Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Time to switch to second-line antiretroviral therapy in children with human immunodeficiency virus in Europe and Thailand

Background. Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods. Children aged <18 years initiating combination ART (.2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of .1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results. Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7.10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9.8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%.23%), with significant regional variations. Median time to switch was 30 (IQR, 16.58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions. One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Time to switch to second-line antiretroviral therapy in children with human immunodeficiency virus in Europe and Thailand

Background. Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods. Children aged <18 years initiating combination ART (.2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of .1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results. Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7.10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9.8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%.23%), with significant regional variations. Median time to switch was 30 (IQR, 16.58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions. One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Children living with HIV in Europe: do migrants have worse treatment outcomes?

Objectives: To assess the effect of migrant status on treatment outcomes among children living with HIV in Europe. Methods: Children aged < 18 years at the start of antiretroviral therapy (ART) in European paediatric HIV observational cohorts where ≥ 5% of children were migrants (defined as born abroad) were included. Three outcomes were considered: (i) severe immunosuppression-for-age; (ii) viraemic viral load (≥ 400 copies/mL) at 1 year after ART initiation; and (iii) AIDS/death after ART initiation. The effect of migrant status was assessed using univariable and multivariable logistic and Cox models. Results: Of 2620 children included across 12 European countries, 56% were migrants. At ART initiation, migrant children were older than domestic-born children (median 6.1 vs. 0.9 years, p < 0.001), with slightly higher proportions being severely immunocompromised (35% vs. 33%) and with active tuberculosis (2% vs. 1%), but a lower proportion with an AIDS diagnosis (14% vs. 19%) (all p < 0.001). At 1 year after beginning ART, a lower proportion of migrant children were viraemic (18% vs. 24%) but there was no difference in multivariable analysis (p = 0.702), and no difference in severe immunosuppression (p = 0.409). However, there was a trend towards higher risk of AIDS/death in migrant children (adjusted hazard ratio = 1.51, 95% confidence interval: 0.96–2.38, p = 0.072). Conclusions: After adjusting for characteristics at ART initiation, migrant children have virological and immunological outcomes at 1 year of ART that are comparable to those who are domestic-born, possibly indicating equity in access to healthcare in Europe. However, there was some evidence of a difference in AIDS-free survival, which warrants further monitoring

Integrase strand transfer inhibitors and neuropsychiatric adverse events in a large prospective cohort

To analyse the frequency and causes of treatment discontinuation in patients who were treated with an integrase strand transfer inhibitor (INSTI), with a focus on neuropsychiatric adverse events (NPAEs)

Immunovirological status in people with perinatal and adult-acquired HIV-1 infection: a multi-cohort analysis from FranceResearch in context

Summary: Background: No study has compared the virological and immunological status of young people with perinatally-acquired HIV infection (P-HIV) with that of people with HIV adulthood (A-HIV) having a similar duration of infection. Methods: 5 French cohorts of P-HIV and A-HIV patients with a known date of HIV-infection and receiving antiretroviral treatment (ART), were used to compare the following proportions of: virological failure (VF) defined as plasma HIV RNA ≥ 50 copies/mL, CD4 cell percentages and CD4:CD8 ratios, at the time of the most recent visit since 2012. The analysis was stratified on time since infection, and multivariate models were adjusted for demographics and treatment history. Findings: 310 P-HIV were compared to 1515 A-HIV (median current ages 20.9 [IQR:14.4–25.5] and 45.9 [IQR:37.9–53.5] respectively). VF at the time of the most recent evaluation was significantly higher among P-HIV (22.6%, 69/306) than A-HIV (3.3%, 50/1514); p ≤ 0.0001. The risk of VF was particularly high among the youngest children (2–5 years), adolescents (13–17 years) and young adults (18–24 years), compared to A-HIV with a similar duration of infection: adjusted Odds-Ratio (aOR) 7.0 [95% CI: 1.7; 30.0], 11.4 [4.2; 31.2] and 3.3 [1.0; 10.8] respectively. The level of CD4 cell percentages did not differ between P-HIV and A-HIV. P-HIV aged 6–12 and 13–17 were more likely than A-HIV to have a CD4:CD8 ratio ≥ 1: 84.1% vs. 58.8% (aOR = 3.5 [1.5; 8.3]), and 60.9% vs. 54.7% (aOR = 1.9 [0.9; 4.2]) respectively. Interpretation: P-HIV were at a higher risk of VF than A-HIV with a similar duration of infection, even after adjusting for treatment history, whereas they were not at a higher risk of immunological impairment. Exposure to viral replication among young patients living with HIV since birth or a very early age, probably because of lower adherence, could have an impact on health, raising major concerns about the selection of resistance mutations and the risk of HIV transmission. Funding: Inserm - ANRS MIE

Reaching the Second and Third Joint United Nations Programme on Human Immunodeficiency Virus (HIV)/AIDS 90-90-90 Targets Is Accompanied by a Dramatic Reduction in Primary HIV Infection and in Recent HIV Infections in a Large French Nationwide HIV Cohort

International audienceAbstract Background In late 2013, France was one of the first countries to recommend initiation of combination antiretroviral therapy (cART) irrespective of CD4 cell count. Methods To assess the impact of achieving the second and third Joint United Nations Programme on HIV/AIDS 90-90-90 targets (ie, 90% of diagnosed people on sustained cART, and, of those, 90% virologically controlled) on human immunodeficiency virus (HIV) incidence, we conducted a longitudinal study to describe the epidemiology of primary HIV infection (PHI) and/or recent HIV infection (patients with CD4 cell count ≥500/mm3 at HIV diagnosis; (PRHI) between 2007 and 2017 in a large French multicenter cohort. To identify changes in trends in PHI and PRHI, we used single breakpoint linear segmented regression analysis. Results During the study period, 61 822 patients were followed in the Dat’AIDS cohort; 2027 (10.0%) had PHI and 7314 (36.1%) had PRHI. The second and third targets were reached in 2014 and 2013, respectively. The median delay between HIV diagnosis and cART initiation decreased from 9.07 (interquartile range [IQR], 1.39–33.47) months in 2007 to 0.77 (IQR, 0.37–1.60) months in 2017. A decrease in PHI (−35.1%) and PRHI (−25.4%) was observed starting in 2013. The breakpoints for PHI and PRHI were 2012.6 (95% confidence interval [CI], 2010.8–2014.4) and 2013.1 (95% CI, 2011.3–2014.8), respectively. Conclusions Our findings show that the achievements of 2 public health targets in France and the early initiation of cART were accompanied by a reduction of about one-third in PHI and PRHI between 2013 and 2017. Clinical Trials Registration NCT02898987

Post‐HCV cure self‐reported changes in physical activity, eating behaviours, and fatigue in people living with HIV (ANRS CO13 HEPAVIH)

International audienc