Effectiveness of dolutegravir‐based regimens as either first‐line or switch antiretroviral therapy: data from the Icona cohort

Abstract

IntroductionConcerns about dolutegravir (DTG) tolerability in the real‐life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG‐based regimens from a large cohort of HIV‐infected individuals.MethodsWe performed a multicentre, observational study including all antiretroviral therapy (ART)‐naïve and virologically suppressed treatment‐experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG‐based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan–Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation.ResultsAbout 1679 individuals (932 ART‐naïve, 747 TE) were included. The one‐ and two‐year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART‐naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART‐naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART‐naïve (2.1%) and TE (1.7%) patients. In ART‐naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG‐based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC‐based triple‐therapies, aHR = 3.56, p = 0.012 for tenofovir‐based) and for toxicity (aHR = 5.26, p = 0.030 for ABC‐based, aHR = 6.60, p = 0.024 for tenofovir‐based). The one‐ and two‐year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group.ConclusionsIn this large cohort, DTG showed excellent efficacy and optimal tolerability both as first‐line and switching ART. The low risk of treatment‐limiting toxicities in ART‐naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice.

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

“…However, to date, the rate of discontinuation of DTG-based therapies for NP-AEs has not been confirmed in a uniform way. Ours (3.9%) is concordant with those reported in some real-life studies, 17-25 which ranged between 1.7% and 5.6%. In contrast, this rate was significantly higher in 2 cohorts 7,8 (8.3% and 9.9%) and lower in the other 2, with only 0.6% and 0.7% of the patients having to stop DTG because of NP-AEs.…”

“…The frequency of AEs identified in our study was high (42.2%), with an incidence of interruptions for this reason of 8.7% at W48 (13.6% and 7.6% in ART-naive and TE patients, respectively). Our rates of AEs leading to DTG/ABC/3TC discontinuation were higher than those reported in clinical trials with DTG 1-6 (which ranged between 2.0% and 4.0% within the first year), but also in the CoRIS 15 and ICONA 17 cohorts, which reported an incidence of 3.6 and 3.9%, respectively. In contrast, the rate reported in the TRIUMPH Cohort 16 was closer to ours, with an incidence of interruptions caused by AEs of 6.9%.…”

Impact of Tenofovir/Lamivudine/Dolutegravir (Tld) on the Health-Related Quality of Life and Clinical Outcomes of HIV/AIDS Patients at a Tertiary Health Facility in Niger State

“…Furthermore, a short duration of 3 months of viral suppression seen as against one-year or longer duration to a achieve reasonable viral suppression with other combinations is in agreement of earlier ndings of Rhangale and colleagues (21). similarly, Annalisa and colleagues have reported the clinical e cacy and tolerability of DTG-based regimen (22). This will prevent the possible development of resistance as seen with other combinations.…”

Treatment Satisfaction and Its Associated Factors of Dolutegravir Based Regimen in a Resource Limited Setting

“…This result agrees with other studies, 22 , 23 which reported high treatment satisfaction with dolutegravir based regimen. This higher treatment satisfaction with dolutegravir based regimen could be due to the reason that dolutegravir based regimen is more effective, 24 easier to use, and has fewer side effects 25 than alternative drugs that are currently used. This can also partially be explained by the fact that dolutegravir reduces pill burden and its simplification which allows once-daily administration, 26 which in turn increases treatment satisfaction.…”