Effect of heterosexual intercourse on mucosal alloimmunisation and resistance to HIV-1 infection

Background Unprotected sexual intercourse between regular heterosexual partners could elicit alloimmune responses that might be associated with inhibition of in-vitro HIV-1 infectivity. We investigated this hypothesis in people practising unprotected sex and those using protection. Methods We recruited 82 participants from an outpatient genitourinary medicine clinic. 29 monogamous heterosexual couples having unprotected sex; and 15 women and 10 men having condom protected or no sex. We used the mixed leucocyte reaction (MLR), stimulating one partner's peripheral blood mononuclear cells (PBMC) with the other partner's irradiated PBMC and compared the resulting response with control PBMC. We studied resistance to HIV-1 infection by challenging activated CD4-positive T cells with CCR5-binding and CXCR4-binding HIV-1 strains, and comparing the infectivity in participants having unprotected sex with those practising protected sex. We used the correlation coefficient to establish the significance of the relation between MLR and HIV-1 infectivity. Findings We recorded a significant increase in the stimulation indices in PBMC from women whose cells were stimulated with irradiated PBMC (2%, 10%, or 50%) from their regular partners. The mean with 10% partner's cells was 8.6 (SD 7.7), compared with those from unrelated cells (4.7 [3.9], p=0.009). Significant alloimmune responses were also seen in corresponding male partners, but only with 50% stimulating cells (p=0.013). Dose-dependent inhibition of activated CD4-positive T cells to HIV-1 infection with both binding strains was noted in vitro in women practising unprotected intercourse, compared with those having protected sex or having no sex for more than 1 year. Highly significant differences were found for CCR5 (p=0.0001) and for CXCR4 (p=0.001) strains of HIV-1 at all four virus-concentrations. Male partners also showed in-vitro inhibition of HIV-1 but this was less than that in women. Interpretation Unprotected sexual intercourse might result in alloimmunisation stimulated by HLA antigens in seminal or cervicovaginal fluid. Mucosal alloimmunisation may reduce infection by HIV-1, and the role of such immunisation in preventive and therapeutic vaccination should be investigated.