Seyler Catherine, Adjé-Touré Christiane, Messou Eugène, Dakoury-Dogbo Nicole, Rouet François, Gabillard Delphine, Nolan Monica, Toure Siaka, Anglaret Xavier
INSERM U593, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France.
AIDS. 2007 May 31;21(9):1157-64. doi: 10.1097/QAD.0b013e3281c615da.
To analyse the association between the presence of resistance mutations and treatment outcomes. The impact of HIV-1 drug resistance mutations in African adults on HAART has so far never been reported.
In 2004 in Abidjan, Côte d'Ivoire, 106 adults on HAART had plasma viral load measurements. Patients with detectable viral loads had resistance genotypic tests. Patients were followed until 2006. Main outcomes were serious morbidity and immunological failure (CD4 cell count < 200 cells/microl).
At study entry, the median previous time on HAART was 37 months and the median CD4 cell count was 266 cells/microl; 58% of patients had undetectable viral loads, 20% had detectable viral loads with no major resistance mutations, and 22% had detectable viral loads with one or more major mutations. The median change in CD4 cell count between study entry and study termination was +129 cells/microl in patients with undetectable viral loads, +51 cells/microl in those with detectable viral loads with no mutations and +3 cells/microl in those with detectable viral loads with resistance mutations. Compared with patients with undetectable viral loads, those with detectable viral loads with resistance mutations had adjusted hazard ratios of immunological failure of 4.32 (95%CI 1.38-13.57, P = 0.01). One patient died. The 18-month probability of remaining free of morbidity was 0.79 in patients with undetectable viral loads and 0.69 in those with resistance mutations (P = 0.19).
In this setting with restricted access to second-line HAART, patients with major resistance mutations had higher rates of immunological failure, but most maintained stable CD4 cell counts and stayed alive for at least 20 months.
分析耐药突变的存在与治疗结果之间的关联。迄今为止,尚未有关于非洲成年人中HIV-1耐药突变对高效抗逆转录病毒治疗(HAART)影响的报道。
2004年在科特迪瓦的阿比让,对106名接受HAART治疗的成年人进行了血浆病毒载量检测。病毒载量可检测到的患者进行了耐药基因检测。对患者进行随访至2006年。主要结局为严重发病和免疫失败(CD4细胞计数<200个/微升)。
研究开始时,此前接受HAART治疗的中位时间为37个月,中位CD4细胞计数为266个/微升;58%的患者病毒载量不可检测,20%的患者病毒载量可检测但无主要耐药突变,22%的患者病毒载量可检测且有一个或多个主要突变。研究开始至结束期间,病毒载量不可检测的患者CD4细胞计数的中位变化为+129个/微升,病毒载量可检测但无突变的患者为+51个/微升,病毒载量可检测且有耐药突变的患者为+3个/微升。与病毒载量不可检测的患者相比,病毒载量可检测且有耐药突变的患者免疫失败的校正风险比为4.32(95%置信区间1.38-13.57,P = 0.01)。1例患者死亡。病毒载量不可检测的患者18个月无发病的概率为0.79,有耐药突变的患者为0.69(P = 0.19)。
在这种获得二线HAART受限的情况下,有主要耐药突变的患者免疫失败率较高,但大多数患者CD4细胞计数保持稳定,并且存活至少20个月。