title: Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda.
abstract: BACKGROUND
  With the scale-up of antiretroviral therapy (ART), monitoring programme performance is needed to maximize ART efficacy and limit HIV drug resistance (HIVDR).
  
  
  METHODS
  We implemented a WHO HIVDR prospective survey protocol at three treatment centers between 2012 and 2013. Data were abstracted from patient records at ART start (T1) and after 12 months (T2). Genotyping was performed in the HIV pol region at the two time points.
  
  
  RESULTS
  Of the 425 patients enrolled, at T2, 20 (4.7%) had died, 66 (15.5%) were lost to follow-up, 313 (73.6%) were still on first-line, 8 (1.9%) had switched to second-line, 17 (4.0%) had transferred out and 1 (0.2%) had stopped treatment. At T2, 272 out of 321 on first and second line (84.7%) suppressed below 1000 copies/ml and the HIV DR prevention rate was 70.1%, just within the WHO threshold of ≥ 70%. The proportion of participants with potential HIVDR was 20.9%, which is higher than the 18.8% based on pooled analyses from African studies. Of the 35 patients with mutations at T2, 80% had M184V/I, 65.7% Y181C, and 48.6% (54.8% excluding those not on Tenofovir) had K65R mutations. 22.9% had Thymidine Analogue Mutations (TAMs). Factors significantly associated with HIVDR prevention at T2 were: baseline viral load (VL) <100,000 copies/ml [Adjusted odds ratio (AOR) 3.13, 95% confidence interval (CI): 1.36-7.19] and facility. Independent baseline predictors for HIVDR mutations at T2 were: CD4 count < 250 cells/μl (AOR 2.80, 95% CI: 1.08-7.29) and viral load ≥ 100,000 copies/ml (AOR 2.48, 95% CI: 1.00-6.14).
  
  
  CONCLUSIONS
  Strengthening defaulter tracing, intensified follow-up for patients with low CD4 counts and/or high VL at ART initiation together with early treatment initiation above 250 CD4 cells/ul and adequate patient counselling would improve ART efficacy and HIVDR prevention. The high rate of K65R and TAMs could compromise second line regimens including NRTIs.
authors.affiliation: Uganda Virus Research Institute, Entebbe, Uganda.|MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.|London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Pontiano
authors.initials: P
authors.lastname: Kaleebu
authors.affiliation: Ministry of Health, AIDS Control Programme, Kampala, Uganda.
authors.forename: Wilford
authors.initials: W
authors.lastname: Kirungi
authors.affiliation: Uganda Virus Research Institute, Entebbe, Uganda.
authors.forename: Christine
authors.initials: C
authors.lastname: Watera
authors.affiliation: Uganda Virus Research Institute, Entebbe, Uganda.
authors.forename: Juliet
authors.initials: J
authors.lastname: Asio
authors.affiliation: Uganda Virus Research Institute, Entebbe, Uganda.|MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
authors.forename: Fred
authors.initials: F
authors.lastname: Lyagoba
authors.affiliation: Uganda Virus Research Institute, Entebbe, Uganda.
authors.forename: Tom
authors.initials: T
authors.lastname: Lutalo
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
authors.forename: Anne A
authors.initials: AA
authors.lastname: Kapaata
authors.affiliation: Uganda Virus Research Institute, Entebbe, Uganda.
authors.forename: Faith
authors.initials: F
authors.lastname: Nanyonga
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
authors.forename: Chris M
authors.initials: CM
authors.lastname: Parry
authors.affiliation: Uganda Virus Research Institute, Entebbe, Uganda.|MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
authors.forename: Brian
authors.initials: B
authors.lastname: Magambo
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
authors.forename: Jamirah
authors.initials: J
authors.lastname: Nazziwa
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
authors.forename: Maria
authors.initials: M
authors.lastname: Nannyonjo
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
authors.forename: Peter
authors.initials: P
authors.lastname: Hughes
authors.affiliation: U.S. Centers for Disease Control and Prevention, Entebbe, Uganda.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hladik
authors.affiliation: Uganda Virus Research Institute, Entebbe, Uganda.
authors.forename: Anthony
authors.initials: A
authors.lastname: Ruberantwari
authors.affiliation: Ministry of Health, AIDS Control Programme, Kampala, Uganda.
authors.forename: Norah
authors.initials: N
authors.lastname: Namuwenge
authors.affiliation: Ministry of Health, AIDS Control Programme, Kampala, Uganda.
authors.forename: Joshua
authors.initials: J
authors.lastname: Musinguzi
authors.affiliation: Uganda Virus Research Institute, Entebbe, Uganda.
authors.forename: Robert
authors.initials: R
authors.lastname: Downing
authors.affiliation: Uganda Virus Research Institute, Entebbe, Uganda.
authors.forename: Edward
authors.initials: E
authors.lastname: Katongole-Mbidde
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents