Impact of antiretroviral treatment on height evolution of HIV infected children

International audienceBackground: Antiretroviral treatment (ART) has been shown to have a beneficial effect on the weight evolution but its effect on height remains unclear. We described patterns of height evolution and identified predictors of catch-up growth in HIV-infected children on ART.Methods: To describe the height evolution from birth to adulthood, we developed a nonlinear mixed effect model using data from perinatally HIV-infected children who initiated ART from 1999 to 2013 in a prospective cohort study in Thailand. The main covariates of interest were: sex, ART regimen (dual nucleoside reverse-transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor (NNRTI)-, or protease inhibitor (PI)-based), baseline CD4 percentage, HIV-RNA load and CDC HIV Classification stage and occurrence of AIDS-defining events.Results: A total 477 children (43% boys) contributed 18,596 height measurements over a median duration of 6.3 years on ART (interquartile range, 3.0 to 8.3). At ART initiation, median age was 6.2 years (1.8 to 9.6), 16% of children were underweight (weight-for-age z-score < − 2), 49% presented stunting (height-for-age z-score < − 2), and 7% wasting (weight-for-height z-score < − 2). The most frequent regimen at ART initiation was NNRTI-based (79%). A model with 4 components, birth length and 3 exponential functions of age accounting for the 3 growth phases was developed and show that the height-growth velocity was inversely associated with the age at ART initiation, the adult height was significantly lower in those who had experienced at least one AIDS-defining event while, as expected, the model found that adult height in females was lower than in males. Age at ART initiation, type of ART regimen, CDC stage, CD4 percentages, and HIV-RNA load were not associated with the final height.Conclusions: he younger the children at ART initiation, the greater the effect on height-growth velocity,supporting the World Health Organization’s recommendation to start ART as early as possible. However, final adult height was not linked to the age at ART initiation

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

Incidence and risk factors of loss to follow-up among HIV-infected children in an antiretroviral treatment program

International audienceIntroductio: The success of antiretroviral treatment (ART) programs can be compromised by high rates of patient loss to follow-up (LTFU). We assessed the incidence and risk factors of LTFU in a large cohort of HIV-infected children receiving ART in Thailand.Methods: All children participating in a multicenter cohort (NCT00433030) between 1999 and 2014 were included. The date of LTFU was 9 months after the last contact date. ART interruption was defined as ART discontinuation for more than 7 days followed by resumption of treatment. Baseline and time-dependent risk factors associated with LTFU were identified using Fine and Gray competing risk regression models with death or referral to another hospital as competing events.Results: Of 873 children who were followed during a median of 8.6 years (interquartile range 4.5–10.6), 196 were LTFU, 73 died, and 195 referred. The cumulative incidence of LTFU was 2.9% at 1 year, 7.3% at 5 years and 22.2% at 10 years. Children aged 13 years and more had a 3-fold higher risk (95% confidence interval 2.06–4.78) of LTFU than those younger. Children who had interrupted ART within the previous year had a 2.5-fold higher risk (1.12–5.91) than those who had not. The risk of LTFU was lower in children stunted (height-for-age Z-scores <-2 SD) (0.42–0.96) or underweight (weight-for-age Z-scores <-2 SD) (0.24–0.97).Conclusion: Adolescence, ART interruption and absence of growth deficit were associated with LTFU. These may be warnings that should draw clinicians’ attention and possibly trigger specific interventions. Children with no significant growth retardation may also be at risk of LTFU

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