Companion diagnostic tests in HIV medicine: the road to personalized medicine.

The terms "pharmacogenetics" and "pharmacogenomics" are often used interchangeably. Other terms include "theranostics" and, more recently, "onocogenomics." The European Committee for Proprietary Medicinal Products, the European Union's equivalent of our FDA, defined pharmacogenetics as the "study of interindividual variations in DNA sequencing relating to drug response." Pharmacogenomics is defined as the "study of the variability of the expression of individual genes relevant to disease susceptibility as well as to the drug response at the cellular, tissue, individual, or population level."3 In this article, the term "pharmacogenomics" is used. COMPANION DIAGNOSTICS Pharmacogenomic tests play an important role in identifying which patients will respond to a medicine. One of the best-known examples is the HER-2 receptor (human epidermal growth factor receptor 2) testing used to select women most likely to respond to the drug trastuzumab (Herceptin) for the treatment of breast cancer.4 The approval of this breast cancer drug, along with the availability of a diagnostic test that would identify those patients most likely to respond, was assumed by many to mark the start of a new era of companion diagnostics in the pharmaceutical industry. Experts believed this era would yield a consistent development of drug/diagnostic combinations to improve patient outcomes. However, the much anticipated pipeline of companion diagnostics ushering in an era of personalized medicine has been slower to develop than expected. Two key reasons are the complexity of the technology involved in bringing such products to market and the time companies need to implement such processes. Also, many of the drugs now reaching the marketplace were already on a specific development track before the benefit of companion diagnostics was fully understood. The drug and diagnostic industries have very different development paths, different selling models, and different tracks for FDA approval.5,6 Nevertheless, there are some similarities. Both industries develop regulated products that require objective clinical data for widespread adoption and reimbursement. As a result, there is potential for the drug and diagnostic industries to follow a carefully coordinated codevelopment path. PHARMACOGENOMICS AND HIV The remainder of this column discusses some companion diagnostics relevant to HIV care: abacavir/HLA B*5701, maraviroc/tropism testing, and psychoactive drugs/cytochrome P-450 (CYP450) testing. Abacavir Hypersensitivity Mallal and colleagues7 described the possible use of HLA screening to identify patients at significantly increased risk for serious life-threatening hypersensitivity reactions to the antiretroviral drug abacavir. More recently, in the large, prospective, double-blind PREDICT-1 trial, the utility of HLA typing was tested using skin-patch results as confirmation of an abacavir hypersensitivity reaction (HSR).8 In this trial of 1956 HIV-infected patients who were scheduled to start regimens containing abacavir, half the patients were randomized to undergo HLA screening at baseline and half were not. Those who underwent screening started abacavir therapy only if they tested negative for HLA B*5701; those who did not undergo screening started abacavir therapy immediately and provided blood samples for later HLA typing. All patients who developed clinical signs of HSR underwent skin-patch testing.