T-SPOT.TB Reactivity in Southern African Children With and Without in Utero Human Immunodeficiency Virus Exposure.
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ABSTRACT:
SUBMITTER: Iwase SC
PROVIDER: S-EPMC10573724 | biostudies-literature | 2023 Oct
REPOSITORIES: biostudies-literature
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T-SPOT.TB Reactivity in Southern African Children With and Without in Utero Human Immunodeficiency Virus Exposure.
Iwase Saori C SC Edlefsen Paul T PT Bhebhe Lynnette L Motsumi Kesego K Moyo Sikhulile S Happel Anna-Ursula AU Shao Danica D Mmasa Nicholas N Schenkel Sara S Gasper Melanie A MA Dubois Melanie M Files Megan A MA Seshadri Chetan C Duffy Fergal F Aitchison John J Netea Mihai G MG Jao Jennifer J Cameron Donald W DW Gray Clive M CM Jaspan Heather B HB Powis Kathleen M KM
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20231001 8
Infants who are human immunodeficiency virus (HIV)-exposed uninfected (iHEU) experience higher risk of infectious morbidity than infants HIV-unexposed uninfected (iHUU). We compared tuberculosis (TB) infection prevalence in 418 Bacillus Calmette-Guérin vaccinated sub-Saharan African iHEU and iHUU aged 9-18 months using T-SPOT.TB. Prevalence of TB infection was low and did not differ by HIV exposure status. ...[more]
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Project description:In countries with high human immunodeficiency virus (HIV) prevalence, up to 30% of pregnant women are living with HIV, with fetal exposure to both HIV and antiretroviral therapy during pregnancy. In addition, pregnant women without HIV but at high risk of HIV acquisition are increasingly receiving HIV preexposure antiretroviral prophylaxis (PrEP). Investments are being made to establish and follow cohorts of children to evaluate the long-term effects of in utero HIV and antiretroviral exposure. Agreement on a key set of definitions for relevant exposures and outcomes is important both for interpreting individual study results and for comparisons across cohorts. Harmonized definitions of in utero HIV and antiretroviral drug (maternal treatment or PrEP) exposure will also facilitate improved classification of these exposures in future observational studies and clinical trials. The proposed definitions offer a uniform approach to facilitate the consistent description and estimation of effects of HIV and antiretroviral exposures on key child health outcomes.
| S-EPMC9410726 | biostudies-literature
Project description:ObjectivesTo estimate the prevalence of elevated point-of-care (POC) capillary blood lactate concentrations in human immunodeficiency virus (HIV)-exposed, uninfected children (HEU) and to determine if POC lactate varies with in utero antiretroviral (ARV) exposure.MethodsThe Surveillance Monitoring for Antiretroviral Therapy Toxicities protocol of the Pediatric HIV/AIDS Cohort Study enrolled 1934 children between 2007 and 2009, 0 to 12 years of age, born to HIV-infected mothers. POC lactate was measured annually on capillary blood using the Lactate Pro device. Associations of POC lactate with in utero ARV exposure and other characteristics were evaluated using logistic regression models, adjusting for maternal characteristics and other confounders.ResultsOf 1641 children with POC measurements (median age, 3.0 years), 3.4% had POC lactate >3 mmol/L. Median POC lactate level decreased with age (1.9 mmol/L, 1.7 mmol/L, and 1.6 mmol/L for children 0-<6 months [99% ≤6 weeks of life], 6-<24 months, and ≥24 months of age, respectively; P < 0.001). Prevalence of elevated POC lactate did not differ by in utero ARV exposure drug class, but was significantly higher in children exposed in utero to emtricitabine or efavirenz, cocaine or opiates, and those of white race.ConclusionsPOC lactate testing is a useful rapid laboratory screening assay for HEU children with ARV exposure. ARV use during pregnancy has resulted in a dramatic decrease in mother-to-child transmission of HIV, and the risk of elevated lactate in HEU children is low. However, as new ARVs and more complex regimens are used during pregnancy by HIV-infected women, continued monitoring for infant toxicities is essential.
