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

Briand, C.; Dollfus, Catherine; Faye, Albert; Kantor, Elie; Avettand-Fènoël, Véronique; Caseris, Marion; Descamps, Diane; Schneider, Véronique; Tabone, Marie‐Dominique; Vaudre, G.; Veber, Florence; Blanche, Stéphane; Frange, Pierre

doi:10.1093/jac/dkw464

Cited by 15 publications

(31 citation statements)

References 8 publications

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“…These rates were similar to those reported in virologically suppressed adults enrolled in the European AIDS Treatment Network (NEAT) 022 trial, in which 93.1% of individuals switching from a ritonavir‐boosted PI to a dolutegravir‐based regimen maintained virological suppression at week 48 . Similarly, previous paediatric cohort studies, involving mainly adolescents and youths, reported high rates of sustained virological success among treatment‐experienced paediatric and young adult patients with viral suppression at dolutegravir initiation . We herein report that similar rates of viral success can be obtained among the three age groups of paediatric and young adult patients, even in the youngest children.…”

Section: Discussionsupporting

confidence: 87%

“…Dolutegravir was well tolerated. The low rate of severe drug‐related adverse events is similar to those previously reported in adults , adolescents and children but lower than that reported in an adult cohort study, in which 13.7% of individuals stopped taking dolutegravir because of intolerability .…”

Section: Discussionsupporting

confidence: 86%

“…Dolutegravir‐based combinations are now approved for use in children aged ≥ 6 years. However, these guidelines were mainly supported by the extrapolation of efficacy data from trials involving adults and data about the efficacy and safety profile of dolutegravir in the paediatric population are scarce, especially in the youngest children . Moreover, unpublished results of the P1093 study showed a high rate of VF (52.2%) among 12‐ to 17‐year‐old participants receiving dolutegravir and frequent emergence of INI resistance in children with VF , contrasting with the virological results of studies involving adults .…”

Section: Introductionmentioning

confidence: 99%

“…However, these guidelines were mainly supported by the Correspondence: Dr Pierre Frange, Laboratoire de Microbiologie clinique, Hôpital Necker -Enfants Malades, 149 rue de S evres, 75015 Paris, France. Tel: 0033 1 44 49 49 61; fax: 0033 1 44 49 49 60; e-mail: pierre.frange@aphp.fr extrapolation of efficacy data from trials involving adults and data about the efficacy and safety profile of dolutegravir in the paediatric population are scarce, especially in the youngest children [3][4][5][6][7][8]. Moreover, unpublished results of the P1093 study showed a high rate of VF (52.2%) among 12-to 17-year-old participants receiving dolutegravir and frequent emergence of INI resistance in children with VF [8], contrasting with the virological results of studies involving adults [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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Objectives 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. Patients and methods 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). Results 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. Conclusions 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.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2019

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“…Studies focusing on the efficacy of dolutegravir‐containing regimens to treat teenagers are scarce and generally had small samples . In our study, a subgroup multivariable analysis restricted to patients aged 13 to 24 years included 21,271 patients and confirmed the findings shown in the overall sample analysis.…”

Section: Resultssupporting

confidence: 82%

Comparison of cumulative viraemia following treatment initiation with different antiretroviral regimens: a real‐life study in Brazil

et al. 2019

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Introduction The relative efficacy of different antiretroviral (ART) regimens has been extensively evaluated in the context of clinical trials, using HIV viral load (VL) measurements at pre‐specified timepoints after ART onset. However, data from real‐life studies using combined longitudinal measurements of cumulative viraemia are scarce. This study aimed to address the independent effect of different ART regimens on HIV cumulative viraemia over the first 12 months after treatment initiation, using programmatic data from the Ministry of Health of Brazil. Methods Retrospective cohort study analysing cumulative viraemia under the most frequently used ART regimens in Brazil (tenofovir, lamivudine and dolutegravir (regimen 1); tenofovir, lamivudine and efavirenz (regimen 2); tenofovir, lamivudine and ritonavir‐boosted atazanavir (regimen 3)). Results and Discussion We included 112,243 patients >12 years old who received their first ART prescription between January 2014 and August 2017. Univariate analysis indicated that cumulative viraemia was significantly lower in patients receiving regimen 1 as compared with those receiving regimens 2 or 3 (p<0.0001 for both pairwise comparisons). In a multivariable analysis adjusted for age, sex, baseline T CD4+ counts and baseline HIV VL, ART regimen persisted with statistically significant effect on 12‐month cumulative viraemia. The model predicted a 45‐unit increase in log10 copy‐days/mL cumulative viraemia for regimen 2 as compared with regimen 1, and a 70‐unit increase in log10 copy‐days/mL cumulative viraemia for regimen 3 as compared with regimen 1 (95%CI 41 to 49 and 61 to 79 respectively; p<0.001 for both comparisons). In models restricted to youths (13 to 24 years old) and female patients, ART regimen had similar effects. ART regimen with dolutegravir in association with a tenofovir‐lamivudine backbone was superior to regimens containing efavirenz or boosted atazanavir in reducing HIV VL, as shown by cumulative viraemia over the first 12 months after treatment initiation. The superiority persisted even after adjusting the analysis for potential confounders. Conclusions Our findings could bring direct benefits to patients as suggested by lower viral replication during treatment, lower risk of HIV transmission, and a potential reduction in resistance mutations in the initial 12 months under ART.

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Projected Life Expectancy for Adolescents With HIV in the US

Neilan,

Ufio,

Brenner

et al. 2024

JAMA Health Forum

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ImportanceLife expectancy is a key measure of overall population health. Life expectancy estimates for youth with HIV in the US are needed in the current HIV care and treatment context to guide health policies and resource allocation.ObjectiveTo compare life expectancy between 18-year-old youth with perinatally acquired HIV (PHIV), youth with nonperinatally acquired HIV (NPHIV), and youth without HIV.Design, Setting, and ParticipantsUsing a US-focused adolescent-specific Monte Carlo state-transition HIV model, we simulated individuals from age 18 years until death. We estimated probabilities of HIV treatment and care engagement, HIV progression, clinical events, and mortality from observational cohorts and clinical trials for model input parameters. The simulated individuals were 18-year-old race and ethnicity–matched youth with PHIV, youth with NPHIV, and youth without HIV; 47%, 85%, and 50% were assigned male sex at birth, respectively. Individuals were categorized by US Centers for Disease Control and Prevention–defined HIV acquisition risk: men who have sex with men, people who ever injected drugs, heterosexually active individuals at increased risk for HIV infection, or average risk for HIV infection. Distributions were 3%, 2%, 12%, and 83% for youth with PHIV and youth without HIV, and 80%, 6%, 14%, and 0% for youth with NPHIV, respectively. Among the simulated youth in this analysis, individuals were 61% Black, 24% Hispanic, and 15% White, respectively.ExposuresHIV status by timing of acquisition.Main OutcomesLife expectancy loss for youth with PHIV and youth with NPHIV: difference between mean projected life expectancy under current and ideal HIV care scenarios compared with youth without HIV. Uncertainty intervals reflect varying adolescent HIV-related mortality inputs (95% CIs).ResultsCompared with youth without HIV (life expectancy: male, 76.3 years; female, 81.7 years), male youth with PHIV and youth with NPHIV had projected life expectancy losses of 10.4 years (95% CI, 5.5-18.1) and 15.0 years (95% CI, 9.3-26.8); female youth with PHIV and youth with NPHIV had projected life expectancy losses of 11.8 years (95% CI, 6.4-20.2) and 19.5 years (95% CI, 13.8-31.6), respectively. When receiving ideal HIV care, life expectancy losses were projected to improve for youth with PHIV (male: 0.5 years [95% CI, 0.3-1.8]: female: 0.6 years [95% CI, 0.4-2.1]) but were projected to persist for youth with NPHIV (male: 6.0 years [95% CI, 5.0-9.1]; female: 10.4 years [95% CI, 9.4-13.6]).ConclusionsThis adolescent-focused microsimulation modeling analysis projected that youth with HIV would have shorter life expectancy than youth without HIV. Projected differences were larger for youth with NPHIV compared with youth with PHIV. Differences in mortality by sex at birth, sexual behavior, and injection drug use contributed to lower projected life expectancy among youth with NPHIV. Interventions focused on HIV care and social factors are needed to improve life expectancy for youth with HIV in the US.

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

Abstract: Dolutegravir was safe and virologically effective in these patients, for whom multiple interventions were required to improve compliance.

Cited by 15 publications

References 8 publications

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

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

Comparison of cumulative viraemia following treatment initiation with different antiretroviral regimens: a real‐life study in Brazil

Projected Life Expectancy for Adolescents With HIV in the US

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