title: Choice of first-line antiretroviral therapy regimen and treatment outcomes for HIV in a middle income compared to a high income country: a cohort study.
abstract: BACKGROUND
  The range of combination antiretroviral therapy (cART) regimens available in many middle-income countries differs from those suggested in international HIV treatment guidelines. We compared first-line cART regimens, timing of initiation and treatment outcomes in a middle income setting (HIV Centre, Belgrade, Serbia - HCB) with a high-income country (Royal Free London Hospital, UK - RFH).
  
  
  METHODS
  All antiretroviral-naïve HIV-positive individuals from HCB and RFH starting cART between 2003 and 2012 were included. 12-month viral load and CD4 count responses were compared, considering the first available measurement 12-24 months post-cART. The percentage that had made an antiretroviral switch for any reason, or for toxicity and the percentage that had died by 36 months (the latest time at which sufficient numbers remained under follow-up) were investigated using standard survival methods.
  
  
  RESULTS
  361/597 (61 %) of individuals initiating cART at HCB had a prior AIDS diagnosis, compared to 337/1763 (19 %) at RFH. Median pre-ART CD4 counts were 177 and 238 cells/mm(3) respectively (p < 0.0001). The most frequently prescribed antiretrovirals were zidovudine with lamivudine (149; 25 %) and efavirenz [329, 55 %] at HCB and emtricitabine with tenofovir (899; 51 %) and efavirenz [681, 39 %] at RFH. At HCB, a median of 2 CD4 count measurements in the first year of cART were taken, compared to 5 at RFH (p < 0.0001). Median (IQR) CD4 cell increase after 12 months was +211 (+86, +359) and +212 (+105, +318) respectively. 287 (48 %) individuals from HCB and 1452 (82 %) from RFH had an available viral load measurement, of which 271 (94 %) and 1280 (88 %) were <400 copies/mL (p < 0.0001). After 36 months, comparable percentages had made at least one antiretroviral switch (77 % HCB vs. 78 % RFH; p = 0.23). However, switches for toxicity/patient choice were more common at RFH. After 12 and 36 months of cART 3 % and 8 % of individuals died at HCB, versus 2 % and 4 % at RFH (p < 0.0001).
  
  
  CONCLUSIONS
  In middle-income countries, cART is usually started at an advanced stage of HIV disease, resulting in higher mortality rates than in high income countries, supporting improved testing campaigns for early detection of HIV infection and early introduction of newer cART regimens.
authors.affiliation: Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia. gozza@beotel.net.
authors.forename: Gordana
authors.initials: G
authors.lastname: Dragovic
authors.affiliation: UCL Research Department of Infection and Population Health, Royal Free Campus, 1st Floor, Rowland Hill Street, London, NW3 2PF, UK. c.smith@ucl.ac.uk.
authors.forename: Colette J
authors.initials: CJ
authors.lastname: Smith
authors.affiliation: Infectious and Tropical Diseases Hospital, School of Medicine, University of Belgrade, Belgrade, Serbia. djordjevtovic@hotmail.com.
authors.forename: Djordje
authors.initials: D
authors.lastname: Jevtovic
authors.affiliation: Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia. drdimitrijevicb@gmail.com.
authors.forename: Bozana
authors.initials: B
authors.lastname: Dimitrijevic
authors.affiliation: Infectious and Tropical Diseases Hospital, School of Medicine, University of Belgrade, Belgrade, Serbia. jovanakusic@yahoo.com.
authors.forename: Jovana
authors.initials: J
authors.lastname: Kusic
authors.affiliation: Department of HIV Medicine, Royal Free London Hospital, London, UK. mike@mikeyoule.com.
authors.forename: Mike
authors.initials: M
authors.lastname: Youle
authors.affiliation: Department of HIV Medicine, Royal Free London Hospital, London, UK. margaret.johnson1@nhs.net.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Johnson
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D019049:Developed Countries; D003906:Developing Countries; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D019983:Guideline Adherence / Q000706:statistics & numerical data*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D008131:London; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data*; D012189:Retrospective Studies; D055771:Serbia; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents