Infectious co-factors in HIV-1 transmission herpes simplex virus type-2 and HIV-1: new insights and interventions.
Infectious co-factors in HIV-1 transmission herpes simplex virus type-2 and HIV-1: new insights and interventions.
复制标题
DOI：
10.2174/157016212800618156
复制
发表时间：
2012-04
影响因子：
1
通讯作者：
Celum C
中科院分区：
文献类型：
--
作者：
Barnabas RV;Celum C
在过去的30年里，流行病学和分子研究表明，单纯疱疹病毒2型（HSV-2）和HIV-1感染的双重流行之间存在强烈的因果关系。虽然前瞻性研究表明HSV-2感染使HIV-1感染的风险增加2 - 3倍，但采用标准预防剂量的HSV-2治疗抑制HSV-2并不能预防HIV-1感染。调和这些差异需要了解最近的HSV-2发病机制研究，该研究表明HSV-2感染不是一种罕见复发的潜伏感染，而是一种几乎恒定的再激活和病毒脱落状态，标准抗病毒药物无法完全抑制这种状态。由于目前的抗病毒药物不能预防或完全抑制HSV-2复制，因此优先考虑的是HSV-2疫苗的开发和在生殖器粘膜中达到高浓度的抗病毒药物，并抑制与生殖器疱疹再激活相关的持续性生殖器炎症，以降低与HSV-2相关的HIV-1感染的易感性增加。HIV-1和HSV-2的协同作用也见于与HSV-2未感染个体相比表现出更高HIV-1病毒载量的合并感染个体中。标准HSV-2治疗适度降低HIV-1病毒载量，并与HIV-1疾病进展缓慢相关。一个有前途的研究领域是更高剂量的HSV-2抑制治疗，实现更大程度的减少血浆HIV-1 RNA，这可能转化为更大程度的减少HIV-1疾病的进展和传染性。然而，仍有许多问题有待回答，包括高剂量HSV-2抑制治疗的潜在有效性和成本效益。在人群水平上HSV-2和HIV-1的数学模型将是评估更高剂量HSV-2抑制治疗的潜在影响和成本效益的有用工具。
Over the last thirty years, epidemiologic and molecular studies indicate a strong and synergist relationship between the dual epidemics of herpes simplex type 2 (HSV-2) and HIV-1 infection. While prospective studies show that HSV-2 infection increases the risk for HIV-1 acquisition by two-three fold, HSV-2 suppression with standard prophylactic doses of HSV-2 therapy did not prevent HIV-1 acquisition. Reconciling these discrepancies requires understanding recent HSV-2 pathogenesis research, which indicates HSV-2 infection is not a latent infection with infrequent recurrence but a near constant state of reactivation and viral shedding which is not completely suppressed by standard antivirals. Because current antivirals do not prevent or fully suppress HSV-2 replication, priorities are HSV-2 vaccine development and antivirals that reach high concentrations in the genital mucosa and suppress the persistent genital inflammation associated with genital herpes reactivation in order to reduce the increased susceptibility to HIV-1 infection associated with HSV-2. HIV-1 and HSV-2 synergy is also seen among co-infected individuals who exhibit higher HIV-1 viral load compared to HSV-2 uninfected individuals. Standard HSV-2 therapy modestly lowers HIV-1 viral load and is associated with slower HIV-1 disease progression. A promising area of research is higher doses of HSV-2 suppressive therapy achieving a greater reduction in plasma HIV-1 RNA, which could translate to greater reductions in HIV-1 disease progression and infectiousness. However, many questions remain to be answered including potential effectiveness and cost-effectiveness of higher dose HSV-2 suppressive therapy. Mathematical models of HSV-2 and HIV-1 at a population level would be useful tools to estimate the potential impact and cost-effectiveness of higher dose HSV-2 suppressive therapy.