Absence of neurocognitive disadvantage associated with paediatric HIV subtype A infection in children on antiretroviral therapy

Abstract

IntroductionInfection with HIV subtype A has been associated with poorer neurocognitive outcomes compared to HIV subtype D in Ugandan children not eligible for antiretroviral therapy (ART). In this study, we sought to determine whether subtype‐specific differences are also observed among children receiving ART.Materials and MethodsChildren were recruited from a clinical trial in which they were randomized to receive either lopinavir (LPV)‐ or non‐nucleoside reverse transcriptase inhibitor (NNRTI)‐ based ART (NCT00978068). Age at initiation of ART ranged from six months to six years. HIV subtype was determined by PCR amplification and population sequencing of the pol region derived from peripheral blood mononuclear cell DNA, followed by application of the REGA and Recombinant Identification Programme algorithms. General cognition was assessed using the Kaufman Assessment Battery for Children (Second Edition), attention using the Test of Variables of Attention, and motor skills using the Bruininks‐Oseretsky Test of Motor Proficiency (Second Edition). Home environment was assessed using the Home Observation for the Measurement of the Environment (HOME). Age‐adjusted test z‐scores were entered into a regression model that adjusted for sex, socio‐economic status score, HOME score, years of schooling, and ART treatment type.ResultsOne hundred and five children were tested; median (interquartile range) age was 7.05 years (6.30 to 8.44), CD4 count was 867.7 cells/mm3 (416.0 to 1203.5), and duration on ART was 4.03 years (3.55 to 4.23). Seventy‐eight children had HIV subtype A and 27 had subtype D; the groups had comparable home and socio‐economic status, except that there were more males among children infected with subtype A than D (64.7% vs. 35.3%, p = 0.02). There were no differences between the subtypes in general cognition (estimated mean difference: 0.20; 95% CI: −0.11 to 0.50); p = 0.21), attention (−0.18, 95% CI: −0.60 to 0.24, p = 0.41) and motor skills (1.60, 95% CI: −0.84 to 4.04, p = 0.20).ConclusionsOur results imply that ART may diminish the neurocognitive disadvantage seen in treatment‐naïve HIV‐infected children with subtype A.

S-EQUOL: a neuroprotective therapeutic for chronic neurocognitive impairments in pediatric HIV

“…In HIV-1 seropositive adults, prominent sex differences in the development and pattern of neurocognitive impairments have been reported (for review, Rubin et al, 2019). In PHIV, however, the effect of biological sex on chronic neurocognitive impairments remains relatively understudied with the exception of a few recent manuscripts (McLaurin et al, 2016;Bangirana et al, 2017). Given the presence of notable sex differences in neurocognitive impairments, an efficacious adjunctive therapeutic for both male and female HIV-1 seropositive individuals would be advantageous.…”

Neruodevelopmental Outcomes in Preschool Children Living With HIV-1 Subtypes A and D in Uganda

“…Also, a similar proportion of children infected with subtype A and D were currently on ART. This could result in less neuropathogenic effects among these children, highlighting the importance of providing treatment to all children living with HIV [19, 36] . However, caution is warranted when interpreting the effects of HIV subtype on children's ND scores given the small sample size and the lack of statistical significance observed when comparing subtype groups.…”

“…Among school aged Ugandan HIV- infected children who had not yet received ART, HIV subtype A infection was associated with children having poorer neurocognitive performance when compared to subtype D [16] . However, Bangirana et al, reported no differences in neurocognitive outcomes when comparing Ugandan children on ART infected by HIV subtype A or D [19] .…”

Propelling the Pediatric HIV Therapeutic Agenda With Science, Innovation, and Collaboration

“…Thus, timing of infant HIV infection (in utero, intrapartum, postnatal), 86 maternal health status, 87 and effective ART initiation are major determinants of frequency and severity of abnormalities. Although severe CNS effects from HIV (ie, encephalopathy) are uncommon since the introduction of earlier ART, more subtle neurobehavioral abnormalities remain in some children and may be related to host, 88 viral, 89 and treatment factors. 90 There may be a critical window of opportunity when abnormalities can be prevented by early ART, 91 , 92 but the precise timing is under investigation.…”