HIV Type 1 Tropism and Inhibitors of Viral Entry: Clinical Implications

Since their discovery in 1996, the two main coreceptors used by human immunodeficiency virus type1 (HIV-1) to enter human cells (CCR5 and CXCR4) have been the subject of numerous scientific articles.A recent search in PubMed (www.pubmed.gov) using “HIV coreceptorâ€? as keywords led to morethan 1100 original research publications and 90 review articles. This number skyrocketed to more thandouble if we used “HIV CCR5â€?. Most of the reviews described in detail several aspects of HIV tropism,viral entry mechanism, coreceptor usage and its implication on disease progression, antiretroviraltherapy, and vaccine development. A few others centered on the tools utilized to measure the abilityof HIV to use these coreceptors to infect target cells. On the other hand, identification of the HIVcoreceptors renewed the effort and expectation to block HIV replication by targeting viral entry intothe target cells. As with HIV tropism, hundreds of articles have been published addressing thistopic (more than 350 original publications and 50 review articles when using “HIV entry inhibitorâ€? asa descriptive word). Therefore, in addition to providing a brief update of the most important aspectsdescribed above, we discuss here how an accurate quantification of HIV coreceptor usage is essentialfor the successful management of HIV-infected individuals in this new era of entry inhibitors,mainly CCR5- or CXCR4-antagonists.