TDF drugs like Truvada can cause lactic acidosis, a potentially fatal complication of kidney failure. Even though the warning label on Truvada mentions lactic acidosis as a side effect of TDF, it downplays the risks. This has caused many people who take Truvada to suffer serious medical problems without being able to avoid it, such as:
- Heart arrhythmias, and
- Organ failure.
In this article, we will discuss:
- 1. The HIV treatment Truvada
- 2. TDF, or tenofovir disoproxil fumarate
- 3. Kidney failure and lactic acidosis
- 4. Studies show Truvada and TDF can cause lactic acidosis
- 5. Gilead representatives repeatedly deny TDF causes lactic acidosis
- 6. Lawsuits against Gilead for injuries caused by lactic acidosis
1. The HIV treatment Truvada
Truvada is an HIV treatment manufactured by the pharmaceutical company Gilead Sciences, Inc. It works by stopping HIV cells that have already entered the body from multiplying and spreading, though it does not eliminate those cells. As a result, Truvada is a treatment for HIV, but not a cure. It has to be taken continually to control the spread of HIV, and is popular as a prophylactic among people who are at risk of contracting HIV, including those who are in intimate relationships with people who are HIV-positive.
There are two drugs in Truvada:
- Emtricitabine, and
- Tenofovir disoproxil fumarate, or TDF.
2. TDF, or tenofovir disoproxil fumarate
TDF is the active ingredient in Truvada, as well as many other HIV drugs made by Gilead Sciences, Inc., including:
- Symfi-Lo, and
The drug TDF has been in use as an HIV treatment since the 1980s. However, it was not until Gilead modified it from a drug that could only be taken intravenously into one that could be taken orally that its use became widespread. Starting in 2001, Gilead began releasing its line of HIV treatments that are based on TDF. Since then, Gilead has cornered the market in HIV treatments.
However, TDF is an incredibly toxic drug. Worse, it is poorly absorbed in the body and so has to be taken in high doses. As a result, it can cause some severe side effects, including:
- A decreased bone density,1
- Kidney damage and renal failure,2 and
- Lactic acidosis.3
3. Kidney failure and lactic acidosis
Lactic acidosis is a medical complication of kidney failure.
One of those severe side effects of TDF-based HIV drugs like Truvada is kidney failure.4 The high levels of toxicity in TDF, together with the poor absorption levels in the body, mean that the kidneys have to work much harder when someone takes a TDF-based pill for their HIV. The toll this takes on the kidneys has been connected to a 34% increase in the risk of kidney damage, every year someone is exposed to TDF, a 33% increase for developing chronic kidney disease, and an 11% increase for a steep and sudden decline in kidney function.5
When kidneys get damaged, they struggle to continue distilling and eliminating a handful of certain chemicals from the bloodstream. These chemicals then back up and accumulate in the blood. When kidneys fail, the pace of this accumulation speeds up because these chemicals are not being eliminated, at all.
One of those accumulating chemicals is lactic acid, or lactate.
When lactate first starts to accumulate over a normal level, it creates the medical condition known as hyperlactatemia. The symptoms of hyperlactatemia include:
- Diarrhea, and
- Abdominal pain.
Because the symptoms of hyperlactatemia are general and not overly severe, they are rarely caught by patients and doctors.
As lactate builds up in the blood, hyperlactatemia turns into lactic acidosis. In lactic acidosis, there is so much lactic acid in the blood that the acidity of the lactate has lowered the blood’s pH level.
Overly acidic blood can cause a host of symptoms and medical complications, including:
- Cardiac arrhythmia, and
- Organ failure.
If not treated quickly and properly, lactic acidosis can be fatal.
4. Studies show Truvada and TDF can cause lactic acidosis
Ever since TDF drugs like Truvada have been in use, medical studies have suggested that they could cause lactic acidosis.
Clinical trials compared Gilead’s early TDF-based drugs with the drug stavudine, or Zerit, the existing HIV treatment. One of Zerit’s big drawbacks was the kidney problems that it was known to create, including lactic acidosis and its precursor, hyperlactatemia. One cohort study had found that Zerit caused hyperlactatemia in 8-21% of the people who took it and caused full-blown lactic acidosis in 1-2% of its patients.6 The clinical trials for TDF-based treatments concluded that there was little difference between TDF and stavudine on a patient’s kidneys, suggesting that Truvada would also pose a threat of causing lactic acidosis.7
A pair of placebo-controlled and randomized studies covering a total of 687 patients supported the inferences produced by these comparisons to Zerit. 16 of the patients in these studies, totaling 2% of the whole, developed lactic acidosis while taking TDF drugs, while no one in the placebo group developed the condition.8
Subsequent medical and case studies have suggested that lactic acidosis, while relatively rare in people taking TDF-based HIV drugs, usually developed within the first 20 months of treatment. Worse, the condition proved to be fatal around half of the time.9
Other studies suggested that lactic acidosis and hyperlactatemia could happen in people taking TDF-based drugs, even without any kidney damage. These studies suggested that TDF stopped HIV cells from spreading, but also inhibited certain mitochondrial DNA processes from happening in the kidney, as well.10
5. Gilead representatives repeatedly deny TDF causes lactic acidosis
In spite of these medical studies that connected TDF drugs like Truvada to lactic acidosis, representatives for Gilead continually downplayed the boxed warning that mentioned the condition on the drugs’ warning labels.
