Insertive condom-protected and condomless vaginal sex both have a profound impact on the penile immune correlates of HIV susceptibility.

Avid Mohammadi,Sara V Good,Zhongtian Shao,Azadeh Fazel,Jessica L Prodger,Wangari Tharao,Sanja Huibner,Yoojin Choi,Sareh Bagherichimeh,David Zuanazzi,Rupert Kaul,Elizabeth Tevlin

doi:10.1371/journal.ppat.1009948

Abstract

The penis is the primary site of HIV acquisition in heterosexual men. Elevated penile inflammatory cytokines increase sexual acquisition risk, and topically applied cytokines enhance foreskin HIV susceptibility in an explant model. However, the impact of penile-vaginal sex on these immune parameters is undefined. Heterosexual couples were recruited to the Sex, Couples and Science (SECS) Study, with the collection of penile swabs, semen, cervico-vaginal secretions, and blood after a period of abstinence, and repeated sampling up to 72 hours after either condomless (n = 30) or condom-protected (n = 8) penile-vaginal sex. Soluble immune parameters were quantified by multiplex immunoassay. Co-primary immune endpoints were penile levels of IL-8 and MIG, cytokines previously linked to penile HIV acquisition. One hour after sex there were dramatic increases in penile IL-8 and MIG levels, regardless of condom use, with a gradual return to baseline by 72 hours; similar patterns were observed for other chemoattractant chemokines. Penile cytokine changes were similar in circumcised and uncircumcised men, and repeated measures ANOVA and ANCOVA models demonstrated that the degree of change after condomless sex was explained by cytokine levels in their partners' cervico-vaginal secretions. This may have important implications for the biology of penile HIV acquisition.

Highlights

Global Human Immunodeficiency Virus (HIV) incidence remains high, with relatively few prevention strategies targeting heterosexual men
The penis is the primary site of Human Immunodeficiency Virus (HIV) acquisition
Eligible couples abstained from sex for at least 48 hours prior to the baseline sampling visit, as indicated by both self-report and a lack of Prostate Specific Antigen (PSA) in vaginal secretions, and abstained again for 48 hours prior to engaging in penile-vaginal sex and undergoing longitudinal post-coital sampling

Summary

Introduction

Global HIV incidence remains high, with relatively few prevention strategies targeting heterosexual men. While the risk of penile HIV acquisition after condomless insertive vaginal sex with an HIV-infected, antiretroviral-naïve female sexual partner is less than 1/1000, this risk varies considerably based on a number of biological factors [3]. Important determinants of transmission risk from an HIV-infected female partner are the viral load in vaginal secretions and blood, and the presence of bacterial vaginosis (BV) [4,5,6]. In an HIV-uninfected male partner, risk factors for penile acquisition include the presence of a foreskin, penile microbiome dysbiosis and/or a sexually transmitted infection (STI) [7,8,9,10]. The common central pathway through which these biological factors enhance transmission is the induction of inflammation in the genital tract, which causes increased HIV RNA shedding in the vagina and a higher density of HIV target cells in penile tissues, as well as reducing epithelial barrier integrity at both sites [11]

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