Biomaterial Database

Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2. 2010

C Celum, and A Wald, and J R Lingappa, and A S Magaret, and R S Wang, and N Mugo, and A Mujugira, and J M Baeten, and J I Mullins, and J P Hughes, and E A Bukusi, and C R Cohen, and E Katabira, and A Ronald, and J Kiarie, and C Farquhar, and G J Stewart, and J Makhema, and M Essex, and E Were, and K H Fife, and G de Bruyn, and G E Gray, and J A McIntyre, and R Manongi, and S Kapiga, and D Coetzee, and S Allen, and M Inambao, and K Kayitenkore, and E Karita, and W Kanweka, and S Delany, and H Rees, and B Vwalika, and W Stevens, and M S Campbell, and K K Thomas, and R W Coombs, and R Morrow, and W L H Whittington, and M J McElrath, and L Barnes, and R Ridzon, and L Corey, and

Department of Global Health, University of Washington, Harborview Medical Center, 325 Ninth Ave., Box 359927, Seattle, WA 98104, USA.

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, > or = 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 log(10) copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.)

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010349	Patient Compliance	Voluntary cooperation of the patient in following a prescribed regimen.	Client Adherence,Client Compliance,Non-Adherent Patient,Patient Adherence,Patient Cooperation,Patient Noncompliance,Patient Non-Adherence,Patient Non-Compliance,Patient Nonadherence,Therapeutic Compliance,Treatment Compliance,Adherence, Client,Adherence, Patient,Client Compliances,Compliance, Client,Compliance, Patient,Compliance, Therapeutic,Compliance, Treatment,Cooperation, Patient,Non Adherent Patient,Non-Adherence, Patient,Non-Adherent Patients,Non-Compliance, Patient,Nonadherence, Patient,Noncompliance, Patient,Patient Non Adherence,Patient Non Compliance,Patient, Non-Adherent,Therapeutic Compliances,Treatment Compliances
D011247	Pregnancy	The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	Gestation,Pregnancies
D005260	Female		Females
D005500	Follow-Up Studies	Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.	Followup Studies,Follow Up Studies,Follow-Up Study,Followup Study,Studies, Follow-Up,Studies, Followup,Study, Follow-Up,Study, Followup
D006558	Herpes Genitalis	Infection of the genitals (GENITALIA) with HERPES SIMPLEX VIRUS in either the males or the females.	Genital Herpes,Herpes Simplex, Genital,Herpes Simplex Virus Genital Infection,Genital Herpes Simplex,Herpes, Genital
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000212	Acyclovir	A GUANOSINE analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.	Acycloguanosine,9-((2-Hydroxyethoxy)methyl)guanine,Aci-Sanorania,Acic,Aciclobeta,Aciclostad,Aciclovir,Aciclovir Alonga,Aciclovir-Sanorania,Acifur,Acipen Solutab,Acivir,Activir,Acyclo-V,Acyclovir Sodium,Antiherpes Creme,Avirax,Cicloferon,Clonorax,Cusiviral,Genvir,Herpetad,Herpofug,Herpotern,Herpoviric,Isavir,Laciken,Mapox,Maynar,Milavir,Opthavir,Supraviran,Viclovir,Vipral,Virax-Puren,Virherpes,Virmen,Virolex,Virupos,Virzin,Wellcome-248U,Zoliparin,Zovirax,Zyclir,aciclovir von ct,Aci Sanorania,Aciclovir Sanorania,Acyclo V,Alonga, Aciclovir,Sodium, Acyclovir,Solutab, Acipen,Virax Puren,ViraxPuren,Wellcome 248U,Wellcome248U
D000293	Adolescent	A person 13 to 18 years of age.	Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults