Syphilis predicts HIV incidence among men and transgender women who have sex with men in a preexposure prophylaxis trial

Marc M Solomon, Kenneth H Mayer, David V Glidden, Albert Y Liu, Vanessa M McMahan, Juan V Guanira, Suwat Chariyalertsak, Telmo Fernandez, Robert M Grant, iPrEx Study Team, Marc M Solomon, Kenneth H Mayer, David V Glidden, Albert Y Liu, Vanessa M McMahan, Juan V Guanira, Suwat Chariyalertsak, Telmo Fernandez, Robert M Grant, iPrEx Study Team

Abstract

Background: Syphilis infection may potentiate transmission of human immunodeficiency virus (HIV). We sought to determine the extent to which HIV acquisition was associated with syphilis infection within an HIV preexposure prophylaxis (PrEP) trial and whether emtricitabine/tenofovir (FTC/TDF) modified that association.

Methods: The Preexposure Prophylaxis Initiative (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily FTC/TDF or placebo. Syphilis prevalence at screening and incidence during follow-up were measured. Hazard ratios for the effect of incident syphilis on HIV acquisition were calculated. The effect of FTC/TDF on incident syphilis and HIV acquisition was assessed.

Results: Of 2499 individuals, 360 (14.4%) had a positive rapid plasma reagin test at screening; 333 (92.5%) had a positive confirmatory test, which did not differ between the arms (FTC/TDF vs placebo, P = .81). The overall syphilis incidence during the trial was 7.3 cases per 100 person-years. There was no difference in syphilis incidence between the study arms (7.8 cases per 100 person-years for FTC/TDF vs 6.8 cases per 100 person-years for placebo, P = .304). HIV incidence varied by incident syphilis (2.8 cases per 100 person-years for no syphilis vs 8.0 cases per 100 person-years for incident syphilis), reflecting a hazard ratio of 2.6 (95% confidence interval, 1.6-4.4; P < .001). There was no evidence for interaction between randomization to the FTC/TDF arm and incident syphilis on HIV incidence.

Conclusions: In HIV-seronegative MSM, syphilis infection was associated with HIV acquisition in this PrEP trial; a syphilis diagnosis should prompt providers to offer PrEP unless otherwise contraindicated.

Keywords: HIV prevention; MSM; chemoprophylaxis; preexposure prophylaxis; syphilis.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Human immunodeficiency virus (HIV) incidence according to incident syphilis and treatment arm. Abbreviation: FTC/TDF, emtricitabine/tenofovir.

