A Current Look at Managing HIV

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William Short, MD, MPH, AAHIVS: One of the things that’s happened in the latest iteration of the Department of Health and Human Services’ guidelines for antiretrovirals in adults and adolescents is that we now are finally seeing a shift to the use of integrase inhibitors as the primary mode of treatment for patients who are naïve to therapy. And that largely has to do with their efficacy, their tolerability for patients, as well as their [adverse] effect profile and drug-drug interaction profile.

That’sbeen the latest shift with the guidelines. And preferably within the integrase class, it’s been to those that we call unboosted, to eliminate those drug-drug interactions.

It really hasn’t limited our treatment options. What it’s done is, the guidelines follow with what’s best for the patient, and they take a look at all the data out there and see what’s most tolerable, what’s most efficacious for their patient, and therefore that shift has occurred as a result of that.

When you look through what’s recommended and preferred, and the way the guidelines have sort of shifted, is that what’s recommend for all patients living with HIV. And what you’ve seen is a shift to the use of 2 nucleoside reverse transcriptase inhibitors [NRTIs]. Largely lamivudine or emtricitabine, in combination with tenofovir-based regimen, and that would either be tenofovir disoproxil fumarate or tenofovir alafenamide, which is the newer version. And those are again going to be combined with either one of the integrase inhibitors. And largely, dolutegravir and bictegravir are the 2 listed as the preferred options. And when you look at why that’s chosen over maybe elvitegravir or raltegravir, it has to do with a couple of factors.

Raltegravir, just for example, is a great drug. It’s a great integrase inhibitor. The downside in using raltegravir is that it’s twice a day as opposed to a once-a-day regimen. And right now it’s not available in a fixed dose combination with others. So you are then looking at multiple pills a day, and a twice-a-day regimen.

Elvitegravir is another integrase inhibitor, what we call first-line integrase. It’s in combination with cobicistat, which is a booster. When you throw cobicistat into the mix, what you have to worry about then is GI [gastrointestinal] intolerance, GI issues, or drug-drug interactions. And as we have patients living longer with HIV, we know that they’re on other concomitant medications, and with that comes a potential for drug-drug interactions. So we try to avoid, if we can, using those booster agents, which could interfere.

What’s happened over time is protease inhibitors, which in 1996 were the first drugs approved that put a really big dent in the mortality and morbidity of people living with HIV, they were really the saviors at the time. And then over time things have changed and new drugs and new combinations have come about, largely being the integrase. Now protease inhibitors are still used, but they’re really used for certain key populations, largely being those where you’re unsure about their ability to adhere to a regimen. That’s where they come in first-line. And unfortunately the non-nukes [non-nucleosides] have fallen out of favor for a couple different reasons. One, our most common drug we used to use was Atripla, and that is coformulated with 2 NRTIs and an NNRTI [non-nucleoside reverse transcriptase inhibitor], and that NNRTI was efavirenz, and it was great in 2006 because it was the first single tablet regimen we had, so everybody wanted to be on that single tablet regimen.

However, looking at the adverse effect profile, this was an issue. There was a lot of central nervous system adverse effects, dizziness, intolerance, sleep disorders. Patients had very vivid dreams. And then there was an analysis done that showed that there was double the rate, or a 2 fold increase in [risk of suicide] with that compound. So as a result, in the guidelines it was lifted off as a preferred option and the integrase was moved up. So when I look [at] what I’m prescribing, largely I’m prescribing integrase inhibitors for naïve patients. And then secondarily for certain situations, a protease inhibitor, and less likely use NNRTIs.