BACKGROUND & AIMS:
:HIV infection remains a major global health burden since its discovery in 1983. Sub-Saharan Africa is the region hardest hit by the HIV/AIDS pandemic where 63% of the 33 million infected people live. While there is marked person-to-person variability in susceptibility, progression, and survival with HIV infection, there is a paucity of predictive diagnostics associated with these clinical endpoints. In this regard, the deficiency in plasma Mannose Binding Lectin (MBL) is a common opsonic defect reported to increase susceptibility infections, including HIV. To the best of our knowledge, we report here the first study on the putative role of MBL deficiency on HIV progression and survival in an African adult population. We hypothesized that MBL deficiency has a role to play in HIV infection by increasing HIV disease progression and decreasing survival. We assessed the role of MBL deficiency on HIV disease progression and survival in a Zimbabwean adult population enrolled in the Mupfure Schistosomiasis and HIV (MUSH) cohort. We analyzed blood samples for MBL levels, MBL2 genotypes, HIV-1 status, viral load, and CD4(+) T cell counts. Participants were followed for 3 years wherein the endpoints were measured at baseline, 6 weeks, and 3, 6, 12, 24, and 36 months. Disease progression was measured as the rate of decline in CD4(+) T cell counts and the rate of increase in HIV viral load. We assessed 197 HIV positive adults where 83% (164) were women with a median age of 31 years. Prevalence of plasma MBL deficiency (less than 100 μg/L) and MBL2 deficient genetic variants (A/O and O/O genotypes) was 21% (42 out of 197) and 39% (74 out of 190), respectively. We did not observe a significant role to explain individual variation in mortality, change of CD4(+) T cell count, and viral load by MBL plasma deficiency or MBL2 genetic variants from baseline to 3 years follow up period in this adult population. We suggest the need for global OMICS research and that the present findings attest to the large between-population variability in a host of factors that can predispose individuals susceptible to HIV progression and mortality. We therefore cannot recommend at this time the use of plasma MBL levels or MBL2 genetic variants as a prognostic marker in HIV infection, disease progression, and survival in this adult population in Africa.
背景与目标:
自从1983年发现艾滋病毒以来,艾滋病毒仍然是全球健康的主要负担。撒哈拉以南非洲地区是艾滋病毒/艾滋病大流行最重的地区,3300万人的感染中有63%生活在该地区。尽管艾滋病毒感染的易感性,进展和生存率在人与人之间存在明显差异,但与这些临床终点相关的预测性诊断却很少。在这方面,血浆甘露糖结合凝集素(MBL)的缺乏是常见的声波缺陷,据报道会增加包括HIV在内的易感性感染。据我们所知,我们在此报告了关于MBL缺乏对非洲成年人口中HIV感染和生存的假定作用的第一项研究。我们假设MBL缺乏会通过增加HIV疾病进展和降低生存率在HIV感染中发挥作用。我们评估了Muffure血吸虫病和HIV(MUSH)队列中的津巴布韦成年人口中MBL缺乏对HIV疾病进展和生存的作用。我们分析了血液样本中的MBL水平,MBL2基因型,HIV-1状态,病毒载量和CD4()T细胞计数。随访参与者3年,其中在基线,6周和3、6、12、24和36个月时测量终点。用CD4()T细胞计数的下降速率和HIV病毒载量的升高速率来衡量疾病的进展。我们评估了197名HIV阳性成人,其中83%(164)是女性,中位年龄为31岁。血浆MBL缺乏症(少于100μg/ L)和MBL2缺乏遗传变异(A / O和O / O基因型)的患病率分别为21%(197名中的42名)和39%(190名中的74名)。我们没有观察到重要的作用来解释从基线到3年随访期该成年人群的死亡率,CD4()T细胞计数变化和MBL血浆缺乏症或MBL2基因变异引起的病毒载量变化。我们建议需要进行全球OMICS研究,并且本研究结果证明了许多因素之间的群体间差异很大,这些因素可能会使易患HIV进展和死亡的个体易感。因此,我们目前不建议使用血浆MBL水平或MBL2基因变异作为该非洲成年人口的HIV感染,疾病进展和生存的预后指标。