Virological efficacy of dual therapy with lamivudine and dolutegravir in HIV-1-infected virologically suppressed patients: long-term data from clinical practice Free

Sir,

We read with interest the work by Joly et al.¹ on the results of the LAMIDOL trial, showing the high efficacy of the switch strategy with lamivudine plus dolutegravir in virologically suppressed HIV-1-infected patients, after 48 weeks of follow-up. Indeed, this dual regimen has drawn much attention from clinicians and different works focus on this switch strategy.^2–5 In particular, we agree with the authors on the necessity of further studies exploring this dual regimen in a wider population, with a longer time from HIV diagnosis, past virological failures and/or the presence of the M184V resistance mutation.

Herein we present the findings from a retrospective study that considered HIV-1-infected, virologically suppressed (defined as HIV-RNA <50 copies/mL), adult (≥18 years old) patients switching to lamivudine plus dolutegravir in a third-level clinical centre (i.e. a university hospital). This was a single-centre study. We used the Kaplan–Meier estimator to evaluate the time to virological failure (defined as one single HIV-RNA determination ≥1000 copies/mL or two consecutive HIV-RNA determinations ≥50 copies/mL) and Cox regression analysis to evaluate predictors of virological failure. We also evaluated the proportion of patients maintaining virological suppression at 48, 96 and 144 weeks. The cumulative burden of low-level HIV-RNA was measured via viraemia copy years.⁶ The study was approved by the local Ethics Committee (protocol number 5284/15) and all patients provided signed informed consent to data recording. We analysed 221 patients; 69 (31.2%) were females and the patients had a median age of 51 years (IQR 43–57), a median time from HIV diagnosis of 14 years (IQR 7–20) and a median time of exposure to ART of 11 years (IQR 5–17). A previous AIDS event was experienced by 65 patients (29.4%), while 96 of them (43.4%) had at least one previous virological failure and 20 of 187 (10.7%) had the M184V resistance mutation in their historical genotype. Full patients’ baseline characteristics are shown in Table 1. The median time of virological suppression at switch was 96 months (IQR 44–140). During 419.7 patient-years of follow-up (PYFU) (median follow-up 2.1 years, IQR 1.2–2.8), seven virological failures occurred, with an incidence of 1.67 per 100 PYFU; five were due to HIV-RNA ≥1000 copies/mL and two to consecutive HIV-RNA ≥50 copies/mL. None of these patients developed resistance mutations. The estimated probability of remaining free from virological failure was 98.0% (95% CI 97.0–99.0), 96.5% (95% CI 95.1–97.9) and 95.3% (95% CI 93.4–97.2) at 48, 96 and 144 weeks, respectively. An increased rate of virological failure (6.34 per 100 PYFU) was found in patients with a zenith HIV-RNA >500 000 copies/mL (Log-Rank P = 0.036). In multivariate analysis, peak HIV-RNA >500 000 copies/mL (adjusted HR 6.35, 95% CI 1.16–34.77, P = 0.041) independently predicted virological failure after adjusting for the presence of the M184V resistance mutation and time of virological suppression. The presence of the M184V resistance mutation alone was not a predictor of virological failure. However, in stratifying by time of virological suppression, we observed that, in patients with time of virological suppression <96 months, the rate of virological failure was higher in the presence of the M184V mutation (10.0 per 100 PYFU versus 1.4 per 100 PYFU, Log-Rank P = 0.05). Conversely, virological failure rates were not different in patients with time of virological suppression >96 months, independently from M184V mutation. Our data confirmed the high virological efficacy of lamivudine and dolutegravir as a maintenance strategy in virologically suppressed patients, as already reported,^1–5 with a 95.3% probability of maintaining virological suppression at 144 weeks. To the best of our knowledge, this is the first study with such a long follow-up. Furthermore, the fact that no patient experiencing virological failure developed new resistance mutations underlines the safety and high genetic barrier of dolutegravir.^1,7 In our cohort, confirming previous findings,⁸ patients with a high peak HIV-RNA were more prone to developing virological failure. Moreover, our data show that the presence of the M184V resistance mutation in patients with a shorter time of virological suppression may cause an increased risk of virological failure, as also described by Gagliardini et al.⁹ All of this evidence suggests that clinicians should carefully monitor the clinical history and virological parameters of patients starting this dual regimen. The retrospective design, the absence of data on patients’ compliance and the lack of data on HIV-DNA determinations represent the main limitations of our study; nonetheless, our study shows that the analysed two-drug regimen is effective and safe as a maintenance strategy in clinical practice, with a cumulative low incidence of virological failures.

Funding

This study was conducted as part of our routine work.

Transparency declarations

A. B. has received non-financial support from Bristol-Myers Squibb and ViiV Healthcare, and personal fees from Gilead Sciences S. D. G. was a paid consultant or member of advisory boards for Gilead, ViiV Healthcare, Janssen-Cilag, Merck Sharp & Dohme and Bristol-Myers Squibb. Both other authors: none to declare.

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