title: Efficacy and safety of lopinavir/ritonavir versus efavirenz-based antiretroviral therapy in HIV-infected pregnant Ugandan women.
abstract: OBJECTIVE
  Combination antiretroviral therapy (ART) is now the global standard for HIV-infected pregnant and breastfeeding women at all CD4⁺ cell counts. We compared the efficacy and safety of an efavirenz versus lopinavir/ritonavir regimen for HIV-infected pregnant women initiating ART in rural Uganda.
  
  
  METHODS
  Randomized clinical trial.
  
  
  METHODS
  We performed a planned secondary analysis comparing viral load suppression (HIV-1 RNA ≤400 copies/ml), safety, and HIV transmission to infants in a trial designed to test the hypothesis that lopinavir/ritonavir versus efavirenz-based ART would reduce placental malaria (PROMOTE, ClinicalTrials.gov, NCT00993031). HIV-infected, ART-naive pregnant women at 12-28 weeks gestation and any CD4⁺ cell count were randomized. ART was provided and participants were counseled to breastfeed for 1 year postpartum.
  
  
  RESULTS
  The median age of the 389 study participants was 29 years; median CD4⁺ cell count was 370 cells/μl. At delivery, virologic suppression was 97.6% in the efavirenz arm and 86.0% in the lopinavir/ritonavir arm (P < 0.001). At 48 weeks postpartum, 91.0% of women on efavirenz and 88.4% on lopinavir/ritonavir had viral suppression (P = 0.49). Grade 1 or 2 gastrointestinal adverse events were higher among women on lopinavir/ritonavir versus efavirenz. Only two infants acquired HIV (both in the lopinavir/ritonavir arm), and HIV-free infant survival was similar between study arms: 92.9% (lopinavir/ritonavir) versus 97.2% (efavirenz) (P = 0.10).
  
  
  CONCLUSIONS
  Virologic suppression at delivery was higher with an efavirenz versus lopinavir/ritonavir-based regimen. However, women in both arms achieved high levels of virologic suppression through 1 year postpartum and the risk of transmission to infants was low.
authors.affiliation: aDepartment of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California, USA bMakerere University-University of California, San Francisco Research Collaboration, Kampala, Uganda cHIV/AIDS Division, San Francisco General Hospital dCenter for AIDS Prevention Studies, University of California, San Francisco, San Francisco, California eDepartment of Obstetrics and Gynecology, New York University, New York, USA fMedical Research Council Unit, The Gambia gDepartment of Pediatrics, University of California, San Francisco, San Francisco, California, USA hDepartment of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Deborah
authors.initials: D
authors.lastname: Cohan
authors.forename: Paul
authors.initials: P
authors.lastname: Natureeba
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Koss
authors.forename: Albert
authors.initials: A
authors.lastname: Plenty
authors.forename: Flavia
authors.initials: F
authors.lastname: Luwedde
authors.forename: Julia
authors.initials: J
authors.lastname: Mwesigwa
authors.forename: Veronica
authors.initials: V
authors.lastname: Ades
authors.forename: Edwin D
authors.initials: ED
authors.lastname: Charlebois
authors.forename: Monica
authors.initials: M
authors.lastname: Gandhi
authors.forename: Tamara D
authors.initials: TD
authors.lastname: Clark
authors.forename: Bridget
authors.initials: B
authors.lastname: Nzarubara
authors.forename: Jane
authors.initials: J
authors.lastname: Achan
authors.forename: Theodore
authors.initials: T
authors.lastname: Ruel
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.forename: Diane V
authors.initials: DV
authors.lastname: Havlir
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000627:therapeutic use*; D001942:Breast Feeding; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D061466:Lopinavir / Q000627:therapeutic use*; D008288:Malaria / Q000188:drug therapy; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000821:virology; D019438:Ritonavir / Q000627:therapeutic use*; D014454:Uganda; D019562:Viral Load
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D061466:Lopinavir; C098320:efavirenz; D019438:Ritonavir