title: The clinical and economic impact of genotype testing at first-line antiretroviral therapy failure for HIV-infected patients in South Africa.
abstract: BACKGROUND
  In resource-limited settings, genotype testing at virologic failure on first-line antiretroviral therapy (ART) may identify patients with wild-type (WT) virus. After adherence counseling, these patients may safely and effectively continue first-line ART, thereby delaying more expensive second-line ART.
  
  
  METHODS
  We used the Cost-Effectiveness of Preventing AIDS Complications International model of human immunodeficiency virus (HIV) disease to simulate a South African cohort of HIV-infected adults at first-line ART failure. Two strategies were examined: no genotype vs genotype, assuming availability of protease inhibitor-based second-line ART. Model inputs at first-line ART failure were mean age 38 years, mean CD4 173/µL, and WT virus prevalence 20%; genotype cost was $300 per test and delay to results, 3 months. Outcomes included life expectancy, per-person costs (2010 US dollars), and incremental cost-effectiveness ratios (dollars per years of life saved [YLS]).
  
  
  RESULTS
  No genotype had a projected life expectancy of 106.1 months, which with genotype increased to 108.3 months. Per-person discounted lifetime costs were $16 360 and $16 540, respectively. Compared to no genotype, genotype was very cost-effective, by international guidance, at $900/YLS. The cost-effectiveness of genotype was sensitive to prevalence of WT virus (very cost-effective when prevalence ≥ 12%), CD4 at first-line ART failure, and ART efficacy. Genotype-associated delays in care ≥ 5 months decreased survival and made no genotype the preferred strategy. When the test cost was <$100, genotype became cost-saving.
  
  
  CONCLUSIONS
  Genotype resistance testing at first-line ART failure is very cost-effective in South Africa. The cost-effectiveness of this strategy will depend on prevalence of WT virus and timely response to genotype results.
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA. jlevison@partners.org
authors.forename: Julie H
authors.initials: JH
authors.lastname: Levison
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Callie A
authors.initials: CA
authors.lastname: Scott
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Ciaranello
authors.forename: Neil A
authors.initials: NA
authors.lastname: Martinson
authors.forename: Corina
authors.initials: C
authors.lastname: Rusu
authors.forename: Elena
authors.initials: E
authors.lastname: Losina
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Freedberg
authors.forename: Rochelle P
authors.initials: RP
authors.lastname: Walensky
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000517:prevention & control*; D000328:Adult; D019380:Anti-HIV Agents / Q000191:economics / Q000627:therapeutic use*; D019411:Clinical Laboratory Techniques / Q000191:economics; D003362:Cost-Benefit Analysis; D005838:Genotype; D006678:HIV / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000191:economics / Q000235:genetics; D006295:Health Resources / Q000191:economics; D006801:Humans; D008962:Models, Theoretical; D013019:South Africa; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents