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|Title: ||Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2.|
|Authors: ||Wang, R.S.|
de Bruyn, G.
Transmission of HIV 1.
|Issue Date: ||20-Jan-2010 |
|Publisher: ||Massachusetts Medical Society|
|Citation: ||Wang, R.S., Mugo, N., Mujugira, A., Celum, C., Wald, A., Lingappa, J.R., Baeten, J.M., Mullins, J.I., Hughes, J.P., Katabira, E.T., Ronald, A., Kiarie, J., Farquhar, C., Stewart, G.J., Makhema, J., Essex, M., Were, E., Fife, K.H., de Bruyn, G., Gray, G.E., McIntyre, J.A., Manongi, R., Kapiga, S., Coetzee, D., Allen, S., Corey, L., Karita, E. (2010). Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2. New England Journal of Medicine|
|Abstract: ||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 log10 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.|
|Appears in Collections:||Research Articles (Health-Sciences)|
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