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The treatment of advanced HIV has improved substantially in the past several years as clinicians have gained a better understanding of how to administer a variety of medications and drug classes, optimize treatment regimens, and manage resistance profiles. A wave of newer drugs is helping salvage more patients than ever before. These emerging drugs are equipped with different mechanisms of action that can better control viral replication.

In 2007, the FDA approved maraviroc for use in combination with other antiretroviral drugs for treating adults with CCR5-tropic HIV who have used other HIV medications and who have evidence of elevated levels of HIV in their blood. Maraviroc works differently from other drugs because it doesn’t fight the virus inside white blood cells; it prevents HIV from entering uninfected cells by blocking the CCR5 co-receptor, a predominant route of entry. It’s estimated that at least half of patients who have previously received HIV medications have circulating CCR5-tropic HIV. Maraviroc represents an important new treatment option for many HIV-infected individuals who have not responded to other therapies and are left with few options. The agent is also the only oral-entry inhibitor that prevents the virus from penetrating T cells.

Long-Term Data Emerging

Although maraviroc has only recently been approved, more safety and efficacy data are being collected. A presentation from the 2007 Interscience Conference on Antimicrobial Agents and Chemotherapy analyzing 48 weeks of data demonstrated that nearly three times as many patients receiving maraviroc—in addition to an optimized background regimen—achieved undetectable levels of HIV when compared with those receiving an optimized regimen alone. These findings reinforce the fact that maraviroc provides significant benefits to certain treatment-experienced patients. Furthermore, the agent significantly increases CD4 cells when used with an optimized background regimen as compared with optimized regimens alone, and adverse event profiles with maraviroc were similar to the use of optimized regimens alone.

While the drug has been an important addition to the HIV treatment armamentarium, it should be noted that maraviroc isn’t recommended for all patients with the virus; only in those with demonstrated CCR5-tropic HIV using a Trofile Assay. For example, no biologic benefit has been observed when maraviroc is used for people with CXCR4-tropic HIV (a different tropism) or a mixture of CCR5 or CXCR4 tropisms.

More to Come

The complete story on the potential benefits of maraviroc is just beginning to unfold. Recent data suggest that individuals with HIV who have a complete deletion of the genes coding for the CCR5 receptor—the so-called “delta-32 homozygotes”—can have repeated exposures to HIV but remain uninfected. While the cause isn’t fully understood, it also appears that partial deletion of CCR5 receptors (the heterozygous state) slows declines in CD4 counts and increases the time patients live before suffering an AIDS-defining event. There are potential advantages and disadvantages to consider, however, when considering blocking CCR5 receptors. CCR5 deletion has been associated with less inflammation, heart disease, and arthritis. However, this deletion could make patients more susceptible to hepatitis C and West Nile virus infections and perhaps some cancers. Researchers are just beginning to unravel some of the clues surrounding CCR5 receptors, but there’s hope that it may help us solve other challenging health problems in the future.

Jacob P. Lalezari, MD has indicated to Physician’s Weekly that he has worked as a consultant and paid speaker and has received grants/financial aid from Pfizer, Inc.