Isentress and Isentress HD

In general, raltegravir is very well tolerated with infrequent side effects. Those reported in up to 3–4% of study participants include insomnia, nausea, and headache. The side effect profile in children is comparable to adults. See weight gain in “More information.”

Isentress may cause elevated levels of creatine phosphokinase (CPK, a muscle enzyme). Inform your provider or pharmacist if you have a history of rhabdomyolysis, myopathy, or increased creatine phosphokinase, or if you also take medications that may contribute to these conditions such as statins, fenofibrate, or gemfibrozil. INSTIs have been associated with adverse neuropsychiatric effects in some retrospective cohort studies and case series. The DHHS guidelines recommend closely monitoring people with pre-existing psychiatric conditions on an INSTI. Chewable tablets contain phenylalanine, which can be harmful to people with phenylketonuria.

It is important to take Isentress HD and Isentress only with other HIV drugs recommended by your provider because they and similar drugs are contained in other HIV medications: Biktarvy, Genvoya, Stribild, Tivicay, Triumeq, Dovato, Cabenuva, and Juluca. Isentress HD cannot be used with rifampin, but Isentress can; increase Isentress to 800 mg twice daily when using rifampin. Remember to decrease the raltegravir back to its original dose when you finish taking rifampin. There are no data on dosing of the chewable tablets with rifampin. There is no need to increase the raltegravir dose with rifabutin. With both Isentress HD and Isentress, avoid Gaviscon and other antacids containing aluminum or magnesium. Calcium-containing antacids such as Tums (calcium carbonate) can be used with Isentress, but not Isentress HD. Other acid reducers (such as Pepcid, Zantac, Prilosec, and Prevacid) are okay to use. Raltegravir is not recommended with carbamazepine or phenobarbital. Raltegravir can be used with Harvoni, Zepatier, or Epclusa. Unlike Isentress, Isentress HD cannot be used with Intelence or boosted Aptivus. Tell your provider or pharmacist about all medications, herbals, and supplements you are taking or thinking of taking, prescribed or not, as there are other drug interactions not listed here.

Isentress HD was approved in 2017. While the original formulation, Isentress, was well tolerated and highly effective, its twice-daily dose was seen by some as a relative inconvenience. According to DHHS HIV treatment guidelines, raltegravir was recently downgraded from a preferred component of an initial regimen in most individuals to a component of a regimen in only certain clinical situations due to the higher pill burden as well as the relatively lower genetic barrier against the development of resistance compared to second generation INSTIs. Raltegravir-based regimens may be preferred for people with high cardiovascular risk. Raltegravir is a preferred drug for PEP (post-exposure prophylaxis—preventing HIV acquisition after a potential exposure) along with dolutegravir. Isentress is one of the preferred INSTI medications in HIV treatment guidelines for pregnancy, 400 mg twice a day in combination with 2 NRTIs. In pediatric HIV guidelines, Isentress was downgraded in 2017 from “preferred” to an “alternative” part of an initial regimen for children ages 6–12.

Pregnant individuals can voluntarily enroll in the Antiretroviral Pregnancy Registry through their provider; go to apregistry.com.

Dr. Melanie Thompson:

Raltegravir, the oldest INSTI, was revolutionary at the time, but has been largely sidestepped in favor of the second-generation INSTIs. It is more susceptible to viral resistance than bictegravir, dolutegravir, or cabotegravir. It also requires twice-daily dosing or, in the HD formulation, two pills taken once daily, and it is not available as an STR. For these reasons, both the DHHS and IAS-USA guideline panels have downgraded raltegravir to “certain situations” for initial therapy. Pregnancy is one of those situations, as raltegravir appears to be safe in pregnancy, but must be given twice daily.

Activist Michael Broder:

Isentress, approved in 2007, was the first INSTI to enter clinical use. Isentress is one pill twice a day (original Isentress) or two pills once a day (Isentress HD). Isentress is currently recommended for initial therapy in certain situations, but not for most people starting treatment for the first time. To put it bluntly, Isentress is not as good, practically speaking, as the INSTIs dolutegravir (Tivicay) or bictegravir (a component of Biktarvy). For one thing, Isentress has a lower barrier to resistance than dolutegravir or bictegravir. In addition, Isentress-based regimens require more pills than other INSTI-based regimens. Moreover, Isentress is the only current INSTI that is not included as part of an STR. Given other available options, there are usually better alternatives to an Isentress-containing regimen. If your provider recommends an Isentress-containing regimen, they may have a good reason, but make sure they tell you what it is.