Virological factors associated with outcome of dual maraviroc/raltegravir therapy (ANRS-157 trial)

Soulié, Cathia; Assoumou, Lambert; Darty, Mélanie; Rodriguez, Christophe; Donati, Flora; Sayon, Sophie; Peytavin, Gilles; Valantin, Marc‐Antoine; Caby, Fabienne; Schneider, Luminita; Canestri, Ana; Costagliola, Dominique; Katlama, Christine; Cálvez, Vincent; Marcelin, Anne–Geneviève

doi:10.1093/jac/dkv280

Cited by 5 publications

(2 citation statements)

References 13 publications

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“…However, in the ROCnRAL study, presence of minority X4-tropic viral variants was not associated with virological failure. 20 (ii) Since the patients were already under antiretroviral treatment in the ROCnRAL study, the tropism was determined on cellular proviral DNA, whilst it was determined on plasma RNA in our study. It has been suggested that proviral DNA was not as representative of the different viral populations as RNA, which could explain the emergence of non-R5 viruses at failure in the ROCnRAL study.…”

Section: Discussionmentioning

confidence: 99%

Maraviroc/raltegravir simplification strategy following 6 months of quadruple therapy with tenofovir/emtricitabine/maraviroc/raltegravir in treatment-naive HIV patients

Pradat

Durant

Brochier

et al. 2016

J. Antimicrob. Chemother.

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Section: Discussionmentioning

confidence: 99%

Maraviroc/raltegravir simplification strategy following 6 months of quadruple therapy with tenofovir/emtricitabine/maraviroc/raltegravir in treatment-naive HIV patients

Pradat

Durant

Brochier

et al. 2016

J. Antimicrob. Chemother.

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“…Indeed, switching to maraviroc and raltegravir dual therapy was too “weak” to maintain virological success [7], with a high risk of emerging resistance. Besides, no predictors of virological failure were identified [9]. Conversely, darunavir/ritonavir or lopinavir/ritonavir monotherapy exhibited efficacy rate concordant with triple drug regimen [10,11], with no selection of major resistant variants at failure [12].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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.

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Current and emerging two-drug approaches for HIV-1 therapy in ART-naïve and ART-experienced, virologically suppressed patients

Rossetti

Montagnani

Luca

2018

Expert Opinion on Pharmacotherapy

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Current guidelines recommend a 2-drug antiretroviral regimen as an alternative to triple antiretroviral therapy (ART) in selected patients to reduce long-term toxicity and costs. Areas covered: This review is intended to provide insight into the efficacy, safety and tolerability of 2-drug versus 3-drug ART in naïve and in treatment-experienced virologically-suppressed patients. Expert opinion: Dual therapy regimens are not feasible in HBV-coinfected individuals and should not be applied during pregnancy. Positive data on 2-drug ART in drug naïve patients are still limited, while, in virologically-suppressed individuals, several regimens have shown non-inferiority as compared to 3-drug regimens. The strongest evidence of efficacy applies to ritonavir-boosted PI regimens combined with lamivudine and to dolutegravir with rilpivirine. Dual therapies showed improved renal function and bone mineral density over tenofovir disoproxil fumarate-based 3-drug regimens. There are also great expectations for ongoing phase 3 trials testing dolutegravir with lamivudine. New and future single tablet co-formulations of dual regimens are expected to improve their suitability. Despite the lack of comparison with tenofovir alafenamide-based 3-drug regimens, the 2-drug regimens showing consistent non-inferiority and safety versus 3-drug regimens will challenge the current paradigm of 3-drug ART.

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Virological factors associated with outcome of dual maraviroc/raltegravir therapy (ANRS-157 trial)

Abstract: Maraviroc plus raltegravir failed to maintain virological suppression in virologically suppressed HIV-1-infected patients. However, neither minority viral variants nor ultrasensitive viraemia was found to be a predictive factor of VF or virological rebound in this context.

Cited by 5 publications

References 13 publications

Maraviroc/raltegravir simplification strategy following 6 months of quadruple therapy with tenofovir/emtricitabine/maraviroc/raltegravir in treatment-naive HIV patients

Maraviroc/raltegravir simplification strategy following 6 months of quadruple therapy with tenofovir/emtricitabine/maraviroc/raltegravir in treatment-naive HIV patients

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

Current and emerging two-drug approaches for HIV-1 therapy in ART-naïve and ART-experienced, virologically suppressed patients

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