title: Efficacy and safety of three second-line antiretroviral regimens in HIV-infected patients in Africa.
abstract: OBJECTIVE
  WHO recommends ritonavir-boosted protease inhibitor with two nucleoside reverse transcriptase inhibitors in HIV-infected patients failing non-nucleoside reverse transcriptase inhibitor-based first-line treatment. Here, we aimed to provide more evidence for the choice of nucleoside reverse transcriptase inhibitor and boosted protease inhibitor.
  
  
  METHODS
  ANRS 12169 is a 48-week, randomized, open-label, non-inferiority trial in three African cities, comparing efficacy and safety of three second-line regimens.
  
  
  METHODS
  Patients failing non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy with confirmed plasma HIV-1 viral load above 1000 copies/ml were randomly assigned to tenofovir/emtricitabine + lopinavir/ritonavir (control group as per WHO recommendations), abacavir + didanosine + lopinavir/ritonavir (ABC/ddI group) or tenofovir/emtricitabine + darunavir/ritonavir (DRV group) regimens. The primary endpoint was the proportion of patients with plasma vral load below 50 copies/ml at week 48 in the modified intention-to-treat population. Non-inferiority was pre-specified with a 15% margin.
  
  
  RESULTS
  Of the 454 randomized patients, 451 were included in the analysis. Globally, 294 (65.2%) and 375 (83.2%) patients had viral load below 50 and 200 copies/ml, respectively, at week 48. The primary endpoint was achieved in 105 (69.1%) control group patients versus 92 (63.4%) in the ABC/ddI (difference 5.6%, 95% confidence interval -5.1 to 16.4) and 97 (63.0%) in the DRV (difference 6.1%, 95% confidence interval -4.5 to 16.7) groups (non-inferiority not shown). Overall, less number of patients with baseline viral load at least 100 000 copies/ml (n = 122) had a viral load below 50 copies/ml at week 48 (37.7 versus 75.4%; P < 0.001).
  
  
  CONCLUSIONS
  The three second-line regimens obtained similar and satisfactory virologic control and confirmed the WHO recommendation (TDF/FTC/LPVr) as a valid option. However, the suboptimal response for patients with high viral load warrants research for improved strategies.
authors.affiliation: aUMI233 Institut de Recherche pour le Développement (IRD), INSERM U1175, University of Montpellier, Montpellier, France bFaculté de Médecine et des Sciences Biomédicales, University of Yaoundé 1, Yaoundé, Cameroon cDay Care Unit, University Hospital Souro Sanou, Bobo-Dioulasso, Burkina-Faso dDepartment of Infectious Diseases, University Hospital, Montpellier, France eDay Care Unit, Central Hospital, Yaoundé, Cameroon fAmbulatory Care Unit, Fann Hospital Dakar, Senegal gVirology Laboratory IMPM/IRD/CREMER, Yaoundé, Cameroon hHIV Unit, Geneva University Hospital, Geneva, Switzerland. *The 2LADY study group members are listed in the Acknowledgements.
authors.forename: Laura
authors.initials: L
authors.lastname: Ciaffi
authors.forename: Sinata
authors.initials: S
authors.lastname: Koulla-Shiro
authors.forename: Adrien
authors.initials: A
authors.lastname: Sawadogo
authors.forename: Vincent
authors.initials: V
authors.lastname: le Moing
authors.forename: Sabrina
authors.initials: S
authors.lastname: Eymard-Duvernay
authors.forename: Susanne
authors.initials: S
authors.lastname: Izard
authors.forename: Charles
authors.initials: C
authors.lastname: Kouanfack
authors.forename: Ndeye Fatou
authors.initials: NF
authors.lastname: Ngom Gueye
authors.forename: Avelin Aghokeng
authors.initials: AA
authors.lastname: Fobang
authors.forename: Jacques
authors.initials: J
authors.lastname: Reynes
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calmy
authors.forename: Eric
authors.initials: E
authors.lastname: Delaporte
mesh_terms: D000328:Adult; D000349:Africa; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects* / Q000379:methods*; D002947:Cities; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000821:virology; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents