Effect of antiretroviral prophylaxis on gene expression in peripheral blood mononuclear cells

It is important to understand how, if at all, antiretroviral prophylaxis with tenofovir disoproxil fumarate (TDF) alone or TDF in conjunction with emtricitabine (FTC) affects gene expression. To ask this question, we used cryopreserved peripheral blood mononuclear cells (PBMC) from women enrolled in the Genital Mucosal Substudy (GMS) [1] of the Partners PrEP Study (NCT02621242) [2]. Partners PrEP was a randomized Phase III trial of oral TDF or TDF/FTC compared to placebo, which showed that either active drug was effective at protecting against HIV-1 infection. Samples were unpaired, with one sample per person, after 24-36 months of oral treatment with placebo, TDF, or TDF/FTC. Treatment adherence was based on plasma TDF concentrations. Covariates included Nugent scores (for bacterial vaginosis), HSV-2 serology, age, and birth control method. Levels of natural and synthetic hormones (medroxyprogesterone acetate [MPA], estradiol [E2], ethinyl estradiol [EE2], levonorgestrel [LNG], etonogestrel [ENG], progesterone [P4], and norethisterone enanthate [NET-EN]) were measured in the serum. 1. Lund, J. M. et al. HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV-1-Exposed Seronegative Women on Oral Preexposure Prophylaxis. J. Virol. 90, 9855–9861 (2016). 2. Baeten, J. M. et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N. Engl. J. Med. 367, 399–410 (2012). Gene expression was measured by Illumina HumanHT-12 v4 Expression BeadChips. Samples were unpaired, with one sample per person, after 24-36 months of oral treatment with placebo, TDF, or TDF/FTC. Samples from the drug arms were excluded if the TDF concentration was below the limit of detection. The final sample sizes were 20 placebo, 36 TDF, and 26 TDF/FTC. Samples were not replicated on the arrays.