Heather Boerner

February 14, 2017

SEATTLE — Imagine starting a patient on antiretroviral therapy without having to individualize the regimen to take into account factors such as hepatitis B, renal function, sensitivity to abacavir, and drug resistance.

A phase 2 study of the new integrase strand transfer inhibitor bictegravir, used in combination with emtricitabine and tenofovir alafenamide, suggests that will be possible.

"Bictegravir has substantial significance," said Joseph Eron, MD, from the University of North Carolina at Chapel Hill, who was not involved in the study. If phase 3 data are consistent with these phase 2 data, time to the initiation of antiretroviral therapy could be shortened, he explained.

"You end up with a therapy that, potentially, you could give to everybody very quickly," Dr Eron told Medscape Medical News. "I can start you on therapy and then, when I get your labs back the next day or the next week, I can figure out if we have to change anything."

In their study, Paul Sax, MD, from Brigham and Women's Hospital in Boston, and his colleagues looked at treatment-naive people living with HIV. All 98 patients received open-label emtricitabine plus tenofovir, and 65 patients were randomized to either bictegravir or dolutegravir.

Dr Sax presented the study results here at the Conference on Retroviruses and Opportunistic Infections 2017.

After 24 weeks, more patients in the bictegravir group than in the dolutegravir group achieved a viral load below 50 copies/mL (97% vs 94%). The same pattern remained at 48 weeks, although the difference was not significant (97% vs 91%).

"The results were outstanding for both treatment arms," Dr Sax told Medscape Medical News.

Both integrase inhibitors were well tolerated. Three patients experienced virologic failure, and one patient in the bictegravir group withdrew from the study because of urticaria. Adverse events were generally of low grade, and included nausea and diarrhea.

However, at 48 weeks, decreases in the estimated glomerular filtration rate, an indication of renal function, were less extensive in the bictegravir group than in the dolutegravir group (–7.0 vs –11.3 mL/min). There was also no interaction between bictegravir and the HLA-B*5701 allele, a marker of extreme sensitivity to abacavir. And because it is a new drug, no drug-resistant mutations have developed yet.

Together, these factors indicate that first-line integrase inhibitors will be a promising treatment option. However, it is not clear when the phase 3 data will be available.

"It's probably a 2018 drug, not a 2017 drug," Dr Eron explained. But "we're getting there."

SWORD 1 and SWORD 2

Results from duplicate phase 3 open-label noninferiority trials of dolutegravir plus rilpivirine — SWORD 1 and SWORD 2 — were also presented at the meeting.

Of the 1024 study participants, 513 patients were switched to the two-drug regimen and the 511 in the control group stayed on their current antiretroviral regimen, which usually involved three or four drugs.

Dolutegravir plus rilpivirine was shown to be noninferior to the current antiretroviral regimens for viral suppression at 12 months in people already on treatment. In fact, in both SWORD 1 and SWORD 2, the rate of viral suppression below 50 copies/mL was around 95% in both treatment groups.

Treatment failure was experienced by two patients in the two-drug group and two in the control group. More patients in the two-drug group than in the control group discontinued therapy because of adverse events, but the difference was not significant (3% vs 1%).

 
Every new drug is costing more and more. At what point is the juice worth the squeeze, so to speak?
 

These data will not change practice drastically, Dr Eron pointed out. However, he explained, "I have patients in mind who have been waiting for smaller pills. Their lives are going to be made better."

Better-tolerated drugs are essential to improve clinical practice, said Carlos del Rio, MD, from Emory University in Atlanta.

Still, he said he is worried about the cost of new drugs. For patients with HIV, cost has resulted in a bifurcation of care, in which low-income people in the United States and around the world are relegated to older therapies and people who can afford to pay $40,000 a year receive current first-line therapies.

The issue, therefore, is not noninferiority, but value for the money, he explained.

"Every new drug is costing more and more," Dr del Rio pointed out. "At what point is the juice worth the squeeze, so to speak? At what point is paying a lot more for a little extra effectiveness not worth it? At what point is a Cadillac good enough, so you don't need a Ferrari?"

The bictegravir study was sponsored by Gilead Sciences. Dr Sax reports receiving research grants from Gilead, AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, Merck, and Janssen Therapeutics. The SWORD trials were paid for by ViiV Healthcare, GlaxoSmithKline, and Janssen. Dr Eron and Dr del Rio have disclosed no relevant financial relationships.

Conference on Retroviruses and Opportunistic Infections (CROI) 2017: Abstracts 0A-04 41 and 44LB. Presented February 14, 2017.

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