{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:05:33Z","timestamp":1791198333533,"version":"4.1.0"},"reference-count":31,"publisher":"American Academy of Pediatrics (AAP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,7,1]]},"abstract":"<jats:p>OBJECTIVE. We sought to determine the impact of highly active antiretroviral therapy on the incidence and prevalence of opportunistic infections in HIV-infected children.<\/jats:p><jats:p>METHODS. Children born from 1986 to 1998 were monitored until 2004 in the Perinatal AIDS Collaborative Transmission Study, sponsored by the Centers for Disease Control and Prevention. We determined the pre\u2013highly active antiretroviral therapy and post\u2013highly active antiretroviral therapy (before and after January 1, 1997, respectively) incidence rates of opportunistic infections among HIV-infected children and characterized the temporal decreases in percentages of CD4+ cells and the mortality rates among patients with and those without incident opportunistic infections.<\/jats:p><jats:p>RESULTS. The overall opportunistic infection incidence declined from 14.4 to 1.1 cases per 100 patient-years; statistically significant reductions were seen in the incidence of the most common opportunistic infections, including Pneumocystis jiroveci pneumonia (5.8 vs 0.3 cases per 100 patient-years), recurrent bacterial infections (4.7 vs 0.2 cases per 100 patient-years), extraocular cytomegalovirus infection (1.4 vs 0.1 cases per 100 patient-years), and disseminated nontuberculous mycobacterial infection (1.3 vs 0.2 cases per 100 patient-years). Kaplan-Meier analysis of time from birth to the first opportunistic infection illustrated more-rapid acquisition of opportunistic infections by HIV-infected children born in the pre\u2013highly active antiretroviral therapy era than by those born later. In the first 3 years of life, there was a faster decline in the percentage of CD4+ cells among children with opportunistic infections. The mortality rate was significantly higher among children with opportunistic infections.<\/jats:p><jats:p>CONCLUSIONS. Reduction in the incidence of opportunistic infections and prolongation of the time to the first opportunistic infection were noted during the post\u2013highly active antiretroviral therapy era. Children who experienced opportunistic infections had higher mortality rates than did those who did not. Younger children (&amp;lt;3 years) who experienced opportunistic infections had faster declines in percentages of CD4+ T cells.<\/jats:p>","DOI":"10.1542\/peds.2006-2052","type":"journal-article","created":{"date-parts":[[2007,7,2]],"date-time":"2007-07-02T16:35:25Z","timestamp":1183394125000},"page":"100-109","source":"Crossref","is-referenced-by-count":86,"title":["Trends in Opportunistic Infections in the Pre\u2013and Post\u2013Highly Active Antiretroviral Therapy Eras Among HIV-Infected Children in the Perinatal AIDS Collaborative Transmission Study, 1986\u20132004"],"prefix":"10.1542","volume":"120","author":[{"given":"Steven R.","family":"Nesheim","sequence":"first","affiliation":[{"name":"Departments of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bill G.","family":"Kapogiannis","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics"},{"name":"Medicine, Division of Infectious Diseases, Emory University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minn M.","family":"Soe","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Abrams","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Harlem Hospital Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Farley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Maryland, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Medicine and Dentistry of New Jersey, Newark, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda J.","family":"Koenig","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Bulterys","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2007,7,1]]},"reference":[{"key":"2021120901592152700_R1","doi-asserted-by":"crossref","unstructured":"Ledergerber B, Egger M, Erard V, et al. AIDS-related opportunistic illnesses occurring after initiation of potent antiretroviral therapy: the Swiss HIV Cohort Study. JAMA.\u20081999;282:2220\u20132226","DOI":"10.1001\/jama.282.23.2220"},{"key":"2021120901592152700_R2","doi-asserted-by":"crossref","unstructured":"Ledergerber B, Mocroft A, Reiss P, et al. Discontinuation of secondary prophylaxis against Pneumocystis carinii pneumonia in patients with HIV infection who have a response to antiretroviral therapy: eight European study groups. N Engl J Med.