Diagnosis of syphilis as an entry point for PrEP initiation among men who have sex with men

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

Solomon MM, Mayer KH, Glidden DV, Liu AY, McMahan VM, Guanira JV, Chariyalertsak S, Fernandez T, Grant RM, iPrEx Study Team. Clin Infect Dis. 2014 Oct;59(7):1020-6. doi: 10.1093/cid/ciu450. Epub 2014 Jun 13.

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.

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Editor’s notes: The Preexposure Prophylaxis Initiative (iPrEx) trial and other recent trials have illustrated clearly that preexposure prophylaxis (PrEP) with emtricitabine/tenofovir (FTC/TDF) dramatically reduces the risk of HIV when used correctly and consistently. There is current discussion about the practical implications of these findings. This paper confirms a strong association between incident syphilis and HIV acquisition among men who have sex with men (MSM), and illustrates that syphilis did not attenuate the protective benefit of FTC/TDF against HIV. Syphilis continues to be prevalent among MSM in many settings, and the screening prevalence of 13% in this study is consistent with global estimates. These results highlight that individuals with syphilis are a key group for HIV acquisition. The results suggest that a new diagnosis of syphilis is an important opportunity for PrEP initiation, unless contraindications are present. This would be in addition to immediate syphilis treatment, and treatment for sexual partners. 

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