title: Frequency and impact of suboptimal immune recovery on first-line antiretroviral therapy within the International Epidemiologic Databases to Evaluate AIDS in East Africa.
abstract: To describe patterns of suboptimal immune recovery (SO-IR) and associated HIV-related-illnesses during the first 5 years following first-line antiretroviral therapy (ART) initiation across seven ART sites in East Africa.
  
  
  
  Retrospective analysis of data from seven ART clinical sites (three Uganda, two Kenya and two Tanzania).
  
  
  
  SO-IR was described by proportions of ART-treated adults with CD4 cell counts less than 200, less than 350 and less than 500 cells/μl. Kaplan-Meier survival analysis techniques were used to assess predictors of SO-IR, and incident rates of HIV-related illnesses at CD4 cell counts less than 200, 200-350, 351-499, and >500 cells/μl, respectively.
  
  
  
  Overall 80 843 adults initiated non-nucleoside reverse transcriptase inhibitor-based first-line ART; 65% were women and median CD4 cell count was 126 [interquartile range (IQR), 52-202] cells/μl. Cumulative probability of SO-IR <200 cells/μl, <350 cells/μl and <500 cells/μl, after 5 years, was 11, 38 and 63%, respectively. Incidence of HIV-related illnesses was higher among those with CD4 cell counts less than 200 and 200-350 cells/μl, than those who achieved CD4 counts above these thresholds. The most common events, at CD4 < 200 cells/μl, were pulmonary tuberculosis [incident rate 15.98 (15.47-16.51)/100 person-years at risk (PYAR), oral candidiasis [incident rate 12.5 (12.03-12.94)] and herpes zoster [incident rate 6.30 (5.99-6.64)] events/100 PYAR. With attainment of a CD4 cell count level 200-350 cells/μl, there was a substantial reduction in events/100 PYAR - by 91% to 1.45 (1.29-1.63) for TB, by 94% to 0.75 (0.64-0.89) for oral candidiasis, by 84% to 0.99 (0.86-1.14) for Herpes Zoster, and by 78% to 1.22 (1.07-1.39) for chronic diarrhea. The incidence of all events decreased further with CD4 counts above these thresholds.
  
  
  
  Around 40% of adults initiated on ART have suboptimal immune recovery with CD4 counts <350 cells/μl after five years. Such patients will require closer monitoring for both HIV-related and non-HIV-related clinical events.
authors.affiliation: aInfectious Diseases Institute, Makerere University College of Health Sciences bDepartment of Medicine, Makerere University College of Health Sciences, Kampala, Uganda cDepartment of Biostatistics, Indiana University School of Medicine dDepartment of Biostatistics, Indiana University, RM Fairbanks School of Public Health eDepartment of Medicine at Indiana University School of Medicine, Indianapolis, Indiana, USA fAcademic Model Providing Access to Healthcare, Eldoret, kenya gFamily AIDS, Care and Education Services, Kenya Medical Research Institute, Kisumu, Kenya hOcean Road Cancer Institute, Dar es salaam, Tanzania, Kisumu iHIV Treatment Program, Masaka Regional Referral Hospital, Masaka, Uganda.
authors.forename: Damalie
authors.initials: D
authors.lastname: Nakanjako
authors.forename: Agnes N
authors.initials: AN
authors.lastname: Kiragga
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Musick
authors.forename: Constantin T
authors.initials: CT
authors.lastname: Yiannoutsos
authors.forename: Kara
authors.initials: K
authors.lastname: Wools-Kaloustian
authors.forename: Lameck
authors.initials: L
authors.lastname: Diero
authors.forename: Patrick
authors.initials: P
authors.lastname: Oyaro
authors.forename: Emanuel
authors.initials: E
authors.lastname: Lugina
authors.forename: John C
authors.initials: JC
authors.lastname: Ssali
authors.forename: Andrew
authors.initials: A
authors.lastname: Kambugu
authors.forename: Philippa
authors.initials: P
authors.lastname: Easterbrook
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology*; D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D000074243:Immune Reconstitution; D007630:Kenya / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012189:Retrospective Studies; D013636:Tanzania / Q000453:epidemiology; D014454:Uganda / Q000453:epidemiology; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents