Juluca

Both dolutegravir and rilpivirine are generally well tolerated. Side effects observed in greater than 2% of study participants were diarrhea and headache. New data associate INSTIs  with weight gain; see “More information.” Go to positivelyaware.com/articles/weighty-concerns and positivelyaware.com/articles/fatty-tissues. Dolutegravir and rilpivirine can each cause a small, reversible increase in a kidney function test (serum creatinine) within the first few weeks of treatment without affecting actual kidney function. There have been rare reports of depression and suicidal ideation, primarily in patients with a history of psychiatric illnesses, in people receiving INSTI-based regimens. The DHHS guidelines recommend closely monitoring patients with pre-existing psychiatric conditions on an INSTI. Liver enzymes should be monitored in people with hepatitis B or C and taking dolutegravir. Call your health care provider right away if you develop any of the following signs or symptoms: yellowing of the skin or whites of the eyes; dark or tea-colored urine; pale-colored bowel movements; nausea or vomiting; loss of appetite; or pain, aching, or tenderness on the right side below the ribs.

Do not take Juluca with rifampin, rifapentine, or the anti-arrhythmic dofetilide (a heart medication). If taking rifabutin, add an Edurant tablet to Juluca dose. If you take antacids, laxatives, or other products that contain aluminum, calcium carbonate, magnesium, or buffered medicines, Juluca should be taken (with a meal, as always) at least 4 hours before or 6 hours after you take these medicines. Alternatively, these medications can be taken at the same time with Juluca and the meal. Take Juluca with a meal 4 hours before or 12 hours after you take H2 blocker acid reducers (Pepcid, Zantac, Tagamet) or buffered medications. Juluca should not be taken with proton pump inhibitors (such as Aciphex, Dexilant, Prilosec, Prevacid, Protonix, Nexium). Avoid taking Juluca with some seizure medicines (carbamazepine, oxcarbazepine, phenobarbital, and phenytoin) or St. John’s wort. DHHS HIV treatment guidelines suggest that metformin be started at the lowest dose and titrated based on tolerability and clinical effect. Monitor for metformin adverse effects.

When starting or stopping Juluca in people taking metformin, dose adjustment of metformin may be necessary to maintain optimal glycemic control. Not intended to be taken with other HIV medications, unless prescribed that way. 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 which are not listed here.

Juluca was the first two-drug combination approved as a complete regimen for HIV. It replaces a three- or four-drug therapy for people with undetectable viral loads who want to switch to a simpler or smaller tablet regimen. People switching to Juluca must be virologically suppressed (with viral loads of less than 50 copies per mL) on a stable antiretroviral regimen for at least six months. This is a new HIV treatment strategy and potentially a game changer, especially with other dual-drug antiviral medications on the way. People who are able to take their medications consistently as directed and achieve undetectable viral load can take advantage of this strategy with less exposure to HIV medications. Currently, people taking HIV treatment must start out with a three-drug regimen (which may include the use of one of the single-tablet regimens, or STRs), then switch to Juluca after being undetectable for six months.

Juluca still works against two stages of the virus life cycle, similar to three-drug regimens. This is how the combination was used in clinical studies to date. DHHS guidelines listed this combination as a “Strategy with good supporting evidence” around the time of its FDA approval. The guidelines also called Juluca “a reasonable option when using nucleoside drugs is not desirable”—for example, due to previous toxicity—with an A1 rating (strong recommendation based on randomized controlled trials). Juluca is the first nucleoside-free STR. Currently, all the STRs except Dovato and Juluca contain two nucleoside drugs. Juluca contains two currently available medications. Weight gain is increasingly recognized as a side effect of INSTIs. In the community, enlargement of the stomach and waist area can be distressing. According to the DHHS HIV treatment guidelines, “Weight gain has been associated with initiation of ART [antiretroviral therapy] and subsequent viral suppression. The increase appears to be greater with INSTIs than with other drug classes. Greater weight increase has also been reported with TAF than with TDF, and greater with DOR than EFV.” Other factors have been associated with weight gain in addition to medication used, including race, sex, and previous overweight status.

There is no word yet on reversibility, but the race is on to find more answers. Juluca is the smallest STR, which may be advantageous to individuals who have difficulty swallowing. For individuals with HIV-2, commonly found outside the U.S., an NNRTI would not be recommended as HIV-2 is inherently resistant to NNRTIs. Rilpivirine is an alternative drug for use during pregnancy, and although dolutegravir is now a preferred medication in pregnancy as well as for those who are trying to conceive, U.S. HIV perinatal treatment guidelines suggest using three-drug regimens. Find the discussion on page C-51 of perinatal guidelines at hivinfo.nih.gov.

Dr. Melanie Thompson:

Juluca, containing dolutegravir and the NNRTI rilpivirine, is a two-drug STR nuke-sparing regimen that was approved only for those whose virus is suppressed with no resistance to either drug. It is a reasonable and simple option for people who have extensive NRTI resistance from the earlier days, but whose virus is still sensitive to rilpivirine and dolutegravir. It also avoids nuke-related side effects.

Juluca does require attention to drug interactions. Proton-pump inhibitors (such as Prilosec and Nexium) reduce the absorption of rilpivirine and rifabutin requires a dose adjustment for rilpivirine. Dofetilide (for abnormal heart rhythm) and some seizure medications are contraindicated. In addition, supplements containing calcium, magnesium, zinc, aluminum, or iron can lower levels of dolutegravir, and dosing recommendations should be observed. 

Juluca must be taken with at least 400 calories of solid food for rilpivirine absorption. This is important because rilpivirine has a low barrier to resistance, so adequate levels are essential.

It should be noted that kidney stones have been associated with rilpivirine. 

The very small increased risk of neural tube defects associated with dolutegravir in the updated Tsempano study should be discussed with persons of childbearing potential. (See Tivicay.)

For a two-drug regimen, Juluca is fairly pricey.

Activist Bridgette Picou:

While in the single-tablet regimen category, Juluca contains only two medications rather than three or four. It is used for patients who have been undetectable (virally suppressed) for at least 6 months. It should be taken with food in a meal containing at least 400 calories, and can be taken at any time of day.