As first-line HIV meds lose their patents, the U.S. health care system stands to save nearly $1 billion a year by switching to generic drugs, but switching may also lower the effectiveness of HIV therapy, according to a study conducted by Massachusetts General Hospital and Weill Cornell Medical College.

Atripla, which is a combination of three brand name drugs—Viread (tenofovir), Emtriva (emtricitabine) and Sustiva (efavirenz)—faces generic competition: A generic form of the antiretroviral lamivudine, which is similar to emtricitabine, was released in 2012, and a generic equivalent of efavirenz is expected soon.

The study projects that using the two generics with Viread would achieve an average lifetime savings of $42,500 over Atripla. However, the increased pill burden—the generic meds would not come in a single, combo tablet—would raise the likelihood of low medication adherence, which can lead to treatment failure. Also, some studies have suggested lamivudine may be somewhat less effective than emtricitabine, as well as more likely to lead to drug resistance.

“Ideally, what we would try to do is identify sub-groups of patients where that substitution would not have adverse effects,” says the study’s senior author, Bruce R. Schackman, PhD, an associate professor of public health at Cornell.