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

Abstract

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

Switching antiretroviral regimes for the treatment of HIV: safety implications

“…A randomized multicentre study [14] has shown that this switch maintained A greater increase in total cholesterol, HDL and LDL was also observed in switch arm without differences in other lipid parameters. Renal function showed a significant improvement in switch arm.…”

“…Another option to simplify the regime in patients on a PI is to switch from tenofovir/emtricitabine (TDF/FTC) + ATV/r to ABC/3TC + ATV [14]. However, it should be noticed that, because of ATV-TDF interaction, the combination of TDF/FTC plus unboosted ATV is not a viable option [15].…”

“…PI present, as their main toxicity problems, a worse lipid profile, eventually leading to an increased cardiovascular risk in the case of lopinavir (LPV) and indinavir (IDV), the appearance of jaundice and hyperbilirubinaemia in the case of ATV, and a greater incidence of renal dysfunction in patients treated with LPV/r and ATV/r (probably due to interaction with TDF) and diarrhoea secondary to RTV [13,14].…”

British HIV Association guidelines for the treatment of HIV‐1‐positive adults with antiretroviral therapy 2015

“…However, switching to simplify to a triple nucleoside regimen is not recommended . For PIs, recent studies have evaluated both within‐class switching and simplification to an unboosted regimen . These changes have been to reduce bilirubin, lipids or bone and renal biomarkers.…”

Ιn Vivo Effects of Tenofovir-DF/Emtricitabine and Abacavir/Lamivudine with Atazanavir-R on Platelet Activating Factor Metabolism in HIV Naive Patients

“…A number of studies also suggest that treatment with tenofovir-DF/ emtricitabine with atazanavir-r decreases inflammatory and hypercoagulation markers [17][18][19] but tenofovir-DF has been associated with renal impairment especially when combined with PIs such as atazanavir-r [20][21][22][23]. On the other hand, conflicting results occur concerning the effect of abacavir/lamivudine/atazanavir-r regimen on markers of systemic and/or chronic inflammation [17,18,24,25].…”