionsIn a real-life multicenter cohort of ART-naïve PLWH, treatment initiation with DTG + 3TC showed high effectiveness and favorable safety results, comparable to those of randomized clinical trials, without treatment-emergent resistance being observed through week 48. Starting treatment before receiving the results of baseline drug resistance testing did not have an impact on the regimen's effectiveness.
| S-EPMC9678299 | biostudies-literature