{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T10:25:37Z","timestamp":1789640737846,"version":"4.0.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Gastrointestinal probiotics play an important role in maintaining intestinal bacteria homeostasis. They might benefit people with human immunodeficiency virus\/acquired immunodeficiency syndrome (HIV\/AIDS), which remains a global health challenge. However, there is a controversy regarding the efficacy of probiotics for the treatment of AIDS. This study systematically reviewed the evidence of the effects of existing probiotic interventions on AIDS and sought to provide information on the role of probiotics in the treatment of HIV\/AIDS patients. A meta-analysis of studies identified by screening multiple databases was performed using a fixed-effects model in Review Manager 5.2 software. The meta-analysis showed that probiotics could reduce the incidence of AIDS-related diarrhea (RR = 0.60 (95% CI: 0.44\u20130.82), <jats:italic>p<\/jats:italic> = 0.001). The short-term use of probiotics (supplementation duration shorter than 30 days) did not reduce the incidence of diarrhea (RR = 0.76 (95% CI: 0.51\u20131.14), <jats:italic>p<\/jats:italic> = 0.19), while the long-term use of probiotics (supplementation duration longer than 30 days) reduced diarrhea (RR = 0.47 (95% CI: 0.29\u20130.76), <jats:italic>p<\/jats:italic> = 0.002). Probiotics had no effect on CD4 cell counts in HIV\/AIDS patients (MD = 21.24 (95% CI: \u221212.95\u201355.39), <jats:italic>p<\/jats:italic> = 0.22). Our data support that probiotics were associated with an obvious reduction in AIDS-related diarrhea, which indicates the need for additional research on this potential preventive strategy for AIDS.<\/jats:p>","DOI":"10.3389\/fphar.2021.570520","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T06:10:21Z","timestamp":1626675021000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Effects of Probiotics on Diarrhea and CD4 Cell Count in People Living With HIV: A Systematic Review and Meta-Analysis"],"prefix":"10.3389","volume":"12","author":[{"given":"Xiao-Li","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Hui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Tao","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juehua","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Qun","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua-You","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun-Hua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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":"B2","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1097\/qai.0000000000001693","article-title":"Effect of Lactobacillus Rhamnosus GG Supplementation on Intestinal Inflammation Assessed by PET\/MRI Scans and Gut Microbiota Composition in HIV-Infected Individuals","volume":"78","author":"Arnbjerg","year":"2018","journal-title":"J. Acquir Immune Defic Syndr."},{"key":"B3","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":"B4","doi-asserted-by":"publisher","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":"B5","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1080\/14712598.2019.1638907","article-title":"Challenges in the Management of HIV Infection: Update on the Role of Probiotic Supplementation as a Possible Complementary Therapeutic Strategy for cART Treated People Living with HIV\/AIDS","volume":"19","author":"Ceccarelli","year":"2019","journal-title":"Expert Opin. Biol. Ther."},{"key":"B6","doi-asserted-by":"publisher","first-page":"S22","DOI":"10.1016\/s0002-9270(99)00813-8","article-title":"Probiotics and Immune Response","volume":"95","author":"Cunninghamrundles","year":"2000","journal-title":"Am. J. Gastroenterol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"615","DOI":"10.3390\/nu9060615","article-title":"Microbiota and Probiotics in Health and HIV Infection","volume":"9","author":"D'Angelo","year":"2017","journal-title":"Nutrients"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e0137200","DOI":"10.1371\/journal.pone.0137200","article-title":"Probiotics Reduce Inflammation in Antiretroviral Treated, HIV-Infected Individuals: Results of the \"Probio-HIV\" Clinical Trial","volume":"10","author":"d'Ettorre","year":"2015","journal-title":"PloS one"},{"key":"B9","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1002\/iid3.160","article-title":"Probiotic Supplementation Promotes a Reduction in T-Cell Activation, an Increase in Th17 Frequencies, and a Recovery of Intestinal Epithelium Integrity and Mitochondrial Morphology in ART-Treated HIV-1-Positive Patients","volume":"5","author":"d'Ettorre","year":"2017","journal-title":"Immun. Inflamm. Dis."