Coitus

We enrolled heterosexual couples in which only one of the partners was seropositive for HIV-1 and that partner was also infected with HSV-2. Couples were recruited at seven sites in southern Africa (Gaborone, Botswana; Gugulethu, Orange Farm, and Soweto in South Africa; and Kitwe, Lusaka, and Ndola in Zambia) and seven sites in East Africa (Eldoret, Kisumu, Nairobi, and Thika in Kenya; Kigali, Rwanda; Moshi, Tanzania; and Kampala, Uganda) between November 2004 and April 2007, as previously described.18 (link) The inclusion criteria for couples were three or more episodes of vaginal intercourse in the 3 previous months and the intention to remain together for at least 24 months. The inclusion criteria for partners infected with HIV-1 were an age of at least 18 years, seropositivity for HIV-1 and HSV-2, a CD4 count of 250 or more cells per cubic millimeter, no conditions associated with acquired immunodeficiency syndrome, and no current antiretroviral therapy. Exclusion criteria for persons infected with HIV-1 were previous adverse reactions to acyclovir, current receipt of therapy for HSV, persistent genital ulcers, current participation in another study, plans for extended travel, and current pregnancy. Inclusion criteria for partners who were not infected with HIV-1 were an age of at least 18 years and HIV-1 seronegativity; the partners who were not infected with HIV-1 could be eligible whether they were seropositive or seronegative for HSV-2.
The protocol was approved by the University of Washington Human Subjects Review Committee and the ethics review committees at all local and collaborating organizations. All study participants provided written informed consent in English or their local language. The Bill and Melinda Gates Foundation funded the study but did not assume responsibility for review of the protocol. The authors designed the study, wrote the protocol, had full access to the raw data, performed all analyses, wrote the manuscript, and had final responsibility for the decision to submit the manuscript for publication.

Participants were instructed to take the study medication daily as randomized, 81 mg aspirin (LDA) or a placebo tablet, throughout six cycles or if pregnant until week 36 of pregnancy. Placebo tablets were manufactured to match on size, color, taste, and weight. The first batch of medication, capsules manufactured by Fisher (Rockville, MD) were difficult to swallow and over-coated tablets were produced for the second, third, and fourth batches by UPM pharmaceutical, Baltimore, MD. All women also received daily 400 mcg folic acid (generic). All received fertility monitors to assist in timing of intercourse (ClearBlue).