Acyclovir and Transmission of HIV-1 from Persons Infected with HIV-1 and HSV-2

被引：391

作者：

Celum, C. ^{[1
,2
,3
]}

Wald, A. ^{[2
,3
,4
,8
]}

Lingappa, J. R. ^{[3
,6
]}

Magaret, A. S. ^{[4
,8
]}

Wang, R. S.

Mugo, N. ^{[10
,11
]}

Mujugira, A.

Baeten, J. M. ^{[3
]}

Mullins, J. I. ^{[3
,4
,5
]}

Hughes, J. P. ^{[7
]}

Bukusi, E. A. ^{[10
,11
,12
]}

Cohen, C. R. ^{[14
]}

Katabira, E. ^{[15
]}

Ronald, A. ^{[16
]}

Kiarie, J. ^{[10
,11
]}

Farquhar, C. ^{[2
,3
]}

Stewart, G. J. ^{[2
,3
]}

Makhema, J. ^{[17
]}

Essex, M. ^{[18
]}

Were, E. ^{[13
]}

Fife, K. H. ^{[19
]}

de Bruyn, G. ^{[20
]}

Gray, G. E. ^{[20
]}

McIntyre, J. A. ^{[20
]}

Manongi, R. ^{[24
]}

Kapiga, S. ^{[24
,25
]}

Coetzee, D. ^{[23
]}

Allen, S. ^{[26
,27
,28
]}

Inambao, M. ^{[26
,27
,28
]}

Kayitenkore, K. ^{[26
,27
,28
]}

Karita, E. ^{[26
,27
,28
]}

Kanweka, W. ^{[26
,27
,28
]}

Delany, S. ^{[21
]}

Rees, H. ^{[21
]}

Vwalika, B. ^{[26
,27
,28
]}

Stevens, W. ^{[22
]}

Campbell, M. S. ^{[3
]}

Thomas, K. K. ^{[3
]}

Coombs, R. W. ^{[3
,4
]}

Morrow, R. ^{[4
]}

Whittington, W. L. H. ^{[3
]}

McElrath, M. J. ^{[3
,8
]}

Barnes, L.

Ridzon, R. ^{[9
]}

Corey, L. ^{[3
,4
,8
]}

机构：

[1] Univ Washington, Harborview Med Ctr, Dept Global Hlth, Seattle, WA 98104 USA

[2] Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA

[3] Univ Washington, Dept Med, Seattle, WA 98104 USA

[4] Univ Washington, Dept Lab Med, Seattle, WA 98104 USA

[5] Univ Washington, Dept Microbiol, Seattle, WA 98104 USA

[6] Univ Washington, Dept Pediat, Seattle, WA 98104 USA

[7] Univ Washington, Dept Biostat, Seattle, WA 98104 USA

[8] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Seattle, WA 98104 USA

[9] Fred Hutchinson Canc Res Ctr, Bill & Melinda Gates Fdn, Seattle, WA 98104 USA

[10] Univ Nairobi, Dept Obstet & Gynecol, Nairobi, Kenya

[11] Kenyatta Natl Hosp, Nairobi, Kenya

[12] Kenya Govt Med Res Ctr, Ctr Microbiol Res, Nairobi, Kenya

[13] Moi Univ, Dept Reprod Hlth, Eldoret, Kenya

[14] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA

[15] Makerere Univ, Infect Dis Inst, Kampala, Uganda

[16] Univ Manitoba, Dept Med, Winnipeg, MB, Canada

[17] Botswana Harvard Partnership, Gaborone, Botswana

[18] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA

[19] Indiana Univ, Dept Med, Indianapolis, IN USA

[20] Univ Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South Africa

[21] Univ Witwatersrand, Reprod Hlth & HIV Res Unit, Johannesburg, South Africa

[22] Univ Witwatersrand, Contract Lab Serv, Johannesburg, South Africa

[23] Univ Cape Town, Infect Dis Epidemiol Unit, ZA-7925 Cape Town, South Africa

[24] Kilimanjaro Christian Med Ctr, Moshi, Tanzania

[25] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London, England

[26] Rwanda Zambia HIV Res Grp, Atlanta, GA USA

[27] Emory Univ, Sch Med, Atlanta, GA USA

[28] Emory Univ, Sch Publ Hlth, Atlanta, GA USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2010年 / 362卷 / 05期

关键词：

HERPES-SIMPLEX-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; PLACEBO-CONTROLLED TRIAL; DISCORDANT COUPLES; CLINICAL-TRIALS; DOUBLE-BLIND; TYPE-1; WOMEN; SUPPRESSION; PLASMA;

D O I：

10.1056/NEJMoa0904849

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

BACKGROUND Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1. METHODS We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, >= 250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses. RESULTS A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization ( an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group ( hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P = 0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log(10) copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2-positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed. CONCLUSIONS Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log10 copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2.

引用

页码：427 / 439

页数：13

共 33 条

[1]

Herpes Simplex Virus (HSV)-Suppressive Therapy Decreases Plasma and Genital HIV-1 Levels in HSV-2/HIV-1 Coinfected Women: A Randomized, Placebo-Controlled, Cross-Over Trial [J].