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e44454","DOI":"10.1371\/journal.pone.0044454","article-title":"Inflammation, Coagulation and Cardiovascular Disease in HIV-Infected Individuals","volume":"7","author":"Duprez","year":"2012","journal-title":"PloS one"},{"key":"B11","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3920\/bm2012.0020","article-title":"Probiotics and Nutrients for the First 1000 Days of Life in the Developing World","volume":"4","author":"Enos","year":"2013","journal-title":"Beneficial Microbes"},{"key":"B12","doi-asserted-by":"publisher","first-page":"8335","DOI":"10.3390\/nu7105396","article-title":"Effect of Probiotic Supplement on Cytokine Levels in HIV-Infected Individuals: A Preliminary Study","volume":"7","author":"Falasca","year":"2015","journal-title":"Nutrients"},{"key":"B13","doi-asserted-by":"publisher","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":"B14","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/s0924-8579(99)00050-3","article-title":"Review of Probiotics Available to Modify Gastrointestinal flora","volume":"12","author":"Gismondo","year":"1999","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B15","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/1475-2891-11-90","article-title":"Synbiotic Therapy Decreases Microbial Translocation and Inflammation and Improves Immunological Status in HIV-Infected Patients: a Double-Blind Randomized Controlled Pilot Trial","volume":"11","author":"Gonz\u00e1lez-Hern\u00e1ndez","year":"2012","journal-title":"Nutr. J."},{"key":"B16","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1078\/1438-4221-00246","article-title":"Intestinal flora and Mucosal Immune Responses","volume":"293","author":"Heller","year":"2003","journal-title":"Int. J. Med. Microbiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"414","DOI":"10.4161\/gmic.21248","article-title":"Micronutrient Supplemented Probiotic Yogurt for HIV-Infected Adults Taking HAART in London, Canada","volume":"3","author":"Hemsworth","year":"2012","journal-title":"Gut microbes"},{"key":"B18","doi-asserted-by":"publisher","first-page":"80","DOI":"10.4161\/gmic.2.2.15787","article-title":"Effect of 25 Weeks Probiotic Supplementation on Immune Function of HIV Patients","volume":"2","author":"Hummelen","year":"","journal-title":"Gut Microbes"},{"key":"B19","doi-asserted-by":"publisher","first-page":"897","DOI":"10.3390\/nu3100897","article-title":"Effect of Micronutrient and Probiotic Fortified Yogurt on Immune-Function of Anti-retroviral Therapy Naive HIV Patients","volume":"3","author":"Hummelen","year":"","journal-title":"Nutrients"},{"key":"B20","doi-asserted-by":"publisher","first-page":"201","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":"B21","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/j.nutres.2011.10.005","article-title":"Probiotic Yogurt Consumption May Improve Gastrointestinal Symptoms, Productivity, and Nutritional Intake of People Living with Human Immunodeficiency Virus in Mwanza, Tanzania","volume":"31","author":"Irvine","year":"2011","journal-title":"Nutr. Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1172\/JCI66227","article-title":"Probiotic\/prebiotic Supplementation of Antiretrovirals Improves Gastrointestinal Immunity in SIV-Infected Macaques","volume":"123","author":"Klatt","year":"2013","journal-title":"J. Clin. Invest."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e203","DOI":"10.1371\/journal.pmed.0050203","article-title":"Inflammatory and Coagulation Biomarkers and Mortality in Patients with HIV Infection","volume":"5","author":"Kuller","year":"2008","journal-title":"Plos Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"605","DOI":"10.4049\/jimmunol.1601355","article-title":"Inside Out: HIV, the Gut Microbiome, and the Mucosal Immune System","volume":"198","author":"Liu","year":"2017","journal-title":"J. Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1089\/apc.2013.0175","article-title":"A Review of the Use of Complementary and Alternative Medicine and HIV: Issues for Patient Care","volume":"27","author":"Lorenc","year":"2013","journal-title":"AIDS Patient Care and STDs"},{"key":"B26","doi-asserted-by":"publisher","first-page":"198","DOI":"10.4161\/gmic.2.3.16106","article-title":"Probiotics and Prebiotics to Combat Enteric Infections and HIV in the Developing World: a Consensus Report","volume":"2","author":"Monachese","year":"2011","journal-title":"Gut microbes"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1000163","DOI":"10.4172\/2155-6113.1000163","article-title":"Socioeconomic Status and Survival of People with Human Immunodeficiency Virus Infection before and after the Introduction of Highly Active Antiretroviral Therapy: A Systematic Literature Review","volume":"3","author":"Pavlova-McCalla","year":"2012","journal-title":"J. AIDS Clin. Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1738676","DOI":"10.1155\/2018\/1738676","article-title":"Type I\/II Interferon in HIV-1-Infected Patients: Expression in Gut Mucosa and in Peripheral Blood Mononuclear Cells and its Modification upon Probiotic Supplementation","volume":"2018","author":"Pinacchio","year":"2018","journal-title":"J. Immunol. Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.puhe.2016.05.004","article-title":"Survival Rate of AIDS Disease and Mortality in HIV-Infected Patients: a Meta-Analysis","volume":"139","author":"Poorolajal","year":"2016","journal-title":"Public health"},{"key":"B30","doi-asserted-by":"publisher","first-page":"4884","DOI":"10.1073\/pnas.87.12.4884","article-title":"Cytokine-stimulated Human Immunodeficiency Virus Replication Is Inhibited by N-Acetyl-L-Cysteine","volume":"87","author":"Roederer","year":"1990","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1310\/6f83-n39q-9ppp-lmvv","article-title":"The Efficacy and Safety of ProbioticLactobacillus rhamnosusGG on Prolonged, Noninfectious Diarrhea in HIV Patients on Antiretroviral Therapy: A Randomized, Placebo-Controlled, Crossover Study","volume":"5","author":"Salminen","year":"2004","journal-title":"HIV Clin. Trials"},{"key":"B32","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/j.clnu.2016.06.005","article-title":"Effectiveness of Nutritional Treatment and Synbiotic Use on Gastrointestinal Symptoms Reduction in HIV-Infected Patients: Randomized Clinical Trial","volume":"36","author":"Santos","year":"2015","journal-title":"Clin. Nutr."},{"key":"B33","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/1472-6882-12-84","article-title":"Randomized Pilot Trial of a Synbiotic Dietary Supplement in Chronic HIV-1 Infection","volume":"12","author":"Schunter","year":"2012","journal-title":"BMC Complement. Altern. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1080\/10408398.2011.594185","article-title":"Probiotics: a Comprehensive Approach toward Health Foods","volume":"54","author":"Sharma","year":"2014","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"B35","doi-asserted-by":"publisher","first-page":"331","DOI":"10.3109\/08923979209009228","article-title":"Effect ofBifidobacterium bifidumandLactobacillus Acidophiluson Gut Mucosa and Peripheral Blood B Lymphocytes","volume":"14","author":"Simone","year":"1992","journal-title":"Immunopharmacology and immunotoxicology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1097\/qai.0000000000000784","article-title":"Reduced Levels of D-Dimer and Changes in Gut Microbiota Composition after Probiotic Intervention in HIV-Infected Individuals on Stable ART","volume":"70","author":"Stiksrud","year":"2015","journal-title":"J. Acquir Immune Defic Syndr."},{"key":"B37","first-page":"318","article-title":"Advances in Nutrition Support for Quality of Life in HIV+\/AIDS","volume":"16","author":"Suttajit","year":"2007","journal-title":"Asia Pac. J. Clin. Nutr."},{"key":"B38","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1177\/096228020000900503","article-title":"Modelling Publication Bias in Meta-Analysis: a Review","volume":"9","author":"Sutton","year":"2000","journal-title":"Stat. Methods Med. Res."},{"key":"B39","doi-asserted-by":"publisher","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":"2008","journal-title":"J. Trop. Pediatr."},{"key":"B40","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1097\/qai.0000000000000468","article-title":"Effect of Probiotics (Saccharomyces Boulardii) on Microbial Translocation and Inflammation in HIV-Treated Patients","volume":"68","author":"Villar-Garc\u00eda","year":"2015","journal-title":"J. Acquir Immune Defic Syndr."},{"key":"B41","doi-asserted-by":"publisher","first-page":"193ra191","DOI":"10.1126\/scitranslmed.3006438","article-title":"Dysbiosis of the Gut Microbiota Is Associated with HIV Disease Progression and Tryptophan Catabolism","volume":"5","author":"Vujkovic-Cvijin","year":"2013","journal-title":"Sci. translational Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1016\/s0278-6915(98)00090-8","article-title":"Safety and Tolerance of Lactobacillus Reuteri Supplementation to a Population Infected with the Human Immunodeficiency Virus","volume":"36","author":"Wolf","year":"1998","journal-title":"Food Chem. Toxicol."},{"key":"B43","doi-asserted-by":"publisher","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"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.570520\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T06:10:27Z","timestamp":1626675027000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.570520\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,19]]},"references-count":43,"alternative-id":["10.3389\/fphar.2021.570520"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.570520","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,19]]},"article-number":"570520"}}