Efficacy, durability, and tolerability of dolutegravir/lamivudine and dolutegravir/rilpivirine for the treatment of HIV in a real‐world setting in Belgium

Abstract

Objectives A paradigm shift from three‐drug regimens to two‐drug regimens (2DRs) is currently taking place in real‐world clinical practice. This study aimed to describe the efficacy, durability, and tolerability of dolutegravir (DTG)/lamivudine (3TC) and DTG/rilpivirine (RPV) in a real‐world setting. Methods This was a retrospective, observational, multicentre (ten centres in Belgium) study involving adult treatment‐naïve and treatment‐experienced people living with HIV on DTG/3TC or DTG/RPV between 1 January 2019 and 30 September 2020. The primary endpoint was rate of virological suppression (VS; plasma HIV‐1 viral load [VL] <50 copies/ml) using an on‐treatment analysis. Main secondary endpoints included the proportion of people that experienced loss of VS (LVS; defined as two consecutive HIV‐1 VLs of >200 copies/ml after initially achieving VS) and a resistance analysis at the time of LVS; rate, incidence, and reasons for discontinuation of treatment (stopping treatment or changing any component of the 2DR); and change in weight, along with the proportion of people reporting a >10% weight gain. Ordinal logistic regression analysis examined associations between baseline variables and >10% on‐treatment weight gain. Results Overall, 948 people were included, of whom 734 (77%) were on DTG/3TC and 214 (23%) were on DTG/RPV. Baseline characteristics included 54% aged ≥50 years, 31% female, 31% Black sub‐Saharan African, 95% treatment‐experienced, and 8% with HIV‐1 VL ≥50 copies/ml. Through 48 weeks, the rate of VS for the overall cohort was 98.3% (99.1% with 3TC; 96.2% with RPV). LVS was observed in 0.5% (n = 5) of the overall population (n = 1 [3TC group], n = 4 [RPV group]). There were 40 treatment discontinuations (4.2%, n = 27 [3TC group]; n = 13 [RPV group]), corresponding to an incidence of 4.7 per 100 patient‐years. The most common reason for discontinuation was an adverse event (1.4%), with neurotoxicity the most frequent (0.5%). Median on‐treatment weight gain at week 48 was 1 kg (interquartile range [IQR] −1–3) overall, 1 kg (IQR −1–3) in the 3TC group, and 2 kg (IQR 0–4) in the RPV group. A >10% weight increase was observed in 6.3% of people. Regression analysis showed that being on a tenofovir disoproxil fumarate‐based regimen prior to 2DR initiation was the only variable associated with a >10% increase in weight from baseline (odds ratio 3.48; 95% confidence interval 1.13–10.68; p = 0.038). Conclusion In this real‐world analysis, the 2DRs analysed were effective, durable, and safe for those who were treatment‐naive and treatment‐experienced. A slight increase in weight was associated with these regimens.

Bictegravir/emtricitabine/tenofovir alafenamide in paediatrics: Real‐life experience from a French cohort (2019–2023)

“…The BIC/FTC/TAF co-formulation was well tolerated, with only one participant (1.4%) discontinuing his treatment during the follow-up because of a suspected adverse event. This finding is consistent with the results of trials and cohorts in adults receiving BIC/FTC/TAF, in which discontinuation rates due to an adverse event were 1-3% [8,9,12]. Of note, our study population had been mostly exposed to ART, and more specifically INSTIs, before BIC/FTC/TAF initiation and would potentially be less likely to experience or more likely to tolerate adverse events, thereby leading to few treatment discontinuations.…”

“…In clinical trials and real-world studies including adults treated with BIC/FTC/TAF (first-line or switch), very low rates of VF (<2%) were observed [8,9,12]. Similarly, the recent phase 2/3 paediatric trial, where all participants were virologically suppressed on a stable ART regimen at baseline, viral suppression was maintained by 98/100 (98%) subjects at week 48 after BIC/FTC/TAF initiation [10].…”

“…Previous studies of BIC/FTC/TAF have demonstrated no or very rare treatment-emergent resistance in adults [8,9,12], even in the case of baseline NRTI resistance [17], and in those dosed only 4-5 days/week [18]. In our cohort with high rate of VF and, in patients experiencing VF, long duration of unsuppressed viraemia on ART, we have demonstrated viral re-suppression in half of the patients and evidenced only one case of treatment-emergent NRTI RAM (1.4% of subjects, 3.6% of those with VF) with no INSTI RAM.…”

Therapeutic drug monitoring and virological response at week 48 in a cohort of HIV‐1‐infected patients switching to dolutegravir/rilpivirine dual maintenance therapy (ANRS‐MIE‐BIRIDER study)

“…[7][8][9] Despite these advantages, a small percentage of PLWHA on dual therapy experience virological failure. [10][11][12] We can hypothesize that these poor outcomes might be partly associated with inadequate drug exposure and therapeutic drug monitoring (TDM) is then an additional tool in management of PLWHA, which can clarify patients' drug exposures, enabling rational adjustment of their medications or adherence interventions. TDM is recognized and used in many clinical settings, particularly in patients on immunosuppressants, but has not yet become routine practice in the field of HIV.…”

“…The aims are to limit cumulative lifetime drug exposure along with associated adverse events related to these drugs while limiting the risk of drug–drug interaction 7–9 . Despite these advantages, a small percentage of PLWHA on dual therapy experience virological failure 10–12 . We can hypothesize that these poor outcomes might be partly associated with inadequate drug exposure and therapeutic drug monitoring (TDM) is then an additional tool in management of PLWHA, which can clarify patients' drug exposures, enabling rational adjustment of their medications or adherence interventions.…”