CNS penetration of ART in HIV-infected children

Hof, Malon Van den; Blokhuis, Charlotte; Cohen, Sophie; Scherpbier, Henriëtte J.; Wit, Ferdinand W. N. M.; Pistorius, Marcel C. M.; Kootstra, Neeltje A.; Teunissen, Charlotte E.; Mathôt, Ron A. A.; Pajkrt, Dasja

doi:10.1093/jac/dkx396

Cited by 23 publications

(21 citation statements)

References 31 publications

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“…This cross-sectional study was part of the prospective observational NOVICE cohort study investigating the effect of perinatal HIV infection and cART exposure on neurological, cognitive and visual performances, conducted at the Amsterdam University Medical Centers (AUMC), University of Amsterdam, the Netherlands [3, 12–18]. Among all PHIV children in the outpatient department of our hospital we newly recruited those who were 12 years or older between February 2017 and July 2018[3].…”

Section: Methodsmentioning

confidence: 99%

Lower IQ and poorer cognitive profiles in treated perinatally HIV-infected children is irrespective of having a background of international adoption

et al. 2019

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BackgroundHIV-associated cognitive deficiency in perinatally HIV-infected (PHIV) children has been studied in Western countries in a population of which an increasing proportion has been internationally adopted. Studies often lack an appropriate internationally adopted HIV-uninfected control group, potentially confounding the relationship between HIV and cognitive functioning. This study aims to further elucidate the association between treated HIV infection and cognitive development by addressing the background of international adoption.MethodsWe cross-sectionally studied the impact of HIV on cognition by comparing PHIV children and HIV- uninfected controls, matched for age-, sex-, ethnicity-, socioeconomic status (SES)- and adoption status. We used a standardized neuropsychological test battery to measure intelligence (IQ), and the cognitive domains of processing speed, working memory, executive function, learning ability and visual-motor function and compared outcomes using lineair regression models, adjusted for IQ. We determined cognitive profiles and cognitive impairment by using multivariate normative comparison (MNC) and explored associations with HIV disease- and treatment-related factors.ResultsWe enrolled fourteen PHIV children (mean age 10.45 years [1.73 SD], 93% adopted from sub-Saharan Africa at a median age of 3.3 years [IQR 2.1–4.2]) and fifteen HIV- uninfected controls. Groups did not clinically nor statistically differ in age, sex, ethnicity, SES, region of birth, adoption status and age at adoption. PHIV scored consistently lower on all cognitive domains and MNC outcomes. Compared to controls, PHIV children had a significant lower IQ (mean 81 [SD 11] versus mean 97 [SD 15], p = 0.005), and a poorer cognitive profile by MNC (Hotelling’s T2 mean -4.36 [SD 5.6] versus mean 0.16 [SD 4.5], p = 0.021), not associated with HIV disease- and treatment-related factors. Two PHIV (14%) and one control (7%) were classified as cognitively impaired (p = 0.598).ConclusionsFindings indicate treated HIV-infection to be independently associated with lower IQ and poorer cognitive profiles in PHIV children, irrespective of a background of international adoption.

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Section: Methodsmentioning

confidence: 99%

Lower IQ and poorer cognitive profiles in treated perinatally HIV-infected children is irrespective of having a background of international adoption

et al. 2019

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“…This theory is supported by Raskino et al's finding that combination of zidovudine and didanosine (both nucleoside reverse transcriptase inhibitors) had more neurocognitive benefit to children than didanosine monotherapy [25]. Furthermore, the study by Van den Hoff et al also suggests that despite the CSF concentration of PIs (lopinavir) being lower than those of non-PIs (Efavirez and Nevirapine), both drug concentrations were within therapeutic range [9].…”

Section: Discussionmentioning

confidence: 90%

“…The central nervous system (CNS) penetration of individual antiretroviral drugs (ARVs) varies. Protease inhibitors (PIs), such as lopinavir, achieve lower drug levels in the cerebrospinal fluid (CSF) compared to reverse transcriptase inhibitors (non PI), such as efavirenz and nevirapine [9]. Persistence of detectable levels of HIV copies in CSF among patients who are serologically suppressed has been described in patients on PIs due to their low CNS penetration when compared to other antiretroviral drugs [10].…”

Section: Introductionmentioning

confidence: 99%

Neurocognitive function among HIV-infected children on protease inhibitor -based versus non-protease inhibitor based antiretroviral therapy in Uganda: a pilot study

Nalwanga¹,

Musiime²,

Bangirana³

et al. 2021

BMC Pediatr

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Background HIV infection is associated with significant neurocognitive deficits making maximization of cognitive function among children receiving antiretroviral therapy (ART) a public health imperative. Non-protease inhibitors (non-PIs) achieve higher drug levels in the cerebral spinal fluid (CSF) compared to PIs, potentially leading to better neurocognitive function by reducing CSF viral load and inflammation. ART that maximises children’s neurodevelopment and school achievement could result in improved quality of life and productivity as adults, but little research to date has examined whether non-PI ART is associated with better neurocognitive outcomes. We compared the neurocognitive function between children living with HIV receiving PI-based and non PI-based ART. Methods We recruited a consecutive sample of clinically stable Ugandan children living with HIV aged 5–12 years who received PI-based or non PI-based ART for ≥ 1 year (viral load < 1000 copies). Neurocognitive function was assessed using the Kaufman Assessment Battery for Children, the Test of Variables of Attention, and Bruininks-Oseretsky Test of Motor Proficiency. Age-adjusted neurocognitive z-scores for the two groups were compared using linear regression models in STATA version 13. The Hommel’s method was used to adjust for multiple testing. Results We enrolled 76 children living with HIV; 34 on PI ART and 42 on non-PI ART. Mean (±SD) age was greater in the non-PI vs. PI group (9.5 ± 1.9 vs. 8.5 ± 2.0) years (p = 0.03). Children in the non-PI group had lower socioeconomic scores (5.7 ± 3.3 vs. 7.4 ± 2.8, p = 0.02). There was no difference in neurocognitive function between the groups (adjusted p > 0.05) for KABC and TOVA. Children in the PI group had better total BOT scores than their counterparts (46.07 ± 1.40) vs. 40.51 (1.24), p = 0.03). Conclusions We detected no difference in neurocognitive function among children on PI and non PI-based ART therapy based on KABC and TOVA tests. Children on PI based ART had better motor function than their counterparts. We recommend a prospective study with a larger sample size.

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“… 33 However, in a PK study of children aged 8–18 years infected with HIV, the median (interquartile range) CSF concentration of 3TC was 97 (51–144) ng/mL, which is much higher than the reported IC 50 of 0.5–3.4 ng/mL, suggesting that 3TC demonstrates antiviral potency in the CSF in children. 34 …”

Section: Pharmacologymentioning

confidence: 99%

Twenty-Five Years of Lamivudine: Current and Future Use for the Treatment of HIV-1 Infection

Quercia

Perno

Koteff

et al. 2018

JAIDS Journal of Acquired Immune Deficiency Syndromes

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CNS penetration of ART in HIV-infected children

Cited by 23 publications

References 31 publications

Lower IQ and poorer cognitive profiles in treated perinatally HIV-infected children is irrespective of having a background of international adoption

Lower IQ and poorer cognitive profiles in treated perinatally HIV-infected children is irrespective of having a background of international adoption

Neurocognitive function among HIV-infected children on protease inhibitor -based versus non-protease inhibitor based antiretroviral therapy in Uganda: a pilot study

Twenty-Five Years of Lamivudine: Current and Future Use for the Treatment of HIV-1 Infection

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