Cimduo and Temixys

Most common adverse events (in more than 10% of people taking it) are headache (14%), pain (13%), depression (11%), diarrhea (11%), and rash (18%) (when studied in combination with efavirenz). TDF is associated with long-term decreases in bone mineral density (BMD). BMD monitoring should be considered in people who have a history of bone fracture due to disease or are at risk for osteopenia or osteoporosis. While calcium and vitamin D levels can be checked to assess the need for these supplements, talk with your provider before starting on your own. TDF can cause kidney toxicities. Tell your provider about any pain in extremities, persistent or worsening bone pain and fractures, with or without muscular pain or weakness, as well as any concerning changes in urinary habits, as these could be signs of bone or kidney problems. Routine monitoring of estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein should be performed in all individuals with mild kidney impairment. Prior to initiation, people should be tested for hepatitis B virus (HBV) infection. Severe exacerbations of hepatitis B have been reported in people co-infected with hepatitis B who have discontinued medication (due to elimination of both lamivudine and TDF, which also treat HBV). Monitor liver enzymes closely in people co-infected with hepatitis B and, if appropriate, initiation of anti-hepatitis B therapy may be warranted upon discontinuation. Call your health care provider right away if you develop any of the following signs or symptoms of hepatitis: 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. Contains lactose, which can cause some abdominal discomfort, especially in patients sensitive to lactose. Read weight discussion in the online version of this page.

Weight gain is being more commonly recognized as a potential side effect. 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.

Do not take with Descovy, Emtriva, Epivir-HBV, Hepsera, Truvada, Vemlidy, or Viread, which are used for the treatment of hepatitis B. Tenofovir DF decreases the concentration levels of Reyataz, therefore when Reyataz is taken with Cimduo or Temixys, it is recommended that Reyataz 300 mg be taken with Norvir 100 mg (all as a single daily dose with food). In addition, Reyataz/Norvir, Prezista/Norvir, and Kaletra increase tenofovir DF concentrations; therefore, it is recommended patients be monitored for TDF-associated adverse events, particularly decreases in kidney function.

Avoid taking with drugs that negatively affect the kidneys, including chronic use or high doses of anti-inflammatory drugs for pain such as Advil or Motrin (ibuprofen) and Aleve (naproxen). Avoid administration of sorbitol with Cimduo and Temixys. Hepatic (liver) decompensation, some fatal, has occurred when using lamivudine and interferon alfa (with or without ribavirin) for hepatitis C (HCV) treatment. (Of note, interferon alfa is no longer used for the treatment of hepatitis C). Cimduo and Temixys may be used with HCV drugs Harvoni or Zepatier, depending on the third drug in the HIV regimen; monitor for tenofovir toxicities if used with Epclusa. 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. 

Cimduo and Temixys are slightly different versions of Truvada, but contain 3TC instead of Truvada’s FTC. The two meds are essentially equivalent. The niche for these medications is that they may be a cheaper option for some insurance plans because they contain generic drugs. They also allow for some new or unique co-formulations (such as with Delstrigo, Symfi, and Symfi Lo). Cimduo and Temixys received DHHS HIV treatment guidelines recommendation as a component for initial ART for most people with HIV. TDF is falling out of favor since the newer formulation tenofovir alafenamide (TAF) was approved. TAF is safer on kidneys and bones than TDF. Unlike Truvada, Cimduo and Temixys are not approved for PrEP (HIV prevention). DHHS treatment guidelines recommend Cimduo, Temixys, Truvada, or Descovy (which contains TAF) over Epzicom as the preferred NRTI component for initial therapy (unless Epzicom is paired with Tivicay). Kidney function must be monitored before and during treatment and these may not be a good option for patients with underlying kidney problems.

When the virologic efficacy of Cimduo was compared to Truvada (each combined with Sustiva or nevirapine or a boosted PI) in a study, Cimduo was associated with higher rates of virologic failure compared to Truvada when paired with an NNRTI; however, there was no difference in the rates of virologic failure when paired with a boosted PI. It should be noted the people in the study who were taking Cimduo generally had higher viral loads, lower CD4 counts, and were more likely to be using injection drugs at the start of the study compared to patients taking Truvada. Another study examining historical data noted viral resistance was more common with Cimduo than with Truvada, however this was not observed in clinical trials. Cimduo and Temixys are recommended by DHHS as one of the preferred NRTI combination components of an ART regimen during pregnancy.

Dr. Melanie Thompson:

Because tenofovir disoproxil fumarate (TDF) and lamivudine (3TC) are both off-patent, new combination tablets are now available. Coformulated TDF/3TC is accepted by guidelines panels as interchangeable with TDF/FTC for treatment (but not prevention!) and is recommended as a nuke backbone option for starting treatment.

Both TDF and 3TC have activity against hepatitis B.

Although this is confusing, these combination tablets are technically “brand”—not generic—drugs, even though both components are off-patent. This means that, unlike for generic drugs, the manufacturers can provide co-pay cards/coupons that cover some out-of-pocket costs, just as happens for other brand-name HIV drugs.

Now, here’s my editorial comment about all of this. It is extremely disappointing that the price of these drugs is still high, with a Wholesale Acquisition Cost (WAC) of $10,000–12,000. They are relatively cheap to make, and the manufacturers, Mylan and Celltrion, didn’t have to do the research to develop them. There are co-pay cards to offset some out-of-pocket costs, but allow the manufacturer to maintain high prices.

Activist Bridgette Picou:

Both medications are fixed-dose combination pills containing two medications, lamivudine and tenofovir DF (TDF). As used in daily dosing, you can take them with or without food. Because of the TDF component, you will need to test for kidney toxicity and bone health. Know your hepatitis B virus (HBV) status. Do not suddenly stop these medications if you have HBV, as it can cause a harmful flare up of your hepatitis. Both are lower-cost alternatives taken in conjunction with other HIV meds to complete a regimen.