Pharmacologic Boosting of Atazanavir in Maintenance HIV-1 Therapy: The COREYA Propensity-Score Adjusted Study

Hocqueloux, Laurent; Choisy, P.; Moal, G. Le; Borsa-Lebas, F.; Plainchamp, D; Legac, Éric; Prazuck, Thiérry; Tribonnière, Xavier de la; Yazdanpanah, Yazdan; Parienti, Jean‐Jacques

doi:10.1371/journal.pone.0049289

Cited by 6 publications

(5 citation statements)

References 20 publications

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“…Atazanavir (ATV) is a well-tolerated protease inhibitor (PI) whose plasma concentration and genetic barrier to resistance are improved by coadministration with low-dose ritonavir (RTV) [1] , [2] . However, use of RTV is associated with higher rates of gastrointestinal adverse events, elevated lipid levels and, when given with ATV, an increased risk of indirect hyperbilirubinemia [1] , [3] – [5] . As an inhibitor of the CYP3A metabolic pathway, RTV also interacts with many drugs and co-administration is contraindicated for a number of antiarrhythmics, ergot derivatives, sedative/hypnotics, and statins, among others.…”

Section: Introductionmentioning

confidence: 99%

Simplification to Abacavir/Lamivudine + Atazanavir Maintains Viral Suppression and Improves Bone and Renal Biomarkers in ASSURE, a Randomized, Open Label, Non-Inferiority Trial

et al. 2014

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ObjectiveSimplification of antiretroviral therapy in patients with suppressed viremia may minimize long-term adverse effects. The study’s primary objective was to determine whether abacavir/lamivudine + atazanavir (ABC/3TC+ATV) was virologically non-inferior to tenofovir/emtricitabine + atazanavir/ritonavir (TDF/FTC+ATV/r) over 24 weeks in a population of virologically suppressed, HIV-1 infected patients.DesignThis open-label, multicenter, non-inferiority study enrolled antiretroviral experienced, HIV-infected adults currently receiving a regimen of TDF/FTC+ATV/r for ≥6 months with no history of virologic failure and whose HIV-1 RNA had been ≤75 copies/mL on 2 consecutive measurements including screening. Patients were randomized 1∶2 to continue current treatment or simplify to ABC/3TC+ATV.MethodsThe primary endpoint was the proportion of patients with HIV-RNA<50 copies/mL at Week 24 by the Time to Loss of Virologic Response (TLOVR) algorithm. Secondary endpoints included alternative measures of efficacy, adverse events (AEs), and fasting lipids. Exploratory endpoints included inflammatory, coagulation, bone, and renal biomarkers.ResultsAfter 24 weeks, ABC/3TC+ATV (n = 199) was non-inferior to TDF/FTC+ATV/r (n = 97) by both the primary analysis (87% in both groups) and all secondary efficacy analyses. Rates of grade 2–4 AEs were similar between the two groups (40% vs 37%, respectively), but an excess of hyperbilirubinemia made the rate of grade 3–4 laboratory abnormalities higher in the TDF/FTC+ATV/r group (30%) compared with the ABC/3TC+ATV group (13%). Lipid levels were stable except for HDL cholesterol, which increased significantly in the ABC/3TC+ATV group. Bone and renal biomarkers improved significantly between baseline and Week 24 in patients taking ABC/3TC+ATV, and the difference between groups was significant at Week 24. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment groups.ConclusionsAfter 24 weeks, simplification to ABC/3TC+ATV from TDF/FTC+ATV/r maintained viral suppression was well-tolerated, and led to improvements in bone and renal biomarkers and HDL cholesterol.Trial RegistrationClinicalTrials.gov NCT01102972 GlaxoSmithKline Clinical Study Register #113734

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Section: Introductionmentioning

confidence: 99%

Simplification to Abacavir/Lamivudine + Atazanavir Maintains Viral Suppression and Improves Bone and Renal Biomarkers in ASSURE, a Randomized, Open Label, Non-Inferiority Trial

et al. 2014

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“…Of note, atazanavir had the highest incidence of DDIs in our study (Figure 1). Removing the booster is only safe for atazanavir and can be attractive among aging PLWH with cardiovascular comorbidities [26]. However, it also increases the risk of subtherapeutic levels due to DDIs.…”

Section: Discussionmentioning

confidence: 99%

Risk and Cost Associated With Drug–Drug Interactions Among Aging HIV Patients Receiving Combined Antiretroviral Therapy in France

