More than their sum in your parts: the mechanisms that underpin the mutually advantageous relationship between HIV and sexually transmitted infections

A quarter of a century after its discovery, HIV continues to cause millions of deaths every year. The immunopathogenetic events that culminate in HIV transmission during unprotected sex are still poorly understood, but it is clear that sexually transmitted infections (STIs) enhance both HIV susceptibility and secondary transmission. Elucidating the mechanisms that underpin this negative synergy is important to inform the rational development of mucosally applied microbicides that aim to prevent the acquisition of both STIs and HIV. Key mechanisms by which STIs enhance HIV transmission include: (1) the impairment of innate mucosal defenses, including the integrity of the mucosal epithelium itself; (2) the local induction of pro-inflammatory cytokines that enhance HIV replication; (3) the recruitment of activated immune cells that might serve as targets for initial HIV infection and enhance local HIV replication; (4) enhanced susceptibility to other STIs and/or alterations in the normal vaginal microflora and (5) impairment of systemic HIV immune control with increased HIV viral levels in both the blood and genital tract. Ironically, several of these same immune mechanisms are likely to underlie the increased HIV acquisition that was seen in phase 3 trials of two early microbicide candidates.

Section editor:W. Conrad Liles – Division of Infectious Diseases, University of Toronto, Ontario, Canada