Zinyama-Gutsire Rutendo B L, Chasela Charles, Kallestrup Per, Rusakaniko Simbarashe, Christiansen Michael, Ngara Bernard, Gomo Exnevia, Ullum Henrik, Erikstrup Christian, Madsen Hans O, Stray-Pedersen Babill, Garred Peter, Mduluza Takafira
1 Faculty of Health Sciences, School of Public Health, University of the Witwatersrand , Johannesburg, South Africa .
2 Medical Research Council of Zimbabwe , Ministry of Health and Child Welfare, Harare, Zimbabwe .
OMICS. 2015 Sep;19(9):542-52. doi: 10.1089/omi.2015.0047.
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.
自1983年被发现以来,艾滋病毒感染仍然是一项重大的全球卫生负担。撒哈拉以南非洲是受艾滋病毒/艾滋病疫情影响最严重的地区,3300万感染者中有63%生活在该地区。虽然艾滋病毒感染在易感性、病情进展和生存方面存在明显的个体差异,但与这些临床终点相关的预测性诊断方法却很匮乏。在这方面,血浆甘露糖结合凝集素(MBL)缺乏是一种常见的调理缺陷,据报道它会增加包括艾滋病毒在内的感染易感性。据我们所知,我们在此报告了关于MBL缺乏在非洲成年人群中对艾滋病毒进展和生存的假定作用的第一项研究。我们假设MBL缺乏通过加速艾滋病毒疾病进展和降低生存率而在艾滋病毒感染中发挥作用。我们在参加穆普弗雷血吸虫病和艾滋病毒(MUSH)队列研究的津巴布韦成年人群中评估了MBL缺乏对艾滋病毒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、艾滋病毒-1感染状况、病毒载量和CD4(+) T细胞计数。对参与者进行了3年的随访,在基线、6周以及3、6、12、24和36个月时测量终点指标。疾病进展通过CD4(+) T细胞计数的下降率和艾滋病毒病毒载量增长率来衡量。我们评估了197名艾滋病毒阳性成年人,其中83%(164人)为女性,中位年龄为31岁。血浆MBL缺乏(低于100μg/L)和MBL2缺乏基因变异(A/O和O/O基因型)的患病率分别为21%(197人中的42人)和39%(190人中的74人)。在该成年人群从基线到3年随访期内,我们未观察到MBL血浆缺乏或MBL2基因变异在解释死亡率、CD4(+) T细胞计数变化和病毒载量的个体差异方面有显著作用。我们建议开展全球组学研究,并且目前的研究结果证明,在一系列可能使个体易患艾滋病毒进展和死亡的因素方面,人群之间存在很大差异。因此,目前我们不能推荐将血浆MBL水平或MBL2基因变异作为非洲该成年人群艾滋病毒感染、疾病进展和生存的预后标志物。