- The antiviral drug tenofovir can be used to treat both HIV and hepatitis B
- Researchers analysed the impact of switching from an older to a newer version of the drug
- People co-infected with HIV and hepatitis B saw improvements in kidney and liver health
If left untreated, chronic hepatitis B virus (HBV) infects the liver and causes ongoing inflammation in this organ. Over time, healthy liver tissue is gradually replaced with scar tissue. As a result, the liver becomes increasingly dysfunctional and shrinks. This can lead to a heightened risk of problems, including persistent fatigue, loss of appetite, nausea, fluid build-up, abdominal infections, and problems with memory and thinking clearly. As scar tissue accumulates in the liver, there is an increased risk for liver cancer and death.
Treatment for HIV and HBV
In Canada and other high-income countries, people who are co-infected with HIV and HBV are usually treated with a combination of several drugs that includes at least the following two drugs:
- TDF (tenofovir DF) + FTC – sold as Truvada and available in generic formulations
- TAF (tenofovir alafenamide) + FTC – sold as Descovy
Tenofovir (regardless of formulation) and FTC have activity against both HIV and HBV. People with HIV who are taking tenofovir + FTC need an additional drug, as those two drugs are not sufficient to suppress HIV. TDF is the older formulation of tenofovir; TAF is the newer formulation. Clinical trials have generally found that TAF is associated with a reduced risk for side effects such as kidney injury and bone thinning compared to TDF.
Fixed-dose combination HIV treatments that have TAF as a component include the following:
- Biktarvy – bictegravir + TAF + FTC
- Odefsey – rilpivirine + TAF + FTC
The need for real world data
In general, for many conditions, large industry-sponsored clinical trials tend to enroll carefully selected participants. These trials may not always be representative of the average population in a clinic, as patients may be older and/or have several health conditions. As a result, researchers sometimes initiate clinical trials with what they call “real world data,” which include a more representative patient population with a condition that they wish to study.
A Canadian study
A team of researchers in several Canadian provinces pooled data from 82 people with both HIV and HBV who initially used TDF in their regimens and who subsequently switched to TAF. The researchers stated that, overall, the switch to TAF had a “positive influence” on several laboratory tests, which found improved kidney health and reduced liver inflammation over the course of two years after switching.
Study details
Researchers at major clinics in British Columbia, Alberta, Saskatchewan and Ontario reviewed data collected from 82 participants who were co-infected with HIV and HBV. Upon entering the study, their average profile was as follows:
- age – 56 years
- 87% men, 13% women
- major ethno-racial groups: White – 51%; Black – 20%; Asian – 9%
- common co-existing health conditions included: kidney injury – 32%; severe liver injury – 23%; high blood pressure – 18%; abnormal lipid levels – 15%; diabetes – 9%; cardiovascular disease – 7%
The researchers did not provide information on HIV-related factors such as the CD4+ counts or viral loads of participants, as no changes would have been expected.
Researchers reviewed data collected prior to the switch to TAF and for about two years after. Medical records indicated that all participants had been taking the older formulation of tenofovir, TDF, for about seven years prior to switching.
Results
At the time participants entered the study (while on TDF), 95% had suppressed levels of HBV in their blood. After switching to TAF, this figure increased to 98%.
Overall, in the course of the study the researchers found an improvement in measures of kidney and liver health.
Kidney health
A common measure of kidney health is called estimated glomerular filtration rate (eGFR). While participants were on TDF, eGFR fell over time, signalling declining kidney health. However, after switching to TAF, the researchers stated that there was a “negligible” average decrease in eGFR from 80 to 79 mL/minute.
Averaging lab test results from different patients can sometimes mask underlying issues, particularly in people who have imperfect health. So, researchers then analysed data from 12 participants who had an eGFR of 60 mL/minute or less while they were taking TDF; that is, these people had a level of reduced kidney health. After switching to TAF, six of these 12 people had their eGFRs rise to 60 mL/minute or greater, indicating that their overall kidney health had improved.
Liver enzyme levels
The level of the liver enzyme alanine transaminase (ALT) in the blood is a common measure of liver health. Elevated levels of ALT are associated with liver inflammation. Overall, researchers found no significant changes in levels of ALT after participants switched to TAF. However, among a subgroup of 29 people who had elevated ALT prior to the switch, ALT levels generally declined after participants began using TAF. This suggests improved liver health.
Lipid levels
After participants switched to TAF, there were no clinically significant changes in levels of the following lipids in the blood:
- total cholesterol
- triglycerides
- LDL-cholesterol
- HDL-cholesterol
When researchers considered factors such as age, gender, kidney health and the use of lipid-lowering medicines called statins, there were still no significant changes in lipid levels after the switch to TAF.
Some other studies of TAF were associated with modestly increased levels of lipids.
Bear in mind
The present study used data that was collected for one purpose and later analysed for another purpose. Such a study design could inadvertently introduce bias when scientists interpret the data. However, this study’s overall findings are similar to what has been reported from a 274-person study in Taiwan that also enrolled co-infected people. In that study, researchers found that the use of TAF was associated with improved kidney health and bone mineral density. The latter assessment was not part of the Canadian study.
The present Canadian study confirms the benefit of switching from TDF to TAF in people with HIV and HBV co-infection.
—Sean R. Hosein
Resources
Hepatitis B – Public Health Agency of Canada
Hepatitis B – Canadian Liver Foundation
Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV — U.S. Department of Health and Human Services
REFERENCES:
- Sarowar A, Coffin CS, Fung S, et al. Effect of antiretroviral switch from tenofovir disoproxil fumarate to tenofovir alafenamide on alanine aminotransferase, lipid profiles, and renal function in HIV/HBV-coinfected individuals in a nationwide Canadian study. JAIDS. 2022 Dec 1;91(4):368-372.
- Dienstag JL. Chapter 341. Chronic Hepatitis. In: Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. eds. Harrison’s Principles of Internal Medicine, 21e New York, NY: McGraw-Hill; 2022.
- Deeks ED. Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs. 2018 Nov;78(17):1817-1828.
- Mayer KH, Molina JM, Thompson MA, et al. Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet. 2020 Jul 25;396(10246):239-254.
- Huang YS, Cheng CY, Liou BH, et al. Efficacy and safety of elvitegravir/cobicistat/ emtricitabine/tenofovir alafenamide as maintenance treatment in HIV/HBV-coinfected patients. JAIDS. 2021 Apr 1;86(4):473-481.