title: Effects of Antiretroviral Therapy on Kaposi's Sarcoma-Associated Herpesvirus (KSHV) Transmission Among HIV-Infected Zambian Children.
abstract: BACKGROUND
  The risk of Kaposi's sarcoma-associated herpesvirus (KSHV) acquisition among children is increased by HIV infection. Antiretroviral therapy (ART) was recently made widely available to HIV-infected children in Zambia. However, the impact of early ART on KSHV transmission to HIV-infected children is unknown.
  
  
  METHODS
  We enrolled and followed a cohort of 287 HIV-exposed, KSHV-negative children under 12 months of age from Lusaka, Zambia, to identify KSHV seroconversion events. Potential factors associated with KSHV infection-with an emphasis on HIV, ART, and immunological measures-were assessed through structured questionnaires and blood analyses. Incidence rate, Kaplan-Meier, and multivariable Cox regression models were used to assess differences in time to event (KSHV seroconversion) between groups. All statistical tests were two-sided.
  
  
  RESULTS
  During follow-up, 151 (52.6%) children underwent KSHV seroconversion. Based on 3552 months of follow-up, we observed similar KSHV incidence rates between HIV-infected and uninfected children. Among HIV-infected children, ART-naïve children had statistically significantly increased risk of KSHV acquisition (adjusted hazard ratio [AHR] = 5.04, 95% confidence interval [CI] = 2.36 to 10.80, P < .001). Time-updated CD4(+) T-cell percentage was also statistically significantly associated with risk of KSHV acquisition (AHR = 0.82, 95% CI = 0.74 to 0.92, P < .001), such that each 5% increase of CD4(+) T-cells represented an 18% decrease in risk of acquiring KSHV.
  