\u20082001;344:168\u2013174","DOI":"10.1056\/NEJM200101183440302"},{"key":"2021120901592152700_R3","doi-asserted-by":"crossref","unstructured":"Mocroft A, Katlama C, Johnson AM, et al. AIDS across Europe, 1994\u201398: the EuroSIDA study. Lancet.\u20082000;356:291\u2013296","DOI":"10.1016\/S0140-6736(00)02504-6"},{"key":"2021120901592152700_R4","doi-asserted-by":"crossref","unstructured":"Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection: HIV Outpatient Study investigators. N Engl J Med.\u20081998;338:853\u2013860","DOI":"10.1056\/NEJM199803263381301"},{"key":"2021120901592152700_R5","doi-asserted-by":"crossref","unstructured":"Gortmaker SL, Hughes M, Cervia J, et al. Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV-1. N Engl J Med.\u20082001;345:1522\u20131528","DOI":"10.1056\/NEJMoa011157"},{"key":"2021120901592152700_R6","doi-asserted-by":"crossref","unstructured":"Sanchez JM, Ramos Amador JT, Fernandez de Miguel S, et al. Impact of highly active antiretroviral therapy on the morbidity and mortality in Spanish human immunodeficiency virus-infected children. Pediatr Infect Dis J.\u20082003;22:863\u2013867","DOI":"10.1097\/01.inf.0000091282.70253.5f"},{"key":"2021120901592152700_R7","doi-asserted-by":"crossref","unstructured":"Baril L, Jouan M, Agher R, et al. Impact of highly active antiretroviral therapy on onset of Mycobacterium avium complex infection and cytomegalovirus disease in patients with AIDS. AIDS.\u20082000;14:2593\u20132596","DOI":"10.1097\/00002030-200011100-00023"},{"key":"2021120901592152700_R8","doi-asserted-by":"crossref","unstructured":"Detels R, Tarwater P, Phair JP, Margolick J, Riddler SA, Munoz A. Effectiveness of potent antiretroviral therapies on the incidence of opportunistic infections before and after AIDS diagnosis. AIDS.\u20082001;15:347\u2013355","DOI":"10.1097\/00002030-200102160-00008"},{"key":"2021120901592152700_R9","doi-asserted-by":"crossref","unstructured":"Williams PL, Currier JS, Swindells S. Joint effects of HIV-1 RNA levels and CD4 lymphocyte cells on the risk of specific opportunistic infections. AIDS.\u20081999;13:1035\u20131044","DOI":"10.1097\/00002030-199906180-00006"},{"key":"2021120901592152700_R10","doi-asserted-by":"crossref","unstructured":"Dankner WM, Lindsey JC, Levin MJ. Correlates of opportunistic infections in children infected with the human immunodeficiency virus managed before highly active antiretroviral therapy. Pediatr Infect Dis J.\u20082001;20:40\u201348","DOI":"10.1097\/00006454-200101000-00008"},{"key":"2021120901592152700_R11","doi-asserted-by":"crossref","unstructured":"Gona P, Van Dyke RB, Williams PL, et al. Incidence of opportunistic and other infections in HIV-infected children in the HAART era. JAMA.\u20082006;296:292\u2013300","DOI":"10.1001\/jama.296.3.292"},{"key":"2021120901592152700_R12","doi-asserted-by":"crossref","unstructured":"Ylitalo N, Brogly S, Hughes MD, et al. Risk factors for opportunistic illnesses in children with human immunodeficiency virus in the era of highly active antiretroviral therapy. Arch Pediatr Adolesc Med.\u20082006;160:778\u2013787","DOI":"10.1001\/archpedi.160.8.778"},{"key":"2021120901592152700_R13","doi-asserted-by":"crossref","unstructured":"Kaplan JE, Hanson D, Dworkin MS, et al. Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy. Clin Infect Dis.\u20082000;30(suppl 1):S5\u2013S14","DOI":"10.1086\/313843"},{"key":"2021120901592152700_R14","doi-asserted-by":"crossref","unstructured":"Nachman S, Gona P, Dankner W, et al. The rate of serious bacterial infections among HIV-infected children with immune reconstitution who have discontinued opportunistic infection prophylaxis. Pediatrics.\u20082005;115(4). Available at: www.pediatrics.org\/cgi\/content\/full\/115\/4\/e488","DOI":"10.1542\/peds.2004-1847"},{"key":"2021120901592152700_R15","doi-asserted-by":"crossref","unstructured":"Powderly WG. Prophylaxis for opportunistic infections in an era of effective antiretroviral therapy. Clin Infect Dis.\u20082000;31:597\u2013601","DOI":"10.1086\/313950"},{"key":"2021120901592152700_R16","doi-asserted-by":"crossref","unstructured":"Freedman D, Koenig LJ, Wiener J, et al. Challenges to re-enrolling perinatally HIV-infected and HIV-exposed but uninfected children into a prospective cohort study: strategies for locating and recruiting hard-to-reach families. Paediatr Perinat Epidemiol.\u20082006;20:338\u2013347","DOI":"10.1111\/j.1365-3016.2006.00742.x"},{"key":"2021120901592152700_R17","doi-asserted-by":"crossref","unstructured":"Simonds RJ, Steketee R, Nesheim S, et al. Impact of zidovudine use on risk and risk factors for perinatal transmission of HIV: Perinatal AIDS Collaborative Transmission Studies. AIDS.\u20081998;12:301\u2013308","DOI":"10.1097\/00002030-199803000-00008"},{"key":"2021120901592152700_R18","doi-asserted-by":"crossref","unstructured":"Abrams EJ, Wiener J, Carter R, et al. Maternal health factors and early pediatric antiretroviral therapy influence the rate of perinatal HIV-1 disease progression in children. AIDS.\u20082003;17:867\u2013877","DOI":"10.1097\/00002030-200304110-00012"},{"key":"2021120901592152700_R19","doi-asserted-by":"crossref","unstructured":"Bulterys M, Nesheim S, Abrams EJ, et al. Lack of evidence of mitochondrial dysfunction in the offspring of HIV-infected women: retrospective review of perinatal exposure to antiretroviral drugs in the Perinatal AIDS Collaborative Transmission Study. Ann N Y Acad Sci.\u20082000;918:212\u2013221","DOI":"10.1111\/j.1749-6632.2000.tb05491.x"},{"key":"2021120901592152700_R20","unstructured":"Centers for Disease Control and Prevention. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep.\u20081992;41(RR-17):1\u201319"},{"key":"2021120901592152700_R21","unstructured":"Gahlinger PM, Abramson JH. Computer Programs for Epidemiologic Analysis. 2nd ed. Stone Mountain, GA: USD; 1995"},{"key":"2021120901592152700_R22","doi-asserted-by":"crossref","unstructured":"Denny T, Yogev R, Gelman R, et al. Lymphocyte subsets in healthy children during the first 5 years of life. JAMA.\u20081992;267:1484\u20131488","DOI":"10.1001\/jama.267.11.1484"},{"key":"2021120901592152700_R23","unstructured":"Centers for Disease Control and Prevention. 1995 revised guidelines for prophylaxis against Pneumocystis carinii pneumonia for children infected with or perinatally exposed to human immunodeficiency virus. MMWR Recomm Rep.\u20081995;44(RR-4):1\u201311"},{"key":"2021120901592152700_R24","unstructured":"Centers for Disease Control and Prevention. Guidelines for prophylaxis against Pneumocystis carinii pneumonia for children infected with human immunodeficiency virus. MMWR Recomm Rep.\u20081991;40(RR-2):1\u201313"},{"key":"2021120901592152700_R25","doi-asserted-by":"crossref","unstructured":"Mofenson LM, Moye J Jr, Korelitz J, Bethel J, Hirschhorn R, Nugent R. Crossover of placebo patients to intravenous immunoglobulin confirms efficacy for prophylaxis of bacterial infections and reduction of hospitalizations in human immunodeficiency virus-infected children: the National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group. Pediatr Infect Dis J.\u20081994;13:477\u2013484","DOI":"10.1097\/00006454-199406000-00003"},{"key":"2021120901592152700_R26","doi-asserted-by":"crossref","unstructured":"Mofenson LM, Moye J Jr, Bethel J, Hirschhorn R, Jordan C, Nugent R. Prophylactic intravenous immunoglobulin in HIV-infected children with CD4+ counts of 0.20 \u00d7 109\/L or more: effect on viral, opportunistic, and bacterial infections: the National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group. JAMA.\u20081992;268:483\u2013488","DOI":"10.1001\/jama.1992.03490040059026"},{"key":"2021120901592152700_R27","doi-asserted-by":"crossref","unstructured":"Spector SA, Gelber RD, McGrath N, et al. A controlled trial of intravenous immune globulin for the prevention of serious bacterial infections in children receiving zidovudine for advanced human immunodeficiency virus infection. N Engl J Med.\u20081994;331:1181\u20131187","DOI":"10.1056\/NEJM199411033311802"},{"key":"2021120901592152700_R28","unstructured":"Centers for Disease Control and Prevention. US Public Health Service recommendations for human immunodeficiency virus counseling and voluntary testing for pregnant women. MMWR Recomm Rep.\u20081995;44(RR-7):1\u201314"},{"key":"2021120901592152700_R29","unstructured":"Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment: Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med.\u20081994;331:1173\u20131180"},{"key":"2021120901592152700_R30","unstructured":"Centers for Disease Control and Prevention. Recommendations of the US Public Health Service Task Force on the use of zidovudine to reduce perinatal transmission of human immunodeficiency virus. MMWR Recomm Rep.\u20081994;43(RR-11):1\u201321"},{"key":"2021120901592152700_R31","doi-asserted-by":"crossref","unstructured":"Barnhart HX, Caldwell MB, Thomas P, et al. Natural history of human immunodeficiency virus disease in perinatally infected children: an analysis from the Pediatric Spectrum of Disease Project. 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