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 type 1 (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 coreceptor" as keywords led to more than 1100 original research publications and 90 review articles. This number skyrocketed to more than double if we used "HIV CCR5". Most of the reviews described in detail several aspects of HIV tropism, viral entry mechanism, coreceptor usage and its implication on disease progression, antiretroviral therapy, and vaccine development. A few others centered on the tools utilized to measure the ability of HIV to use these coreceptors to infect target cells. On the other hand, identification of the HIV coreceptors renewed the effort and expectation to block HIV replication by targeting viral entry into the target cells. As with HIV tropism, hundreds of articles have been published addressing this topic (more than 350 original publications and 50 review articles when using "HIV entry inhibitor" as a descriptive word). Therefore, in addition to providing a brief update of the most important aspects described above, we discuss here how an accurate quantification of HIV coreceptor usage is essential for the successful management of HIV-infected individuals in this new era of entry inhibitors, mainly CCR5- or CXCR4-antagonists.