Renal Safety of SOF/LDV in Combination With TDF in HCV/HIV Coinfected Patients

Although use of sofosbuvir/ledipasvir (SOF/LDV) may decrease the mean glomerular filtration rate (GFR) in patients who are hepatitis C virus (HCV)/HIV coinfected, concomitant use of tenofovir (TDF) is not associated with an increase in renal toxicity, according to an observational study published in BMC Infectious Diseases.¹

Recent studies have indicated that concomitant use of LDV and boosted protease inhibitors, such as SOF, may increase the risk for TDF nephrotoxicity because both these medications can increase TDF levels.^2,3 Therefore, most guidelines recommend changing the antiretroviral therapy or the direct-acting antiviral therapy; however, if a triple combination is still recommended, renal function must be closely monitored.^2,4-6

Researchers in Portugal analyzed the data from 273 HIV/HCV coinfected patients treated with SOF/LDF, 145 of whom received a non-TDF regimen, 78 of whom received a nonboosted TDF scheme, and 50 of whom received TDF and a boosted protease inhibitor.¹

Although the researchers observed a statistically significant decrease in estimated GFR during treatment in all study groups, the decrease was more pronounced in those receiving nonboosted TDF.

The decrease in estimated GFR was greater in patients treated for 24 weeks and in cirrhotic patients, but at the end of follow-up, the estimated GFR recovered in all groups. Thus, the decrease was small and reversible after SOF/LCD discontinuation, and TDF was not associated with an increase in renal toxicity.

“We observed a significant decrease in eGFR during treatment in all study groups, that was small and reversible after SOF/LDV discontinuation. TDF was not associated with an increase in renal toxicity,” concluded the authors.¹ However, they also noted that, “if TDF is used in patients who are receiving SOF/LDV, signs of nephrotoxicity should be carefully monitored, especially in cirrhotic patients.”

References

1. Soeiro CASP, Gonçalves CAM, Marques MSC, et al. Glomerular filtration rate change during chronic hepatitis C treatment with sofosbuvir/ledipasvir in HCV/HIV coinfected patients treated with tenofovir and a boosted protease inhibitor: an observational prospective study. BMC Infect Dis 2018;18(1):364.
2. El-Sherif O, Khoo S, Solas C. Key drug-drug interactions with direct-acting antiviral in HIV-HCV coinfection. Curr Opin HIV AIDS. 2015;10:348-354.
3. German P, Garrison K, Pang PS, et al. Drug-Drug interactions between anti-HCV regimen ledipasvir/sofosbuvir and antiretrovirals. In: Conference on Retroviruses and Opportunistic Infections; 2015; Seattle. Abstract 82. Available from http://www.croiconference.org/sessions/drug-drug-interactions-between-anti-hcv-regimen-ledipasvirsofosbuvir-and-antiretrovirals. Accessed February 23-26, 2015.
4. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2016. J Hepatol. 2017;66:153-194.
5. AASLD/IDSA HCV Guidance Panel. AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Available from: https://www.hcvguidelines.org/references/aasld-idsa-2015. Accessed July 2017.
6. Kaur K, Gandhi MA, Slish J. Drug-drug interactions among hepatitis C virus (HCV) and human immunodeficiency virus (HIV) medications. Infect Dis Ther. 2015;4:159-172.