title: Evaluation of treatment outcomes for patients on first-line regimens in US President's Emergency Plan for AIDS Relief (PEPFAR) clinics in Uganda: predictors of virological and immunological response from RV288 analyses.
abstract: OBJECTIVE
  Viral load (VL) monitoring is recommended, but seldom performed, in resource-constrained countries. RV288 is a US President's Emergency Plan for AIDS Relief (PEPFAR) basic programme evaluation to determine the proportion of patients on treatment who are virologically suppressed and to identify predictors of virological suppression and recovery of CD4 cell count. Analyses from Uganda are presented here.
  
  
  METHODS
  In this cross-sectional, observational study, patients on first-line antiretroviral therapy (ART) (efavirenz or nevirapine+zidovudine/lamivudine) from Kayunga District Hospital and Kagulamira Health Center were randomly selected for a study visit that included determination of viral load (HIV-1 RNA), CD4 cell count and clinical chemistry tests. Subjects were recruited by time on treatment: 6-12, 13-24 or >24 months. Logistic regression modelling identified predictors of virological suppression. Linear regression modelling identified predictors of CD4 cell count recovery on ART.
  
  
  RESULTS
  We found that 85.2% of 325 subjects were virologically suppressed (viral load<47 HIV-1 RNA copies/ml). There was no difference in the proportion of virologically suppressed subjects by time on treatment, yet CD4 counts were higher in each successive stratum. Women had higher median CD4 counts than men overall (406 vs. 294 cells/μL, respectively; P<0.0001) and in each time-on-treatment stratum. In a multivariate logistic regression model, predictors of virological suppression included efavirenz use [odds ratio (OR) 0.47; 95% confidence interval (CI) 0.22-1.02; P=0.057], lower cost of clinic visits (OR 0.815; 95% CI 0.66-1.00; P=0.05), improvement in CD4 percentage (OR 1.06; 95% CI 1.014-1.107; P=0.009), and care at Kayunga vs. Kangulamira (OR 0.47; 95% CI 0.23-0.92; P=0.035). In a multivariate linear regression model of covariates associated with CD4 count recovery, time on highly active antiretroviral therapy (ART) (P<0.0001), patient satisfaction with care (P=0.038), improvements in total lymphocyte count (P<0.0001) and haemoglobin concentration (P=0.05) were positively associated, whereas age at start of ART (P=0.0045) was negatively associated with this outcome.
  
  
  CONCLUSIONS
  High virological suppression rates are achievable on first-line ART in Uganda. The odds of virological suppression were positively associated with efavirenz use and improvements in CD4 cell percentage and total lymphocyte count and negatively associated with the cost of travel to the clinic. CD4 cell reconstitution was positively associated with CD4 count at study visit, time on ART, satisfaction with care at clinic, haemoglobin concentration and total lymphocyte count and negatively associated with age.
authors.affiliation: U.S. Military HIV Research Program (MHRP), Global Health Programs, Walter Reed Army Institute of Research, Bethesda, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
authors.forename: K W
authors.initials: KW
authors.lastname: Crawford
authors.forename: S
authors.initials: S
authors.lastname: Wakabi
authors.forename: F
authors.initials: F
authors.lastname: Magala
authors.forename: H
authors.initials: H
authors.lastname: Kibuuka
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: T E
authors.initials: TE
authors.lastname: Hamm
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology / Q000635:transmission; D000367:Age Factors; D019380:Anti-HIV Agents / Q000008:administration & dosage; D018791:CD4 Lymphocyte Count / Q000379:methods; D003430:Cross-Sectional Studies; D003695:Delivery of Health Care / Q000458:organization & administration; D018450:Disease Progression; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006078:Government Programs / Q000458:organization & administration; D007391:International Cooperation; D009316:National Institutes of Health (U.S.); D009939:Organizations, Nonprofit / Q000458:organization & administration; D015397:Program Evaluation; D012367:RNA, Viral / Q000187:drug effects / Q000302:isolation & purification; D016896:Treatment Outcome; D014454:Uganda / Q000453:epidemiology; D014481:United States; D019562:Viral Load / Q000187:drug effects; D016903:Drug Monitoring
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral
keywords: US President's Emergency Plan for AIDS Relief (PEPFAR); Uganda; first-line regimen; sub-Saharan Africa; treatment outcomes; virological suppression