Department of Biochemistry and Molecular Biology, Kilimanjaro Christian Medical University College (KCMUCo), Moshi, Kilimanjaro, Tanzania.
Department of Medical Laboratory Services, Kibong'oto Infectious Diseases Hospital (KIDH), Siha, Kilimanjaro, Tanzania.
PLoS One. 2020 Sep 28;15(9):e0232649. doi: 10.1371/journal.pone.0232649. eCollection 2020.
Emergence of HIV drug resistance poses a serious risk of inactivity to all currently approved antiretroviral drugs. Profiles of HIV drug resistance mutations (HIVDRM) and virological failure (VF) are not extensively studied in Tanzania. This study aimed to determine HIVDRM and predictors of VF in HIV-infected individuals failing first-line HIV drugs in Moshi, Northern Tanzania. A case-control study was conducted at Kilimanjaro Christian Medical Centre, Mawenzi, Pasua and Majengo health facilities with HIV-care and treatment clinics from October, 2017 to August, 2018. Cases and controls were HIV-infected individuals with VF and viral suppression (VS) respectively. HIV-1 reverse transcriptase and protease genes were amplified and sequenced. Stanford University's HIV drug resistance database and REGA subtyping tool 3.0 determined HIVDRM and HIV-1 subtypes respectively. Odds ratios (OR) with 95% confidence interval (95% CI) investigated predictors of VF. P-value < 5% was considered statistically significant. A total of 124 participants were recruited, of whom 63 (50.8%) had VF, 61 (49.2%) had VS and 82 (66.1%) were females. Median [IQR] age and duration on ART were 45 [35-52] years and 72 [48-104] months respectively. Twenty-five out of 26 selected samples from cases were successfully sequenced. Twenty-four samples (96%) had at least one major mutation conferring resistance to HIV drugs, with non-nucleoside analogue reverse transcriptase inhibitor (NNRTI)-resistance associated mutations as the majority (92%). Frequent NNRTI-resistance associated mutations were K103N (n = 11), V106M (n = 5) and G190A (n = 5). Prevalent nucleoside analogue reverse transcriptase inhibitors-resistance associated mutations were M184V (n = 17), K70R (n = 7) and D67N (n = 6). Dual-class resistance was observed in 16 (64%) samples. Thirteen samples (52%) had at least one thymidine analogue-resistance associated mutation (TAM). Three samples (12%) had T69D mutation with at least 1 TAM. Two samples (8%) had at least one mutation associated with protease inhibitor resistance. Age [aOR = 0.94, 95% CI (0.90-0.97), p < 0.001] and occupation [aOR = 0.35, 95% CI (0.12-1.04), p = 0.059] associated with VF. In conclusion, HIV drug resistance is common among people failing antiretroviral therapy. Resistance testing will help to guide switching of HIV drugs.
HIV 耐药性的出现对所有目前批准的抗逆转录病毒药物的活性构成严重威胁。在坦桑尼亚，HIV 耐药性突变（HIVDRM）和病毒学失败（VF）的特征并未得到广泛研究。本研究旨在确定在坦桑尼亚北部莫希的 HIV 感染者中，接受一线抗 HIV 药物治疗失败后 HIVDRM 和 VF 的预测因素。这是一项病例对照研究，于 2017 年 10 月至 2018 年 8 月在 Kilimanjaro Christian Medical Centre、Mawenzi、Pasua 和 Majengo 卫生设施以及 HIV 护理和治疗诊所进行。病例和对照分别为 VF 和病毒抑制（VS）的 HIV 感染者。扩增并测序了 HIV-1 逆转录酶和蛋白酶基因。斯坦福大学的 HIV 耐药性数据库和 REGA 亚型 3.0 分别确定了 HIVDRM 和 HIV-1 亚型。95%置信区间（95%CI）的优势比（OR）调查了 VF 的预测因素。p 值<0.05 被认为具有统计学意义。共招募了 124 名参与者，其中 63 名（50.8%）发生了 VF，61 名（49.2%）实现了 VS，82 名（66.1%）为女性。中位[IQR]年龄和 ART 持续时间分别为 45[35-52]岁和 72[48-104]个月。26 份病例样本中有 25 份成功测序。24 份样本（96%）至少有一种导致 HIV 药物耐药的主要突变，其中非核苷类逆转录酶抑制剂（NNRTI）耐药相关突变占大多数（92%）。常见的 NNRTI 耐药相关突变包括 K103N（n=11）、V106M（n=5）和 G190A（n=5）。常见的核苷类逆转录酶抑制剂耐药相关突变包括 M184V（n=17）、K70R（n=7）和 D67N（n=6）。观察到双重耐药性的有 16 例（64%）。13 例（52%）至少有一种胸苷类似物耐药相关突变（TAM）。3 例（12%）有至少一种 TAM 的 T69D 突变。2 例（8%）有至少一种与蛋白酶抑制剂耐药相关的突变。年龄[aOR=0.94，95%CI（0.90-0.97），p<0.001]和职业[aOR=0.35，95%CI（0.12-1.04），p=0.059]与 VF 相关。总之，HIV 耐药性在接受抗逆转录病毒治疗失败的人群中很常见。耐药性检测将有助于指导 HIV 药物的更换。
