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Composition of Gut Microbiota of Children and Adolescents With Perinatal Human Immunodeficiency Virus Infection Taking Antiretroviral Therapy in Zimbabwe.

ABSTRACT: BACKGROUND:Human immunodeficiency virus (HIV) infection causes impairment of the gastrointestinal barrier, with substantial depletion of CD4+ T cells in the gut. Antiretroviral therapy (ART) restores CD4+ counts and may have beneficial effects on gut microbiota in adults. Little is known about effect of long-term ART on gut microbiome in HIV-infected children. We investigated composition of gut microbiota in HIV-infected and -uninfected children and assessed associations between gut microbiota and patient characteristics. METHODS:In a cross-sectional study, rectal swabs were collected from 177 HIV-infected and 103 HIV-uninfected controls. Gut microbial composition was explored using 16S ribosomal ribonucleic acid sequencing. RESULTS:Human immunodeficiency virus-infected children had significantly lower alpha-diversity and higher beta-diversity compared to HIV-uninfected. No association was observed between microbiome diversity and CD4+ T-cell count, HIV viral load, or HIV-associated chronic lung disease. We found enriched levels of Corynebacterium (P < .01), Finegoldia (P < .01), and Anaerococcus (P < .01) in HIV-infected participants and enrichment of Enterobacteriaceae (P = .02) in participants with low CD4+ counts (<400 cells/mm3). Prolonged ART-treatment (≥10 years) was significantly associated with a richer gut microbiota by alpha diversity. CONCLUSIONS:Human immunodeficiency virus-infected children have altered gut microbiota. Prolonged ART may restore the richness of the microbiota closer to that of HIV-uninfected children.

SUBMITTER: Flygel TT

PROVIDER: S-EPMC7457326 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Composition of Gut Microbiota of Children and Adolescents With Perinatal Human Immunodeficiency Virus Infection Taking Antiretroviral Therapy in Zimbabwe.

Flygel Trym T TT Sovershaeva Evgeniya E Claassen-Weitz Shantelle S Hjerde Erik E Mwaikono Kilaza S KS Odland Jon Ø JØ Ferrand Rashida A RA Mchugh Grace G Gutteberg Tore J TJ Nicol Mark P MP Cavanagh Jorunn P JP Flægstad Trond T

The Journal of infectious diseases 20200101 3

<h4>Background</h4>Human immunodeficiency virus (HIV) infection causes impairment of the gastrointestinal barrier, with substantial depletion of CD4+ T cells in the gut. Antiretroviral therapy (ART) restores CD4+ counts and may have beneficial effects on gut microbiota in adults. Little is known about effect of long-term ART on gut microbiome in HIV-infected children. We investigated composition of gut microbiota in HIV-infected and -uninfected children and assessed associations between gut micr ...[more]

PMID: 31549151

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Project description:BackgroundAdolescents with HIV (AWH) frequently exhibit impaired growth, which manifests as stunting and wasting. We studied trajectories in leg-length (appendicular), sitting (axial), and standing height among AWH on antiretroviral therapy (ART), determining peak height velocity (PHV) and age at PHV (aPHV).MethodsAnalyses used VITALITY trial data from Zimbabwe and Zambia (PACTR20200989766029), which recruited AWH (11-19 years) established on ART to determine whether vitamin D3/calcium supplementation improves bone health. The study enrolled participants between January and December 2021. Weight-for-age and height-for-age z-scores (WAZ/HAZ) were calculated from 12-weekly anthropometry over 96 weeks. Height trajectory analyses used SuperImposition by Translation And Rotation (SITAR) methods adjusting for height, tempo (aPHV) and velocity. Linear associations between vitamin D/calcium supplementation, HIV-specific factors, WAZ, HAZ, and SITAR parameters were determined.ResultsOverall, 842 participants (53·2% female; median age 15·5 [IQR:13·2-17·9] years), were taking ART for median 9·8(IQR:6·3-12·3) years. Mean(SD) HAZ was 1·21(1·05) in females, -1·68(1·05) in males. Overall, 251(29·8%) AWH were stunted (HAZ < -2) and 253(30%) wasted (WAZ < -2). Standing, appendicular and axial aPHVs were: Female 13·4, 13·3, 13·9 years; Males 15·3, 15·0, 15·8 years. Unsuppressed viral-load(VL) and delayed ART initiation (age > 4-years) were associated with later aPHV and shorter axial height in females. In all, unsuppressed VL had a more negative effect on aPHV for axial (Females: β = 0·39 years [95%CI:0·12,0·65]; Males: β = 0·45 [95%CI:0·10,0·80]) than appendicular growth (Females: β = 0.31 [95%CI 0·08,0·53]; Males: β = 0·2 [95%CI:-0·17,0·56]). Conversely, delayed ART initiation was more negatively related to aPHV for appendicular (Females: β = 0·25 [95% CI:0·08,0·43]; Males: β = 0·63 [95%CI:0·32, 0·93] than axial growth (Females: β = 0·13 [95%CI:-0·08,0·34]; Males: β = 0·56 [95%CI:0·28,0·86]. Lower HAZ and WAZ were associated with lower height, later aPHV and lower PHV. At 48-week vitamin-D3/calcium supplementation had no effect on the growth pattern.ConclusionUnsuppressed viral load and delayed ART-initiation predicted later aPHV. Stunting and wasting were associated with attenuated growth velocity and later aPHV. Adolescents with HIV experience persistent linear growth impairments, potentially persisting into adulthood.Trial registration(PACTR20200989766029|| http://www.pactr.org/ ); First registered on 03/09/2020.

