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A double-edged sword: does highly active antiretroviral therapy contribute to syphilis incidence by impairing immunity to Treponema pallidum?
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  • Published on:
    Data from the iPrEx Trial Does Not Support This Hypothesis
    • David V. Glidden, Professor University of California, San Francisco
    • Other Contributors:
      • Kenneth H. Mayer, Medical Director and Co-Chair
      • Robert M. Grant, Betty Jean and Hiro Ozawa Endowed Investigator

    The authors impute a biological mechanism to the high incidence of syphilis in men who have sex with men using anti-retroviral drugs (in particular, HAART). We suggest, empiric data do not support the biological hypothesis, and behavioral explanations (i.e. increased condomless sex and selection of higher risk partners) are supported by stronger evidence.

    Randomized double-blind trials of pre-exposure prophylaxis (PrEP) for HIV prevention [1] provide a rigorous test of the author’s hypothesis. The methodological strength includes an unconfounded and clearly unexposed control group and an exposed group which received an agent that would putatively increase susceptibility — tenofovir disoproxil fumarate (TDF) co-formulated with emtricitabine (FTC). A unique feature is that these trials were blinded and PrEP was unproven that the time trials were undertaken; hence, we would not expect that the TDF/FTC-exposed group would adopt higher risk practices.

    An analysis of the iPrEx trial [2], a randomized PrEP trial in men who have sex with men/trans women, found [1] a relative rate of syphilis acquisition for TDF/FTC of 1.14 with a 0.95 confidence interval (0.90 to 1.45) compared to placebo. Incident syphilis, can be difficult to differentiate from a previous infection. Among those with a negative rapid plasma reagin titer at screening the relative rate of an on-study infection was 1.03, 0.95 CI (0.76 to 1.38). Adherence, was low in the iPrEx study and when pharmaco...

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    Conflict of Interest:
    None declared.