*Programme PAC-CI/ANRS, Abidjan, Côte d'Ivoire; †INSERM, Centre 897, France; ‡University of Bordeaux, ISPED, France; §Laboratoire de Virologie, Université Paris Descartes, Sorbonne Paris Cité, AP-HP, CHU Necker-Enfants Malades, Paris; ‖CeDReS, CHU de Treichville, Abidjan, Côte d'Ivoire; and ¶Service des Maladies Infectieuses et Tropicales, CHU de Treichville, Abidjan, Côte d'Ivoire.
J Acquir Immune Defic Syndr. 2013 Oct 1;64(2):211-9. doi: 10.1097/QAI.0b013e3182a009e4.
In sub-Saharan Africa, most HIV-infected patients receive antiretroviral therapy (ART) without virological monitoring. Longitudinal data on secondary resistance are rare.
We conducted a prospective cohort study of HIV-1-infected adults initiating ART in 3 clinics using computerized monitoring systems. Patients had plasma HIV-1 RNA viral load (VL) tests at months 12 (M12) and 24 (M24) after ART initiation and HIV-1 resistance genotype tests if VL was detectable (≥300 copies/mL).
Overall, 1573 patients initiated ART with stavudine/zidovudine plus lamivudine plus nevirapine/efavirenz. At M12 and M24, 944 and 844 patients, respectively, remained in active follow-up. Among them, 25% (M12) and 27% (M24) had detectable VLs and 12% (M12) and 19% (M24) had virus resistant to at least 1 antiretroviral drug, accounting for 54% (M12) and 75% (M24) of patients with detectable VLs. Among the resistant strains, 95% (M12) and 97% (M24) were resistant to lamivudine/emtricitabine, efavirenz, and/or nevirapine, the frequency of thymidine analog mutations increased from 8.1% (M12) to 14.7% (M24) and etravirine resistance increased from 13.5% (M12) to 24.5% (M24).
Of the patients with detectable VLs at M24, 25% still did not harbor resistant virus. Preventing mutations from emerging with adherence reinforcement in patients with detectable VLs remains important beyond M24. Switching therapy early in patients with resistance to 3 TC/FTC and/or to nonnucleoside reverse transcriptase inhibitors to prevent extended resistance to nucleoside reverse transcriptase inhibitors and etravirine resistance from occurring is also a major challenge.
在撒哈拉以南非洲地区,大多数感染 HIV 的患者在未进行病毒学监测的情况下接受抗逆转录病毒治疗(ART)。关于继发耐药的纵向数据较为少见。
我们对在 3 家诊所接受 ART 治疗的 HIV-1 感染成年患者进行了一项前瞻性队列研究,使用计算机化监测系统。患者在开始 ART 后第 12 个月(M12)和第 24 个月(M24)进行血浆 HIV-1 RNA 病毒载量(VL)检测,如果 VL 可检测到(≥300 拷贝/mL)则进行 HIV-1 耐药基因型检测。
共有 1573 例患者接受了齐多夫定/扎西他滨+拉米夫定+奈韦拉平/依非韦伦治疗。在 M12 和 M24 时,分别有 944 和 844 例患者在积极随访中。其中,分别有 25%(M12)和 27%(M24)的患者 VL 可检测到,12%(M12)和 19%(M24)的患者对至少 1 种抗逆转录病毒药物耐药,分别占 VL 可检测到患者的 54%(M12)和 75%(M24)。在耐药株中,95%(M12)和 97%(M24)对拉米夫定/恩曲他滨、依非韦伦和/或奈韦拉平耐药,胸苷类似物突变的频率从 M12 的 8.1%增加到 M24 的 14.7%,依曲韦林耐药从 M12 的 13.5%增加到 M24 的 24.5%。
在 M24 时 VL 可检测到的患者中,仍有 25%的患者未携带耐药病毒。在 M24 之后,通过强化依从性来防止出现耐药突变仍然很重要。对于对 3TC/FTC 和/或非核苷类逆转录酶抑制剂耐药的患者,早期进行治疗转换以防止核苷类逆转录酶抑制剂和依曲韦林耐药的进一步发展也是一个主要挑战。