Project description:BackgroundManagement of co-morbidities among persons living with HIV is an emerging priority, which may require additional medication over and above life-long antiretroviral therapy (ART). We explored factors associated with adherence to the trial drug among children and adolescents with perinatally acquired HIV taking antiretroviral therapy (ART) in the Bronchopulmonary Function in Response to Azithromycin Treatment for Chronic Lung Disease in HIV-Infected Children (BREATHE) trial.MethodsThe BREATHE trial recruited 6-19 year olds with perinatally acquired HIV and co-morbid chronic lung disease as measured by FEV1. This two-site trial was individually randomised (1:1), double-blind and placebo-controlled. Participants received a once-weekly weight-based dose of 1-5 tablets of azithromycin (AZM: 250mg) or placebo, taken orally. We used pharmacy dispensing records and count of returned pills to measure adherence to study medication. Logistic regression was used to explore factors associated with adherence coverage. Poisson regression with Lexis expansion for time was used to explore whether adherence modified the effect of azithromycin on the incidence of acute respiratory exacerbation, a secondary outcome of the trial. Trial registration: ClinicalTrials.gov NCT02426112.ResultsThe 347 participants (median age 15.3, 51% male) consumed 14,622 doses of study medication over 16,220 person-weeks under study. Adherence was higher for those randomised to AZM (73.4%) than placebo (68.4%) and declined over the 48 weeks of the study (Score test for trend <0.02). Those with unsuppressed HIV viral load at baseline had 2.08 (95% CI: 1.19, 3.63) times the odds of non-adherence than those with viral suppression. Differences were also observed between trial sites.ConclusionThe majority of children and adolescents tolerated the addition of a once-weekly dose of medication to their pill burden. Barriers in adhering to treatment for co-morbid conditions are likely common to barriers in adhering to ART. Control of co-morbidities will therefore present additional challenges in HIV care.

Project description:BackgroundThe widespread availability of antiretroviral therapy (ART) has dramatically reduced mortality and improved life expectancy for people living with HIV (PLWH). However, even with HIV-1 suppression, chronic immune activation and elevated inflammation persist and have been linked to a pro-inflammatory gut microbiome composition and compromised intestinal barrier integrity. PLWH in urban versus rural areas of sub-Saharan Africa experience differences in environmental factors that may impact the gut microbiome and immune system, in response to ART, yet this has not previously been investigated in these groups. To address this, we measured T cell activation/exhaustion/trafficking markers, plasma inflammatory markers, and fecal microbiome composition in PLWH and healthy participants recruited from an urban clinic in the city of Harare, Zimbabwe, and a district hospital that services surrounding rural villages. PLWH were either ART naïve at baseline and sampled again after 24 weeks of first-line ART and the antibiotic cotrimoxazole or were ART-experienced at both timepoints.ResultsAlthough expected reductions in the inflammatory marker IL-6, T-cell activation, and exhaustion were observed with ART-induced viral suppression, these changes were much more pronounced in the urban versus the rural area. Gut microbiome composition was the most highly altered from healthy controls in ART experienced PLWH, and characterized by both reduced alpha diversity and altered composition. However, gut microbiome composition showed a pronounced relationship with T cell activation and exhaustion in ART-naïve PLWH, suggesting a particularly significant role for the gut microbiome in disease progression in uncontrolled infection. Elevated immune exhaustion after 24 weeks of ART did correlate with both living in the rural location and a more Prevotella-rich/Bacteroides-poor microbiome type, suggesting a potential role for rural-associated microbiome differences or their co-variates in the muted improvements in immune exhaustion in the rural area.ConclusionSuccessful ART was less effective at reducing gut microbiome-associated inflammation and T cell activation in PLWH in rural versus urban Zimbabwe, suggesting that individuals on ART in rural areas of Zimbabwe may be more vulnerable to co-morbidity related to sustained immune dysfunction in treated infection. Video Abstract.

Dataset Information

Composition of Gut Microbiota of Children and Adolescents With Perinatal Human Immunodeficiency Virus Infection Taking Antiretroviral Therapy in Zimbabwe.

Publications

Composition of Gut Microbiota of Children and Adolescents With Perinatal Human Immunodeficiency Virus Infection Taking Antiretroviral Therapy in Zimbabwe.

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