AIDS research and human retroviruses
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AIDS Res. Hum. Retroviruses · Jan 2020
Randomized Controlled Trial Multicenter StudyWeek 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials.
Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is being investigated in two Phase III trials, AMBER (NCT02431247; treatment-naive adults) and EMERALD (NCT02269917; treatment-experienced, virologically suppressed adults). Week 48 AMBER and EMERALD resistance analyses are presented. Postbaseline samples for genotyping/phenotyping were analyzed from protocol-defined virologic failures (PDVFs) with viral load (VL) ≥400 copies/mL at failure/later time points. ⋯ D/C/F/TAF has a high genetic barrier to resistance; no darunavir, primary PI, or tenofovir RAMs were observed through 48 weeks in AMBER and EMERALD. Only one postbaseline M184I/V RAM was observed in HIV-1 of an AMBER participant. In EMERALD, baseline archived RAMs to darunavir, emtricitabine, and tenofovir in participants with prior VF did not preclude virologic response.
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AIDS Res. Hum. Retroviruses · Jan 2019
Multicenter Study Observational StudyImmunosuppression and HIV Viremia Associated with More Atherogenic Lipid Profile in Older People with HIV.
To explore reasons for the disproportionate metabolic and cardiovascular disease burdens among older HIV-infected persons, we investigated whether associations of CD4 count and HIV viral load (VL) with non-high-density lipoprotein cholesterol (non-HDL-C) and high-density lipoprotein cholesterol [HDL-C] differed by age. Longitudinal clinical and laboratory data were collected between 2011 and 2016 for HIV-infected outpatients in the DC Cohort study. Using data for patients aged ≥21 years with ≥1 cholesterol result and contemporaneous CD4/VL results, we created multivariable linear regression models with generalized estimating equations. ⋯ Although no age differences were detected for HDL-C, VL ≥200 copies/mL was more strongly associated with lower HDL-C concentrations when CD4 count was <200 cells/μL [β = -7.0 mg/dL (95% CI: -9.7 to -4.3)] versus 200-500 cells/μL [β = -4.2 (95% CI: -5.9 to -2.6)] or >500 cells/μL [β = -2.2 (95% CI: -3.7 to -0.8)] (CD4-VL interaction, p < .01). We detected a novel age-modified relationship between immunosuppression and viremia and atherogenic cholesterol patterns. These findings may contribute to our understanding of the high risk of dyslipidemia observed among persons aging with HIV.
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AIDS Res. Hum. Retroviruses · Apr 2018
Randomized Controlled Trial Multicenter Study Comparative Study Clinical TrialSuperior Efficacy and Improved Renal and Bone Safety After Switching from a Tenofovir Disoproxil Fumarate- to a Tenofovir Alafenamide-Based Regimen Through 96 Weeks of Treatment.
We previously demonstrated superior efficacy and safety advantages in HIV-infected, virologically suppressed adults switched to a regimen containing tenofovir alafenamide (TAF) as compared with those remaining on a tenofovir disoproxil fumarate (TDF) regimen through week 48. We now report long-term data through week 96. In this randomized, active-controlled, multicenter, open-label, noninferiority trial (ClinicalTrials.gov No. ⋯ Significant improvements in urine protein or albumin to creatinine ratios were also seen among those in the TAF group versus TDF through week 96 (p < .001). There were no cases of investigator-reported proximal renal tubulopathy in the TAF group as compared with one case in the TDF group. Switching to EVG/COBI/FTC/TAF (E/C/F/TAF) was associated with statistically significant efficacy and safety advantages over remaining on a standard-of-care TDF-based regimen.
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AIDS Res. Hum. Retroviruses · Sep 2013
Multicenter StudySafety and immunovirologic outcomes with maraviroc combination regimens in patients with a history of past treatment failures and virologic resistance in Brazil: an open-label, multicenter phase 3b study.
Maraviroc is a first-in-class chemokine coreceptor type-5 (CCR5) antagonist with demonstrated immunovirologic activity in treatment-experienced (TE) patients with CCR5 (R5)-tropic HIV-1; however, experience in regimens containing newer antiretroviral agents is limited. The primary objective of this 96-week open-label, noncomparative, multicenter Phase 3b study (NCT00478231) was to assess the safety of maraviroc in combination with optimized background therapy (OBT), which could include recently introduced agents such as darunavir and raltegravir in TE patients in Brazil with R5 HIV-1 and limited therapeutic options. Immunovirologic activity was a secondary endpoint. ⋯ Median CD4(+) cell count increased throughout the study; the mean change from baseline to end of treatment was 174.1 cells/μl. In conclusion, maraviroc, combined with different agents from multiple classes, was well tolerated in highly TE patients. Maraviroc plus OBT was associated with an immunovirologic response in this population.
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AIDS Res. Hum. Retroviruses · Apr 2009
Randomized Controlled Trial Multicenter Study Comparative StudyComparison of once-daily fosamprenavir boosted with either 100 or 200 mg of ritonavir, in combination with abacavir/lamivudine: 96-week results from COL100758.
The long-term efficacy of once-daily (qd) fosamprenavir (FPV) 1400 mg boosted by ritonavir 100 mg (FPV/r100) has not been evaluated previously. A 96-week open-label, randomized, multicenter study compared the efficacy/safety of FPV/r100 with FPV 1400 mg boosted by ritonavir 200 mg qd (FPV/r200), plus abacavir/lamivudine 600 mg/300 mg qd, in antiretroviral-naive, HIV-infected patients with viral load (VL)> or =1000 copies/ml. Primary endpoints were proportion of patients achieving VL <400 copies/ml or discontinuing for drug-related reasons. ⋯ At week 96, more FPV/r100-treated patients had VL <400 copies/ml [ITT-E,M = F: 78% (45/58) vs. 53% (30/57), p = 0.006; observed: 98% (45/46) vs. 94% (30/32)] and VL<50 copies/ml [ITT-E,M = F: 66% (38/58) vs. 53% (30/57); observed: 83% (38/46) vs. 94% (30/32)]. The FPV/r100 and FPV/r200 arms were similar at week 96 regarding median change from baseline in CD4(+) count (+265 vs. +260 cells/mm(3)) and total cholesterol (+33 vs. +35 mg/dl), and in total-cholesterol:HDL-cholesterol ratio (4.0 vs. 4.1) and type/frequency of treatment-related grade 2-4 adverse events, although FPV/r100 was associated with a lower elevation in triglycerides (+27 vs. +48 mg/dl). In conclusion, through 96 weeks, FPV/r100 was more effective and prompted less elevation in triglycerides than FPV/r200.