Daily acyclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial.
Daily acyclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial.
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DOI：
10.1016/s0140-6736(09)62038-9
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发表时间：
2010-03-06
期刊：
影响因子：
168.9
通讯作者：
Celum, Connie
中科院分区：
文献类型：
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作者：
Lingappa, Jairam R.;Baeten, Jared M.;Wald, Anna;Hughes, James P.;Thomas, Katherine K.;Mujugira, Andrew;Mugo, Nelly;Bukusi, Elizabeth A.;Cohen, Craig R.;Katabira, Elly;Ronald, Allan;Kiarie, James;Farquhar, Carey;Stewart, Grace John;Makhema, Joseph;Essex, Myron;Were, Edwin;Fife, Kenneth H.;de Bruyn, Guy;Gray, Glenda E.;McIntyre, James A.;Manongi, Rachel;Kapiga, Saidi;Coetzee, David;Allen, Susan;Inambao, Mubiana;Kayitenkore, Kayitesi;Karita, Etienne;Kanweka, William;Delany, Sinead;Rees, Helen;Vwalika, Bellington;Magaret, Amalia S.;Wang, Richard S.;Kidoguchi, Lora;Barnes, Linda;Ridzon, Renee;Corey, Lawrence;Celum, Connie
需要耐受性良好的药物来减缓 HIV-1 疾病进展并延迟抗逆转录病毒治疗 (ART) 的开始。大多数 HIV-1 感染者双重感染 2 型单纯疱疹病毒 (HSV-2)。每日 HSV-2 抑制可降低血浆 HIV-1 水平，但 HSV-2 抑制是否会延缓 HIV-1 疾病进展尚不清楚。在一项旨在减少 HIV-1 传播的 HSV-2 抑制治疗（阿昔洛韦 400 毫克，每日两次）的随机、安慰剂对照试验中，对 3381 名 HSV-2/HIV-1 双重感染的非洲异性恋患者进行了长达 24 个月的随访，这些非洲人在入组时 CD4 计数≥250 个细胞/mm3，且未接受 ART。我们评估了阿昔洛韦对 HIV-1 疾病进展的影响，定义为首次出现 CD4 计数<200 个细胞/mm3、开始 ART 或非创伤相关死亡的主要复合终点。作为一项探索性分析，我们评估了 CD4 下降至 <350 个细胞/mm3 的终点。入组时，CD4 中位数为 462 个细胞/mm3，HIV-1 血浆 RNA 中位数为 4.1 log10 拷贝/mL。阿昔洛韦降低了 HIV-1 疾病进展的风险：使用阿昔洛韦的 284 名参与者与使用安慰剂的 324 名参与者达到了主要终点（风险比 [HR] 0.84，95% 置信区间 [CI] 0.71–0.98，p=0.03）。在 CD4 计数≥350 个细胞/mm3 的参与者中，阿昔洛韦可延迟 CD4 下降至 <350 个细胞/mm3 的风险（HR 0.81，95% CI 0.71-0.93，p=0.002）。使用阿昔洛韦抑制 HSV-2 可将 HIV-1 疾病进展的风险降低 16%（95% CI 2-29%）。在开始 ART 之前抑制 HSV-2 在减少 HIV-1 疾病进展方面的作用值得考虑 (ClinicalTrials.gov #NCT00194519)。
Well-tolerated medications that slow HIV-1 disease progression and delay initiation of antiretroviral therapy (ART) are needed. Most HIV-1-infected persons are dually-infected with herpes simplex virus type 2 (HSV-2). Daily HSV-2 suppression reduces plasma HIV-1 levels, but whether HSV-2 suppression delays HIV-1 disease progression is unknown. Within a randomized, placebo-controlled trial of HSV-2 suppressive therapy (acyclovir 400 mg orally bid) to decrease HIV-1 transmission, 3381 HSV-2/HIV-1 dually-infected heterosexual Africans who at enrollment had CD4 counts ≥250 cells/mm3 and were not taking ART were followed for up to 24 months. We evaluated the effect of acyclovir on HIV-1 disease progression, defined by a primary composite endpoint of first occurrence of CD4 count <200 cells/mm3, ART initiation, or non-trauma related death. As an exploratory analysis, we evaluated the endpoint of CD4 decline to <350 cells/mm3. At enrollment, median CD4 was 462 cells/mm3 and median HIV-1 plasma RNA was 4.1 log10 copies/mL. Acyclovir reduced risk of HIV-1 disease progression: 284 participants on acyclovir versus 324 on placebo reached the primary endpoint (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.71–0.98, p=0.03). Among participants with CD4 counts ≥350 cells/mm3, acyclovir delayed risk of CD4 decline to <350 cells/mm3 (HR 0.81, 95% CI 0.71–0.93, p=0.002). HSV-2 suppression with acyclovir reduced the risk of HIV-1 disease progression by 16% (95% CI 2–29%). The role of HSV-2 suppression in reducing HIV-1 disease progression prior to ART initiation warrants consideration (ClinicalTrials.gov #NCT00194519).