Growth, clinical and neurodevelopmental outcomes at school age are similar for children who received 1-year lamivudine or lopinavir/ritonavir HIV prophylaxis in early life

Abstract

In the ANRS 12174 trial, HIV-exposed uninfected African neonates who received lopinavir-ritonavir (LPV/r) prophylaxis for 1 year exhibited slower growth from birth to week 50 compared with those receiving lamivudine (3TC). We assessed whether this difference in growth persisted over time, and was accompanied by differences in neuropsychological and clinical outcomes. Between February 2017 and February 2018, we conducted a cross-sectional clinical evaluation among former trial participants who completed the 50-week follow-up and who were not HIV-infected. In addition to clinical examination, neuropsychological outcomes were assessed using the tests Kaufman-ABCII, Test of Variables of Attention, Movement Assessment Battery for Children and the Strengths and Difficulties questionnaire, parent version. Of 1101 eligible children, aged 5–7 years, 553 could be traced and analysed (274 in the LPV/r and 279 in the 3TC groups). Growth, clinical and neuropsychological outcomes did not differ between treatment groups. At school age, children exposed to LPV/r and 3TC at birth for 1 year had comparable growth and neuropsychological outcomes without evidence of long-term side-effects of LPV/r. It provides reassuring data on clinical outcomes for all HIV-infected children treated with this antiretroviral drug in early life.

Long-Term Persistence of Mitochondrial DNA Instability in HIV-Exposed Uninfected Children during and after Exposure to Antiretroviral Drugs and HIV

“…A detailed sample selection flow is given in Supplementary Materials Figure S1 . All demographic, anthropometric, and clinical data were obtained from both the PROMISE-PEP and the PROMISE M&S trial databases [ 30 , 31 ].…”

“…Hematological and biochemical results were categorized based on the DAIDS tables for grading the severity of adult and pediatric severe adverse events [ 34 ]. Neuropsychological global performance scoring methodology has been previously described elsewhere [ 31 ].…”

Longitudinal Follow-Up of Blood Telomere Length in HIV-Exposed Uninfected Children Having Received One Year of Lopinavir/Ritonavir or Lamivudine as Prophylaxis

“…These uninfected children at birth received seven days of NVP as per national guidelines and were thereafter randomly assigned to receive LPV/r or 3TC from seven days after birth (day-7) until one week after breastfeeding discontinuation, for a maximal duration of fifty weeks (W50). The PROMISE M&S study (recruitment from February 2017 to February 2018) consisted of a one- or two-day visit for a growth, clinical, and neuropsychological evaluation of the PROMISE PEP trial participants aged 5 to 7 years old who were HIV negative at the end of the prophylaxis period [ 37 ]. Among PROMISE M&S participants, we randomly selected 198 CHEU with 1:1 sex and prophylactic regimen ratios.…”

“…For this purpose, we first investigated the association between telomere shortening at week-50 and growth indicators (weight-for-age Z-score, height-for-age Z-score and body mass index Z-score) as well as neuropsychological performances (global scores obtained from the Strengths and Difficulties Questionnaire, SDQ-25; the Test Of Variable of Attention, TOVA; the Movement Assessment Battery for Children second edition, MABC-2 and the Kaufman Assessment Battery for Children second edition, KABC-II) at year-6, using linear regressions. Methodology for scores analysis and main findings is described elsewhere [ 37 ]. A square transformation was applied to SDQ-25 score in order to obtain a normal distribution.…”

“…The main outcomes of this study were percent HIV transmission and regimen safety. Furthermore, we conducted a follow-up study of these trial participants at six years of age to evaluate growth, clinical, and neurodevelopment outcomes post-ARV exposure (PROMISE-M&S trial, NCT03519503) [ 37 ]. These children received ARV prophylaxis of LPV/r or 3TC up to one year of age, providing a unique population to evaluate the impact of these drugs on telomere length among uninfected children, and without interference of other drugs from combined therapy.…”