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Project description:ImportanceMost studies examining the association of prenatal antiretroviral (ARV) exposures with congenital anomalies (CAs) in children born to human immunodeficiency virus (HIV)-infected women have been reassuring, but some evidence suggests an increased risk with specific ARV agents.ObjectiveTo evaluate the association of in utero ARV exposures with CAs in HIV-exposed uninfected children.Design, setting, and participantsProspective cohort study design. The Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring of ART Toxicities (SMARTT) Study was performed at 22 US medical centers among 2580 HIV-exposed uninfected children enrolled in the SMARTT Study between March 23, 2007, and June 18, 2012.ExposuresFirst-trimester exposure to any ARV and to specific ARV medications.Main outcomes and measuresThe primary end point was a CA based on physician review of infant physical examinations according to the Antiretroviral Pregnancy Registry modification of the Metropolitan Atlanta Congenital Defects Program. Rates of CAs were estimated overall and by birth year. Logistic regression models were used to evaluate the association of CAs with first-trimester ARV exposures, adjusting for demographic and maternal characteristics.ResultsCongenital anomalies occurred in 175 of 2580 children, yielding a prevalence of 6.78% (95% CI, 5.85%-7.82%); 242 major CAs were confirmed, including 72 musculoskeletal and 55 cardiovascular CAs. The prevalence of CAs increased significantly among successive birth cohorts (3.8% for children born before 2002 and up to 8.3% for those born 2008-2010). In adjusted models, no association of first-trimester exposures with CAs was found for any ARV, for combination ARV regimens, or for any drug class. No individual ARV in the reverse transcriptase inhibitor drug classes was associated with an increased risk of CAs. Among protease inhibitors, higher odds of CAs were observed for atazanavir sulfate (adjusted odds ratio [aOR], 1.95; 95% CI, 1.24-3.05) and for ritonavir used as a booster (aOR, 1.56; 95% CI, 1.11-2.20). With first-trimester atazanavir exposure, risks were highest for skin (aOR, 5.23) and musculoskeletal (aOR, 2.55) CAs.Conclusions and relevanceFew individual ARVs and no drug classes were associated with an increased risk of CAs in HIV-exposed infants after adjustment for calendar year and maternal characteristics. While the overall risk remained low, a relative increase was observed in successive years and with atazanavir exposure. Given the low absolute CA risk, the benefits of recommended ARV therapy use during pregnancy still outweigh such risks, although further studies are warranted.
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Project description:Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share transmission routes and are endemic in sub-Saharan Africa. The objective of the present study was to use the Taormina definition of occult HBV infection, together with stringent amplification conditions, to determine the prevalence and characteristics of HBV infection in antiretroviral treatment (ART)-naïve HIV(+ve) adults in a rural cohort in South Africa. The presence of HBV serological markers was determined by enzyme linked immunoassay (ELISA) tests. HBV DNA-positivity was determined by polymerase chain reaction (PCR) of at least two of three different regions of the HBV genome. HBV viral loads were determined by real-time PCR. Liver fibrosis was determined using the aspartate aminotransferase-to-platelet ratio index. Of the 298 participants, 231 (77.5%) showed at least one HBV marker, with 53.7% HBV DNA(-ve) (resolved) and 23.8% HBV DNA(+ve) (current) [8.7% HBsAg(+ve): 15.1% HBsAg(-ve)]. Only the total number of sexual partners distinguished HBV DNA(+ve) and HBV DNA(-ve) participants, implicating sexual transmission of HBV and/or HIV. It is plausible that sexual transmission of HBV and/or HIV may result in a new HBV infection, superinfection and re-activation as a consequence of immunesuppression. Three HBsAg(-ve) HBV DNA(+ve) participants had HBV viral loads <200 IU/ml and were therefore true occult HBV infections. The majority of HBsAg(-ve) HBV DNA(+ve) participants did not differ from HBsAg(+ve) HBV DNA(+ve) (overt) participants in terms of HBV viral loads, ALT levels or frequency of liver fibrosis. Close to a quarter of HIV(+ve) participants were HBV DNA(+ve), of which the majority were HBsAg(-ve) and were only detected using nucleic acid testing. Detection of HBsAg(-ve) HBV DNA(+ve) subjects is advisable considering they were clinically indistinguishable from HBsAg(+ve) HBV DNA(+ve) individuals and should not be overlooked, especially if lamivudine is included in the ART.
