Infectious Diseases Institute, Makerere University, Kampala, Uganda.
J Infect Dis. 2011 Dec 15;204(12):1912-7. doi: 10.1093/infdis/jir649. Epub 2011 Oct 12.
Standard-dose HSV-2 suppressive therapy (acyclovir 400 mg twice daily) reduces plasma HIV-1 levels by 0.25-0.50 log(10) copies/mL. It is not known if higher doses might further suppress HIV-1 levels.
We enrolled 32 HIV-1/HSV-2 dually infected Kenyan individuals who were not on antiretroviral therapy (ART) into a randomized, crossover trial of 2 dosing regimens of HSV-2 suppression: valacyclovir 1.5 g vs acyclovir 400 mg, both twice daily for 12 weeks, then a 2-week washout, and then the alternative for 12 weeks. Weekly plasma HIV-1 RNA quantity was measured (ClinicalTrials.gov number NCT01026454).
Mean plasma HIV-1 levels were significantly lower on valacyclovir compared with acyclovir: 2.94 vs 3.56 log(10) copies/mL, an average difference of 0.62 log(10) copies/mL (95% confidence interval [CI]: -0.68, -0.55; P < .001), a 76% decrease. Valacyclovir resulted in a 1.23 log(10) copies/mL decrease compared with baseline HIV-1 levels without HSV-2 suppression. Adherence was similar (99.4% of dispensed study tablets taken), and high-dose valacyclovir was well tolerated.
High-dose valacyclovir reduced plasma HIV-1 viral levels by 0.62 log(10) copies/mL compared with standard-dose acyclovir. The potential for higher-dose HSV-2 suppressive therapy to slow HIV-1 disease progression and reduce HIV-1 infectiousness among HIV-1/HSV-2 coinfected persons not yet eligible for ART warrants further evaluation.
标准剂量 HSV-2 抑制疗法（阿昔洛韦 400mg，每日两次）可使血浆 HIV-1 水平降低 0.25-0.50log(10) 拷贝/ml。目前尚不清楚更高剂量是否能进一步降低 HIV-1 水平。
我们招募了 32 名未接受抗逆转录病毒治疗（ART）的肯尼亚 HIV-1/HSV-2 双重感染个体，将其纳入一项 HSV-2 抑制的随机交叉试验，该试验比较了两种剂量方案：伐昔洛韦 1.5g 与阿昔洛韦 400mg，均每日两次，持续 12 周，然后进行 2 周洗脱期，然后再进行 12 周的替代治疗。每周测量血浆 HIV-1 RNA 量（ClinicalTrials.gov 编号：NCT01026454）。
与阿昔洛韦相比，伐昔洛韦的平均血浆 HIV-1 水平显著降低：2.94 与 3.56log(10) 拷贝/ml，平均差异为 0.62log(10) 拷贝/ml（95%置信区间 [CI]：-0.68，-0.55；P<0.001），降低了 76%。与未抑制 HSV-2 的基线 HIV-1 水平相比，伐昔洛韦使 HIV-1 水平降低了 1.23log(10) 拷贝/ml。依从性相似（服用的研究片剂 99.4%），高剂量伐昔洛韦耐受性良好。
与标准剂量阿昔洛韦相比，高剂量伐昔洛韦使血浆 HIV-1 病毒水平降低了 0.62log(10) 拷贝/ml。对于尚未符合 ART 条件的 HIV-1/HSV-2 合并感染人群，更高剂量 HSV-2 抑制治疗可能会减缓 HIV-1 疾病进展并降低 HIV-1 传染性，这值得进一步评估。
