Early upper digestive tract side effects of zidovudine with tenofovir plus emtricitabine in West African adults with high CD4 counts

• Published in: Journal of the International AIDS Society Vol. 16; no. 1; pp. 18059 - n/a
• Main Authors: Ouattara, Eric, Danel, Christine, Moh, Raoul, Gabillard, Delphine, Peytavin, Gilles, Konan, Romuald, Carrou, Jérome Le, Bohoussou, Franck, Eholie, Serge P, Anglaret, Xavier
• Format: Journal Article
• Language: English
• Published: Switzerland International AIDS Society 30.04.2013; John Wiley & Sons, Inc
• Subjects: 3 nucleoside reverse transcriptase inhibitors; Acquired immune deficiency syndrome; Adenine - administration & dosage; Adenine - adverse effects; Adenine - analogs & derivatives; Adult; adults; AIDS; Analysis; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Antiretroviral agents; Antiretroviral drugs; antiretroviral treatment; Care and treatment; CD4 Lymphocyte Count; Cote d'Ivoire; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Disease prevention; DNA polymerases; Drug therapy; Drug Therapy, Combination - adverse effects; Drug Therapy, Combination - methods; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - pathology; early treatment; Emtricitabine; Female; Gastrointestinal Diseases - chemically induced; Gastrointestinal Diseases - epidemiology; Genetic aspects; Health aspects; Health care access; Highly active antiretroviral therapy; HIV; HIV infection; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - immunology; Human immunodeficiency virus; Humans; Immune system; Immunology; Infections; Investigations; Male; Middle Aged; Mortality; Organophosphonates - administration & dosage; Organophosphonates - adverse effects; Patient outcomes; Pharmacokinetics; Physiological aspects; Plasma; Prophylaxis; Side effects; sub‐Saharan Africa; Tenofovir; tolerance; Zidovudine - administration & dosage; Zidovudine - adverse effects; Cote d'Ivoire; Sub-Saharan Africa; France; Africa; Ivory Coast; 3 nucleoside reverse transcriptase inhibitors; sub-Saharan Africa; adults; side effects; HIV infection; antiretroviral treatment; early treatment; tolerance
• ISSN: 1758-2652; 1758-2652
• DOI: 10.7448/IAS.16.1.18059

Introduction 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/mm3) 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. Clinical Trial Number: NCT00495651.