Switch to Ritonavir-Boosted versus Unboosted Atazanavir plus Raltegravir Dual-Drug Therapy Leads to Similar Efficacy and Safety Outcomes in Clinical Practice.

Pierre Gantner,Michèle Treger,Pascal Pugliese,Thomas Jovelin,Firouze Bani-Sadr,Rodolphe Garraffo,Pierre-Marie Roger,David Rey

doi:10.1371/journal.pone.0164240

Abstract

ObjectivesTo assess immunovirological response, safety and pharmacokinetic of NRTI-sparing regimen dual therapy of atazanavir (ATV) and raltegravir (RAL) in maintenance strategy.MethodsA retrospective analysis was conducted on a cohort of HIV-infected adults followed in French centers (Dat’AIDS cohort), comparing the proportions of virological and therapeutic failures between ATV + RAL and ATV/ritonavir + RAL dual therapy regimens.Results283 patients were assessed: 185 switched for ATV + RAL and 98 for ATV/ritonavir + RAL dual therapy. Virological failure rate at week 96 was 13.8% (95% CI, 9.8–17.8), without difference between the two groups (Log-rank Test, p = 0.87). The cumulative percentages of patients remaining free of therapeutic failure at week 24, 48 and 96 of dual therapy were 74.9% (95% CI, 69.9–80.0), 65.4% (95% CI, 59.8–70.9) and 53.4% (95% CI, 47.5–59.2), respectively. Four out of 39 confirmed virological failures developed RAL resistance. By multivariate analysis, virological failure was associated with high HIV-1 RNA zenith (p = 0.02), low CD4+ T-cell count at baseline (p<0.001) and short duration on antiretroviral therapy (p<0.001). Before week 96, dual therapy was discontinued in 44 patients (16%) because of various adverse events, with no difference between the two groups. Minimal plasma levels were targeted in 84% and 87% of patients for ATV and RAL, respectively, and both were significantly higher in ritonavir-boosted regimen.ConclusionsEmerging RAL-resistance and discontinuations for adverse events resulted in moderate efficacy rates of ATV and RAL dual therapy in heavily pretreated patients.

Highlights

HIV-1 antiretroviral therapy (ART) is a life-long treatment
Virological failure rate at week 96 was 13.8%, without difference between the two groups (Log-rank Test, p = 0.87)
Virological failure was associated with high HIV-1 RNA zenith (p = 0.02), low CD4+ T-cell count at baseline (p

Summary

Introduction

While virological success is achieved in most patients [1], ART often needs to be modified due to adverse events or to prevent long-term toxicity. These long-term complications, have been related to other factors than ART toxicity [2,3] such as a higher prevalence of traditional risk factors [4,5] and HIV replication [6], preventing drug-related toxicity should be considered for ART switch. Switching to maraviroc and raltegravir dual therapy was too “weak” to maintain virological success [7], with a high risk of emerging resistance. Due to insufficient diffusion in cerebro-spinal fluid of the boosted protease inhibitor, a sanctuary replication in central nervous system was noticed [13]

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Conclusion