Programme PACCI, Abidjan, Côte d'Ivoire; Univ. Bordeaux, ISPED, F-33000 Bordeaux, France.
J Int AIDS Soc. 2013 Apr 30;16(1):18059. doi: 10.7448/IAS.16.1.18059.
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.
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.
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.
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.
NCT00495651.
替诺福韦（TDF）联合恩曲他滨（FTC）和齐多夫定（ZDV）是一种公认的替代一线抗逆转录病毒（ART）方案，适用于不能开始使用非核苷类逆转录酶抑制剂（NNRTIs）治疗的患者。目前缺乏比较 TDF+FTC+ZDV 与其他方案的临床研究。
在科特迪瓦（Temprano ANRS 12136）进行的早期 ART 试验中的参与者开始接受 TDF/FTC 联合依非韦伦（EFV）或 ZDV（HIV-1+2 双重感染患者和拒绝避孕或以前用过奈韦拉平的患者）治疗。我们比较了治疗的前 6 个月内 TDF/FTC+EFV 和 TDF/FTC+ZDV 患者上消化道严重不良事件（sAE）的发生率。sAE 定义为 3-4 级 AE 或持续 1-2 级 AE 导致停药。
共 197 例（76%为女性，中位 CD4 计数为 395/mm3）开始接受 TDF/FTC 治疗，其中 126 例接受 EFV 治疗，71 例接受 ZDV 治疗。在 ART 的前 6 个月内，94 例患者出现任何等级的消化不良事件（恶心/呕吐）（EFV 36/126，29%；ZDV 58/71，82%，p<0.0001），包括 20 例 sAE（EFV 3/126，5%；ZDV 17/71，24%，p<0.0001）。在因消化不良事件而服用 TDF/FTC+ZDV 的住院患者中，首次出现症状的中位时间为 2 天（IQR：1-4）。血浆 ZDV（Cmax）分布和药丸 ZDV 剂量均正常。有消化不良事件的患者血红蛋白水平较高，体重指数较高，且更频繁地接受过复方新诺明（CTX）预防。
我们在科特迪瓦观察到，西非人，尤其是女性，在开始 TDF/FTC+ZDV 治疗 3 种核药物的 ART 时，出现了异常高的消化道 sAE 发生率。这些成年人参加了早期 ART 试验，他们的 CD4 计数比目前在撒哈拉以南非洲地区常规开始 ART 的患者高得多。他们都同时接受了 ZDV 和 CTX。我们建议，应密切监测进一步早期处方 TDF+XTC+ZDV 的情况，并尽可能比较不同药物方案治疗的住院患者中早期上消化道不良事件的发生率。
NCT00495651。
