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

Effect of Hepatitis C Virus Coinfection on the Progression of Vertically Acquired Human Immunodeficiency Virus Infection During Childhood and Adolescence

The Pediatric National AIDS Research Network of Spain (CoRISpe) integrated in the Translational Research Network in Pediatric Infectious Diseases (RITIP).Data for a total of 57 patients vertically coinfected with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) and 365 HIV-monoinfected patients were compared until their transition to adult care. No differences regarding the dynamics of CD4 and/or CD8 T-cell counts during childhood were found. The coexistence of HCV does not increase the risk of disease progression in vertically HIV-infected patients.This study was supported by the Spanish National Pediatric Network (CoRISpe) for HIV-Infected Children and Adolescents, integrated in the Spanish AIDS Research Network (RIS), Instituto de Salud Carlos III, Spanish Health Ministry (grant RD06/0025), and a Fellowship from Gilead 2014 (GLD 14/00264). T. S. has been funded by the Spanish Society of Pediatric Infectious Diseases (ESPID Research Fellowship) and is now funded by the Spanish Ministry of Health– Instituto de Salud Carlos III (ISCIII) and cofunded by the European Union (FEDER) (Contratos Juan Rodés, grant JR16/00021)

Longitudinal evolution of vertically HIV/HCV–co‐infected vs HCV–mono‐infected children

Pediatric National AIDS Research Network of Spain (CORISPE) integrated in the Translational Research Network in Pediatric Infectious Diseases (RITIP).HIV co‐infection has been suggested to play a deleterious role on the pathogenesis of liver fibrosis among vertically HCV‐infected children. The aim of this study was to describe the longitudinal evolution of vertically acquired HIV/HCV co‐infection in youths, in comparison with HCV infection alone. This was a retrospective, multicentre study including vertically HIV/HCV–co‐infected patients and age‐ and sex‐matched vertically HCV–mono‐infected patients. Progression to advanced liver fibrosis, defined as F3 or more by elastography or METAVIR biopsy staging, and response to treatment were compared by means of univariate and multivariate regression analyses and Cox regression models. Sixty‐seven co‐infected patients were compared with 67 matched HCV–mono‐infected patients. No progression to advanced liver disease was observed during the first decade. At a median age of 20.0 [19.0, 22.0] years, 26.7% co‐infected vs 20% mono‐infected had progressed to advanced fibrosis (P = .617). Peg‐IFN/RBV for HCV treatment was given to 37.9% vs 86.6% (P‐value < .001). At treatment initiation, co‐infected patients were older (16.9 ± 4.1 vs 11.7 ± 4.5 years, P < .001), and 47.1% vs 7.1% showed advanced fibrosis (P < .003), with no differences in hard‐to‐treat genotype distribution. Sustained viral response was comparable between groups (43.5% vs 44.0%, P = .122). In vertically HIV/HCV–co‐infected patients, the progression to liver fibrosis was rare during childhood. At the end of adolescence, over 25% of patients displayed advanced liver disease. Response to Peg‐IFN/RBV was poor and comparable in both groups, supporting the need for fast access to early treatment with direct‐acting antivirals against HCV for vertically co‐infected patients.This study was supported by the Instituto de Salud Carlos III, FEDER—Spanish Ministry of Science an Innovation [The Spanish National Cohort of HIV‐infected Children (CoRISpe)], included in the Spanish National AIDS Research Network (RIS) [Grant no RD16/0025] and a Fellowship from Gilead 2014 [GLD 14/00264]. The study is part of the FARO project: characterization of young adults transitioned to adult care units (RIS‐EPICLIN‐06/2013). TS has been funded by the European Society of Pediatric Infectious Diseases (ESPID Research Fellowship) and is now funded by the Instituto de Salud Carlos III—Spanish Ministry of Health and Innovation [contratos Juan Rodés, Grant JR16/00021] cofunded by Fondos FEDER of the EU

Prevalence and Clinical Outcomes of Poor Immune Response Despite Virologically Suppressive Antiretroviral Therapy Among Children and Adolescents With Human Immunodeficiency Virus in Europe and Thailand: Cohort Study

International audienceIn human immunodeficiency virus (HIV)-positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART

Prevalence and Clinical Outcomes of Poor Immune Response Despite Virologically Suppressive Antiretroviral Therapy Among Children and Adolescents With Human Immunodeficiency Virus in Europe and Thailand: Cohort Study

BACKGROUND: In human immunodeficiency virus (HIV)-positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. METHODS: Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children &lt;18 years at ART initiation, with sustained viral suppression (VS) (≤400 copies/mL) for ≥1 year were included. The prevalence of PIR (defined as World Health Organization advanced/severe immunosuppression for age) at 1 year of VS was described. Factors associated with PIR were assessed using logistic regression. Rates of acquired immunodeficiency syndrome (AIDS) or death on suppressive ART were calculated by PIR status. RESULTS: Of 2318 children included, median age was 6.4 years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis B coinfection, and residing in Thailand (all P ≤ .03). Rates of AIDS/death (95% confidence interval) per 100 000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92; P &lt; .001). CONCLUSIONS: One in eight children in our cohort experienced PIR despite sustained VS. While the overall rate of AIDS/death was low, children with PIR had a 4-fold increase in risk of event as compared with immune responders