title: High level of viral suppression and low switch rate to second-line antiretroviral therapy among HIV-infected adult patients followed over five years: retrospective analysis of the DART trial.
abstract: In contrast to resource-rich countries, most HIV-infected patients in resource-limited countries receive treatment without virological monitoring. There are few long-term data, in this setting, on rates of viral suppression or switch to second-line antiretroviral therapy. The DART trial compared clinically driven monitoring (CDM) versus routine laboratory (CD4/haematology/biochemistry) and clinical monitoring (LCM) in HIV-infected adults initiating therapy. There was no virological monitoring in either study group during follow-up, but viral load was measured in Ugandan participants at trial closure. Two thousand three hundred and seventeen (2317) participants from this country initiated antiretroviral therapy with zidovudine/lamivudine plus tenofovir (n = 1717), abacavir (n = 300), or nevirapine (n = 300). Of 1896 (81.8%) participants who were alive and in follow-up at trial closure (median 5.1 years after therapy initiation), 1507 (79.5%) were on first-line and 389 (20.5%) on second-line antiretroviral therapy. The overall switch rate after the first year was 5.6 per 100 person-years; the rate was substantially higher in participants with low baseline CD4 counts (<50 cells/mm3). Among 1207 (80.1%) first-line participants with viral load measured, HIV RNA was <400 copies/ml in 963 (79.8%), 400-999 copies/ml in 37 (3.1%), 1,000-9,999 copies/ml in 110 (9.1%), and ≥10,000 copies/ml in 97 (8.0%). The proportion with HIV RNA <400 copies/ml was slightly lower (difference 7.1%, 95% CI 2.5 to 11.5%) in CDM (76.3%) than in LCM (83.4%). Among 252 (64.8%) second-line participants with viral load measured (median 2.3 years after switch), HIV RNA was <400 copies/ml in 226 (89.7%), with no difference between monitoring strategies. Low switch rates and high, sustained levels of viral suppression are achievable without viral load or CD4 count monitoring in the context of high-quality clinical care.
  
  
  BACKGROUND
  ISRCTN13968779.
authors.affiliation: Joint Clinical Research Centre, Kampala, Uganda.
authors.forename: Cissy
authors.initials: C
authors.lastname: Kityo
authors.affiliation: MRC Clinical Trials Unit at UCL, London, United Kingdom.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Gibb
authors.affiliation: School of Population Health, University of Queensland, Australia.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Gilks
authors.affiliation: MRC Clinical Trials Unit at UCL, London, United Kingdom.
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Goodall
authors.affiliation: Infectious Diseases Institute, Mulago, Uganda.
authors.forename: Ivan
authors.initials: I
authors.lastname: Mambule
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
authors.forename: Pontiano
authors.initials: P
authors.lastname: Kaleebu
authors.affiliation: University College London, London, United Kingdom.
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Kasirye
authors.affiliation: Joint Clinical Research Centre, Kampala, Uganda.
authors.forename: Peter
authors.initials: P
authors.lastname: Mugyenyi
authors.affiliation: MRC Clinical Trials Unit at UCL, London, United Kingdom.
authors.forename: A Sarah
authors.initials: AS
authors.lastname: Walker
authors.affiliation: MRC Clinical Trials Unit at UCL, London, United Kingdom.
authors.forename: David T
authors.initials: DT
authors.lastname: Dunn
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D003430:Cross-Sectional Studies; D015224:Dideoxynucleosides / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000627:therapeutic use; D011336:Probability; D012367:RNA, Viral / Q000378:metabolism; D012189:Retrospective Studies; D000068698:Tenofovir / Q000627:therapeutic use; D014454:Uganda; D019562:Viral Load / Q000187:drug effects; D015215:Zidovudine / Q000627:therapeutic use; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D004338:Drug Combinations; D019259:Lamivudine; D019829:Nevirapine; D012367:RNA, Viral; D000068698:Tenofovir; D015215:Zidovudine; D000099227:Abacavir; C109078:lamivudine, zidovudine drug combination