{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T21:26:31Z","timestamp":1770067591088,"version":"3.49.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Indian Council for Medical Research (ICMR), New Delhi, India"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Depletion of CD4+ T-cells in the gut-associated lymphoid tissue is the hallmark of HIV infection, with only partial restoration by potent antiretroviral therapy (ART). Gut dysbiosis, together with disruption of mucosal integrity contributes to chronic immune activation that further exacerbates the disease. Data from randomized controlled trials in pediatric HIV patients have indicated potential of probiotics in complementing routine ART in managing HIV-associated gastrointestinal complications. We have systematically extracted data from these trials and performed meta-analysis to quantify the effect of probiotics on CD4+ T-cell counts and any adverse events associated with their supplementation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A systematic search through multiple databases yielded three studies that were pooled using fixed-effect model. Risk of bias assessment was done by the Cochrane risk of bias tool and publication bias was assessed by Egger\u2019s test.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Included studies had moderate risk of bias and Egger\u2019s statistics revealed no publication bias (p &amp;gt; 0.05). Pooled analysis showed significant improvement in CD4+ T-cell counts, with mean difference, 123.92 (95% CI: 104.36\u2013143.48), p &amp;lt; 0.0001, no heterogeneity (I2=0) among the included trials. Subgroup analysis also depicted improvement in CD4+ T-cell counts irrespective of treatment duration, in both ART na\u00efve and treated patients. No adverse effects with probiotic consumption were reported.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Probiotics supplementation led to an improvement in CD4+ T-cell counts among HIV-infected children with no observed adverse effects. Despite the inherent limitations of included studies, our systematic review would justify more well-designed, large-scale trials in children, which may guide pediatricians on whether to incorporate probiotics as an adjunct therapy to routine ART.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/tropej\/fmac006","type":"journal-article","created":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T20:16:42Z","timestamp":1643833002000},"source":"Crossref","is-referenced-by-count":7,"title":["Effect of Probiotics on the Frequency of CD4+ T-Cells in HIV-Infected Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials"],"prefix":"10.1093","volume":"68","author":[{"given":"Meenakshi","family":"Sachdeva","sequence":"first","affiliation":[{"name":"Advanced Pediatric Center, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harnoor K","family":"Sra","sequence":"additional","affiliation":[{"name":"Advanced Pediatric Center, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Department of Telemedicine, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anil","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Department of Telemedicine, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pranita","family":"Pradhan","sequence":"additional","affiliation":[{"name":"Advanced Pediatric Center, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9653-1708","authenticated-orcid":false,"given":"Manvi","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Telemedicine, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2224-2743","authenticated-orcid":false,"given":"Meenu","family":"Singh","sequence":"additional","affiliation":[{"name":"Advanced Pediatric Center, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India"},{"name":"Department of Telemedicine, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"key":"2022020901114970900_fmac006-B1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1128\/mr.57.1.183-289.1993","article-title":"Pathogenesis of human immunodeficiency virus infection","volume":"57","author":"Levy","year":"1993","journal-title":"Microbiol Rev"},{"key":"2022020901114970900_fmac006-B2","author":"AIDSinfo.unaids.org. UNAIDS epidemiological estimates, 2021"},{"key":"2022020901114970900_fmac006-B3","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1002\/JLB.4MR1019-189R","article-title":"Incomplete immune reconstitution in HIV\/AIDS patients on antiretroviral therapy: challenges of immunological non-responders","volume":"107","author":"Yang","year":"2020","journal-title":"J Leukoc Biol"},{"key":"2022020901114970900_fmac006-B4","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/imr.12082","article-title":"Dendritic cell dysregulation during HIV-1 infection","volume":"254","author":"Miller","year":"2013","journal-title":"Immunol Rev"},{"key":"2022020901114970900_fmac006-B5","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.cyto.2016.08.010","article-title":"Increased expression of negative regulators of cytokine signaling during chronic HIV disease cause functionally exhausted state of dendritic cells","volume":"91","author":"Sachdeva","year":"2017","journal-title":"Cytokine"},{"key":"2022020901114970900_fmac006-B6","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/j.1365-2796.2008.02043.x","article-title":"Immune dysregulation in human immunodeficiency virus infection: know it, fix it, prevent it?","volume":"265","author":"Boasso","year":"2009","journal-title":"J Intern Med"},{"key":"2022020901114970900_fmac006-B7","first-page":"114","article-title":"HIV disease progression: immune activation, microbes, and a leaky gut","volume":"15","author":"Douek","year":"2007","journal-title":"Top HIV Med"},{"key":"2022020901114970900_fmac006-B8","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1038\/nm1511","article-title":"Microbial translocation is a cause of systemic immune activation in chronic HIV infection","volume":"12","author":"Brenchley","year":"2006","journal-title":"Nat Med"},{"key":"2022020901114970900_fmac006-B9","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/imr.12079","article-title":"HIV-associated chronic immune activation","volume":"254","author":"Paiardini","year":"2013","journal-title":"Immunol Rev"},{"key":"2022020901114970900_fmac006-B10","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/j.1365-2249.2007.03526.x","article-title":"Immune reconstitution in human immunodeficiency virus type 1-infected children with different virological responses to anti-retroviral therapy","volume":"150","author":"Anselmi","year":"2007","journal-title":"Clin Exp Immunol"},{"key":"2022020901114970900_fmac006-B11","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/hiv.13012","article-title":"Endothelial activation is associated with intestinal epithelial injury, systemic inflammation and treatment regimen in children living with vertically acquired HIV-1 infection","volume":"22","author":"Choudhury","year":"2021","journal-title":"HIV Med"},{"key":"2022020901114970900_fmac006-B12","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/nrgastro.2014.66","article-title":"The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic","volume":"11","author":"Hill","year":"2014","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2022020901114970900_fmac006-B13","doi-asserted-by":"crossref","first-page":"596166","DOI":"10.3389\/fcimb.2020.596166","article-title":"Viral infections, the microbiome, and probiotics","volume":"10","author":"Harper","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"key":"2022020901114970900_fmac006-B14","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1097\/MCG.0b013e31802c7465","article-title":"Yogurt containing probiotic Lactobacillus rhamnosus GR-1 and L. reuteri RC-14 helps resolve moderate diarrhea and increases CD4 count in HIV\/AIDS patients","volume":"42","author":"Anukam","year":"2008","journal-title":"J Clin Gastroenterol"},{"key":"2022020901114970900_fmac006-B15","doi-asserted-by":"crossref","first-page":"e201","DOI":"10.1097\/MCG.0b013e3181d8fba8","article-title":"Probiotic yogurt consumption is associated with an increase of CD4 count among people living with HIV\/AIDS","volume":"44","author":"Irvine","year":"2010","journal-title":"J Clin Gastroenterol"},{"key":"2022020901114970900_fmac006-B16","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1089\/aid.2014.0181","article-title":"Immunomodulation of antiretroviral drug-suppressed chronic HIV-1 infection in an oral probiotic double-blind placebo-controlled trial","volume":"30","author":"Yang","year":"2014","journal-title":"AIDS Res Hum Retroviruses"},{"key":"2022020901114970900_fmac006-B17","doi-asserted-by":"crossref","first-page":"570520","DOI":"10.3389\/fphar.2021.570520","article-title":"Effects of probiotics on diarrhea and CD4 cell count in people living with HIV: a systematic review and meta-analysis","volume":"12","author":"Zhang","year":"2021","journal-title":"Front Pharmacol"},{"key":"2022020901114970900_fmac006-B18","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1080\/19390211.2017.1380103","article-title":"Effect of probiotic supplementation on CD4 cell count in HIV-infected patients: a systematic review and