Background: HIV-exposed, uninfected subjects (EUs) are more likely to exhibit HIV-specific immune responses than persons at low risk for HIV infection. Here we examine the effect of route of exposure on induction of virus specific immunity.

Methods: Group 1 (n = 21) included persons exposed to HIV via unprotected sex with HIV-infected partners; all denied intravenous HIV exposure. Of these 14 were men having sex with men (MSM) and 7 were heterosexual EUs in HIV discordant couples. The mucosally exposed population were further classified according to route of exposure (Table 1). Group 2 (n = 30) included subjects who admitted to sharing needles with HIV-infected partners and who denied HIV exposure via high-risk sexual contact. The IFN-γ ELIspot assay was used to detect HIV-specific effector activity to a panel of HLA restricted peptides.

Results: Responses to HIV in EUs is associated with HIV exposure (0/18 low risk controls versus 12/21 [57.1%] mucosally and 19/30 [63.3%] intravenously exposed subjects had HIV-specific responses [p < 0.01, c²-test for both comparisons]). A similar proportion of group 1 and 2 subjects exhibited virus specific responses (p = 0.66, c²-test). No between group differences were seen for the breadth and intensity of HIV-specific responses. Although we saw no statistically significant differences between the proportion of MSM and the heterosexual EUs having HIV-specific activity (p = 0.4, Fisher`s exact t-test) or the proportion of females exposed to HIV vaginally (2/3 [66.7%]) versus MSM exposed anally via receptive sex (3/8 [37.5%]) with HIV-specific responses (p = 0.5455, Fisher`s t-test), the small sample size of the comparison groups limits our ability to draw conclusions from these comparisons. More MSM than heterosexual men exposed to HIV via insertive intercourse exhibited HIV-specific ELIspot reactivity (p = 0.0333; Fisher`s exact t-test). This interesting observation warrants further exploration.

Conclusions: Both intravenous and mucosal exposure to HIV can induce HIV-specific immune responses in the absence of seroconversion. In EUs, vaginal and anal receptive and insertive sexual exposure to HIV can induce virus-specific immune responses not seen in low risk controls.

 

Table 1. HIV-specific reactivity among the mucosally exposed population

MSM 9/14 (64.3%)		Heterosexuals 3/7 (42.9%)
Receptive and insertive	Insertive only	Vaginal receptive (females)	Vaginal insertive (males)
3/8 (37.5%)	6/6 (100%)	2/3 (66.7%)	1/4 (25%)