ABSTRACT
BACKGROUND: Dual therapies decrease toxicity, pill-burden and treatment-associated cost. The combination of high genetic barrier drugs such as dolutegravir plus boosted-darunavir may be suitable as simplification regimen for patients harbouring multidrug-resistant virus. METHODS: Patients switched to a once-daily regimen consisting of dolutegravir plus darunavir, boosted with cobicistat or ritonavir, were included in this cohort study. The primary end point was the proportion of patients with HIV RNA viral load <37 copies/ml at week 48 (NCT02491242). RESULTS: Overall, 51 patients were enrolled. At baseline, all patients had failed to ≥2 antiretroviral classes. Genotypic resistance profiles showed a mean of primary mutations of 1.2 for non-nucleoside reverse transcriptase inhibitors, 2.4 for nucleoside/nucleotide reverse transcriptase inhibitors and 3.5 for protease inhibitors (PIs), but they were virologically suppressed for a median of 33 months (IQR 12-60). Only five patients had reduced sensitivity to darunavir and mean genotypic susceptibility score of dual therapy was 1.95 over 2. At week 48, there were no virological failures, three patients discontinued the regimen due to neuropsychiatric adverse events, two were lost to follow-up, and therefore the efficacy was 90% (95% CI, 82, 99%, intention-to-treat analysis). Mean estimated glomerular filtration rate decreased by 8.8 ml/min/1.73 m2, though kidney tubular parameters, high density lipoprotein-cholesterol and triglycerides levels improved after switching to dual therapy. CONCLUSIONS: In highly treatment-experienced patients who were virologically suppressed, switching to the combination of dolutegravir plus boosted-darunavir dual therapy was effective and well tolerated, improving lipid and renal parameters.
Subject(s)
Darunavir/administration & dosage , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/drug effects , Heterocyclic Compounds, 3-Ring/administration & dosage , Adult , Aged , Antiretroviral Therapy, Highly Active , Darunavir/adverse effects , Drug Resistance, Viral , Female , Heterocyclic Compounds, 3-Ring/adverse effects , Humans , Male , Middle Aged , Oxazines , Piperazines , Pyridones , Treatment Outcome , Viral LoadABSTRACT
INTRODUCTION: Triple combinations of antiretroviral therapy (ART) drugs are the standard treatment for human immunodeficiency virus (HIV) infection, but the challenges include long-term side effects, high costs, and adherence. The recent advent of potent and well-tolerated ART has renewed the interest for newer ART strategies. A dual regimen with the combination of dolutegravir (DTG) and rilpivirine (RPV), two well-tolerated, metabolic-friendly, and potent drugs could offer additional benefits. Areas covered: A review of recent randomized trials and observational cohorts concerning the use of a dual therapy with DTG plus RPV as a switching strategy in patients with viral suppression. Expert commentary: Currently, data of more of 900 patients switched to this dual regimen are available. This combination shows a high rate of virological suppression, above 90% at 48 weeks, few discontinuations due to adverse events, improvement in bone and kidney parameters for patients discontinuing tenofovir disoproxil fumarate, lack of loss of the inflammatory control achieved with triple therapy, and a neutral effect on lipid parameters. Thus, for the first time, a dual regimen without protease inhibitors is effective, avoiding metabolic side effects and drug interactions. Longer follow-up is needed, but this dual regimen appears as a promising strategy for aging HIV-infected patients.
