Evolution of Estimated Glomerular Filtration Rate in Human Immunodeficiency Virus and Hepatitis C Virus-coinfected Patients Receiving Sofosbuvir-based Direct-acting Antivirals and Antiretroviral Therapy

Chen-Hua Liu; Hsin-Yun Sun; Szu-Min Hsieh; Wen-Chun Liu; Wang-Hui Sheng; Chun-Jen Liu; Tung-Hung Su; Tai-Chung Tseng; Pei-Jer Chen; Chien-Ching Hung; Jia-Horng Kao

Disclosures

J Viral Hepat. 2021;28(6):887-896. 

In This Article

Results

Participant Characteristics

Of the 190 HIV/HCV-coinfected participants on ART for ≥6 months prior to the initiation of DAAs for HCV, 20 were excluded from the study because of eGFR <15 ml/min/1.73 m2 (n = 1), HBV coinfection (n = 5), receiving non-SOF-based DAAs (n = 12) or refusing to provide informed consent (n = 2). Among the 170 participants who were eligible for the study, 116 and 54 received TFV-based and TFV-free ART, respectively. During the SOF-based DAA therapy for HCV, three participants on TFV-free ART switched to TFV-based ART and were excluded from the analysis. Finally, 116 (69.5%) and 51 (30.5%) of the 167 HIV/HCV-coinfected participants on TFV-based and TFV-free ART were included in the analysis. Furthermore, 85 and 31 participants receiving TDF-based and TAF-based ART were put into the subgroup analysis (Figure 1).

Figure 1.

Study flow

All participants received SOF-based DAAs for 12 weeks, and all had a baseline CKD stage of 1 (eGFR ≥90 ml/min/1.73 m2) or 2 (eGFR 60–89 ml/min/1.73 m2). Among the participants on TFV-based ART, 35 (30.2%), 50 (43.1%), 24 (20.7%), 4 (3.4%) and 3 (2.6%) were treated by efavirenz/emtricitabine/TDF (EFV/FTC/TDF), rilpivirine/FTC/TDF (RPV/FTC/TDF), elvitegravir/cobicistat/FTC/TAF (EVG/COBI/FTC/TAF), bictegravir/FTC/TAF (BIC/FTC/TAF), and RPV/FTC/TAF, respectively. All 51 participants on TFV-free ART were treated by dolutegravir/lamivudine/abacavir (DTG/3TC/ABC). The participants' characteristics were comparable between TFV-based and TFV-free groups (Table 1).

One hundred sixty-three (97.6%) participants achieved SVR12 by SOF-based DAA treatment. Among the four participants who failed to achieve SVR12, two were lost to follow-up at HCV on-treatment week 4 and off-treatment week 4, respectively, and the other two had viral relapse. Of the 1670 scheduled eGFR tests, 1659 (99.3%) had available data for the analysis.

Evolution of eGFR in Participants on TFV-based and TFV-free ART During and After SOF-based DAA Therapy

During SOF-based DAA therapy, the crude slope coefficients of eGFR were significantly different for HCV genotype (−0.27 ml/min/1.73 m2/month [95% CI: −0.51 to −0.03], p = 0.03 for genotype 1 vs. non-genotype 1), and ART regimen (−1.03 ml/min/1.73 m2/month [95% CI: −1.32 to −0.74], p < 0.001 for TFV-based vs. TFV-free ART). Multivariate adjusted analysis showed that ART regimen (−0.82 ml/min/1.73 m2/month [95% CI: −1.21 to −0.43], p < 0.001 for TFV-based vs. TFV-free ART) was independently associated with the slope coefficient difference of eGFR. After discontinuing SOF-based DAAs, the crude slope differences were comparable with regard to all factors of interest (Table 2, Figure 2).

Figure 2.

Slope coefficient differences in participants on TFV-based and TFV-free ART: (1) adjusted analysis for HCV genotype (p < 0.001) during SOF-based DAA therapy, and (2) crude analysis (p = 0.42) after SOF-based DAA therapy

Evolution of eGFR in Participants on TDF-based and TAF-based ART During and After SOF-based DAA Therapy

During SOF-based DAA therapy, the crude slope coefficient of eGFR was significantly different for ART regimen (−0.31 ml/min/1.73 m2/month [95% CI: −0.50 to −0.12], p = 0.01 for TDF-based ART vs. TAF-based ART). After discontinuing SOF-based DAA therapy, the crude slope differences were comparable with regard to all factors of interest (Table 3, Figure 3).

Figure 3.

Slope coefficient differences in participants on TDF-based and TAF-free ART: (1) crude analysis (p = 0.01) during SOF-based DAA therapy, and (2) crude analysis (p = 0.91) after SOF-based DAA therapy

Severity of eGFR Changes in Participants on TFV-based and TFV-free ART Between Baseline and On-treatment Week 12 and Between Baseline and SVR12

The mean percentages of eGFR changes in participants on TFV-based ART were significantly different from participants on TFV-free ART between the time points of baseline and on-treatment week 12 (−1.4% vs. 5.2%, p < 0.001), and between baseline and SVR12 (−0.7% vs. 2.9%, p < 0.001). Four (3.4%) and 8 (6.8%) of the 116 participants receiving TFV-based ART had one grade of eGFR improvement between baseline and on-treatment week 12, and between baseline and SVR12. Nine (18.0%) of the 50 participants and 6 (12.2%) of the 49 participants receiving TFV-free ART had one grade of eGFR improvement between baseline and on-treatment week 12, and between baseline and SVR12 (Table S1). Three (2.6%) and 2 (1.7%) participants receiving TFV-based ART had one grade of eGFR worsening between baseline and on-treatment week 12, and between baseline and SVR12. One participant receiving TFV-free ART had one grade of eGFR worsening from baseline to on-treatment week 12 (eGFR change: −16%), who also presented with one grade of eGFR worsening from baseline to SVR12 (eGFR change: −13%) (Table S2). The distribution of eGFR grade changes for participants on TFV-based and TFV-free ART was different between baseline and on-treatment week 12 (p = 0.005), but was comparable between baseline and SVR12 (p = 0.52) (Figure 4).

Figure 4.

Severity of eGFR changes by DAIDS grading system in participants on TFV-based and TFV-free ART: (A) between the time points of baseline and on-treatment week 12 (p = 0.005) and (B) between the time points of baseline and SVR12 (p = 0.52). One participant on TFV-free ART who was lost to follow-up at on-treatment week 4 did not have on-treatment week 12 eGFR data for analysis. Two participants on TFV-free ART who were lost to follow-up at on-treatment week 4 and at off-treatment week 4 did not have SVR12 eGFR data for analysis

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