Isentress HD (and Isentress)

In general, raltegravir is very well tolerated with infrequent side effects. Those reported in up to 3–4% of study participants include insomnia, nausea, headache and fatigue. The side effect profile in children is comparable to adults. INSTIs have been associated with weight gain.

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 (such as depression, sleep disturbances and dizziness) in some retrospective cohort studies and case series. The HHS 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 considered by some as a relative inconvenience. According to HHS HIV treatment guidelines, raltegravir was 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 along with Truvada or Descovy is a preferred drug regimen for PEP (post-exposure prophylaxis—preventing HIV acquisition after a potential exposure), as well as two other regimens: Biktarvy or Tivicay plus Truvada or Descovy. Isentress, but not Isentress HD, 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, but the powder formulation remains a preferred initial regimen for newborn and infant treatment and PEP following birth.

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

Dr. Melanie Thompson:

Raltegravir, the oldest INSTI, is no longer recommended for initial therapy by HHS or IAS-USA guidelines panels because newer INSTIs are less susceptible to viral resistance and can be given once daily with lower pill burden in most situations. The HD formulation allows two pills to be taken once daily, but it is not available as an STR. In pregnancy, raltegravir must be given at 400 mg twice daily. When given with rifampin for tuberculosis, the dose of raltegravir is 800 mg twice daily.

Activist Joey Wynn:

About 17 years ago Isentress came onto the scene as the first integrase strand transfer inhibitor (INSTI). It is currently prescribed for initial therapy in certain situations, but not for the majority of folks just starting treatment. Pregnancy is the biggest reason for using this older but easy to take treatment; it’s still a viable option, so don’t count this well tolerated option out just yet. In retrospect, I’ve not heard anyone taking Isentress HD complain about weight gain like other agents in its class. I hope someone does some kind of formal study to confirm if this is a true (beneficial) characteristic of this particular agent.