The Challenges of Assessing Guideline Adherence in a Rapidly Changing Treatment Landscape

Clinical trials are the gold standard for understanding the true efficacy of a drug. The U.S. Department of Health and Human Services (DHHS) uses trial data to develop treatment recommendations, but doctors don't always follow its advice.

With more than 20 approved HIV antiretrovirals in the United States, physicians have many options for their patients -- they can choose one of the "preferred" drug regimens or deviate from the guidelines entirely.

According to data presented by Yunfeng Tie, Ph.D., at IDWeek 2015 in San Diego, shocking estimates indicate that only half of doctors stick to guidelines when prescribing antiretrovirals (ART). "HIV providers should continue to be encouraged to prescribe ART according to established guidelines when clinically appropriate," Tie concluded.

Tie's team found that only 52% of patients were prescribed "preferred" medications and 6% were prescribed "alternative" regimens according to the 2014 DHHS guidelines. Of the remaining patients, 29% were prescribed non-recommended regimens and 13% were prescribed "other."

The off-guideline prescribing practices seemed to have a negative impact on patients -- those prescribed non-recommended or "other" drugs were less likely to achieve long-term viral suppression, a key indicator of successful treatment. They were also more likely to report side effects.

However, these results should be interpreted with extreme caution. Tie and her colleagues analyzed data gathered from 2009 to 2012 through the Medical Monitoring Project, a surveillance system set up by the Centers for Disease Control and Prevention to learn more about the real-life experiences of patients with HIV. The analysis included 18,095 participants. Yet in examining this 2009 to 2012 data, the team compared physician's prescribing practices with 2014 guidelines.

The problem with comparing 2009 to 2012 data with the 2014 guidelines is that, on average, DHHS guidelines are updated once a year, according to Joel Gallant, M.D., M.P.H, an HIV doctor at Southwest CARE Center in Santa Fe, New Mexico.

"I certainly think that if you're going to look at a patient population in a certain time period you need to use the guidelines [that correspond to the year the medication was prescribed]," Gallant said.

During her oral presentation at IDWeek, Tie noted that one of the study's limitations was the fact that "DHHS guidelines change over time." In fact, more than 40% of patients enrolled in the Medical Monitoring Project had been taking antiretroviral drugs for 10 years, and only 5% of participants had started therapy within the past year.

"Many patients are going to be on regimens that are no longer recommended," Gallant said. "That is perfectly consistent with guidelines," he added, noting that for people on older regimens who are doing well, there is no need to change treatment.

One of the main objectives of this study was to learn more about the real-world experiences of patients with HIV. The high rates of viral suppression observed in highly controlled clinical trials rarely stack up against results observed in a real-life setting such as that of the Medical Monitoring Project.

The researchers evaluated the health outcomes of patients measured by viral suppression. They found that 92% of HIV-infected adults were prescribed antiretroviral therapy. Of those, 80% achieved viral suppression, but after one year durable viral suppression fell to 66%.

This is significantly lower than the 90% response rates typical in clinical trials. However, Tie pointed out that another limitation of the study is that, unlike a clinical trial, the Medical Monitoring Project was not designed to specifically study effectiveness. Also substantially different from clinical trial effectiveness studies, many patients with different treatment backgrounds were included.

In 2015, DHHS guidelines changed once again. Therefore, some of the preferred regimens according to the 2014 guidelines are no longer considered appropriate first-choice treatments for newly diagnosed patients. Interestingly, according to Tie's recent findings, from 2009 to 2012 the most commonly prescribed treatment regimen was efavirenz with tenofovir/emtricitabine (Atripla).

In April 2015, efavirenz was replaced by the better-tolerated integrase inhibitors as a first-choice treatment in the DHHS recommended guidelines. Today, the five preferred regimens include four integrase strand transfer inhibitor (INSTI)-based regimens and one ritonavir-boosted protease inhibitor (darunavir/ritonavir plus tenofovir/emtricitabine).

According to Gallant, if you look at the five recommended regimens right now, moving forward, there should be "a minority" of treatment-naive patients prescribed off-guideline regimens.