Predictors of first-line antiretroviral therapy failure among adults and adolescents living with HIV/AIDS in a large prevention and treatment program in Nigeria.
Predictors of first-line antiretroviral therapy failure among adults and adolescents living with HIV/AIDS in a large prevention and treatment program in Nigeria.
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DOI：
10.1186/s12981-020-00317-9
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发表时间：
2020-11-03
影响因子：
2.2
通讯作者：
Dakum P
中科院分区：
文献类型：
--
作者：
Ndembi N;Murtala-Ibrahim F;Tola M;Jumare J;Aliyu A;Alabi P;Mensah C;Abimiku A;Quiñones-Mateu ME;Crowell TA;Rhee SY;Shafer RW;Gupta R;Blattner W;Charurat ME;Dakum P
在尼日利亚，相当多的艾滋病毒感染者在接受一线抗逆转录病毒治疗（ART）时没有经历持久的病毒抑制。了解一线治疗失败的风险因素有助于患者监测实践和二线治疗方案有限资源的分配。我们在尼日利亚阿布贾的一个大型抗逆转录病毒治疗项目中确定了免疫和病毒学失败的预测因素。利用尼日利亚阿布贾2005年2月至2014年12月的数据，在三级卫生保健机构阿布贾大学教学医院开展了一项回顾性队列研究。所有年龄≥15岁且开始抗逆转录病毒治疗且随访至少6个月并进行一次CD4测量的PLWH纳入研究。免疫功能衰竭定义为CD4下降到或低于ART前水平，或在ART治疗6个月后CD4持续< 100个细胞/ mm3。病毒学失败（VF）被定义为在至少6个月的抗逆转录病毒治疗和加强依从性咨询后，连续两次HIV-1 RNA水平达到1000拷贝/mL。使用Stanford HIV数据库算法分析HIV耐药性（Sanger序列），并对常见核苷类逆转录酶抑制剂（NRTIs）和非核苷类逆转录酶抑制剂（NNRTIs）的耐药性进行评分。采用单变量和多变量对数二项回归模型估计相对危险度（rr）和95%置信区间（ci）。在随访的12452名患者中，共有5928名患者接受了至少6个月的随访和一次CD4测量。3924人（66.2%）是通过项目自己的自愿咨询和检测（VCT）中心进入的，1310人（22.1%）是从外部诊所/项目转介的，332人（5.6%）是住院患者，373人（6.3%）是通过包括预防母婴传播（PMTCT）在内的其他进入点或从其他项目转来的。在护理入组时，平均CD4为268±23.7个细胞/ mm3，平均HIV-1 RNA为3.3±1.3。log10拷贝/毫升。共有3468人（80.5%）接受奈韦拉平（NVP）治疗，2260人（19.5%）接受依非韦伦（EFV）治疗。共有2140人（36.1%）接受了替诺福韦（TDF）治疗；2662例（44.9%），齐多夫定；司他夫定1126例（19.0%）。在接受TDF的患者中，45.0%同时接受了恩曲他滨（FTC）。在多变量模型中，与男性相比，女性PLWH患者的免疫功能衰竭更为常见[RR (95% CI) 1.22(1.07-1.40)]，而在该计划的VCT中心接受治疗的患者中，与其他切入点相比[0.79 (0.64-0.91)]，who 3/4期与1/2期相比[0.19(0.16-0.22)]，或CD4 200 +细胞/ mm3相比[0.19(0.16-0.22)]较少见。与其他切入点相比，在该计划的VCT中心接受治疗的PLWH中病毒学失败更为常见[RR (95% CI) 1.45(1.11-1.91)]，而在进入护理时CD4 < 200细胞/ mm3的患者的病毒学失败高于其他切入点[1.71(1.36-2.16)]。在病毒学失败期间测序的198例患者来源样本中，42例（21%）为野生型；145例（73%）携带NNRTI耐药突变；151 (76.3%) m184i / v；29例（14.6%）患者有≥3个TAMs， 37例（18.7%）患者有K65R，其中所有患者均使用含tdf的一线方案。在这个尼日利亚PLWH随访9年的队列中，免疫标准很难预测病毒学失败。此外，一部分样本显示，抗逆转录病毒治疗长期失败的患者携带有耐药突变的HIV-1毒株。
A substantial number of persons living with HIV (PLWH) in Nigeria do not experience durable viral suppression on first-line antiretroviral therapy (ART). Understanding risk factors for first-line treatment failure informs patient monitoring practices and distribution of limited resources for second-line regimens. We determined predictors of immunologic and virologic failures in a large ART delivery program in Abuja, Nigeria. A retrospective cohort study was conducted at the University of Abuja Teaching Hospital, a tertiary health care facility, using data from February 2005 to December 2014 in Abuja, Nigeria. All PLWH aged ≥ 15 years who initiated ART with at least 6-month follow-up and one CD4 measurement were included. Immunologic failure was defined as a CD4 decrease to or below pre-ART level or persistent CD4 < 100 cells per mm3 after 6 months on ART. Virologic failure (VF) was defined as two consecutive HIV-1 RNA levels > 1000 copies/mL after at least 6 months of ART and enhanced adherence counselling. HIV drug resistance (Sanger sequences) was analyzed using the Stanford HIV database algorithm and scored for resistance to common nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Univariate and multivariate log binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Of 12,452 patients followed, a total of 5928 initiated ART with at least 6 months of follow-up and one CD4 measurement. The entry point for 3924 (66.2%) was through the program’s own voluntary counseling and testing (VCT) center, while 1310 (22.1%) were referred from an outside clinic/program, 332 (5.6%) in-patients, and 373 (6.3%) through other entry points including prevention of mother to child transmission (PMTCT) and transferred from other programs. The mean CD4 at enrollment in care was 268 ± 23.7 cells per mm3, and the mean HIV-1 RNA was 3.3 ± 1.3.log10 copies/mL. A total of 3468 (80.5%) received nevirapine (NVP) and 2260 (19.5%) received efavirenz (EFV)—based regimens. A total of 2140 (36.1%) received tenofovir (TDF); 2662 (44.9%) zidovudine (AZT); and 1126 (19.0%) stavudine (d4T). Among those receiving TDF, 45.0% also received emtricitabine (FTC). In a multivariate model, immunologic failure was more common among PLWH with female gender as compared to male [RR (95% CI) 1.22 (1.07–1.40)] and less common among those who entered care at the program’s VCT center as compared to other entry points [0.79 (0.64–0.91)], WHO stage 3/4 as compared to 1/2 [0.19 (0.16–0.22)], or CD4 200 + cells per mm3 as compared to lower [0.19 (0.16–0.22)]. Virologic failure was more common among PLWH who entered care at the program’s VCT center as compared to other entry points [RR (95% CI) 1.45 (1.11–1.91) and those with CD4 < 200 cells per mm3 at entry into care as compared to higher [1.71 (1.36–2.16)]. Of 198 patient-derived samples sequenced during virologic failure, 42 (21%) were wild-type; 145 (73%) carried NNRTI drug resistance mutations; 151 (76.3%) M184I/V; 29 (14.6%) had ≥ 3 TAMs, and 37 (18.7%) had K65R, of whom all were on TDF-containing first-line regimens. In this cohort of Nigerian PLWH followed for a period of 9 years, immunologic criteria poorly predicted virologic failure. Furthermore, a subset of samples showed that patients failing ART for extended periods of time had HIV-1 strains harboring drug resistance mutations.
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