PD02.01
Background: Identification of biologic factors robustly associated with resistance to HIV-1 infection among highly HIV exposed seronegative (HESN) individuals is a priority. We quantified HIV exposure among HIV-1 uninfected women in HIV serodiscordant couples and evaluated protein abundances as potential biomarkers of HIV resistance by comparing HESN versus low exposure (non-HESN) women.
Methods: 33 vaginal swabs from 10 HESN (16 swabs) and 10 non-HESN (17 swabs) women in the placebo arm of the Partners PrEP Study had tandem mass spectrometry (MS) to assess frequency of 435 human and 247 bacterial proteins. We assessed differences by generalized estimating equations (GEE) adjusting for bacterial vaginosis, and calculated false discovery rates (FDRs).
Results: Of HESN women, 100% reported unprotected sex versus 0% of non-HESN and had HIV infected partners with higher median plasma HIV RNA log10 copies/mL (5.0 [interquartile range (IQR):4.9,5.1]) than non-HESN women (1.6 [IQR:1.6,1.9]). Based on these factors, HESN had>100-fold higher risk of infection than non-HESN. Hierarchical clustering of differentially abundant proteins distinguished HESN from non-HESN with 88% and 76% sensitivity and specificity, respectively. Nine proteins had FDR<5%, including elafin, azurocidin and β2 integrin. Elafin was 8 times more abundant among HESN (95% CI=[4.0-16.0];FDR=8.9x10−7), while β2 integrin was 4 times less abundant among HESN (95% CI=[1.9-9.2];FDR=0.046).
Conclusions: The vaginal proteome differs in HESN and non-HESN women. Consistent with an earlier study, elafin, a mucosal anti-protease that may inhibit HIV, is more abundant among purportedly HIV resistant women; β2 integrin, which may facilitate cell-to-cell transfer of HIV, was decreased in HESN despite high exposure. Further research is needed to clarify if these factors mark HIV exposure or host resistance to HIV.