  
  CONCLUSIONS
  Our data suggest that early ART and prevention of immune suppression reduce the risk of KSHV acquisition among HIV-infected children in an area where both viruses are highly endemic. This study highlights the importance of programs in Africa to provide children with ART immediately after HIV infection is diagnosed.
authors.affiliation: Nebraska Center for Virology and School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE (LNO, VM, JTW); Department of Pediatrics and Child Health, University Teaching Hospital, Lusaka, Zambia (CG, CK); Department of Pediatrics and Department of Nutrition, University of California, San Francisco, CA (JW); Department of Pediatric Immunology/Infectious Diseases, University of Miami School of Medicine, Miami, FL (CM); Nebraska Center for Virology and School of Biological Sciences (CW) and Department of Biochemistry (CW), University of Nebraska-Lincoln, Lincoln, NE. Current affiliation: Department of Epidemiology, College of Public Health, University of Nebraska Medical Center, Omaha NE (VM).
authors.forename: Landon N
authors.initials: LN
authors.lastname: Olp
authors.affiliation: Nebraska Center for Virology and School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE (LNO, VM, JTW); Department of Pediatrics and Child Health, University Teaching Hospital, Lusaka, Zambia (CG, CK); Department of Pediatrics and Department of Nutrition, University of California, San Francisco, CA (JW); Department of Pediatric Immunology/Infectious Diseases, University of Miami School of Medicine, Miami, FL (CM); Nebraska Center for Virology and School of Biological Sciences (CW) and Department of Biochemistry (CW), University of Nebraska-Lincoln, Lincoln, NE. Current affiliation: Department of Epidemiology, College of Public Health, University of Nebraska Medical Center, Omaha NE (VM).
authors.forename: Veenu
authors.initials: V
authors.lastname: Minhas
authors.affiliation: Nebraska Center for Virology and School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE (LNO, VM, JTW); Department of Pediatrics and Child Health, University Teaching Hospital, Lusaka, Zambia (CG, CK); Department of Pediatrics and Department of Nutrition, University of California, San Francisco, CA (JW); Department of Pediatric Immunology/Infectious Diseases, University of Miami School of Medicine, Miami, FL (CM); Nebraska Center for Virology and School of Biological Sciences (CW) and Department of Biochemistry (CW), University of Nebraska-Lincoln, Lincoln, NE. Current affiliation: Department of Epidemiology, College of Public Health, University of Nebraska Medical Center, Omaha NE (VM).
authors.forename: Clement
authors.initials: C
authors.lastname: Gondwe
authors.affiliation: Nebraska Center for Virology and School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE (LNO, VM, JTW); Department of Pediatrics and Child Health, University Teaching Hospital, Lusaka, Zambia (CG, CK); Department of Pediatrics and Department of Nutrition, University of California, San Francisco, CA (JW); Department of Pediatric Immunology/Infectious Diseases, University of Miami School of Medicine, Miami, FL (CM); Nebraska Center for Virology and School of Biological Sciences (CW) and Department of Biochemistry (CW), University of Nebraska-Lincoln, Lincoln, NE. Current affiliation: Department of Epidemiology, College of Public Health, University of Nebraska Medical Center, Omaha NE (VM).
authors.forename: Chipepo
authors.initials: C
authors.lastname: Kankasa
authors.affiliation: Nebraska Center for Virology and School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE (LNO, VM, JTW); Department of Pediatrics and Child Health, University Teaching Hospital, Lusaka, Zambia (CG, CK); Department of Pediatrics and Department of Nutrition, University of California, San Francisco, CA (JW); Department of Pediatric Immunology/Infectious Diseases, University of Miami School of Medicine, Miami, FL (CM); Nebraska Center for Virology and School of Biological Sciences (CW) and Department of Biochemistry (CW), University of Nebraska-Lincoln, Lincoln, NE. Current affiliation: Department of Epidemiology, College of Public Health, University of Nebraska Medical Center, Omaha NE (VM).
authors.forename: Janet
authors.initials: J
authors.lastname: Wojcicki
authors.affiliation: Nebraska Center for Virology and School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE (LNO, VM, JTW); Department of Pediatrics and Child Health, University Teaching Hospital, Lusaka, Zambia (CG, CK); Department of Pediatrics and Department of Nutrition, University of California, San Francisco, CA (JW); Department of Pediatric Immunology/Infectious Diseases, University of Miami School of Medicine, Miami, FL (CM); Nebraska Center for Virology and School of Biological Sciences (CW) and Department of Biochemistry (CW), University of Nebraska-Lincoln, Lincoln, NE. Current affiliation: Department of Epidemiology, College of Public Health, University of Nebraska Medical Center, Omaha NE (VM).
authors.forename: Charles
authors.initials: C
authors.lastname: Mitchell
authors.affiliation: Nebraska Center for Virology and School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE (LNO, VM, JTW); Department of Pediatrics and Child Health, University Teaching Hospital, Lusaka, Zambia (CG, CK); Department of Pediatrics and Department of Nutrition, University of California, San Francisco, CA (JW); Department of Pediatric Immunology/Infectious Diseases, University of Miami School of Medicine, Miami, FL (CM); Nebraska Center for Virology and School of Biological Sciences (CW) and Department of Biochemistry (CW), University of Nebraska-Lincoln, Lincoln, NE. Current affiliation: Department of Epidemiology, College of Public Health, University of Nebraska Medical Center, Omaha NE (VM).
authors.forename: John T
authors.initials: JT
authors.lastname: West
authors.affiliation: Nebraska Center for Virology and School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE (LNO, VM, JTW); Department of Pediatrics and Child Health, University Teaching Hospital, Lusaka, Zambia (CG, CK); Department of Pediatrics and Department of Nutrition, University of California, San Francisco, CA (JW); Department of Pediatric Immunology/Infectious Diseases, University of Miami School of Medicine, Miami, FL (CM); Nebraska Center for Virology and School of Biological Sciences (CW) and Department of Biochemistry (CW), University of Nebraska-Lincoln, Lincoln, NE. Current affiliation: Department of Epidemiology, College of Public Health, University of Nebraska Medical Center, Omaha NE (VM). cwood1@unl.edu.
authors.forename: Charles
authors.initials: C
authors.lastname: Wood
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000097:blood; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D006566:Herpesviridae Infections / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control* / Q000635:transmission*; D019288:Herpesvirus 8, Human / Q000187:drug effects* / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D016016:Proportional Hazards Models; D012306:Risk; D012514:Sarcoma, Kaposi / Q000517:prevention & control; D012698:Serologic Tests; D011795:Surveys and Questionnaires; D019562:Viral Load; D015024:Zambia / Q000453:epidemiology
chemical_list: D044966:Anti-Retroviral Agents; D000914:Antibodies, Viral