title: Early upper digestive tract side effects of zidovudine with tenofovir plus emtricitabine in West African adults with high CD4 counts.
abstract: BACKGROUND
  Tenofovir (TDF) with emtricitabine (FTC) and zidovudine (ZDV) is a recognized alternate first-line antiretroviral (ART) regimen for patients who cannot start treatment with non-nucleoside reverse transcriptase inhibitors (NNRTIs). Clinical studies comparing TDF+FTC+ZDV to other regimens are lacking.
  
  
  METHODS
  Participants in a trial of early ART in Côte d'Ivoire (Temprano ANRS 12136) started treatment with TDF/FTC plus either efavirenz (EFV) or ZDV (HIV-1+2 dually infected patients and women refusing contraception or previously treated with nevirapine). We compared rates of upper digestive serious adverse events (sAEs) between TDF/FTC+EFV and TDF/FTC+ZDV patients during the first six months of treatment. sAEs were defined as either grade 3-4 AEs or persistent grade 1-2 AEs leading to drug discontinuation.
  
  
  RESULTS
  A total of 197 patients (76% women, median CD4 count 395/mm(3)) started therapy with TDF/FTC, 126 with EFV and 71 with ZDV. During the first six months of ART, 94 patients had digestive AEs (nausea/vomiting) of any grade (EFV 36/126, 29%; ZDV 58/71, 82%, p<0.0001), including 20 sAEs (EFV 3/126, 5%; ZDV 17/71, 24%, p<0.0001). In-patients on TDF/FTC+ZDV with digestive AEs, the median time to the first symptom was two days (IQR: 1-4). Plasma ZDV (Cmax) distributions and pill ZDV dosages were normal. Patients with digestive AEs had higher haemoglobin levels and tended to have higher body mass indices and more frequent past histories of cotrimoxazole (CTX) prophylaxis.
  
  
  CONCLUSIONS
  We observed an unexpectedly high rate of digestive sAEs in West African adults, mostly women, who started a 3-nuc ART with TDF/FTC+ZDV in Côte d'Ivoire. These adults were participating in a trial of early ART and had much higher CD4 counts than those who currently routinely start ART in sub-Saharan Africa. They all received CTX concomitantly with ZDV. We suggest that further early prescriptions of TDF+XTC+ZDV should be carefully monitored and that whenever possible, the rate of early upper digestive adverse events should be compared to that occurring in-patients taking other drug regimens.
  
  
  BACKGROUND
  NCT00495651.
authors: Programme PACCI, Abidjan, Côte d'Ivoire; Univ. Bordeaux, ISPED, F-33000 Bordeaux, France.
authors: Eric
authors: E
authors: Ouattara
authors: Christine
authors: C
authors: Danel
authors: Raoul
authors: R
authors: Moh
authors: Delphine
authors: D
authors: Gabillard
authors: Gilles
authors: G
authors: Peytavin
authors: Romuald
authors: R
authors: Konan
authors: Jérome Le
authors: JL
authors: Carrou
authors: Franck
authors: F
authors: Bohoussou
authors: Serge P
authors: SP
authors: Eholie
authors: Xavier
authors: X
authors: Anglaret
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D007560:Cote d'Ivoire; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology; D000068679:Emtricitabine; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000453:epidemiology; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D000068698:Tenofovir; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D015215:Zidovudine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine
keywords: 3 nucleoside reverse transcriptase inhibitors; HIV infection; adults; antiretroviral treatment; early treatment; side effects; sub-Saharan Africa; tolerance
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