HIV PEP drugs: Truvada® combination therapy

As HIV PEP drugs develop, companies are striving to make the drug schedule easier to follow and for patients to take. One of the most successful combination therapies is Truvada® by Gilead Sciences. This drug, which is a combination of a reverse transcriptase inhibitor emtricitabine (Emtriva®) and the defective nucleoside analogue tenofovir (Viread®), integrates into the DNA strand during translation from RNA to DNA and stops the process cold. Truvada® is effective both for PrEP (pre-exposure prophylaxis) used by those at risk of exposure to HIV as a preventative, and PEP (post-exposure prophylaxis) by those believed to have been exposed to the virus to prevent integration and chronic infection.

This clinic commonly uses Truvada® in combination with raltegravir (Isentress®) for PEP due to the effectiveness of the combination and lack of negative interaction between the two drugs.

Side effects

Side effects of Truvada® are those seen with most of the nucleoside and nuclease inhibitors. Most common is gastrointestinal distress such as

  • nausea
  • diarrhoea
  • gastric pain

Side effects also can include

  • difficulty in sleeping
  • tiredness and possible depression and anxiety that results from little sleep
  • headaches and dizziness
  • redistribution of fat from the limbs to the torso.

Hepatitis & Liver Dysfunction

Hepatitis and liver dysfunction are two most dangerous potential side effect of Truvada® due to the stress the drugs put on the liver – the organ responsible for breaking down the drugs before passing them to the kidneys to be cleared. Symptoms to watch out for are

  • jaundice (yellowing of the skin)
  • dark urine
  • clay coloured stool
  • fatigue
  • loss of appetite
  • gastric upset
  • weight loss.

If you have any of these symptoms after starting on Truvada®, seek immediate medical advice. Hepatitis B virus (HBV) may be inhibited by Truvada® and some patients with HBV have reported acute hepatitis when stopping PEP as a result of the HBV recovering and causing illness. Make sure your doctor is aware of any liver disease or HBV infection so that they can provide extra support.

Kidney Disorder

Kidney disorder is the other dangerous side effect to watch for. The drugs are cleared by the kidneys following metabolism from the liver and this puts and extra strain on the organs.  Unlike liver disease, there are few early warning symptoms that the kidneys are struggling so your doctor will have you taking regular blood tests to check creatinine levels as well as urine tests to look for increased glucose or protein or serum phosphorous. These are annoying but having to do dialysis weekly for the rest of your life will be even more of a strain on your schedule so it is essential that you get these tests done. Ensure your doctor is aware of any prior kidney disease as they will need to offer extra support while you are on PEP.

Lactic Acidosis

A rare but possibly life-threatening side effect of both drugs in Truvada® is lactic acidosis. Lactic acid is produced by the muscles during exercise and is what makes your muscles ache afterwards. Overproduction of lactic acid can increase the acidity of the blood to dangerous levels and can even lead to death. Symptoms to watch for are

  • unexplained muscle aches or weakness
  • shortness of breath
  • unexplained fatigue
  • cold hands and feet
  • irregular or racing heartbeat
  • dizziness

While dizziness and fatigue are a common side effect of Truvada®, if seen in combination with any of the above symptoms, or if you are experiencing any of the others listed, seek medical attention immediately. Do not continue with Truvada® until it is confirmed that the drug is not causing your symptoms and the doctor has advised it is safe to continue. This side effect is not common so while you should be aware of it and watch for the symptoms, you should not be overly concerned about the possibility.

Other rare side effects seen with Truvada® are weakening of the bones, so inform your doctor if you have osteoporosis or other bone disorders. Unusual dreams have been experienced with Truvada® so you should not be concerned if you start experiencing vivid dreams, they are not an omen, just a side effect. Not all side effects are listed here so if you are experiencing discomfort that you believe is linked to starting Truvada®, inform your doctor and they will advise if the condition is likely a result of the drug and if you should be concerned.

Immune reconstitution syndrome

Immune reconstitution syndrome can occur with all PEP drugs. This is due to the immune system recovering from the HIV attack and getting a bit overexcited. You may experience mild flu-like symptoms or localised inflammation as the immune system responds to the invasion.This is uncomfortable but generally a good sign that your body is fighting back. If the symptoms remain mild there should be no danger, though you should inform your doctor of any changes to your health. If you develop a fever or the symptoms are severe, you should seek medical attention as an overactive immune system can cause damage if it gets out of control.

Allergic Reactions

As with all medications, an allergic reaction is always a possibility and depending on the severity, can be life threatening. A rash is often the first sign. On its own, that is usually not dangerous but seek urgent medical attention if you have any of the following symptoms:

  • difficulty breathing
  • rapid heart rate
  • fever
  • swollen tongue or airways
  • swelling of the face
  • rash
  • The above symptoms in combination with dizziness and/or unexplained weakness.

Contraindications

Most are listed above as they relate to the side effects. Hepatitis or liver function problems, as well as any history of kidney disease should be made known to your doctor. Previous allergies to HIV medications, specifically the nucleoside analogue reverse transcriptase inhibitors or the direct reverse transcriptase inhibitors should be mentioned as well as any history, or family history, of osteoporosis or other bone disorders.

Truvada® is not believed to be damaging to the fetus during pregnancy, but there is insufficient data to say that for sure. Inform your doctor if you are pregnant and they will decide if you require the drug based on your risk factors for HIV infection. Truvada® and HIV are both transmitted through breastmilk and you should not breastfeed while taking Truvada® or if you have a suspected HIV infection as the virus can be passed to your baby.

Drug interactions

Most anti-HIV drugs contain similar analogues to emtricitabine and tenofovir and combining them can lead to overdose and severe side effects. The dose of the drug is carefully controlled to give the most effectiveness for the least side effects. Often doubling up does not increase the drugs action against HIV but will make the side effects worse. If you do miss a dose, you are advised to continue the next dosage as normal and not take an extra one. Inform your doctor of any anti-HIV drugs, as well as any other anti-virals (e.g. for Hepatitis B), you may be taking as a number of the anti-HIV drugs have been shown to be effective against other viruses and may in some circumstances be prescribed for conditions not normally used for.

Drugs that stress the liver or kidneys can increase your chances of these organs being damaged. Your doctor will be aware of what drugs can exacerbate these symptoms so be sure to inform them of anything else you are taking. Other drugs to watch out for are those such as the antibiotic rifampicin which is often prescribed for common infections but which increases liver metabolism and thus the speed at which the liver clears drugs. It may result in clearing the PEP drugs out of your system too soon and your doctor needs to be aware of such drugs as it may be necessary to increase your dose for it to remain effective.

Herbal remedies are not always safe and can interact with prescription drugs. It is important that you give your doctor a list of any supplements or traditional medicines you are on so they can ensure they are not going to negatively impact your treatment.

Additional information

Truvada® was approved by the FDA as recently as 2012 as one of the first combination therapies for HIV. It leads what is a now a rapidly expanding field of combination medication that is not just making life simpler for those affected by HIV, but is also saving lives in Third World countries.

Anti-virals that target viral proteins, while effective, are often the first drugs that the virus is able to develop resistance to. This is the reason for the combination therapy, they not only knock the virus out quicker but also knock out any that has managed to develop resistance to one of the drugs. However, where HIV medication is scarce or expensive, there is always the temptation to reduce the dose down to a single drug. By combining the drugs into a single tablet, the drug companies are effectively combating incorrect dosing due to poverty or corrupt medical policies. These single-drug combinations are not only saving lives of those currently affected by HIV but also lives in the future as it delays the development of drug-resistant strains.

The HIV combination therapies have also paved the way for effective use of drug combinations in other diseases, initially in people with HIV comorbidity with other diseases. Trials are starting to combine HIV and tuberculosis treatments, a huge problem in many Third World countries. The same poverty and resistance cycle is seen with tuberculosis as like HIV as it requires multiple drugs over a long treatment period. Tuberculosis is making an unfortunate comeback across the world and this may well be one of the most viable strategies to stem the tide.

Other areas to watch are combination therapies for HIV and HBV. These diseases are often seen together and a number of antivirals for HIV are showing promise as a treatment for HBV as well as a surprising number of unrelated viruses. In the future, it may be that you will be able to have a single pill prescribed that is designed to treat your specific combination of medical conditions. While it is not nice to have to take Truvada®, you can take some comfort in the fact you are participating in medical history, at the forefront of a field that will change the way medicine is practiced worldwide.

For more information see:

WebMD – Truvada®

http://www.webmd.com/drugs/2/drug-91482/truvada+oral/details

Truvada® official website.

http://www.truvada.com/

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