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Project description:BackgroundCombination antiretroviral therapy (cART) during pregnancy prevents vertical transmission, but many antiretrovirals cross the placenta and several can affect mitochondria. Exposure to maternal human immunodeficiency virus (HIV) and/or cART could have long-term effects on children who are HIV exposed and uninfected (CHEU). Our objective was to compare blood mitochondrial DNA (mtDNA) content in CHEU and children who are HIV unexposed and uninfected (CHUU), at birth and in early life.MethodsWhole-blood mtDNA content at birth and in early life (age 0-3 years) was compared cross-sectionally between CHEU and CHUU. Longitudinal changes in mtDNA content among CHEU was also evaluated.ResultsAt birth, CHEU status and younger gestational age were associated with higher mtDNA content. These remained independently associated with mtDNA content in multivariable analyses, whether considering all infants, or only those born at term. Longitudinally, CHEU mtDNA levels remained unchanged during the first 6 months of life, and gradually declined thereafter. A separate age- and sex-matched cross-sectional analysis (in 214 CHEU and 214 CHUU) illustrates that the difference in mtDNA between the groups remains detectable throughout the first 3 years of life.ConclusionThe persistently elevated blood mtDNA content observed among CHEU represents a long-term effect, possibly resulting from in utero stresses related to maternal HIV and/or cART. The clinical impact of altered mtDNA levels is unclear.
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Project description:Aims/objectivesThrough interviews with clinical service providers, we explored stigma's impact on HIV service provision for African Americans during COVID-19.BackgroundAfrican Americans experience disproportionate rates of HIV and COVID-19. We explored COVID-19's impact on HIV services for African American adults in a Southern city.DesignThe study was qualitative and observational.MethodsKey informant interviews were conducted (n = 11) across two healthcare centres and two community-based organisations and thematically analysed using phenomenological approaches by two coders. Interviews explored pre- and post-COVID-19 service provision and parallels between COVID-19 and HIV, particularly as related to stigma. The COREQ checklist was utilised to ensure research quality.ResultsAccording to the providers interviewed, all providers offered HIV prevention/treatment, but PrEP and preventive services diminished greatly early in the COVID-19 pandemic. Successful transition to telehealth depended on existing telehealth use. Challenges exacerbated by COVID-19 included food/housing insecurity and physical distancing constraints. Clients' COVID-19 informational needs shifted from concerns to vaccine requests over time. Interviewees stated HIV and COVID-19 both carry 'risk taking'; however, HIV risk was more physically intimate than COVID-19. Notably, some providers used stigmatising language referring to clients with HIV/COVID and omitted person-centred language.ConclusionsFindings suggest need to address challenges in telehealth to improve client experiences now and for future pandemics. More research is needed to examine intersectional stigmatisation of COVID-19 and HIV for African Americans to design person-centred counselling interventions.Relevance to clinical practiceResults demonstrate need for provider training to reframe stigma discussions using client centeredness, educating African Americans on HIV and COVID-19 prevention, and coordination with local organisations to address multiple care needs.Patient/public contributionThis research highlights needs of clients based on the views of healthcare providers caring for predominantly African American communities in a Southern city. However, no patients, service users, caregivers or members of the public were directly involved in this study.
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Project description:Pneumococcal nasopharyngeal colonization is a pre-requisite for pneumococcal disease; the risk for pneumococcal disease is high in children born to women living with human immunodeficiency virus (HIV). We investigated pneumococcal colonization, serotype distribution and antibiotic susceptibility of Streptococcus pneumoniae isolates carried by perinatal HIV-infected and HIV-exposed-uninfected (HEU) children.Serial nasopharyngeal swabs were collected from 331 HIV-infected and 491 HEU children, at up to 6 scheduled timepoints, between median ages of 25 to 181 weeks. Pneumococcus was identified by culture; serotyping and antibiotic susceptibility testing were done by conventional methods. No pneumococcal vaccine was given.HIV-infected children were less likely to be colonized with 7-valent pneumococcal conjugate vaccine 7 serotypes than HEU at a median of 25 weeks of age (23% vs 36%; P < .001); however, no differences in colonization between the 2 groups were observed at subsequent study-visits. Over the 36-months study-period pneumococcal colonization increased in both HIV-infected (from 45% to 77%) and HEU (from 57% to 61%) children. Over the study-period, pneumococcal isolates non-susceptible to cotrimoxazole decreased from 92% to 57% and had a similar trend to penicillin (from 65% to 42%) in HIV-infected children. Similarly, pneumococcal nonsusceptible to cotrimoxazole decreased from 93% to 57% and to penicillin from 69% to 37% in HEU children.Vaccine serotype colonization was common in this population and similar rates were observed in HIV-infected and HEU children. The prevalence of pneumococcal isolates non-susceptible to cotrimoxazole and penicillin decreased with age.
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