Once considered part of the gold standard of HIV treatment, alternative regimens can now alleviate concerns about birth defects, psychiatric problems, and even suicide caused by the drug efavirenz.

Research published this week shows that three alternative, first-line HIV treatments that do not include efavirenz are just as good at suppressing the virus and are better tolerated. Efavirenz is known to cause nightmares and birth defects, and has been linked to suicide. 

Efavirenz, which goes by the brand name Sustiva, is widely used as an ingredient in the once-daily HIV regimen Atripla. In the study, appearing in the Annals of Internal Medicine, Dr. Jeffrey Lennox of Emory University in Atlanta studied 1,809 people who were given alternative first-line treatments. None of the participants in the study had previously been treated.

All of the participants received emtricitabine (Emtriva) and tenofovir disoproxil fumarate (Viread). Those two medications are combined in a once-daily pill called Truvada.

Those drugs were paired with either atazanavir plus ritonavir, raltegravir (Isentress) alone, or darunavir plus ritonavir.

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Researchers studied the patients over the course of two years. All three regimens suppressed the virus to 50 copies per milliliter of blood or less — undetectable levels — in about 90 percent of the patients.

The raltegravir-containing regimen proved superior to the other two options that included protease inhibitors. Lennox told Healthline that protease inhibitors were once the “go-to class” of drugs to treat HIV, and they still are a safe alternative for many people.

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Now, more powerful non-nucleoside reverse transcriptase inhibitors (NNRTIs) have emerged. Efavirenz is an NNRTI, but better alternatives for those who can’t tolerate it are badly needed.

Lennox said new once-daily HIV medications have come on the market since his research that use nevirapine (an NNRTI) or Kaletra (a protease inhibitor) instead of efavirenz. Plus, two new once-daily HIV treatment regimens now include raltegravir, a integrase inhibitor, Lennox said.

Different drug combinations work better for different people, Lennox said.

A study published in July in the Annals of Internal Medicine showed that someone taking efavirenz is twice as likely to commit suicide or to have suicidal thoughts as someone not taking the drug. This is problematic since depression is widespread among people with HIV. A 2001 meta-analysis showed that people with HIV have double the risk of depression, compared to people who don’t have the disease.

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Dr. David Hardy, an associate professor of infectious diseases at the University of California, Los Angeles, and a member of the board of directors of the HIV Medicine Association, told Healthline, “The shine began to come off the polish of efavirenz a while back.” It was considered part of the gold standard of Atripla when that drug was introduced in 2006 as a once-daily regimen.

Hardy said sales of Atripla are falling as other single-tablet regimens come on the market. He said trials such as the Lennox study, which took place under the umbrella of the AIDS Clinical Trial Group, are important because they involve research pharmaceutical companies would never do on their own. 

Sustiva has been around since 1998. Hardy says patients have complained of feeling woozy or dizzy about an hour after taking it, as well as waking up groggy after taking a dose at bedtime. Some patients have very vivid dreams, Hardy said.

While one study showed that the neuro-psychiatric side effects of efavirenz go away in 10 to 12 weeks, “The study stopped at 24 weeks,” Hardy said. “While [side effects] do go away, they don’t go away in all patients. In some they have persisted for years.”

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