Demessine

Paul

Gardner

et al. 2019

Open Forum Infectious Diseases

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Background We aimed to describe the frequency, risk factors, and costs attributable to drug–drug interactions (DDIs) among an aging French HIV population. Methods We conducted a retrospective cohort study using French nationwide health care e-records: the SNIIRAM database. People living with HIV (PLWH) aged >65 years and receiving combined antiretroviral treatment (cART) during 2016 were included. A DDI was defined as “These drugs should not be co-administered,” represented by a red symbol on the University of Liverpool website. Attributable DDIs’ cost was defined as the difference between individuals with and without DDIs regarding all reimbursed health care acts. Results Overall, 9076 PLWH met the study criteria. Their baseline characteristics were: mean age, 71.3 ± 4.9 years; 25% female; median HIV duration (interquartile range [IQR]), 16.2 (9.5–20.3) years; median comorbidities (IQR), 2 (1–3). During 2016, they received a median (IQR) of 14 (9–21) comedications (non-cART), and 1529 individuals had at least 1 DDI (16.8%; 95% confidence interval [CI], 16.1–17.6). In multivariate analysis, raltegravir or dolutegravir plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs) significantly and independently reduced the risk of DDIs (adjusted odds ratio [aOR], 0.02; 95% CI, 0.005–0.050; P < .0001) compared with non-nucleoside reverse-transcriptase inhibitor plus 2 NRTIs, whereas cART with boosted agents (protease inhibitors or elvitegravir) significantly increased the risk (aOR, 4.12; 95% CI, 3.34–5.10; P < .0001). Compared with propensity score–matched PLWH without DDIs, the presence of DDIs was associated with a $2693 additional cost per year (P < .0001). Conclusions The presence of DDIs is frequent and significantly increases health care costs in the aging population of PLWH.

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“…Depending on the other regimen components, ritonavir discontinuation may also eliminate concern about cytochrome P4503A (CYP3A)‐mediated drug interactions with other drugs [2–10]. While atazanavir is a generally well‐tolerated protease inhibitor (PI) whose plasma concentration and genetic barrier to resistance are improved by coadministration with ritonavir, the combination is also associated with an increased risk of indirect hyperbilirubinaemia [11–13], which, when accompanied by scleral icterus, can prompt treatment discontinuation [14].…”

Section: Introductionmentioning

confidence: 99%

The ASSURE study: HIV‐1 suppression is maintained with bone and renal biomarker improvement 48 weeks after ritonavir discontinuation and randomized switch to abacavir/lamivudine + atazanavir

Wohl

Bhatti

et al. 2015

HIV Medicine

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Objectives HIV treatment guidelines endorse switching or simplification of antiretroviral therapy in therapy‐experienced patients with suppressed viraemia; ritonavir discontinuation may also enhance tolerability and reduce long‐term adverse events (AEs). This open‐label, multicentre, noninferiority study enrolled HIV‐1‐infected, treatment‐experienced adults with confirmed HIV‐1 RNA ≤ 75 HIV‐1 RNA copies/mL currently receiving tenofovir/emtricitabine + atazanavir/ritonavir (TDF/FTC + ATV/r) for ≥ 6 months with no reported history of virological failure.MethodsParticipants were randomized 1:2 to continue current treatment or switch to abacavir/lamivudine + atazanavir (ABC/3TC + ATV). Endpoints included the proportion of participants with HIV‐1 RNA < 50 copies/mL by time to loss of virological response (TLOVR), AEs, fasting lipids, and inflammatory, coagulation, bone and renal biomarkers.ResultsAfter 48 weeks, 76% (152 of 199) of ABC/3TC + ATV‐treated and 79% (77 of 97) of TDF/FTC + ATV/r‐treated participants had HIV‐1 RNA < 50 copies/mL (TLOVR; P = 0.564). Other efficacy analyses yielded similar results. Rates of new grade 2–4 AEs were 45% in both groups, but an excess of hyperbilirubinaemia made the rate of treatment‐emergent grade 3–4 laboratory abnormalities higher with TDF/FTC + ATV/r (36%) compared with ABC/3TC + ATV (19%). Most fasting lipid levels remained stable over time; high‐density lipoprotein (HDL) cholesterol increased modestly in ABC/3TC + ATV‐treated participants. Bone and renal biomarkers improved significantly between baseline and week 48 in participants taking ABC/3TC + ATV and were stable in participants taking TDF/FTC + ATV/r. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment groups.ConclusionsThe ABC/3TC + ATV treatment‐switch group had similar viral suppression rates up to 48 weeks to the TDF/FTC + ATV/r comparator group, with lower rates of moderate‐ to high‐grade hyperbilirubinaemia and improvements in bone and renal biomarkers.

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Pharmacologic Boosting of Atazanavir in Maintenance HIV-1 Therapy: The COREYA Propensity-Score Adjusted Study

Cited by 6 publications

References 20 publications

Simplification to Abacavir/Lamivudine + Atazanavir Maintains Viral Suppression and Improves Bone and Renal Biomarkers in ASSURE, a Randomized, Open Label, Non-Inferiority Trial

Simplification to Abacavir/Lamivudine + Atazanavir Maintains Viral Suppression and Improves Bone and Renal Biomarkers in ASSURE, a Randomized, Open Label, Non-Inferiority Trial

Risk and Cost Associated With Drug–Drug Interactions Among Aging HIV Patients Receiving Combined Antiretroviral Therapy in France

The ASSURE study: HIV‐1 suppression is maintained with bone and renal biomarker improvement 48 weeks after ritonavir discontinuation and randomized switch to abacavir/lamivudine + atazanavir

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