title: Monitoring of HIV viral loads, CD4 cell counts, and clinical assessments versus clinical monitoring alone for antiretroviral therapy in rural district hospitals in Cameroon (Stratall ANRS 12110/ESTHER): a randomised non-inferiority trial.
abstract: BACKGROUND
  Scaling up of antiretroviral therapy in low-resource countries is done on the basis of decentralised, integrated HIV care in rural facilities; however, laboratory monitoring is generally unavailable. We aimed to assess the effectiveness and safety of clinical monitoring alone (CLIN) in terms of non-inferiority to laboratory and clinical monitoring (LAB).
  
  
  METHODS
  We did a randomised, open-label, non-inferiority trial in nine rural district hospitals in Cameroon. Eligible participants were adults (≥18 years) infected with HIV-1 group M (WHO disease stage 3-4) who had not previously received antiretroviral therapy, and were followed-up for 2 years by health-care workers in routine activities. We randomly assigned participants (1:1) to CLIN or LAB (counts of HIV viral load and CD4 cell every 6 months) groups with a computer-generated list. The primary outcome was non-inferiority of CLIN to LAB in terms of increase in CD4 cell count with a non-inferiority margin of 25%. We did all analyses in participants who attended at least one follow-up visit. This trial is registered with ClinicalTrials.gov, number NCT00301561.
  
  
  RESULTS
  238 (93%) of 256 participants assigned to CLIN and 221 (93%) of 237 assigned to LAB were eligible for analysis. CLIN was not non-inferior to LAB; the mean increase in CD4 cell count was 175 cells per μL (SD 190, 95% CI 151-200) with CLIN and 206 (190, 181-231) with LAB (difference -31 [-63 to 2] and non-inferiority margin -52 [-58 to -45]). Furthermore, in the predefined secondary outcome of treatment changes, 13 participants (6%) in the LAB group switched to second-line regimens whereas no participants in the CLIN group did so (p<0·0001). By contrast, other predefined secondary outcomes were much the same in both groups-viral suppression (<40 copies per mL; 465 [49%] of 952 measurements in CLIN vs 456 [52%] of 884 in LAB), HIV resistance (23 [10%] of 238 participants vs 22 [10%] of 219 participants), mortality (44 [18%] of 238 vs 32 [14%] of 221), disease progression (85 [36%] of 238 vs 64 [29%] of 221), adherence (672 [63%] of 1067 measurements vs 621 [61%] of 1011), loss to follow-up (21 [9%] of 238 vs 17 [8%] of 221), and toxic effects (46 [19%] of 238 vs 56 [25%] of 221).
  
  
  CONCLUSIONS
  Our findings support WHO's recommendation for laboratory monitoring of antiretroviral therapy. However, the small differences that we noted between the strategies suggest that clinical monitoring alone could be used, at least temporarily, to expand antiretroviral therapy in low-resource settings.
  
  
  BACKGROUND
  French National Agency for Research on AIDS (ANRS) and Ensemble pour une Solidarité Thérapeutique Hospitalière En Réseau (ESTHER).
authors.affiliation: Institut de Recherche pour le Développement (IRD), University Montpellier 1, UMI 233, Montpellier, France. Electronic address: christian.laurent@ird.fr.
authors.forename: Christian
authors.initials: C
authors.lastname: Laurent
authors.affiliation: Central Hospital, UMI 233, Yaoundé, Cameroon.
authors.forename: Charles
authors.initials: C
authors.lastname: Kouanfack
authors.affiliation: French Ministry of Foreign Affairs, Yaoundé, Cameroon.
authors.forename: Gabrièle
authors.initials: G
authors.lastname: Laborde-Balen
authors.affiliation: Institut de Recherche pour le Développement (IRD), University Montpellier 1, UMI 233, Montpellier, France; Virology laboratory IRD/IMPM/CREMER, UMI 233, Yaoundé, Cameroon.
authors.forename: Avelin Fobang
authors.initials: AF
authors.lastname: Aghokeng
authors.affiliation: Institut de Recherche pour le Développement (IRD), University Montpellier 1, UMI 233, Montpellier, France; National Advanced School of Engineering, University Yaoundé 1, Yaoundé, Cameroon.
authors.forename: Jules Brice Tchatchueng
authors.initials: JBT
authors.lastname: Mbougua
authors.affiliation: INSERM, IRD, University Aix Marseille, UMR 912, Marseille, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Boyer
authors.affiliation: INSERM, IRD, University Aix Marseille, UMR 912, Marseille, France.
authors.forename: Maria Patrizia
authors.initials: MP
authors.lastname: Carrieri
authors.affiliation: IRD, UMI 233, Yaoundé, Cameroon.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Mben
authors.affiliation: IRD, UMI 233, Yaoundé, Cameroon.
authors.forename: Marlise
authors.initials: M
authors.lastname: Dontsop
authors.affiliation: IRD, UMI 233, Yaoundé, Cameroon.
authors.forename: Serge
authors.initials: S
authors.lastname: Kazé
authors.affiliation: UMR 729 MISTEA, Montpellier, France; Department of Biostatistics, University Hospitals, Nimes and Montpellier, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Molinari
authors.affiliation: Institut de Recherche pour le Développement (IRD), University Montpellier 1, UMI 233, Montpellier, France; Department of Infectious and Tropical Diseases, University Hospital, Montpellier, France.
authors.forename: Anke
authors.initials: A
authors.lastname: Bourgeois
authors.affiliation: Virology laboratory IRD/IMPM/CREMER, UMI 233, Yaoundé, Cameroon.
authors.forename: Eitel
authors.initials: E
authors.lastname: Mpoudi-Ngolé
authors.affiliation: INSERM, IRD, University Aix Marseille, UMR 912, Marseille, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Spire
authors.affiliation: Central Hospital, UMI 233, Yaoundé, Cameroon; University Yaoundé 1, UMI 233, Yaoundé, Cameroon.
authors.forename: Sinata
authors.initials: S
authors.lastname: Koulla-Shiro
authors.affiliation: Institut de Recherche pour le Développement (IRD), University Montpellier 1, UMI 233, Montpellier, France; Department of Infectious and Tropical Diseases, University Hospital, Montpellier, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Delaporte
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D002163:Cameroon; D018450:Disease Progression; D015658:HIV Infections / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008991:Monitoring, Physiologic / Q000379:methods; D010349:Patient Compliance; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood; D012424:Rural Population; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral