Efficacy and tolerance of dolutegravir-based combined ART in perinatally HIV-1-infected adolescents: a French multicentre retrospective study.

To assess the safety and efficacy of a dolutegravir-based regimen in perinatally HIV-1-infected adolescents. We conducted a retrospective multicentre study of 50 adolescents beginning dolutegravir-based treatment regimens between January 2014 and December 2015. Clinical and biological data collected before and after dolutegravir initiation were analysed. The primary endpoint was the proportion of patients achieving a plasma viral load (PVL) <50 copies/mL within 3 months of dolutegravir initiation (for patients with detectable viraemia at baseline) and maintaining virological suppression (PVL <50 copies/mL) until the last follow-up visit (for all patients). Virological suppression was noted for 17/50 adolescents at baseline. Dolutegravir-based regimens maintained virological success in 14/17 patients (82%). The other three patients experienced a transient viral rebound, before PVL fell to < 50 copies/mL again, with no need to change the antiretroviral regimen. Thirty-three viraemic adolescents were enrolled. All but one had already received antiretroviral drugs. Virological success was achieved and maintained in 19/33 subjects (58%). Another three adolescents with initial virological failure had an undetectable PVL at the end of follow-up, with reinforced measures to improve compliance. Overall, sustained virological success was observed in 66% of patients and 78% of patients had an undetectable PVL at the last visit. Dolutegravir was well tolerated. Only one patient stopped treatment for severe drug-related adverse effects (dizziness and sleep disturbance). No emergence of resistance mutations was observed in patients with virological failure. Dolutegravir was safe and virologically effective in these patients, for whom multiple interventions were required to improve compliance.

Briand C ，Dollfus C ，Faye A ，Kantor E ，Avettand-Fenoel V ，Caseris M ，Descamps D ，Schneider V ，Tabone MD ，Vaudre G ，Veber F ，Blanche S ，Frange P ... -  《-》

Similar efficacy and safety of dolutegravir between age groups of HIV-1-infected paediatric and young adult patients aged 5 years and older.

The aim of the study was to carry out a comparison of the safety and efficacy of dolutegravir-based regimens among age groups of HIV-1-infected paediatric and young adult patients. This retrospective monocentric study included 109 patients infected since childhood who began receiving dolutegravir between January 2014 and December 2017. The patients were divided into three groups according to age at the time of dolutegravir initiation: 5-11, 12-17 and 18-25 years old. The primary endpoint was the proportion of patients achieving a plasma viral load (PVL) < 50 HIV-1 RNA copies/mL within 3 months of dolutegravir initiation (for patients with detectable viraemia at baseline), and maintaining virological suppression (PVL < 50 copies/mL) until the last follow-up visit (for all patients). Most of the subjects were antiretroviral-experienced (91.7%) and virologically suppressed at baseline (66.7%, 54.9% and 56.0% in the 5-11, 12-17 and 18-25 year age groups, respectively). Median follow-up was 24 months (range 6-54 months). Sustained virological success throughout follow-up was observed in 79.8% of patients, with similar rates among age groups (87.9%, 72.5% and 84.0%, respectively; 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 among age groups (93.9%, 84.3% and 88.0%, respectively; P = 0.51). No emergence of resistance mutations was observed in the 22 patients with virological failure. Dolutegravir was well tolerated; only one patient stopped treatment for severe drug-related side effects. The virological efficacy and safety of dolutegravir were similar among the three age groups. Because of its high genetic barrier to resistance, dolutegravir could be especially useful in the paediatric population, in which the risk of poor treatment adherence is high.

Frange P ，Avettand-Fenoel V ，Veber F ，Blanche S ... -  《-》

Dolutegravir in HIV-2-Infected Patients With Resistant Virus to First-line Integrase Inhibitors From the French Named Patient Program.

Dolutegravir has shown in vitro activity against human immunodeficiency virus type 2 (HIV-2). We report safety and efficacy data of regimens containing dolutegravir (50 mg twice daily) in antiretroviral-experienced, HIV-2-infected patients. HIV-2-infected patients experiencing virological failure to raltegravir received dolutegravir with optimized background antiretroviral combinations within the French Named Patient Program (NPP). Plasma HIV-2 RNA (pVL) was assessed at time of dolutegravir initiation (baseline), month 3, and month 6. Antiretroviral trough plasma concentrations (C12h) were determined using liquid chromatography coupled with tandem mass spectrometry. Thirteen HIV-2-infected-patients, with a median duration of 15 years' infection and given 16 previous antiretroviral regimens, were included in NPP. Median follow-up was 9 months (min-max, 3-15 months). Median baseline pVL and CD4 cell count were 9544 copies/mL (inter quartile range [IQR], 3096-23 120 copies/mL) and 100 cells/µL (IQR, 77-171 cells/µL), respectively. Available integrase genotypic resistance patterns were Y143C/G/H/R (n = 5), Q148R/K (n = 2), and N155H (n = 4). Optimized background antiretroviral regimens conferring a genotypic sensitivity score ≤2 in 10 patients included nucleoside reverse transcriptase inhibitors associated with darunavir/ritonavir (n = 12), saquinavir/ritonavir (n = 2), and maraviroc (n = 3). At months 3 and 6, pVL was undetectable in 6 of 13 and 4 of 12 patients, respectively, and median CD4 count was 161 (101-188) cells/µL and 167 (135-1353) cells/µL, respectively. Median dolutegravir C12h was 4086 (1756-5717 ng/mL) ng/mL in 9 patients. No serious events were notified except 1 death from progressive multifocal leukoencephalopathy at month 4. Optimized dolutegravir-containing antiretroviral regimens supported by good plasma exposure provide a substantial initial efficacy rate for salvage therapy in heavily antiretroviral-experienced HIV-2-infected patients with virus harboring resistance to first-generation integrase inhibitors. Larger numbers of patients and longer follow-up are needed to confirm these findings.

Descamps D ，Peytavin G ，Visseaux B ，Tubiana R ，Damond F ，Campa P ，Charpentier C ，Khuong-Josses MA ，Duvivier C ，Karmochkine M ，Lukiana T ，Matheron S ... -  《-》

Dolutegravir-based monotherapy or dual therapy maintains a high proportion of viral suppression even in highly experienced HIV-1-infected patients.

Dolutegravir is a powerful, well-tolerated integrase inhibitor with a high genetic barrier to resistance and may thus constitute the backbone of lightened regimens. This was a monocentric, retrospective study. HIV-1-infected patients receiving dolutegravir as monotherapy (mDGV) or dual therapy (dDGV) were systematically identified. The primary outcome was the proportion of patients who maintained undetectable (<50 copies/mL) plasma HIV RNA [plasma viral load (PVL)]. We identified 21 patients on mDGV (50 mg/day) and 31 on dDGV (50 or 100 mg/day, with atazanavir  ±  ritonavir, n = 12; rilpivirine, n = 11; maraviroc, n = 3; lamivudine, n = 3; darunavir/ritonavir, n = 1; or abacavir, n = 1). All of the patients were treatment experienced and 48% had experienced at least one virological failure. The baseline characteristics were as follows (for the mDGV/dDGV patients, respectively): 5%/29% had a history of AIDS; the median (IQR) highest PVL was 4.5 (4.3-5.5)/5.3 (4.7-5.6) log copies/mL; the median (IQR) nadir CD4+ count was 310 (280-468)/199 (134-281) cells/mm(3); 100% had undetectable PVL before the mDGV for a median (IQR) duration of 5.9 (3.5-9.9) years/81% had undetectable PVL before the dDGV for a median (IQR) duration of 3.7 (1.4-8.3) years; and the median (IQR) HIV DNA level was 2.7 (2.1-3.1)/2.9 (2.7-3) log copies/10(6) PBMCs. At the last follow-up visit, 100% and 97% of patients showed undetectable PVL following mDGV and dDGV, respectively [median (IQR) follow-up of 32 (29-45) and 50 (30-74) weeks, respectively]. In our experience, dolutegravir-based lightened regimens provided a high proportion of viral suppression, even in highly treatment-experienced patients.

Gubavu C ，Prazuck T ，Niang M ，Buret J ，Mille C ，Guinard J ，Avettand-Fènoël V ，Hocqueloux L ... -  《-》

High virological suppression regardless of the genotypic susceptibility score after switching to a dolutegravir-based regimen: week 48 results in an observational cohort.

Charpentier C ，Peytavin G ，Lê MP ，Joly V ，Cabras O ，Perrier M ，Le Gac S ，Phung B ，Yazdanpanah Y ，Descamps D ，Landman R ... -  《-》