title: The virological durability of first-line ART among HIV-positive adult patients in resource limited settings without virological monitoring: a retrospective analysis of DART trial data.
abstract: Few low-income countries have virological monitoring widely available. We estimated the virological durability of first-line antiretroviral therapy (ART) after five years of follow-up among adult Ugandan and Zimbabwean patients in the DART study, in which virological assays were conducted retrospectively.
  
  
  
  DART compared clinically driven monitoring with/without routine CD4 measurement. Annual plasma viral load was measured on 1,762 patients. Analytical weights were calculated based on the inverse probability of sampling. Time to virological failure, defined as the first viral load measurement ≥200 copies/mL after 48 weeks of ART, was analysed using Kaplan-Meier plots and Cox regression models.
  
  
  
  Overall, 65% of DART trial patients were female. Patients initiated first-line ART at a median (interquartile range; IQR) age of 37 (32-42) and with a median CD4 cell count of 86 (32-140). After 240 weeks of ART, patients initiating dual-class nucleoside reverse-transcriptase inhibitor (NRTI) -non-nucleoside reverse-transcriptase (NNRTI) regimens containing nevirapine + zidovudine + lamivudine had a lower incidence of virological failure than patients on triple-NRTI regimens containing tenofovir + zidovudine + lamivudine (21% vs 40%; hazard ratio (HR) =0.48, 95% CI:0.38-0.62; p < 0.0001). In multivariate analyses, female patients (HR = 0.79, 95% CI: 0.65-0.95; p = 0.02), older patients (HR = 0.73 per 10 years, 95% CI: 0.64-0.84; p < 0.0001) and patients with a higher pre-ART CD4 cell count (HR = 0.64 per 100 cells/mm3, 95% CI: 0.54-0.75; p < 0.0001) had a lower incidence of virological failure after adjusting for adherence to ART. No difference in failure rate between the two randomised monitoring strategies was observed (p= 0.25).
  
  
  
  The long-term durability of virological suppression on dual-class NRTI-NNRTI first-line ART without virological monitoring is remarkable and is enabled by high-quality clinical management and a consistent drug supply. To achieve higher rates of virological suppression viral-load-informed differentiated care may be required.
  
  
  
  Prospectively registered on 18/10/2000 as ISRCTN13968779 .
authors.affiliation: MRC Clinical Trials Unit at UCL, London, UK.
authors.forename: David I
authors.initials: DI
authors.lastname: Dolling
authors.affiliation: MRC Clinical Trials Unit at UCL, London, UK. r.goodall@ucl.ac.uk.
authors.forename: Ruth L
authors.identifier: 0000-0003-0622-5035
authors.initials: RL
authors.lastname: Goodall
authors.affiliation: University of Zimbabwe, Harara, Zimbabwe.
authors.forename: Michael
authors.initials: M
authors.lastname: Chirara
authors.affiliation: University of Zimbabwe, Harara, Zimbabwe.
authors.forename: James
authors.initials: J
authors.lastname: Hakim
authors.affiliation: Joint Clinical Research Centre, Kampala, Uganda.
authors.forename: Peter
authors.initials: P
authors.lastname: Nkurunziza
authors.affiliation: Joint Clinical Research Centre, Kampala, Uganda.
authors.forename: Paula
authors.initials: P
authors.lastname: Munderi
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
authors.forename: David
authors.initials: D
authors.lastname: Eram
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
authors.forename: Dinah
authors.initials: D
authors.lastname: Tumukunde
authors.affiliation: MRC Clinical Trials Unit at UCL, London, UK.
authors.forename: Moira J
authors.initials: MJ
authors.lastname: Spyer
authors.affiliation: School of Population Health, University of Queensland, Brisbane, Australia.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Gilks
authors.affiliation: Joint Clinical Research Centre, Kampala, Uganda.
authors.forename: Pontiano
authors.initials: P
authors.lastname: Kaleebu
authors.affiliation: MRC Clinical Trials Unit at UCL, London, UK.
authors.forename: David T
authors.initials: DT
authors.lastname: Dunn
authors.affiliation: Africa Centre for Health and Population Studies, University of KwaZulu Natal, Durban, South Africa.
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D003906:Developing Countries; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016896:Treatment Outcome; D014454:Uganda; D019562:Viral Load; D015030:Zimbabwe
chemical_list: D019380:Anti-HIV Agents
keywords: HIV-infected adults; Low-income; Resource-limited; Treatment outcomes; Virological failure