Optimizing Outcomes in HIV Treatment - Episode 16

Treatment-Naïve Patients with HIV

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The HCPLive Peer Exchange: Optimizing Outcomes in HIV Treatment features insight and opinion on the latest developments in HIV research, diagnosis, and management from leading physician specialists.

This Peer Exchange is moderated by Paul Doghramji, MD, who is a family physician at Collegeville Family Practice in Collegeville, PA, and Medical Director of health services at Ursinus College, also in Collegeville, PA.

The panelists are:

  • Alfred A. DeLuca, MD, Infectious Disease Specialist at CentraState Healthcare System in Manalapan, NJ
  • Ian Frank, MD, Director of Anti-Retroviral Clinical Research and Director of Clinical Core at Penn Center for AIDS Research, and Professor of Medicine at the Hospital of the University of Pennsylvania in Philadelphia, PA
  • Paul Sax, MD, Associate Professor of Medicine at Harvard Medical School and Clinical Director of the Division of Infectious Diseases and the HIV Program at Brigham and Women's Hospital, in Boston, MA

This segment focuses first on the SPRING-2 trial in treatment-naïve patients, followed by a discussion of the SAILING trial, which studied a treatment-resistant population. SPRING-2 was one of the key phase 3 studies in a treatment-naïve population. Patients were treated with dolutegravir 50 mg once daily or raltegravir 400 mg twice daily with a background regimen of two nucleoside reverse transcriptase inhibitors for 48 weeks. Frank says, it “demonstrated that dolutegravir performed in a noninferior way to raltegravir.”

In addition to virologic outcomes, “one of the fascinating observations so far with dolutegravir is that,” Sax says, “so far, we have not seen, in a treatment-naïve patient, anyone develop resistance to this drug.” It also could be helpful for resistant patients, he says. “It’s replacing one of our best drugs, which is raltegravir, because the only differences between them is dolutegravir may be a little bit better in most ways, once a day, higher barrier resistance, smaller pill,” says Sax. The exceptions to these are slightly fewer drug-drug interactions with raltegravir, which also does not inhibit tubular secretion of creatinine, he says.

For patients who have failed treatment, DeLuca says “your goal is to have at least three fully active agents in their regimen and sometimes praying.” But treatment failure is not completely unavoidable due to resistance, or patients who were “victims of sequential monotherapy. They’ve been here throughout the whole entire thing where they had AZT and then DDI, one drug added to another failing drug, led to multiple failing resistant mutations,” he says.

Thanks to advances in therapeutic options, there are now patients with HIV who have had the diagnosis and have been treated for decades. “I have a lot of patients I’ve been taking care of for more than 20 years,” says Frank. As for DeLuca, he says, “My oldest patient is 75 years old, and when I met him, he was on a ventilator with three opportunistic infections at the same time. He not only made it, he’s doing well.” In Sax’s practice, he says, “We have three patients in their 80s. They were diagnosed many years ago.”

Since the beginning of HIV treatment, a big change took place when raltegravir was approved in 2007, says Sax. “Once that happened, suddenly a lot of the patients that had struggled with resistance, we were able to put together regimens using a combination of raltegravir and other drugs selected by resistance testing, so that virtually everyone in practice now who’s come into their care is virologically suppressed,” he says.

This is because, as Frank points out, “these drugs work if people take them.” He says that the combination of boosted darunavir, raltegravir, and etravirine “enabled almost everybody who had not had the opportunity to be on an effective regiment to get their viral load undetectable.” And, as long as it is not very advanced disease with many comorbidities and co-infections, Frank says, “HIV is a very easy disease to manage.”

While SPRING-2 tackled treatment-naïve disease, the SAILING trial included patients with HIV-1 who were resistant to two or more classes of antiretroviral drugs. They were treated with dolutegravir 50 mg once daily or raltegravir 400 mg twice daily with a background regimen of two nucleoside reverse transcriptase inhibitors for 48 weeks. “In this study, dolutegravir was superior to raltegravir. In addition, resistance occurred less commonly in the people on dolutegravir than on raltegravir,” says Sax.

A subanalysis of the SAILING trial showed that, in patients who received dolutegravir or raltegravir plus background regimens of just nucleoside analogs, “the dolutegravir arm had zero failures versus about a third of the patients in the raltegravir group, again implying something about the barrier to resistance, because often those nucleoside analogs were not fully active,” says Sax. He adds, “The take-home lesson from this study is in treatment-experienced patients, dolutegravir is really the preferred integrase inhibitor used.”