The U.S. Department of Health and Human Services has released new treatment guidelines for adults and adolescents, and these contain some important changes. Key among these is a major shakeup in the "Recommended Regimen Options" for initial therapy.
|Efavirenz/TDF/FTC (Atripla) has been removed from the "Recommended" list and now is designated as an "Alternative Regimen Option"--this is owing to higher rates of adverse effects and tolerability issues (particularly CNS toxicity) seen in recent comparative trials (see previous articles on studies comparing efavirenz with regimens containing dolutegravir and elvitegravir/cobicistat as well as the possible association of efavirenz with suicidality).|
|Atazanavir/ritonavir/TDF/FTC also has been moved to the "Alternative" list, because of the higher rates of adverse effects compared with RAL or DRV/r in the ACTG 5257 study.|
|The combinations that previously were "Recommended Regimens" for patients with baseline HIV RNA <100,000 copies/mL have been demoted to other categories.|
Other changes include the addition of certain regimens containing cobicistat-boosted ATV and DRV in "Alternative" and "Other" categories, and the inclusion in the "Other" list of two regimens that contain one or no NRTIs, and are suggested (based on few data) for use when TDF or ABC cannot be used.
Of course, as in previous years, the panel states that "Alternative" or "Other" regimens may be indicated for specific patients, and a new table (Table 7) offers guidance on ARV selection in different clinical situations.
Clinical Bottom Line
The DHHS Guidelines list of "Recommended" regimens now includes 4 integrase inhibitor-containing regimens and 1 boosted-PI regimen. Remarkably, these guidelines mark not only the demotion of Atripla from its long-held position as a gold-standard regimen, but also the elimination of NNRTI-containing "Recommended" first-line regimens altogether. Additionally, the Guidelines recognize DRV/r as the only PI in a "Recommended" regimen. These are important changes, and ones made possible by the excellent efficacy and tolerability of newer anchor drugs, especially the integrase inhibitors.
While other ARVs and other regimens clearly will continue to be important for some patients, these guidelines will promote the use of regimens that generally are both effective and better tolerated than others, and (though it is not their intention) will provoke thought about our standards for changing ART in patients who are doing well on other regimens.