Effectiveness, Safety, and Costs of Dolutegravir/Abacavir/Lamivudine Single-Tablet Regimen in a Real-Life Cohort of HIV-1 Adult Infected Patients

Abstract

Background: Real-life data on single-tablet regimen (STR) dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) is scarce, and concerns about DTG neuropsychiatric adverse events (NP-AEs) have recently arisen. Objective: To explore the effectiveness and safety, in particular NP-AEs, of DTG/ABC/3TC in a cohort of HIV-1 adult infected patients. Pill burden, adherence to this STR, and the impact of switching on costs were also evaluated. Methods: This was an observational, retrospective study. The study population included antiretroviral therapy (ART)-naive and treatment-experienced (TE) patients who started DTG/ABC/3TC between February 1, 2016, and October 31, 2016. Effectiveness and safety were analyzed at week 48 (W48) by intention-to-treat analysis. The Cox regression model was used to investigate predictors of DTG/ABC/3TC discontinuation. Results: A total of 253 patients were included (44 ART naïve, 209 TE). At W48, the proportion of patients with virological suppression was 72.7% (95% CI = 58.4-87.0) in ART-naive patients, 85.6% (95% CI = 80.3-90.9) in previously suppressed TE patients, and 86.4% (95% CI = 65.1-97.1) in previously not suppressed TE patients. The rate of protocol-defined virological failure was 4.3%. The incidence of AEs was higher in the subgroup of ART-naive patients (56.1% vs 39.0%), with a rate of interruptions for this reason of 13.6% and 7.6%, respectively. The incidence of NP-AEs was 20.6%, with 3.9% of patients requiring discontinuation. Patients who had switched from a raltegravir-containing regimen discontinued DTG/ABC/3TC because of AEs more frequently (relative risk = 2.83; 95% CI = 1.04-7.72; P = 0.041) in the multivariate analysis. After switching to DTG/ABC/3TC, the median pill burden was reduced from 3 to 1 and the proportion of patients with an adherence <90%, from 20.1% to 12.0%. The annual per-patient ART costs increased by €48 (0.6% increase). Conclusion and Relevance: DTG/ABC/3TC is an effective strategy as first-line and switching ART. Our data suggest a worse tolerance in ART-naive patients, although the rate of discontinuation resulting from NP-AEs was relatively low. In the short-term, the adherence was slightly improved without significant changes in costs.

Experience With Dolutegravir in Hiv Patients at a Public Sector Hospital in Karachi, Pakistan

“…We reported adverse effects attributed to DTG in 19.7%, whereas in other studies adverse effects in 35%, 39% and 42.2% of patients have been reported. 8,11,15 Discontinuation rates due to neuropsychiatric effects were reported in 5.6% of patients by Hoffman et al, and in 6.9% by Cid-Silva et al, whereas only 1 patient reported depression after starting DTG which did not lead to discontinuation in this study. 16,17 SACP centre demonstrated prompt initiation of ARV and maintained a steady supply of ARVs.…”

Adherence, Effectiveness and Safety of Dolutegravir Based Antiretroviral Regimens among HIV Infected Children and Adolescents in Tanzania

“… 43 , 46 , 47 The increase in serum creatinine during DTG treatment is due to inhibition of the renal organic cation transporter (OCT) 2 which reduces the tubular secretion of creatinine. 46 Only a small proportion of DTG dose (< 1%) is excreted unchanged in the urine; therefore, currently, no dosage adjustments are recommended for DTG in patients with renal impairment. 48 In our study, the mean creatinine level of patients was in a normal range.…”

Efficacy and durability of two‐ vs. three‐drug integrase inhibitor‐based regimens in virologically suppressed HIV‐infected patients: Data from real‐life ODOACRE cohort

“…As a consequence, InSTI-based regimens are currently recommended by major international guidelines as first-line therapy [8,9] and they are increasingly used for treatment optimization in order to improve short-and long-term tolerability, reduce drug-drug interactions and improve convenience (e.g. reduced pill burden and/or dosing frequency) of ART [10][11][12][13].…”