HIV-1 Superinfection and its Implications for Vaccine Design

Bhavna      H. Chohan; Anne      Piantadosi; Julie      Overbaugh

Abstract

HIV-1 superinfection, which refers to a subsequent HIV-1 infection from a different source partner after the first HIV-1 infection is established, has now been well documented in multiple populations. Some studies suggest that the risk of superinfection may be close to that of initial infection, suggesting that the immunity induced by chronic HIV-1 infection may not be adequate to confer protection from another HIV-1 strain. Detailed studies that examined immune responses in individuals who became superinfected generally support this hypothesis, but such studies have been limited. Indeed, superinfection represents one of the few settings, apart from vaccine trials, where there is an opportunity to gain insights into the role of HIV-specific immunity in protection in humans, and this should be exploited. Likewise, studies of superinfection in HIV-1 positive individuals on antiretroviral therapy who continue to be exposed to HIV could provide insight into the role of antiretroviral treatment in protecting from HIV-1 infection, a concept that is also being explored for its potential to prevent a first HIV-1 infection. To address these questions, larger population-based studies that define the incidence and timing of superinfection and include collection of samples for immunological studies are needed.

Keywords: HIV transmission, superinfection, antiretroviral treatment, immune protection, HIV-1 positive individuals, drug resistant viruses, recombinant viruses, cross-sectional studies, co-infection, viral load, phylogenetic, heterosexual contact, injection drug users (IDU), potent immune responses, prophylaxis, drug resistance screening, seroconcordant couples, viremia, mosaic genomes, ultra deep-sequencing methods, immune deficits, cytotoxic T lymphocyte (CTL), antibody-dependent cytotoxicity, neutralizing antibodies (NAb), humoral responses, vaccine protection, sterilizing protection, immune milieau