Physician's Weekly Article - Guidance on Antiretroviral Therapy in HIV

       Early initiation of antiretroviral therapy and performing appropriate laboratory resistance testing are important messages from newly released guidelines for treating adults and adolescents with HIV infection.

      The treatment of adults and adolescents with HIV infection has improved greatly in the past several years largely because of new developments in antiretroviral therapy. Since 1997, many new agents have been approved by the FDA, featuring new mechanisms of action, increased potency, enhanced dosing convenience, and better safety profiles. In addition, clinicians have gained a better understanding about potential drawbacks of other agents. However, while resistance testing is now used more commonly, interactions among antiretroviral agents and other drugs have become more challenging to manage.

      As the HIV treatment landscape continues to evolve, reference tools are being created to help clinicians stay up to date. In December 2007, the Department of Health and Human Services (DHHS) updated its “Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents,” a resource that was first created in 1997. “The guidelines outline our understanding of how clinicians should use antiretroviral drugs to treat adults and adolescents with HIV infection,” says John G. Bartlett, MD, who co-chaired the DHHS panel that created the guidelines. “Since 1997, these guidelines have been (and will continue to be) revisited and adjusted on a regular basis based on emerging evidence.”

      When to Start Antiretroviral Therapy

      There is now a greater understanding of when to initiate therapy in patients with HIV, according to the guidelines. Previous recommendations were to initiate HIV treatment for patients with CD4 counts below 200 cells/mm³; therapy was considered for individuals with CD4 counts between 200 cells/mm³ and 350 cells/mm³. The updated DHHS guidelines now state that patients should be treated if they have CD4 counts less than 350 cells/mm³ (Table 1). Study data have shown that patients with higher CD4 counts can achieve greater benefits with newer antiretroviral therapies; these drugs are more likely to be effective, safer, and better tolerated when CD4 counts are higher.

      The guidelines also no longer define groups of patients who should not be treated. Previous recommendations stated that therapy should be deferred if CD4 counts were approximately 350 cells/mm³ and viral loads were below 100,000 copies/mL, but the updated guidelines indicate that some people should be treated at higher CD4 counts, including pregnant women and those with HIV-associated nephropathy or hepatitis B coinfection. “A CD4 count of 350 cells/mm³ is no longer an absolute cutoff value,” Dr. Bartlett says. “We should treat patients earlier depending on their specific characteristics.”

      Furthermore, the guidelines now recommend that therapy may be appropriate for some individuals with higher CD4 counts based on potential risks and benefits as well as on patients’ willingness to adhere to therapy. “There are certain obstacles to treatment—substance abuse, for example—that can influence patients’ readiness to adhere to medication regimens,” adds Dr. Bartlett. “Efforts are needed to break down these barriers and treat all patients who qualify.”

      Administer Appropriate Testing

      Laboratory testing is another key issue addressed in the new DHHS guidelines. Previous guidelines have recommended baseline resistance testing with genotype tests before initiating therapy in treatment-naive patients. The updated guidelines recommend performing resistance tests at the time patients enter into clinical care, regardless of whether or not there is a plan to initiate therapy (Table 2). “These tests are most accurate shortly after HIV infection,” says Dr. Bartlett. “As time goes on, they increasingly miss the presence of resistant virus. The sooner resistance testing is completed, the better. And resistance test results should be saved because it could be years before patients start therapy; having access to these results will be helpful.”

      According to Dr. Bartlett, two specific tests are recommended for patients with HIV who are being considered for specific medications. “Before initiating a CCR5 antagonist, such as the newly approved maraviroc, tropism testing should be performed,” he says. “Patients with certain types of the HIV virus may not respond virologically to CCR5 antagonists. In addition to this assay, HLA-B*5701 testing is recommended prior to initiating abacavir, a commonly used HIV therapy. This is an effective test to reduce the risk of hypersensitivity reactions, which can be serious and perhaps life-threatening.”

      While the new guidelines are extensive—they run 144 pages in length—Dr. Bartlett says they are of great value to clinicians. “The guidelines are a great resource for finding the latest information on HIV therapy. Even expert clinicians can still learn from them. When used in conjunction with guidelines that address other specific populations—including pediatric patients, antiretroviral agents in pregnancy, HIV prevention, HIV primary care, and opportunistic infections—these guidelines may significantly improve outcomes for individuals with HIV.”

      John G. Bartlett, MD has indicated to Physician’s Weekly that he has received research support from Gilead Sciences. He serves on the advisory boards of Abbott Laboratories, Bristol-Myers Squibb, GlaxoSmithKline and Pfizer, Inc.