Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide as Maintenance Treatment in HIV/HBV-coinfected Patients

Yu-Shan Huang, MD; Chien-Yu Cheng, MD; Bo-Huang Liou, MD; Po-Liang Lu, MD, PhD; Shu-Hsing Cheng, MD, PhD; Yuan-Ti Lee, MD; Chun-Eng Liu, MD; Hsin-Yun Sun, MD; Chia-Jui Yang, MD; Hung-Jen Tang, MD; Shih-Ping Lin, MD; Mao-Wang Ho, MD; Sung-Hsi Huang, MD; Hung-Chin Tsai, MD, PhD; Chen-Hsiang Lee, MD; Chien-Ching Hung, MD, PhD


J Acquir Immune Defic Syndr. 2021;86(4):473-481. 

In This Article

Abstract and Introduction


Background: The efficacy and safety of switching from tenofovir disoproxil fumarate-based antiretroviral therapy to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (E/C/F/TAF) has not been widely investigated in HIV/hepatitis B virus (HBV)-coinfected Asian population.

Methods: Between February and October 2018, HIV/HBV-coinfected patients who had achieved HIV viral suppression with tenofovir disoproxil fumarate-containing regimens were switched to E/C/F/TAF. Assessments of plasma HBV and HIV viral load, HBV serology, renal function, lipid profiles, and bone mineral density (BMD) were performed at weeks 24 and 48 after switch.

Results: A total of 274 HIV/HBV-coinfected participants were enrolled, with 12.8% testing HBeAg-positive and 94.2% having plasma HBV DNA <20 IU/mL at baseline. At weeks 24 and 48, 92.7% and 89.8% achieved plasma HBV DNA <20 IU/mL; 4.7% and 5.1% had HBV DNA ≥20 IU/mL; and 2.6% and 5.1% had no data, respectively. At weeks 24 and 48, 95.6% and 94.2% of participants maintained HIV RNA <50 copies/mL, respectively. Compared with baseline, the median urine β2-microglobulin-to-creatinine ratio at week 48 decreased significantly from 165 to 90 μg/g (P < 0.001). The mean BMD of the spine and hip improved at week 48 (+1.77% and +1.33%, respectively). Significantly higher lipid profiles were observed after switch to E/C/F/TAF. Thirteen (4.7%) patients withdrew from the study before week 48, with 7 (2.6%) patients because of adverse effects.

Conclusions: Switch to E/C/F/TAF maintained HBV and HIV viral suppression and resulted in the improvement of proteinuria and BMD of the spine and hip but increased lipid levels in HIV/HBV-coinfected patients at week 48.


In Asia, approximately 15%–25% of the HIV-infected patients have concurrent chronic hepatitis B virus (HBV) infection.[1,2] HIV/HBV-coinfected patients are at a higher risk for acute hepatitis, chronic hepatic complications, and liver-related mortality than those with HBV monoinfection.[3,4] Therefore, sustained maintenance of HBV viral suppression is important for HIV/HBV-coinfected patients to prevent HBV-related liver damage.[5]

Tenofovir disoproxil fumarate (TDF), an antiretroviral agent used to treat HIV and HBV, has demonstrated long-term HBV suppression and a high genetic barrier to emergence of HBV resistance.[6,7] For patients coinfected with HIV and HBV, combination antiretroviral therapy (ART) containing TDF plus lamivudine (3TC) or emtricitabine (FTC) in addition to a third agent is the recommended first-line regimen.[8] However, long-term exposure to TDF may lead to nephrotoxicity and a greater loss in bone mineral density (BMD),[9,10] particularly among individuals who are aging and have small body habitus and multiple comorbidities.[11,12]

Tenofovir alafenamide (TAF) is a newer prodrug of tenofovir that achieves high active metabolite concentrations in peripheral blood mononuclear cells and lower plasma tenofovir levels.[13] In HIV-monoinfected patients, switching from TDF-containing to TAF-containing ART maintains HIV suppression and shows improvement in glomerular function, overall and tubular proteinuria, and BMD.[14,15] Clinical data also support the use of TAF-containing regimens in HIV-infected patients with mild-to-moderate renal impairment and those on hemodialysis.[16] For patients with chronic HBV monoinfection, 2 large studies reported similar rates of HBV viral suppression between TAF-treated and TDF-treated patients.[17–19] Although TAF is effective for HIV and HBV therapy, data on the efficacy of TAF in maintaining HBV viral suppression remain limited among HIV/HBV-coinfected patients. In a multinational study in which 72 HIV/HBV-coinfected patients were switched to coformulated elvitegravir, cobicistat, emtricitabine, and TAF (E/C/F/TAF),[20] 91.7% of the participants achieved virologic suppression for both HIV and HBV at 48 weeks. Improvements in creatinine clearance and proteinuria and declines in markers of bone turnover were observed; however, BMD was not assessed, and only 7 participants were Asians.[20] Current data from Asian populations living in areas of high HBV endemicity are scarce.

To further the understanding of the efficacy and safety of TAF-containing ART among HIV/HBV-coinfected patients, we conducted this multicenter observational study in Taiwan, where 15%–20% of HIV-infected patients born before the implementation of universal neonatal HBV vaccination have chronic HBV infection.[21]