Classical Sexually Transmitted Diseases Drive the Spread of HIV-1: Back to the Future

Abstract

The transmission of human immunodeficiency virus type 1 (HIV-1) depends on the infectiousness of the index case (ie, vector) and the susceptibility of the host [1]. The probability of the transmission event has been extensively studied [1–3], and the risk is often described as about 1 in 1000 coital events [4]. However, large numbers of exposures like these are often derived from studies of stable, heterosexual, discordant couples [4, 5]. By definition, the HIV-1–negative partners in these couples can be defined as “exposed and uninfected” at the time of enrollment. The transmission of HIV-1 is almost certainly often more efficient than reflected in studies of couples and is likely enhanced by amplifying factors [6]. Perhaps no other HIV transmission cofactor has attracted as much attention as sexually transmitted diseases (STDs). More than 20 years ago, Wasserheit and colleagues described the transparent and omnipresent relationship between classical STDs and HIV-1, coining this unfortunate marriage of pathogens “epidemiologic synergy” [7].We subsequently showed that infection with Neisseria gonorrhoeae greatly increased shedding of HIV-1from the male genital tract in seminal plasma, offering a biological view of such synergy [8]. In recent years, however, interest in the relationship between STDs and HIV-1 has waned, primarily because it has proven nearly impossible to reduce the spread of HIV-1 through directed or empirical treatment of STDs [9]. In this issue of The Journal of Infectious Diseases, Mlisana et al [10] contribute to this consideration. Because of the limited laboratory infrastructure in lowand middle-income countries, treatment of STDs in women often depends on the recognition of signs and symptoms of vaginal discharge, leading to empirical treatment with antibiotics [11, 12]. Syndromic management is important but often suboptimal since a substantial number of people using this method are overor undertreated [11, 12]. Mlisana and colleagues [10] have further expanded our concerns about syndromic management. Two-hundred forty-two women at risk for HIV-1 infection were enrolled in a prospective cohort. Four things were measured: the presence or absence of a vaginal discharge, detection of ≥1 STD pathogens, vaginal cytokine concentrations, and HIV-1 acquisition. The results offered a stark reality for HIV-1 prevention and demonstrate yet again that STDs represent a “hidden epidemic,” the title of a compelling Institute of Medicine report published more than a decade ago [13]. Only 12.3% of women infected with a pathogen that might cause a vaginal discharge had signs or symptoms of infection. Women with STDs were >3-fold more likely to acquire HIV-1 than those who harbored no pathogens. Women with gonococcal infections, among the most inflammatory of the classical STD agents [14], had had an eye-opening 7fold increased risk of HIV-1 acquisition, bringing us full circle to earlier reports [8]. Surprisingly, inflammatory cytokines were not significantly different in women with symptomatic STDs, compared with asymptomatic infections, although they were greater than in women with no STDs or with bacterial vaginosis. Passmore et al [15] have reported that some unique inflammatory cytokine profiles predict risk for HIV acquisition. How can we fit these observations into sensible HIV-1 prevention strategies? Padian et al [9] have provided an exhaustive summary of interventions designed to prevent HIV-1 transmission, emphasizing the general lack of prevention benefit with treatment of classical STDs. The failure of this approach, in my opinion, is not because STDs are not critically important. Rather, we are simply unable to treat the right infections with the right drugs at the right times, and so the results of the interventions prove disappointing. Sadly, except for hepatitis B virus vaccine and HPV vaccine, STD vaccines are not available. Received 10 February 2012; accepted 13 February 2012; electronically published 19 April 2012. Correspondence: Myron S. Cohen, MD, 130 Mason Farm Rd, CB 7030, University of North Carolina, Chapel Hill, NC 27599-7030 (mscohen@med.unc.edu). The Journal of Infectious Diseases 2012;206:1–2 © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@ oup.com. DOI: 10.1093/infdis/jis303