Nagot N, Ouedraogo A, Konate I, Weiss H A, Foulongne V, Defer M C, Sanon A, Becquart P, Segondy M, Sawadogo A, Van de Perre P, Mayaud P
Centre Muraz, Burkina Faso.
J Infect Dis. 2008 Jul 15;198(2):241-9. doi: 10.1086/589621.
Few longitudinal studies have described the interactions between reactivation of herpes simplex virus type 2 (HSV-2) infection (hereafter, "HSV-2 reactivation") and genital and systemic replication of human immunodeficiency virus type 1 (HIV-1).
Women in Burkina Faso who were seropositive for both HIV-1 and HSV-2 were enrolled in a randomized placebo-controlled trial of therapy to suppress reactivation of HSV-2 infection (hereafter, "HSV suppressive therapy"). During the baseline phase, 6 enriched cervicovaginal lavage specimens were obtained over 12 weeks to detect and quantify the HIV-1 RNA and HSV-2 DNA loads.
Women with genital ulcer disease (GUD) detected at least once were more likely than women in whom GUD was not detected (risk ratio [RR], 1.23; 95% confidence interval [CI], 1.09-1.37) to have genital HIV-1 RNA detected during >or=1 visit. Similarly, women with genital HSV-2 DNA detected during >or=1 clinic visit were more likely than women in whom genital HSV-2 DNA was not detected (RR, 1.17; 95% CI, 1.01-1.34) to have genital HIV-1 RNA detected at least once. In addition, the mean genital HIV-1 RNA loads for women with GUD detected during >or=1 visit and women with HSV-2 genital shedding detected during >or=1 visit were greater than that for women in whom genital HSV-2 DNA or GUD was never detected. The plasma HIV-1 RNA load was increased among women for whom >or=1 visit revealed GUD (+0.25 log(10) copies/mL; 95% CI, -0.05-0.55) or genital HSV-2 DNA (+0.40 log(10) copies/mL; 95% CI, 0.15-0.66), compared with women who did not experience GUD or HSV-2 genital shedding, respectively. The association of HSV-2 reactivations on HIV-1 replication tended to be stronger in patients with a higher CD4(+) cell count (i.e., >500 cells/microL). The contribution of HSV-2 to HIV-1 replication among women with CD4(+) cell count of <or=500 cells/microL was reduced because almost all experienced HIV-1 genital shedding.
Both clinical and subclinical HSV-2 reactivations play a role in increasing the rate of HIV-1 replication. HSV suppressive therapy is a promising tool for HIV control. Initiation of such therapy when the CD4(+) cell count is >500 cells/microL deserves further investigation.
The ANRS 1285 Study is registered with the National Institutes of Health (registration number NCT00158509).
很少有纵向研究描述2型单纯疱疹病毒（HSV-2）感染再激活（以下简称“HSV-2再激活”）与人免疫缺陷病毒1型（HIV-1）的生殖器及全身复制之间的相互作用。
布基纳法索中HIV-1和HSV-2血清学均呈阳性的女性参加了一项抑制HSV-2感染再激活（以下简称“HSV抑制疗法”）的随机安慰剂对照治疗试验。在基线期，在12周内采集6份富集的宫颈阴道灌洗标本，以检测和定量HIV-1 RNA及HSV-2 DNA载量。
至少有一次检测到患有生殖器溃疡疾病（GUD）的女性比未检测到GUD的女性在≥1次就诊时检测到生殖器HIV-1 RNA的可能性更高（风险比[RR]，1.23；95%置信区间[CI]，1.09 - 1.37）。同样，在≥1次门诊就诊时检测到生殖器HSV-2 DNA的女性比未检测到生殖器HSV-2 DNA的女性至少有一次检测到生殖器HIV-1 RNA的可能性更高（RR，1.17；95% CI，1.01 - 1.34）。此外，≥1次就诊时检测到GUD的女性以及≥1次就诊时检测到HSV-2生殖器脱落的女性的平均生殖器HIV-1 RNA载量高于从未检测到生殖器HSV-2 DNA或GUD的女性。对于分别有≥1次就诊显示有GUD（+0.25 log₁₀拷贝/mL；95% CI， - 0.05 - 0.55）或生殖器HSV-2 DNA（+0.40 log₁₀拷贝/mL；95% CI，0.15 - 0.66）的女性，其血浆HIV-1 RNA载量增加，而未经历GUD或HSV-2生殖器脱落的女性则无此情况。在CD4⁺细胞计数较高（即>500个细胞/μL）的患者中，HSV-2再激活与HIV-1复制之间的关联往往更强。在CD4⁺细胞计数≤500个细胞/μL的女性中，HSV-2对HIV-1复制的作用降低，因为几乎所有人都经历了HIV-1生殖器脱落。
临床和亚临床HSV-2再激活均在增加HIV-1复制率方面发挥作用。HSV抑制疗法是控制HIV的一种有前景的工具。当CD4⁺细胞计数>500个细胞/μL时开始这种治疗值得进一步研究。
ANRS 1285研究已在美国国立卫生研究院注册（注册号NCT00158509）。
