Mayor susceptibilidad para Sifilis en ptes HIV+ y con HAART.

Comportamiento, farmaco y enfermedad se combinan para incrementar la incidencia de Sífilis en esta población.

A Double-Edged Sword

Does Highly Active Antiretroviral Therapy Contribute to Syphilis Incidence by Impairing Immunity to Treponema Pallidum?

Michael L Rekart; Wilfred Ndifon; Robert C Brunham; Jonathan Dushoff; Sang Woo Park; Sanjana Rawat; Caroline E Cameron

DISCLOSURES 

Sex Transm Infect. 2017;93(5):374-378. 

Discussion 

Biological Plausibility

Protection against the extracellular pathogen T. pallidum, the causative agent of syphilis, is dependent upon T cell expansion and the generation of an early Th1-stimulating, interferon γ (IFN γ)-producing host proinflammatory response that potentiates the primary clearance mechanism of T. pallidum, macrophage-mediated opsonophagocytosis.^[25] The latter process is dependent on unperturbed mitochondrial function to ensure peak metabolic activity within macrophages,^[26] opsonic antibody production and IFN γ-mediated macrophage activation.^[27] Opsonic antibody quality is reduced in individuals infected with HIV-1^[28] and certain HAART agents significantly suppress mitochondrial function,^[26] the proinflammatory response^[29] and macrophage activation,^[30]leading to reduced treponemal clearance via opsonophagocytosis. InSTIs have been shown to suppress the proinflammatory response in cohort studies^[29] and opsonophagocytosis is reduced in vitro following treatment of macrophages with NRTIs, consistent with mitochondrial damage.^[26]

Further, the well-documented depletion of CD4⁺ memory T cells in individuals infected with HIV-1^[30] would enhance their susceptibility to syphilis reinfection. NRTIs, especially TDF, have been shown to inhibit telomerase activity leading to accelerated shortening of telomerase length in peripheral blood mononuclear cells (PBMCs),^[31] which may lead to the accumulation of replicative senescent cells^[32] with limited ability to protect against pathogens such as T. pallidum. Reciprocally, upregulation of monocyte expression of CCR5 receptors by treponemal lipoproteins enhances the susceptibility of monocytes to HIV-1 infection,^[33]further weakening the innate and adaptive immune responses to T. pallidum.

Collectively, these observations provide viable explanations for (1) an enhanced susceptibility of individuals infected with HIV-1, especially those on HAART, to syphilis infection and reinfection and (2) higher syphilis incidence among individuals treated with HAART compared with chlamydia and gonorrhoea, infections caused by pathogens that are less reliant on opsonophagocytosis for clearance.