PharmAccess Foundation, Department of Global Health, Academic Medical Centre of University of Amsterdam, Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands.
Lancet Infect Dis. 2011 Oct;11(10):750-9. doi: 10.1016/S1473-3099(11)70149-9. Epub 2011 Jul 27.
BACKGROUND: There are few data on the epidemiology of primary HIV-1 drug resistance after the roll-out of antiretroviral treatment (ART) in sub-Saharan Africa. We aimed to assess the prevalence of primary resistance in six African countries after ART roll-out and if wider use of ART in sub-Saharan Africa is associated with rising prevalence of drug resistance. METHODS: We did a cross-sectional study in antiretroviral-naive adults infected with HIV-1 who had not started first-line ART, recruited between 2007 and 2009 from 11 regions in Kenya, Nigeria, South Africa, Uganda, Zambia, and Zimbabwe. We did population-based sequencing of the pol gene on plasma specimens with greater than 1000 copies per mL of HIV RNA. We identified drug-resistance mutations with the WHO list for transmitted resistance. The prevalence of sequences containing at least one drug-resistance mutation was calculated accounting for the sampling weights of the sites. We assessed the risk factors of resistance with multilevel logistic regression with random coefficients. FINDINGS: 2436 (94.1%) of 2590 participants had a pretreatment genotypic resistance result. 1486 participants (57.4%) were women, 1575 (60.8%) had WHO clinical stage 3 or 4 disease, and the median CD4 count was 133 cells per μL (IQR 62-204). Overall sample-weighted drug-resistance prevalence was 5.6% (139 of 2436; 95% CI 4.6-6.7), ranging from 1.1% (two of 176; 0.0-2.7) in Pretoria, South Africa, to 12.3% (22 of 179; 7.5-17.1) in Kampala, Uganda. The pooled prevalence for all three Ugandan sites was 11.6% (66 of 570; 8.9-14.2), compared with 3.5% (73 of 1866; 2.5-4.5) for all other sites. Drug class-specific resistance prevalence was 2.5% (54 of 2436; 1.8-3.2) for nucleoside reverse-transcriptase inhibitors (NRTIs), 3.3% (83 of 2436; 2.5-4.2) for non-NRTIs (NNRTIs), 1.3% (31 of 2436; 0.8-1.8) for protease inhibitors, and 1.2% (25 of 2436; 0.7-1.7) for dual-class resistance to NRTIs and NNRTIs. The most common drug-resistance mutations were K103N (43 [1.8%] of 2436), thymidine analogue mutations (33 [1.6%] of 2436), M184V (25 [1.2%] of 2436), and Y181C/I (19 [0.7%] of 2436). The odds ratio for drug resistance associated with each additional year since the start of the ART roll-out in a region was 1.38 (95% CI 1.13-1.68; p=0.001). INTERPRETATION: The higher prevalence of primary drug resistance in Uganda than in other African countries is probably related to the earlier start of ART roll-out in Uganda. Resistance surveillance and prevention should be prioritised in settings where ART programmes are scaled up. FUNDING: Ministry of Foreign Affairs of the Netherlands.
背景：在撒哈拉以南非洲地区推出抗逆转录病毒治疗（ART）后，关于原发性 HIV-1 耐药性的流行病学数据较少。我们旨在评估六个非洲国家在 ART 推出后的原发性耐药流行率，以及撒哈拉以南非洲地区更广泛使用 ART 是否与耐药率上升有关。
方法：我们在肯尼亚、尼日利亚、南非、乌干达、赞比亚和津巴布韦的 11 个地区，对未接受过抗逆转录病毒治疗的 HIV-1 感染的成年初治患者进行了一项横断面研究。我们对 HIV RNA 大于 1000 拷贝/ml 的血浆标本进行了基于人群的 pol 基因测序。我们使用世卫组织的传播耐药性清单来确定耐药突变。计算包含至少一种耐药突变的序列的流行率，同时考虑到采样点的抽样权重。我们使用具有随机系数的多水平逻辑回归评估耐药的危险因素。
结果：2590 名参与者中有 2436 名（94.1%）接受了治疗前基因耐药性检测。1486 名参与者（57.4%）为女性，1575 名（60.8%）为世卫组织临床分期 3 或 4 期疾病，中位 CD4 计数为 133 个细胞/μL（IQR 62-204）。总体样本加权耐药流行率为 5.6%（139/2436；95%CI 4.6-6.7），范围从南非比勒陀利亚的 1.1%（176 例中的 2 例；0.0-2.7）到乌干达坎帕拉的 12.3%（179 例中的 22 例；7.5-17.1）。所有三个乌干达地点的汇总流行率为 11.6%（570 例中的 66 例；8.9-14.2），而所有其他地点的流行率为 3.5%（1866 例中的 73 例；2.5-4.5）。特定药物类别的耐药流行率为：核苷逆转录酶抑制剂（NRTIs）为 2.5%（2436 例中的 54 例；1.8-3.2），非核苷逆转录酶抑制剂（NNRTIs）为 3.3%（2436 例中的 83 例；2.5-4.2），蛋白酶抑制剂为 1.3%（2436 例中的 31 例；0.8-1.8），NRTIs 和 NNRTIs 双重耐药为 1.2%（2436 例中的 25 例；0.7-1.7）。最常见的耐药突变是 K103N（43 [1.8%] 例中的 2436 例）、胸腺嘧啶类似物突变（33 [1.6%] 例中的 2436 例）、M184V（25 [1.2%] 例中的 2436 例）和 Y181C/I（19 [0.7%] 例中的 2436 例）。与一个地区开始 ART 推广以来的每增加一年相关的耐药比值比为 1.38（95%CI 1.13-1.68；p=0.001）。
结论：乌干达原发性耐药率高于其他非洲国家，这可能与乌干达较早开始推广 ART 有关。在扩大 ART 项目的地区，应优先进行耐药监测和预防。
资助：荷兰外交部。
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