Dataset Information

Mitochondrial Impairment in Well-Suppressed Children with Perinatal HIV-Infection on Antiretroviral Therapy.

ABSTRACT: Mitochondrial impairment is reported in HIV-infected children receiving antiretroviral therapy (ART), as well as those naive to ART. Whether mitochondrial function recovers with early initiation of ART and sustained viral suppression on long-term ART is unclear. In this study, we evaluate mitochondrial markers in well-suppressed perinatally HIV-infected children initiated on ART early in life. We selected a cross-sectional sample of 120 HIV-infected children with viral load <400 copies/mL and 60 age-matched uninfected children (22 HIV-exposed uninfected) enrolled in a cohort study in Johannesburg, South Africa. Complex IV (CIV) and citrate synthase (CS) activity were measured by spectrophotometry. Mitochondrial DNA (mtDNA) content relative to nuclear DNA (nDNA) was measured by quantitative real-time polymerase chain reaction and expressed as copies/nDNA. Mitochondrial markers were impaired in HIV-infected children, including lower mean CIV activities [1.76 vs. 1.40 optical densities (OD)/min], higher risk of a CIV/CS ratio ?0.22 (third quartile; odds ratio?=?3.03, 95% confidence interval: 1.38-6.66), and lower mtDNA content. Children with shorter versus longer ART duration (<6.3 vs. ?6.3 years) had lower means of CIV activity (1.22-1.58 OD/min) and mtDNA content (386-907 copies/nDNA). There were no differences in mitochondrial markers between children who started ART earlier (<6 months) or later (6-24 months). CIV activity was impaired in children with lower height-for-age Z-scores (HAZs). Despite early treatment and prolonged viral suppression, HIV-infected children had detectable mitochondrial impairment, particularly among those with stunted growth. Further study is required to determine if continued treatment will lead to full recovery of mitochondrial function in HIV-infected children.

SUBMITTER: Shen J

PROVIDER: S-EPMC6944140 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Mitochondrial Impairment in Well-Suppressed Children with Perinatal HIV-Infection on Antiretroviral Therapy.

Shen Jing J Liberty Afaaf A Shiau Stephanie S Strehlau Renate R Pierson Sheila S Patel Faeezah F Wang LiQun L Burke Megan M Violari Avy A Coovadia Ashraf A Abrams Elaine J EJ Arpadi Stephen S Foca Marc M Kuhn Louise L

AIDS research and human retroviruses 20190715 1

Mitochondrial impairment is reported in HIV-infected children receiving antiretroviral therapy (ART), as well as those naive to ART. Whether mitochondrial function recovers with early initiation of ART and sustained viral suppression on long-term ART is unclear. In this study, we evaluate mitochondrial markers in well-suppressed perinatally HIV-infected children initiated on ART early in life. We selected a cross-sectional sample of 120 HIV-infected children with viral load <400 copies/mL and 60 ...[more]

PMID: 31179720

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Project description:BACKGROUND:Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking. METHODS:We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum "tail" of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety. RESULTS:The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, -1.3 percentage points; repeated confidence interval, -2.1 to -0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was associated with higher rates than zidovudine-based ART of very preterm delivery before 34 weeks (6.0% vs. 2.6%, P=0.04) and early infant death (4.4% vs. 0.6%, P=0.001), but there were no significant differences between tenofovir-based ART and zidovudine alone (P=0.10 and P=0.43). The rate of HIV-free survival was highest among infants whose mothers received zidovudine-based ART. CONCLUSIONS:Antenatal ART resulted in significantly lower rates of early HIV transmission than zidovudine alone but a higher risk of adverse maternal and neonatal outcomes. (Funded by the National Institutes of Health; PROMISE ClinicalTrials.gov numbers, NCT01061151 and NCT01253538 .).

Dataset Information

Mitochondrial Impairment in Well-Suppressed Children with Perinatal HIV-Infection on Antiretroviral Therapy.

Publications

Mitochondrial Impairment in Well-Suppressed Children with Perinatal HIV-Infection on Antiretroviral Therapy.

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