Preventing HIV infection without targeting the virus: how reducing HIV target cells at the genital tract is a new approa
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Lajoie et al. AIDS Res Ther (2017) 14:46 DOI 10.1186/s12981-017-0166-7
Open Access
REVIEW
Preventing HIV infection without targeting the virus: how reducing HIV target cells at the genital tract is a new approach to HIV prevention Julie Lajoie1,2, Lucy Mwangi2 and Keith R. Fowke1,2,3*
Abstract For over three decades, HIV infection has had a tremendous impact on the lives of individuals and public health. Microbicides and vaccines studies have shown that immune activation at the genital tract is a risk factor for HIV infection. Furthermore, lower level of immune activation, or what we call immune quiescence, has been associated with a lower risk of HIV acquisition. This unique phenotype is observed in highly-exposed seronegative individuals from different populations including female sex workers from the Pumwani cohort in Nairobi, Kenya. Here, we review the link between immune activation and susceptibility to HIV infection. We also describe a new concept in prevention where, instead of targeting the virus, we modulate the host immune system to resist HIV infection. Mimicking the immune quiescence phenotype might become a new strategy in the toolbox of biomedical methods to prevent HIV infection. Clinical trial registration on clinicaltrial.gov: #NCT02079077 Keywords: HIV, Immune activation, Protection, Highly exposed seronegative (HESN), Immune quiescence Background According to the latest UNAIDS report, 36.7 million people are living with HIV/AIDS worldwide. Despite the development of new antiretroviral drugs and better access to care and prevention programs, the number of new HIV cases has remained over 2 million per annum over the past 10 years with a very slow rate of decline [1]. Clearly, existing prevention methods are not sufficient and new approaches are required. However, to develop new biomedical prevention methods, we need a better understanding of the factors driving susceptibility to HIV infection.
*Correspondence: [email protected] 1 Department of Medical Microbiology and Infectious Diseases, University of Manitoba, 539‑745 Bannnatyne Avenue, Winnipeg, MB R2N 1V3, Canada Full list of author information is available at the end of the article
Learning from the past Immune activation and susceptibility to HIV infection
Mucosal surfaces of the genital and gastrointestinal tracts are the major routes of entry of HIV. In general, the presence of a pathogen leads to recruitment and activation of immune cells at the site of infection leading to the elimination of the pathogen. In the case of HIV infection, this recruitment and cell activation serves to increase the number of HIV target cells thereby actually facilitating the establishment of an infection. As such, increased immune activation is considered an important risk factor for acquiring HIV [2]. The presence of sexually transmitted infections (STIs) is associated with susceptibility to HIV infection [3, 4]. This increased risk is due to the presence of microlesions caused by the pathogen, which may facilitate HIV entry, or by the recruit
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