在莫桑比克的一项纵向研究中，接受基于标准胸苷类似物的一线抗逆转录病毒治疗且出现病毒学失败的患者中HIV-1耐药性的累积：对二线治疗方案活性的影响
Accumulation of HIV-1 drug resistance in patients on a standard thymidine analogue-based first line antiretroviral therapy after virological failure: implications for the activity of next-line regimens from a longitudinal study in Mozambique.
作者信息
De Luca Andrea, Sidumo Zita Jorge, Zanelli Giacomo, Magid Noorjehan Abdul, Luhanga Richard, Brambilla Davide, Liotta Giuseppe, Mancinelli Sandro, Marazzi Maria Cristina, Palombi Leonardo, Ceffa Susanna
机构信息
UOC Malattie Infettive Universitarie, AOU Senese and Department of Medical Biotechnologies, Siena University Hospital, Viale Bracci 16, 53100, Siena, Italy.
DREAM Program, Maputo, Mozambique.
出版信息
BMC Infect Dis. 2017 Sep 5;17(1):605. doi: 10.1186/s12879-017-2709-x.
BACKGROUND
We describe the accumulation of HIV-1 drug resistance and its effect on the activity of next-line components in patients with virological failure (HIV-1 RNA >1000 copies/mL) after 1 year (t1) of first-line antiretroviral therapy (ART) not switching to second-line drugs for one additional year (t2) in low-middle income countries (LMIC).
METHODS AND RESULTS
We selected 48 patients from the DREAM cohort (Maputo, Mozambique); their median pre-ART CD4+ cell count was 165 cells/μl. At t1 patients were receiving ART since a median of 12.2 months (mainly zidovudine/lamivudine/nevirapine), their median HIV RNA was 3.8 log10 copies/mL, 43 (89.6%) presented at least one resistance-associated mutation (RAM), most frequently for lamivudine/emtricitabine, nevirapine and efavirenz. Resistance to tenofovir, was 10% at 1 year and higher than 20% at 2 years, while projection at 3 years was >30%. At t2, 42 (89.4%) had a predicted low-level or higher resistance to at least 1 s-line drug. At t1, the frequency of RAM in patients with a lower adherence to pharmacy appointments (<95%) was significantly lower (12/20, 60% for NRTI and 14/20, 70% for NNRTI) than in those with a better adherence (26/28, 92.8% for NRTI and 25/28, 89.3% for NNRTI) (OR 0.12, 95% CI 0.02-0.63, p = 0.012 and OR 0.28, 95% CI 0.06-1.29, p = 0.103, respectively). Overall thymidine analogue mutations (TAMs) accumulation rate was 0.32/year, 0.50/year in the subgroup with HIV RNA >10,000 copies/mL; NNRTI RAM accumulation rate was 0.15/year, 0.40/year in the subgroup with HIV RNA >10,000 copies/mL.
CONCLUSIONS
While the activity of NNRTIs is compromised early during failure, tenofovir and zidovudine activity are reduced more frequently after 1 year of documented virological failure of thymidine analogue-based first-line ART, with RAMs accumulating faster in patients with higher viral loads. The present observation may help informing decisions on when to switch to a second line ART in patients on virological failure in LMIC.
背景
我们描述了在低收入和中等收入国家（LMIC），一线抗逆转录病毒疗法（ART）治疗1年（t1）后病毒学失败（HIV-1 RNA>1000拷贝/毫升）且未再换用二线药物治疗1年（t2）的患者中HIV-1耐药性的积累及其对后续治疗药物活性的影响。
方法与结果
我们从DREAM队列（莫桑比克马普托）中选取了48例患者；其ART治疗前CD4+细胞计数中位数为165个/微升。在t1时，患者接受ART治疗的中位数时间为12.2个月（主要是齐多夫定/拉米夫定/奈韦拉平），其HIV RNA中位数为3.8 log10拷贝/毫升，43例（89.6%）出现至少一种耐药相关突变（RAM），最常见于拉米夫定/恩曲他滨、奈韦拉平和依非韦伦。对替诺福韦的耐药率在1年时为10%，2年时高于20%，而3年时预测超过30%。在t2时，42例（89.4%）对至少一种二线药物有预测的低水平或更高耐药性。在t1时，药房预约依从性较低（<95%）的患者中RAM的发生率显著低于依从性较好的患者（NRTI为12/20，60%；NNRTI为14/20，70%）（分别为NRTI：OR 0.12，95%CI 0.02 - 0.63，p = 0.012；NNRTI：OR 0.28，95%CI 0.06 - 1.29，p = 0.103）。总体胸苷类似物突变（TAM）积累率为0.32/年，HIV RNA>10000拷贝/毫升亚组为0.50/年；NNRTI RAM积累率为0.15/年，HIV RNA>10000拷贝/毫升亚组为0.40/年。
结论
虽然在治疗失败早期NNRTIs的活性就受到损害，但在基于胸苷类似物的一线ART治疗出现病毒学失败1年后，替诺福韦和齐多夫定的活性更频繁地降低，病毒载量较高的患者中RAM积累更快。本观察结果可能有助于为LMIC中病毒学失败患者何时换用二线ART治疗提供决策依据。
Zotero 插件