References

    1. World Health Organization . Global incidence and prevalence of selected curable sexually transmitted infections—2008. Geneva, Switzerland: WHO; 2012.
    1. Sexton J, Garnett G, Rottingen JA. Metaanalysis and metaregression in interpreting study variability in the impact of sexually transmitted diseases on susceptibility to HIV infection. Sex Transm Dis. 2005;32:351–7.
    1. Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect. 1999;75:3–17.
    1. Dickerson MC, Johnston J, Delea TE, White A, Andrews E. The causal role for genital ulcer disease as a risk factor for transmission of human immunodeficiency virus. An application of the Bradford Hill criteria. Sex Transm Dis. 1996;23:429–40.
    1. Clottey C, Dallabetta G. Sexually transmitted diseases and human immunodeficiency virus. Epidemiologic synergy? Infect Dis Clin North Am. 1993;7:753–70.
    1. Wasserheit JN. Epidemiological synergy. Interrelationships between human immunodeficiency virus infection and other sexually transmitted diseases. Sex Transm Dis. 1992;19:61–77.
    1. Mertens TE, Hayes RJ, Smith PG. Epidemiological methods to study the interaction between HIV infection and other sexually transmitted diseases. AIDS. 1990;4:57–65.
    1. Cameron DW, Padian NS. Sexual transmission of HIV and the epidemiology of other sexually transmitted diseases. AIDS. 1990;4(suppl 1):S99–103.
    1. Fox J, Fidler S. Sexual transmission of HIV-1. Antiviral Res. 2010;85:276–85.
    1. Ward H, Ronn M. Contribution of sexually transmitted infections to the sexual transmission of HIV. Curr Opin HIV AIDS. 2010;5:305–10.
    1. Jarzebowski W, Caumes E, Dupin N, et al. Effect of early syphilis infection on plasma viral load and CD4 cell count in human immunodeficiency virus-infected men: results from the FHDH-ANRS CO4 cohort. Arch Intern Med. 2012;172:1237–43.
    1. Buchacz K, Klausner JD, Kerndt PR, et al. HIV incidence among men diagnosed with early syphilis in Atlanta, San Francisco, and Los Angeles, 2004 to 2005. J Acquir Immune Defic Syndr. 2008;47:234–40.
    1. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363:2587–99.
    1. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367:399–410.
    1. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012;367:423–34.
    1. Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2013;381:2083–90.
    1. Duwal S, Schutte C, von Kleist M. Pharmacokinetics and pharmacodynamics of the reverse transcriptase inhibitor tenofovir and prophylactic efficacy against HIV-1 infection. PLoS One. 2012;7:e40382.
    1. Anderson PL, Glidden DV, Liu A, et al. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med. 2012;4:151ra25.
    1. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2006. Atlanta, GA: CDC; 2006.
    1. Aynalem G, Smith L, Bemis C, Taylor M, Hawkins K, Kerndt P. Commercial sex venues: a closer look at their impact on the syphilis and HIV epidemics among men who have sex with men. Sex Transm Infect. 2006;82:439–43.
    1. Bernstein KT, Marcus JL, Nieri G, Philip SS, Klausner JD. Rectal gonorrhea and chlamydia reinfection is associated with increased risk of HIV seroconversion. J Acquir Immune Defic Syndr. 2010;53:537–43.
    1. Feng Y, Wu Z, Detels R, et al. HIV/STD prevalence among men who have sex with men in Chengdu, China and associated risk factors for HIV infection. J Acquir Immune Defic Syndr. 2010;53(suppl 1):S74–80.
    1. Hope-Rapp E, Anyfantakis V, Fouere S, et al. Etiology of genital ulcer disease. A prospective study of 278 cases seen in an STD clinic in Paris. Sex Transm Dis. 2010;37:153–8.
    1. Huhn GD, McIntyre AF, Broad JM, et al. Factors associated with newly diagnosed HIV among persons with concomitant sexually transmitted diseases. Sex Transm Dis. 2008;35:731–7.
    1. Katz KA, Lee MA, Gray T, Marcus JL, Pierce EF. Repeat syphilis among men who have sex with men—San Diego County, 2004–2009. Sex Transm Dis. 2011;38:349–52.
    1. Scott KC, Philip S, Ahrens K, Kent CK, Klausner JD. High prevalence of gonococcal and chlamydial infection in men who have sex with men with newly diagnosed HIV infection: an opportunity for same-day presumptive treatment. J Acquir Immune Defic Syndr. 2008;48:109–12.
    1. Torrone EA, Bertolli J, Li J, et al. Increased HIV and primary and secondary syphilis diagnoses among young men—United States, 2004–2008. J Acquir Immune Defic Syndr. 2011;58:328–35.
    1. Wilkinson D, Rutherford G. Population-based interventions for reducing sexually transmitted infections, including HIV infection. Cochrane Database Syst Rev. 2001 CD001220.
    1. World Health Organization. Data on other STIs: men who have sex with men (MSM) with active syphilis by country. Available at: . Accessed 14 April 2014.
    1. Centers for Disease Control and Prevention. STDs in men who have sex with men. Available at: . Accessed 14 April 2014.
    1. Pinkerton SD. Sexual risk compensation and HIV/STD transmission: empirical evidence and theoretical considerations. Risk Anal. 2001;21:727–36.
    1. Cassell MM, Halperin DT, Shelton JD, Stanton D. Risk compensation: the Achilles’ heel of innovations in HIV prevention? BMJ. 2006;332:605–7.
    1. Blower SM, McLean AR. Prophylactic vaccines, risk behavior change, and the probability of eradicating HIV in San Francisco. Science. 1994;265:1451–4.
    1. Marcus JL, Glidden DV, Mayer KH, et al. No evidence of sexual risk compensation in the iPrEx trial of daily oral HIV preexposure prophylaxis. PLoS One. 2013;8:e81997.
    1. Workowski KA, Berman S. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010;59:1–110.
    1. Gilead Sciences. Highlights of prescribing information. Available at: . Accessed 14 April 2014.
    1. Centers for Disease Control and Prevention. Interim guidance for clinicians considering the use of preexposure prophylaxis for the prevention of HIV infection in heterosexually active adults. MMWR Morb Mortal Wkly Rep. 2012;61:586–9.
    1. Centers for Disease Control and Prevention. Interim guidance: preexposure prophylaxis for the prevention of HIV infection in men who have sex with men. MMWR Morb Mortal Wkly Rep. 2011;60:65–8.
    1. Buchbinder SP, Glidden DV, Liu AY, et al. HIV pre-exposure prophylaxis in men who have sex with men and transgender women: a secondary analysis of a phase 3 randomised controlled efficacy trial. Lancet Infect Dis. 2014;14:468–75.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi