Geretti Anna Maria
Royal Free Hospital and Royal Free and University College Medical School, London, UK.
Curr Opin Infect Dis. 2006 Feb;19(1):1-7. doi: 10.1097/01.qco.0000200293.45532.68.
This review presents an update on the molecular epidemic patterns of HIV-1 infection and the effects of subtype-related genetic variability on transmission, disease progression, response to antiretroviral therapy and drug-resistance pathways.
The molecular epidemiology of HIV-1 infection is complex and evolving. The emergence of new variants reflects HIV-1 prevalence, subtype epidemiology and risk-behaviour patterns in different geographical areas. Evidence indicates that certain subtypes may have a transmission advantage while others display higher replicative efficiency. The molecular mechanisms underlying these differences are being identified and include both virus- and host-related factors. Although drug susceptibility varies and clinical evidence remains limited, current antiretroviral regimens appear to have comparable efficacy in patients infected with B and non-B subtypes. Subtype-related variability influences resistance pathways. However, the major treatment-associated resistance mutations seen in subtype B also confer resistance in non-B subtypes and vice versa.
Genetic differences among HIV-1 variants can influence the virus biological properties, susceptibility to existing and candidate antiretroviral drugs, and evolution of antiretroviral drug resistance. Further studies are required to define the impact of this variability on risk of transmission, disease outcomes, responses to antiretroviral therapy and resistance pathways. Meanwhile, plasma viral load and CD4 count remain the important predictors of disease outcome, regardless of the infecting subtype. Current antiretroviral regimens can be used reliably to treat patients with both B and non-B subtypes, and resistance interpretation algorithms provide adequate guidance. The limitations of current evidence should be acknowledged and instigate ongoing vigilance.
本综述介绍了HIV-1感染的分子流行模式的最新情况,以及亚型相关基因变异性对传播、疾病进展、抗逆转录病毒治疗反应和耐药途径的影响。
HIV-1感染的分子流行病学复杂且不断演变。新变异体的出现反映了不同地理区域的HIV-1流行情况、亚型流行病学和风险行为模式。有证据表明,某些亚型可能具有传播优势,而其他亚型则表现出更高的复制效率。正在确定这些差异背后的分子机制,包括病毒和宿主相关因素。尽管药物敏感性存在差异且临床证据仍然有限,但目前的抗逆转录病毒治疗方案对感染B亚型和非B亚型的患者似乎具有相当的疗效。亚型相关的变异性影响耐药途径。然而,在B亚型中出现的主要治疗相关耐药突变在非B亚型中也会导致耐药,反之亦然。
HIV-1变异体之间的基因差异可影响病毒生物学特性、对现有和候选抗逆转录病毒药物的敏感性以及抗逆转录病毒药物耐药性的演变。需要进一步研究来确定这种变异性对传播风险、疾病结局、抗逆转录病毒治疗反应和耐药途径的影响。同时,无论感染的亚型如何,血浆病毒载量和CD4细胞计数仍然是疾病结局的重要预测指标。目前的抗逆转录病毒治疗方案可可靠地用于治疗B亚型和非B亚型患者,耐药性解读算法提供了充分的指导。应认识到当前证据的局限性,并持续保持警惕。