title: Delayed switch of antiretroviral therapy after virologic failure associated with elevated mortality among HIV-infected adults in Africa.
abstract: OBJECTIVE
  Routine monitoring of plasma HIV RNA among HIV-infected patients on antiretroviral therapy (ART) is unavailable in many resource-limited settings. Alternative monitoring approaches correlate poorly with virologic failure and can substantially delay switch to second-line therapy. We evaluated the impact of delayed switch on mortality among patients with virologic failure in Africa.
  
  
  METHODS
  A cohort.
  
  
  METHODS
  We examined patients with confirmed virologic failure on first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from four cohorts with serial HIV RNA monitoring in Uganda and South Africa. Marginal structural models aimed to estimate the effect of delayed switch on mortality in a hypothetical trial in which switch time was randomly assigned. Inverse probability weights adjusted for measured confounders including time-updated CD4+ T-cell count and HIV RNA. Results: Among 823 patients with confirmed virologic failure, the cumulative incidence of switch 180 days after failure was 30% [95% confidence interval (CI) 27-33]. The majority of patients (74%) had not failed immunologically as defined by WHO criteria by the time of virologic failure. Adjusted mortality was higher for individuals who remained on first-line therapy than for those who had switched [odds ratio (OR) 2.1, 95% CI 1.1-4.2]. Among those without immunologic failure, the relative harm of failure to switch was similar (OR 2.4; 95% CI 0.99-5.8) to that of the entire cohort, although of borderline statistical significance.
  
  
  CONCLUSIONS
  Among HIV-infected patients with confirmed virologic failure on first-line ART, remaining on first-line therapy led to an increase in mortality relative to switching. Our results suggest that detection and response to confirmed virologic failure could decrease mortality.
authors: Maya L
authors: ML
authors: Petersen
authors: Linh
authors: L
authors: Tran
authors: Elvin H
authors: EH
authors: Geng
authors: Steven J
authors: SJ
authors: Reynolds
authors: Andrew
authors: A
authors: Kambugu
authors: Robin
authors: R
authors: Wood
authors: David R
authors: DR
authors: Bangsberg
authors: Constantin T
authors: CT
authors: Yiannoutsos
authors: Steven G
authors: SG
authors: Deeks
authors: Jeffrey N
authors: JN
authors: Martin
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D015331:Cohort Studies; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000401:mortality*; D006801:Humans; D011446:Prospective Studies; D012367:RNA, Viral / Q000187:drug effects* / Q000276:immunology; D013019:South Africa / Q000453:epidemiology; D013997:Time Factors; D017211:Treatment Failure; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load / Q000187:drug effects* / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral