Dolutegravir (DTG)-based cART are now approved for use in HIV+ children aged ≥6 years in many countries worldwide. However, published data about its efficacy and its safety profile in the pediatric population are scarce, especially in youngest children. This retrospective monocentric study compared data about safety and efficacy of DTG in patients followed in a French pediatric unit and divided into three groups of age at the time of DTG initiation: 5-12 (Group 1), 12-18 (Group 2) and ≥ 18 year old (Group 3).
Clinical and biological data from 109 patients, who initiated DTG-based cART between January 2014 and December 2017 were retrospectively analysed: 33 in Group 1, 51 in Group 2 and 25 in Group 3. The primary endpoint was the proportion of patients who reached virological suppression (i.e. plasma viral load (PVL) <50 copies/mL obtained ≤ 3 months after DTG initiation) for viremic patients, and remained controlled until the last follow-up visit for all patients. The secondary endpoint was safety.
Most of the individuals were antiretroviral experienced (91.7%) and 12 (11%) were previously exposed to INSTI. INSTI-associated resistance associated mutations (RAMs) were previously isolated in 4 patients: E157Q in 2 cases, N155H in 2 individuals (who were treated with twice-daily DTG). The proportions of patients with virological suppression at baseline in each of the groups were 66.7%, 54.9% and 56.0%. Median follow-up was 24 months (range 6-54). Sustained virological success was obtained in 79.8% of patients, with similar rates observed in the 3 groups (87.9%, 72.5% and 84.0%, p=0.22). With reinforced measures to improve adherence, undetectable PVL was obtained at the last visit in 88.1% of patients, with similar proportions in the 3 groups (93.9%, 84.3% and 88.0%, p=0.51). Sustained virological success and undetectable PVL at the last visit were obtained in 91.7% and 100.0% of INSTI-experienced patients, respectively. No emergence of resistance mutation was observed in the 22 patients with virological failure. DTG was well tolerated; only 1 patient (Group 2) stopped treatment for severe drug-related side effect (dizziness, sleep disturbance). None of the three Grade 3 laboratory events were study drug related.
Virological efficacy and safety of DTG were similar between the 3 groups of age. Because of its high genetic barrier to resistance, DTG could be especially useful in the paediatric population, in which the risk of poor treatment adherence is high.