Persistent genital inflammation increases HIV risk

2 June 2015

R esearch conducted by the mucosal immunology team at CAPRISA indicates that the risk of HIV acquisition in South African women was significantly higher in those with persistently raised genital inflammatory cytokine concentrations (including HIV target cell-recruiting chemokines MIP-1α, MIP-1β and IP10).

This study, which was led by Dr Lindi Masson, investigated whether genital inflammation influenced HIV acquisition.

Twelve selected cytokines, including 9 inflammatory cytokines and chemokines (IL-1α, IL-1β, IL-6, TNF-α, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β), hematopoeitic IL-7 and GM-CSF, and regulatory IL-10 were measured prior to HIV infection in cervicovaginal lavages from 58 HIV seroconvertors and 58 matched uninfected controls and plasma from a subset of 107 of these women from the CAPRISA 004 tenofovir gel trial.

HIV seroconversion was associated with raised genital inflammatory cyto kines. The risk of HIV acquisition was significantly higher in women with evidence of genital inflammation, defined by at least 5 of 9 inflammatory cytokines being raised [OR 3.2; 95% confidence interval 1.3-7.9; p=0.014] (Figure). Genital cytokine concentrations were persistently raised (for about one year before infection), with no readily identifiable cause despite extensive investigation of several potential factors, including sexually transmitted infections.

While a fraction of the genital inflammation may be attributed to asymptomatic STIs, the dominant cause of genital inflammation remains to be elucidated. Treatment of asymptomatic STIs and topical agents to modulate inflammation are potentially important mechanisms for reducing susceptibility to HIV infection, especially in young women, where the epidemic is most severe in Africa.

For further reading see:
Masson L, et al. Genital inflammation and the risk of HIV acquisition in women. Clinical Infectious Diseases 2015 ; DOI: 10.1093/cid/ civ298 Figure

Figure . Unsupervised hierarchical clustering was used to visualize the variation in cytokine concentrations in individual women and to cluster women according to the similarities of their cytokine expression profiles (using Qlucore Omics Explorer). Women who later became infected with HIV (n = 58; blue blocks) had upregulated pre-infection cervicovaginal lavage cytokine concentrations and tended to cluster together, while women who remained HIV-uninfected had lower cytokine concentrations and also clustered together (n = 58; yellow blocks).