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Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1.

ABSTRACT: Limited data compare once-daily options for initial therapy for HIV-1.To compare time to virologic failure; first grade-3 or -4 sign, symptom, or laboratory abnormality (safety); and change or discontinuation of regimen (tolerability) for atazanavir plus ritonavir with efavirenz-containing initial therapy for HIV-1.A randomized equivalence trial accrued from September 2005 to November 2007, with median follow-up of 138 weeks. Regimens were assigned by using a central computer, stratified by screening HIV-1 RNA level less than 100 000 copies/mL or 100 000 copies/mL or greater; blinding was known only to the site pharmacist. (ClinicalTrials.gov registration number: NCT00118898)59 AIDS Clinical Trials Group sites in the United States and Puerto Rico.Antiretroviral-naive patients.Open-label atazanavir plus ritonavir or efavirenz, each given with with placebo-controlled abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine.Primary outcomes were time to virologic failure, safety, and tolerability events. Secondary end points included proportion of patients with HIV-1 RNA level less than 50 copies/mL, emergence of drug resistance, changes in CD4 cell counts, calculated creatinine clearance, and lipid levels.463 eligible patients were randomly assigned to receive atazanavir plus ritonavir and 465 were assigned to receive efavirenz, both with abacavir-lamivudine; 322 (70%) and 324 (70%), respectively, completed follow-up. The respective numbers of participants in each group who received tenofovir DF-emtricitabine were 465 and 464; 342 (74%) and 343 (74%) completed follow-up. Primary efficacy was similar in the group that received atazanavir plus ritonavir and and the group that received efavirenz and did not differ according to whether abacavir-lamivudine or tenofovir DF-emtricitabine was also given. Hazard ratios for time to virologic failure were 1.13 (95% CI, 0.82 to 1.56) and 1.01 (CI, 0.70 to 1.46), respectively, although CIs did not meet prespecified criteria for equivalence. The time to safety (P = 0.048) and tolerability (P < 0.001) events was longer in persons given atazanavir plus ritonavir than in those given efavirenz with abacavir-lamivudine but not with tenofovir DF-emtricitabine.Neither HLA-B*5701 nor resistance testing was the standard of care when A5202 enrolled patients. The third drugs, atazanavir plus ritonavir and efavirenz, were open-label; the nucleoside reverse transcriptase inhibitors were prematurely unblinded in the high viral load stratum; and 32% of patients modified or discontinued treatment with their third drug.Atazanavir plus ritonavir and efavirenz have similar antiviral activity when used with abacavir-lamivudine or tenofovir DF-emtricitabine.National Institutes of Health.

SUBMITTER: Daar ES

PROVIDER: S-EPMC3430716 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1.

Daar Eric S ES Tierney Camlin C Fischl Margaret A MA Sax Paul E PE Mollan Katie K Budhathoki Chakra C Godfrey Catherine C Jahed Nasreen C NC Myers Laurie L Katzenstein David D Farajallah Awny A Rooney James F JF Pappa Keith A KA Woodward William C WC Patterson Kristine K Bolivar Hector H Benson Constance A CA Collier Ann C AC

Annals of internal medicine 20110214 7

<h4>Background</h4>Limited data compare once-daily options for initial therapy for HIV-1.<h4>Objective</h4>To compare time to virologic failure; first grade-3 or -4 sign, symptom, or laboratory abnormality (safety); and change or discontinuation of regimen (tolerability) for atazanavir plus ritonavir with efavirenz-containing initial therapy for HIV-1.<h4>Design</h4>A randomized equivalence trial accrued from September 2005 to November 2007, with median follow-up of 138 weeks. Regimens were assi ...[more]

PMID: 21320923

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Project description:The current study was conducted to determine if efavirenz (EFV) or atazanavir/ritonavir (ATV/r)-based combination antiretroviral therapy (cART) impacted steady-state atovaquone plasma concentrations in human immunodeficiency virus (HIV)-infected patients receiving treatment doses of atovaquone.Thirty HIV-infected volunteers were recruited, 10 taking no cART and 10 each taking cART that included EFV or ATV/r. Subjects were randomly assigned to atovaquone 750 mg twice daily (BID) for 14 days followed by atovaquone 1500 mg BID for 14 days, or vice-versa, with a washout period in between. On day 14 of each phase, blood was sampled for pharmacokinetic studies, and the area under the concentration-time curve (AUC?) and average concentration (C avg) were calculated and compared using an unpaired t test.Twenty-nine subjects completed both dosing cohorts. Subjects receiving EFV-based cART had 47% and 44% lower atovaquone AUC? than subjects not receiving cART at atovaquone doses of 750 mg BID and 1500 mg BID, respectively (P? .01). Only 5 of 10 subjects receiving EFV-based cART plus atovaquone 750 mg BID had an atovaquone C avg>15 µg/mL, which has previously been associated with successful treatment of Pneumocystis jirovecipneumonia. AUC? and Cavg did not significantly differ for concurrent ATV/r for 750 mg BID or 1500 mg BID when compared to the group not receiving cART. Nine of 10 subjects not receiving cART, 8 of 10 subjects receiving ATV/r, and 2 of 10 subjects receiving EFV in combination with atovaquone 750 mg BID achieved an atovaquone C avg>18.5 µg/mL, a concentration that has previously been associated with successful treatment of Toxoplasmaencephalitis (TE).These data suggest that the currently recommended dose of atovaquone 750 mg BID for treatment of mild to moderate PCP may not be adequate in patients receiving concurrent EFV. Furthermore, doses lower than the currently recommended dose of 1500 mg BID may achieve plasma concentrations adequate to treat TE in HIV-infected patients not receiving EFV.NCT01479361.

Project description:BackgroundAlbuvirtide (ABT), a fusion inhibitor against human immunodeficiency virus (HIV) infection, has good efficacy and tolerability for HIV treatment. However, there is a paucity of data regarding ABT-based regimen as second-line therapy. This current study evaluated the efficacy and safety of switching to ABT + ritonavir-boosted lopinavir (LPV/r) treatment in a cohort of HIV-infected individuals who failed initial treatment.MethodsThis retrospective comparative cohort study included patients who failed initial treatment and switched to either ABT + LPV/r (the ABT group) or two nucleotide reverse transcriptase inhibitors (NRTIs) + LPV/r (the NRTI group) between November 2019 and December 2020 in the People's Hospital of Zhaojue County in Liangshan Yi Autonomous Prefecture, China. All individuals were followed up from baseline to 12 weeks after conversion, or until the patient developed unacceptable toxic effects or was loss of follow-up. The proportion of patients who achieved virological suppression (viral load <50 copies/mL) at week 12 was considered a primary efficacy endpoint. Safety outcomes included the incidence of adverse events and laboratory abnormalities. All participants underwent resistance testing before regimen conversion. The linear regression model was applied to evaluate the association of CD4+ T cell count with the patient's clinical characteristics.ResultsA total of 71 patients were included in this study, the two groups were comparable at baseline in terms of age, sex, CD4+ T cell count, and viral load. The suppression of HIV-1 RNA to levels <50 copies/mL was achieved in 82.4% (28/31) and 29.7% (11/34) of patients in the ABT group and the NRTI group, respectively (P<0.001). Older age (P=0.016) and higher alkaline phosphatase (ALP) levels (P=0.038), but not rescue regimen, were associated with attenuated CD4+ T cell recovery. Most adverse events mild in severity, with abdominal pain as the most reported event in two groups (26.8%, 19/71), and no severe adverse events were detected.ConclusionsConversion to ABT + LPV/r therapy appears to be an effective and safe strategy. This treatment regimen has great potential to be generalized in the HIV-infected population, although further testing in a larger patient population is required to verify these results.

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Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1.

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Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1.

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