Mucosal Immunology: Prevention of Systemic HIV Infection

There has been an abundant and continuous effort to create vaccines that prevent HIV infection, to date the effort has been unsuccessful. Haase argues that this is due to the paradoxical role the innate immune response plays in HIV infection. Moreover, developing a vaccine to prevent HIV may not necessary be the most effective means of preventing systemic infection; a microbiocide combined with pre-exposure prophylaxis targeting the mucosal membranes during the initial stages of infection, is a promising and more effective method to preventing vaginal transmission of HIV.

According to Haase, viral HIV RNA is not detectable in plasma until 10 days after vaginal mucosal exposure, the eclipse phase. Following the eclipse phase viral RNA is exponentially increased at about 21-28 days—with a depletion of CD4 T cells and an established lymphatic reservoir. To prevent systemic infection an intervention must be administered closer to the time and location of exposure and prior to systemic infection.

HIV may gain access initially to only a small number of susceptible target cells of the vaginal mucosal membrane at the time of infection, which is when HIV is the most vulnerable, presenting an opportunity to decrease the ability of the virus to disseminate and reach genital lymph nodes, where T-cells are proliferated and provide more target cells for the virus to spread systemically, systemic phase. In the systemic phase, Haase argues that it is unlikely, when administering a vaccine, to eradicate HIV and opportunities to control the infection are limited. Furthermore, a microbiocide coupled with pre-exposure prophylaxis can block systemic infection by moderating local target cell response. The use of a microbiocide, such as glycerol manolaurate (GML), blocks T-cell activation, preventing the initial mucosal signaling responsible for recruiting target cells. In a rhesus macaques animal model, GML decreased MIPS-α/CCL20 levels in cervical and vaginal fluids and protected animals against systemic infection from as many as four vaginal exposures to SIV in doses that exceed the highest exposure to HIV during the acute stage of infection in humans.

While this research is promising, the feasibility is questionable. Considering vaginal transmission of HIV can be prevented with the use of condoms, if individuals are not using condoms, will they be more likely to apply a microbiocide and be compliant with pre-exposure prophylaxis? Additionally, what will be the cost of a microbiocide, is it easy to store, and how easily will individuals, with the highest rates of newly infected HIV, have access to the treatment?

Haase, A.T. (2011) Early Events in Sexual Transmission of HIV and SIV and Opportunities for Interventions. The Annual Review of Medicine. 62: 127-39