The recognition of a coreceptor for human immunodeficiency virus (HIV) entry, along with the cluster of differentiation (CD) 4 receptor, was a pivotal discovery in the late 1990s. Soon thereafter, scientists identified viral strains that may use either CC chemokine receptor type 5 (CCR5) or CXC chemokine receptor type 4 (CXCR4), or both, as coreceptors. HIV isolates using CCR5 tended to be less pathogenic than were those using CXCR4.
During the last decade, many molecules that block CCR5 have been tested as potential antiretroviral agents. Maraviroc is the only one, however, that has gained approval. Given its unique mechanism of action, this drug does not exhibit cross-resistance with other antiretroviral drugs and, therefore, can be given to patients who have failed other regimens. Moreover, its immunomodulatory properties have been tested in distinct scenarios, particularly in patients experiencing poor CD4 recovery despite lengthy therapy with complete viral suppression under other antiretroviral agents. A further advantage of maraviroc is its good safety profile and convenient posology (few pills once or twice daily). The downside of using CCR5 antagonists is the need to ensure in advance that the dominant virus infecting the individual considered for treatment harbors R5, and not X4, viruses. Complicated and expensive phenotypic tests were originally designed for this purpose, which more recently have been replaced by genotypic methods that infer viral tropism based on the sequences of the V3-enveloped region of circulating viruses.
I am pleased to introduce a group of worldwide, well-known experts in the field of HIV diagnostics and therapeutics, with particular expertise in HIV tropism. They will address 3 different aspects of special relevance regarding the use of CCR5 antagonists, all of them with clear clinical implications. Lee, Cheung, Swenson, and Harrigan (Canada) discuss the role of genotypic methods for assessing HIV tropism. van Lunzen, Schulze zur Wiesch, and Stellbrink (Germany) provide updated and new insights about the immunological effects of these drugs. Finally, Poveda (Spain) discusses the most recent clinical data using CCR5 antagonists, including the performance of maraviroc as part of simplification or intensification antiretroviral regimens. I trust you will enjoy reading this issue of Hot Topics in HIV and Other Retroviruses and expect you find appropriated answers to all your questions regarding the use of CCR5 antagonists.