meta-analysis","volume":"15","author":"Kazemi","year":"2018","journal-title":"J Diet Suppl"},{"key":"2022020901114970900_fmac006-B19","doi-asserted-by":"crossref","first-page":"ofw164","DOI":"10.1093\/ofid\/ofw164","article-title":"Probiotics in human immunodeficiency virus infection: a systematic review and evidence synthesis of benefits and risks","volume":"3","author":"Carter","year":"2016","journal-title":"Open Forum Infect Dis"},{"key":"2022020901114970900_fmac006-B20","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3920\/BM2015.0163","article-title":"The effect of probiotics on CD4 counts among people living with HIV: a systematic review","volume":"7","author":"Miller","year":"2016","journal-title":"Benef Microbes"},{"key":"2022020901114970900_fmac006-B21","doi-asserted-by":"crossref","first-page":"7947342","DOI":"10.1155\/2020\/7947342","article-title":"The effect of probiotics, prebiotics, and synbiotics on CD4 counts in HIV-infected patients: a systematic review and meta-analysis","volume":"2020","author":"Fu","year":"2020","journal-title":"Biomed Res Int"},{"key":"2022020901114970900_fmac006-B22","article-title":"Effect of probiotics on HIV-infected children and adolescents: A systematic review","volume-title":"PROSPERO","author":"Sachdeva","year":"2021"},{"key":"2022020901114970900_fmac006-B23","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"2022020901114970900_fmac006-B24","doi-asserted-by":"crossref","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration's tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"2022020901114970900_fmac006-B25","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Stat Med"},{"key":"2022020901114970900_fmac006-B26","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1007\/s12098-014-1407-6","article-title":"Role of multivitamins, micronutrients and probiotics supplementation in management of HIV infected children","volume":"81","author":"Gautam","year":"2014","journal-title":"Indian J Pediatr"},{"key":"2022020901114970900_fmac006-B27","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/tropej\/fmm066","article-title":"Use of probiotics in HIV-infected children: a randomized double-blind controlled study","volume":"54","author":"Trois","year":"2007","journal-title":"J Trop Pediatr"},{"key":"2022020901114970900_fmac006-B28","first-page":"137","article-title":"Effect of Lactobacillus plantarum IS-10506 on blood lipopolysaccharide level and immune response in HIV-infected children","volume":"11","author":"Athiyyah","year":"2019","journal-title":"Iran J Microbiol"},{"key":"2022020901114970900_fmac006-B29","author":"Higgins","year":"2021"},{"key":"2022020901114970900_fmac006-B30","first-page":"ED000142","article-title":"Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions","volume":"10","author":"Cumpston","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"key":"2022020901114970900_fmac006-B31","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jana.2012.04.004","article-title":"A systematic review of probiotics as a potential intervention to restore gut health in HIV infection","volume":"24","author":"Wilson","year":"2013","journal-title":"J Assoc Nurses AIDS Care"},{"key":"2022020901114970900_fmac006-B32","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3920\/BM2014.0079","article-title":"The administration of probiotics and synbiotics in immune compromised adults: is it safe?","volume":"6","author":"Van den Nieuwboer","year":"2015","journal-title":"Benef Microbes"},{"key":"2022020901114970900_fmac006-B33","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1097\/QCO.0000000000000612","article-title":"Probiotics to manage inflammation in HIV infection","volume":"33","author":"Reikvam","year":"2020","journal-title":"Curr Opin Infect Dis"}],"container-title":["Journal of Tropical Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/tropej\/article-pdf\/68\/2\/fmac006\/42403337\/fmac006.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/tropej\/article-pdf\/68\/2\/fmac006\/42403337\/fmac006.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T01:32:36Z","timestamp":1644370356000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/tropej\/article\/doi\/10.1093\/tropej\/fmac006\/6523053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,3]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2,3]]}},"URL":"https:\/\/doi.org\/10.1093\/tropej\/fmac006","relation":{},"ISSN":["0142-6338","1465-3664"],"issn-type":[{"value":"0142-6338","type":"print"},{"value":"1465-3664","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,4,1]]},"published":{"date-parts":[[2022,2,3]]},"article-number":"fmac006"}}