HSV-2治疗可降低HIV-1病毒载量

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Valacyclovir Decreases Plasma HIV-1 RNA in HSV-2 Seronegative Individuals: A Randomized Placebo-Controlled Crossover Trial

Valacyclovir reduces HIV-1 levels — even when patients do not have herpes -- results from a resent study indicate. The result not only means that Valacyclovir can be used effectively with a broader range of HIV-1 patients, but also suggests promising new avenues for the development of HIV-fighting drugs. This insight is particularly significant given that some forms of HIV-1 have become resistant to existing medications.

Background. Acyclovir (ACV), a highly specific anti-herpetic drug, acts as a DNA chain terminator for several human herpesviruses (HHVs), including HHV-2 (HSV-2), a common HIV-1 co-pathogen. Several trials demonstrated that HSV-2 suppressive therapy using ACV or its prodrug valacyclovir (valACV) reduced plasma HIV-1 viral load (VL) in HIV-1/HSV-2 coinfected persons, and this was proposed to be due to a decrease in generalized immune activation. Recently, however, we found that ACV directly suppresses HIV-1 ex vivo in tissues free of HSV-2 but endogenously coinfected with other HHVs. Here, we asked whether valACV suppresses VL in HIV-1 infected HSV-2-seronegative persons.

Methods. 18 HIV-1 infected HSV-2-seronegative individuals were randomly assigned in a double blind placebo-controlled, crossover trial. Eligible participants had CD4 cell counts of ≥500 cells/μL and were not taking antiretroviral therapy. Subjects in group A received 12 weeks of valACV 500 mg given twice daily by mouth followed by two weeks of a no treatment washout and then 12 weeks of placebo; subjects in group B received 12 weeks of placebo followed by 2 weeks of no treatment washout and then 12 weeks of valACV 500 mg twice daily.

Results. HIV-1 VL in plasma of patients treated with valACV 500 mg twice daily for 12 weeks was reduced on average by 0.37 log10 copies/mL.

Conclusions. These data indicate that the effects of valACV on HIV-1 replication are not related to the suppression of HSV-2-mediated inflammation and are consistent with a direct effect of ACV on HIV-1 replication.

另外2007年，也有类似报道。
据Medscape.com 2月21日报道（原载N Engl J Med 2007;356:790-799,854-856），研究发现,双重感染HIV-1和疱疹病毒-2（HSV-2）的女性患者，在应用伐昔洛韦抗HSV治疗后可降低血液和生殖器分泌物中HIV-1的RNA水平。
　　伦敦卫生和热带医学院的Nicolas Nagot博士和他的同事们指出，多项研究已证明HSV-2的感染可以增加HIV-1感染的风险，还有一些报道称HSV感染可能会增加生殖器HIV-1 RNA的数量。而他们的试验设计是观察这种关系是否可以逆转，即抑制HSV的治疗能否降低HIV-1的复制。这项研究包括136名均未接受过HAART治疗的双重感染的女性患者。在基线阶段，每2周从病人体内获得标本，然后她们被随机分入安慰剂组和治疗组，治疗组使用伐昔洛韦，每天两次，每次500mg，共治疗3个月，且按照指示每2周回来进行检查。治疗后生殖器分泌物中HIV-1 RNA检出率显著降低（0.41），且生殖器HIV-1 RNA数量也显著下降（平均下降0.29log-10/ml,P<0.001）。而且，这两种检查得到的治疗效果随着时间均有所增加（P="0.001）。实验室结果也显示血浆HIV-1" RNA显著下降（-0.53log-10/ml）,同样也是随着时间延长下降越明显（P<0.001）。HSV-2也同样受伐昔洛韦治疗的影响，生殖器HSV-2 DNA检测值与生殖器溃疡发生率均有所下降。
　　Nicolas Nagot博士和他的同事们指出，这些结果最有可能的解释是：抑制HSV-2的治疗措施可以防止由于HIV-1病毒载量的增加所引起的HIV-1临床和亚临床的复活。如果血浆和生殖器中HIV-1 RNA 数量降低会使得传染性降低的话,持续控制HSV-2（不管是抗病毒治疗还是有效的疫苗）可能会降低HIV-1的传播。
　　Lawrence Corey博士在一篇相关报道中称，这些观察结果在理论上具有重要意义，世界范围内的大多数通过性传播而感染HIV的人群也都伴有活动性HSV-2感染，所以这项妇女患者的研究提出了筛查和治疗亚临床HSV-2感染可能给治疗HIV感染带来好处。