title: Pretreatment HIV drug resistance increases regimen switches in sub-Saharan Africa.
abstract: BACKGROUND
  After the scale-up of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection in Africa, increasing numbers of patients have pretreatment drug resistance.
  
  
  METHODS
  In a large multicountry cohort of patients starting standard first-line ART in six African countries, pol genotyping was retrospectively performed if viral load (VL) ≥1000 cps/mL. Pretreatment drug resistance was defined as a decreased susceptibility to ≥1 prescribed drug. We assessed the effect of pretreatment drug resistance on all-cause mortality, new AIDS events and switch to second-line ART due to presumed treatment failure, using Cox models.
  
  
  RESULTS
  Among 2579 participants for whom a pretreatment genotype was available, 5.5% had pretreatment drug resistance. Pretreatment drug resistance was associated with an increased risk of regimen switch (adjusted hazard ratio [aHR] 3.80; 95% confidence interval [CI], 1.49-9.68; P = .005) but was not associated with mortality (aHR 0.75, 95% CI, .24-2.35; P = .617) or new AIDS events (aHR 1.06, 95% CI, .68-1.64; P = .807). During three years of follow up, 106 (4.1%) participants switched to second-line, of whom 18 (17.0%) switched with VL < 1000 cps/mL, 7 (6.6%) with VL ≥ 1000 cps/mL and no drug resistance mutations (DRMs), 46 (43.4%) with VL ≥ 1000 cps/mL and ≥1 DRMs; no HIV RNA data was available for 32 (30.2%) participants.
  
  
  CONCLUSIONS
  Given rising pretreatment HIV drug resistance levels in sub-Saharan Africa, these findings underscore the need for expanded access to second-line ART. VL monitoring can improve the accuracy of failure detection and efficiency of switching practices.
authors.affiliation: Amsterdam Institute for Global Health and Development and Department of Global Health.
authors.forename: T Sonia
authors.initials: TS
authors.lastname: Boender
authors.affiliation: Amsterdam Institute for Global Health and Development and Department of Global Health.
authors.forename: Bernice M
authors.initials: BM
authors.lastname: Hoenderboom
authors.affiliation: Amsterdam Institute for Global Health and Development and Department of Global Health Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center of the University of Amsterdam, The Netherlands.
authors.forename: Kim C E
authors.initials: KC
authors.lastname: Sigaloff
authors.affiliation: Amsterdam Institute for Global Health and Development and Department of Global Health Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center of the University of Amsterdam, The Netherlands.
authors.forename: Raph L
authors.initials: RL
authors.lastname: Hamers
authors.affiliation: Newlands Clinic, Harare, Zimbabwe.
authors.forename: Maureen
authors.initials: M
authors.lastname: Wellington
authors.affiliation: Newlands Clinic, Harare, Zimbabwe.
authors.forename: Tinei
authors.initials: T
authors.lastname: Shamu
authors.affiliation: Lusaka Trust Hospital.
authors.forename: Margaret
authors.initials: M
authors.lastname: Siwale
authors.affiliation: Coptic Hospital, Lusaka, Zambia.
authors.forename: Eman E F
authors.initials: EE
authors.lastname: Labib Maksimos
authors.affiliation: Joint Clinical Research Centre, Kampala, Uganda.
authors.forename: Immaculate
authors.initials: I
authors.lastname: Nankya
authors.affiliation: Joint Clinical Research Centre, Kampala, Uganda.
authors.forename: Cissy M
authors.initials: CM
authors.lastname: Kityo
authors.affiliation: Department of Haematology and Blood Transfusion, University of Lagos, Nigeria University Teaching Hospital, Nigeria.
authors.forename: Titilope A
authors.initials: TA
authors.lastname: Adeyemo
authors.affiliation: Department of Haematology and Blood Transfusion, University of Lagos, Nigeria University Teaching Hospital, Nigeria.
authors.forename: Alani Sulaimon
authors.initials: AS
authors.lastname: Akanmu
authors.affiliation: Coast Province General Hospital, Mombasa, Kenya.
authors.forename: Kishor
authors.initials: K
authors.lastname: Mandaliya
authors.affiliation: Muelmed Hospital, Pretoria, South Africa.
authors.forename: Mariette E
authors.initials: ME
authors.lastname: Botes
authors.affiliation: Amsterdam Institute for Global Health and Development and Department of Global Health.
authors.forename: Pascale
authors.initials: P
authors.lastname: Ondoa
authors.affiliation: Amsterdam Institute for Global Health and Development and Department of Global Health.
authors.forename: Tobias F
authors.initials: TF
authors.lastname: Rinke de Wit
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000293:Adolescent; D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000592:standards; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015751:Genes, pol; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D016016:Proportional Hazards Models; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents
keywords: HIV-1 drug resistance; antiretroviral therapy; mortality; regimen switch; sub-Saharan Africa