Early warning labels for TDF-based HIV drugs included a boxed warning that detailed the risks of developing lactic acidosis.11
However, representatives for Gilead Sciences, Inc. repeatedly claimed that this boxed warning – the most severe warning that could be required by the U.S. Food and Drug Administration (FDA) – was “a ‘wait and see’ warning” that had to be put on all drugs that worked like TDF. This insinuated that the boxed warning was a “class effect warning” that did not really apply to Truvada or Gilead’s other TDF-based HIV treatments. Instead, the representatives insisted that TDF drugs were “extremely safe” and had “no toxicities” that could lead to lactic acidosis. The FDA twice reprimanded Gilead with warning letters for their misleading claims.12
6. Lawsuits against Gilead for injuries caused by lactic acidosis
The injuries caused by lactic acidosis are severe and life-threatening. Because lactic acidosis can be caused by TDF-based drugs like Truvada, hundreds of lawsuits have been filed against Gilead Sciences, Inc. for their failure to warn doctors and patients of the risks of taking their drugs. These lawsuits also claim that Gilead withheld a safer alternative to TDF – a drug called tenofovir alafenamide fumarate, or TAF – in order to extend their market protection for HIV treatments.
These Truvada lawsuits demand punitive damages be assessed against Gilead for withholding TAF and putting innocent people at risk of getting hurt by a more dangerous drug. They also seek compensatory damages for:
- Pain and suffering,
- Past and anticipated medical expenses,
- Professional repercussions of a long recovery, including lost wages and reduced earning capacity, and
- Loss of consortium for the victim’s family.
Similar lawsuits have been filed against Gilead for injuries caused by their other HIV treatment pills, including:
A classic example of a mass tort claim that involves hundreds of people suffering similar injuries from the same course of conduct, it is likely that these lawsuits will be consolidated into a multidistrict litigation (MDL) in the future.
- Iwen F Grigsby, Lan Pham, Louis M Mansky, Raj Gopalakrishnan, and Kim C Mansky, “Tenofovir-associated bone density loss,” Therapeutics and Clinical Risk Management 6:41-7 (2010).
- Willem D.F. Venter, June Fabian, and Charles Feldman, “An overview of tenofovir and renal disease for the HIV-treating clinician,” South African Journal of HIV Medicine 19(1):817 (2018).
- Pablo Rivas, Jorge Polo, Miguel de Górgolas, Manuel L Fernández Guerrero, “Drug points: Fatal lactic acidosis associated with tenofovir,” British Medical Journal 327:711 (2003).
- See generally, Ustianowski A, Arends JE, “Tenofovir: What We Have Learnt After 7.5 Million Person-Years of Use,” Infectious Diseases and Therapy 4(2):145-57 (June 2, 2015).
- Scherzer R, Estrella M, Li Y, Choi AI, Deeks SG, Grunfeld C, Shlipak MG, “Association of tenofovir exposure with kidney disease risk in HIV infection,” AIDS 26(7):867-75 (April 24, 2012) and Steve Tokar, “Tenofovir, Leading HIV Medication, Linked with Risk of Kidney Damage,” University of California – San Francisco News Report (February 10, 2012).
- Boubaker K, et al., “Hyperlactatemia and antiretroviral therapy: the Swiss HIV Cohort Study,” Clinical Infectious Diseases 33(11):1931-7 (December 1, 2001).
- Gallant JE, et al., “Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial,” Journal of the American Medical Association 292(2):191-201 (July 14, 2004).
- Schooley RT, Ruane P, Myers RA, et al., “Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized double-blind study,” AIDS 16(9):1257-63 (June 14, 2002) and Cheng A, Barriere S, Coakley D, Chen SS, Wulfsohn M, Toole JJ, “Safety profile of tenofovir DF in treatment-experienced patients from randomized, placebo-controlled clinical trials,” Poster 4460 at the XIV International AIDS Conference, July 7-12, 2002 (Barcelona, Spain).
- Falcó V, et al., “Severe nucleoside-associated lactic acidosis in human immunodeficiency virus-infected patients: report of 12 cases and review of the literature,” Clinical Infectious Diseases 34(6):838-46 (March 15, 2002).
- See Murphy MD, O’Hearn M, Chou S, “Fatal lactic acidosis and acute renal failure after addition of tenofovir to an antiretroviral regimen containing didanosine,” Clinical Infectious Diseases 36(8):1082-5 (April 15, 2003) and Kakuda TN, “Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced mitochondrial toxicity,” Clinical Therapeutics 22(6):685-708 (June 2000).
- See e.g., Warning Label for Viread – Revised 2008.
- FDA Warning Letter to Gilead Sciences, Inc. – March 14, 2002 and FDA Warning Letter to Gilead Sciences, Inc. – July 29, 2003.