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Article Dans Une Revue Journal of Antimicrobial Chemotherapy Année : 2016

Dolutegravir as monotherapy in HIV-1-infected individuals with suppressed HIV viraemia

A. Denis

Résumé

Background Reducing drug burden is a key challenge for achieving lifelong suppressive HIV therapy. Dolutegravir, with a high potency, long half-life and high genetic barrier, offers potential for monotherapy. Methods This observational single-centre study enrolled all patients with HIV RNA (viral load) <50 copies/mL for at least 12 months, with CD4 >350 cells/mm3 and with no failure under integrase inhibitor therapy who had switched from suppressive ART to dolutegravir monotherapy (50 mg/day). Primary outcome was proportion of patients with viral load <50 copies/mL at week 24. Results Twenty-eight patients treated for a median ART duration of 17 years (IQR 11–20), virally suppressed for a median of 79 months (IQR 42–95) and with a median CD4 count of 624 cells/mm3 (IQR 524–761), were enrolled. Baseline ART consisted of a three-drug (n = 10), two-drug (n = 10) or single-drug (n = 8) regimen with integrase inhibitor exposure in 13 patients. The proportion of patients maintaining viral load <50 copies/mL was 96% (95% CI 79%–100%) at week 4, 100% (95% CI = 85%–100%) at week 8, 93% (95% CI 76%–99%) at week 12 and 92% (75–99) at week 24. Three patients (3.70%; 95% CI 3.4%–10.8%) with prior integrase inhibitor experience had HIV RNA rebound with the presence of resistance mutations. Genotyping of HIV DNA using the Sanger method or ultradeep sequencing showed no integrase inhibitor resistance-associated mutations (RAMs) except for the mutation 74I in a patient on a suppressive elvitegravir regimen. The median within- and between-subject variability of dolutegravir C24 was 25% and 34%, respectively. Nine patients with a year of follow-up remained virally suppressed. Conclusions Dolutegravir has the potency to be further investigated as a single ART in randomized studies, particularly in patients with no prior exposure to integrase inhibitors.
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Dates et versions

hal-01340219 , version 1 (30-06-2016)

Identifiants

Citer

C. Katlama, C. Soulié, F. Caby, A. Denis, C. Blanc, et al.. Dolutegravir as monotherapy in HIV-1-infected individuals with suppressed HIV viraemia. Journal of Antimicrobial Chemotherapy, 2016, 71 (9), pp.2646-2650. ⟨10.1093/jac/dkw186⟩. ⟨hal-01340219⟩
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