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Successful treatment with tenofovir alafenamide of a HIV/hepatitis B virus coinfected patient with HIV and hepatitis B virus drug resistance, end-stage renal disease on haemodialysis

Tartaglia, Alessandra; Ferrara, Sergio Maria; Sica, Salvatore; Santantonio, Teresa

doi: 10.1097/QAD.0000000000001623
Correspondence
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Dipartimento di Medicina Clinica e Sperimentale, SC Malattie Infettive, Università degli Studi di Foggia, Foggia, Italy.

Correspondence to Alessandra Tartaglia, Dipartimento di Medicina Clinica e Sperimentale, SC Malattie Infettive, Università degli Studi di Foggia, viale L. Pinto 1, Foggia, Italy. Fax: +39 0881 732204; e-mail: alessandratartaglia@yahoo

Received 13 July, 2017

Accepted 14 July, 2017

Herein, we report a case of a 27-year-old Black African woman with HIV-1/hepatitis B virus (HBV) coinfection, end-stage kidney disease and development of HIV and HBV drug resistance, successfully treated with tenofovir alafenamide (TAF). At first observation in February 2012, the patient showed CD4+ cell count = 462 cells/μl (23%, CD4+/CD8 0.36), HIV RNA = 12467600 IU/ml, subtype 02-AG, HBV DNA = 2155000 IU/ml, HBV genotype E, quantitative HBsAg = 56437 IU/ml, serum creatinine (sCr) = 0.93 mg/dl. HIV drug resistance testing at baseline did not show any mutation. She started the following antiretroviral therapy (ART): efavirenz 800 mg/day, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). In June 2013, viral suppression for both HIV RNA and HBV DNA was achieved, but sCR increased up to 1.86 mg/dl and her estimated glomerular filtration (eGFR) by chronic kidney disease epidemiology collaboration creatinine equation fell to 43.3 ml/min.

In April 2014, the patient experienced a virological failure because of poor compliance to ART. Drug resistance testing demonstrated the presence of K65R, A98G, L100I, K101E, M184V, G190A mutations and no major mutation for protease inhibitors. Based on genotypic resistance results, the ART regimen was switched to raltegravir, zidovudine/lamivudine. In subsequent laboratory tests, sCR was stable (1.70 mg/dl, eGFR 48 ml/min/1.73 m2), and ramipril was introduced for secondary hypertension. Moreover, we prescribed entecavir 0.5 mg/day for the treatment of chronic HBeAg-positive hepatitis B; however, the drug was refused and never taken by the patient.

In July 2014, poor adherence to ART led to a new virological failure with appearance of drug resistance to integrase inhibitors (mutation Y143R and G163R). Serum HBV DNA levels remained high (viral load 36,091,211 IU/ml) and mutations associated with resistance to lamivudine and telbivudine (L180M, M204V) were documented. In May 2015, because of further renal impairment (sCr 2.87 mg/dl, eGFR 25.3 ml/min) with stage 4 CKD, ART was switched to darunavir 600 mg/bid, ritonavir 100 mg/bid, lamivudine 100 mg/day, zidovudine 300 mg/day, TDF 245 mg every 72 h. During this regimen, HIV RNA suppression was achieved, and HBV DNA levels decreased (8892 IU/ml).

In February 2016, the patient maintained HIV-1 more than 30 IU/ml, good immunological profile (CD4+ cell count 618, 30%), but HBV viremia was still detectable. Owing to CKD, we obtained for this patient the compassionate use of the new coformulation of TAF 10 mg/FTC 200 mg. In April 2016, because of worsening renal function (sCr 18.5 mg/dl, eGFR 2.6 ml/min), the patient started haemodialysis three times a week and a regimen of darunavir 600 mg/bid, ritonavir 100 mg/bid, TAF 10 mg/FTC200 mg administered after haemodialysis. After the introduction of TAF, HIV replication remained suppressed, whereas HBV DNA levels slowly decreased and became undetectable after 12 months. Moreover, TAF was well tolerated without significant side-effects.

The case described here shows the beneficial effect of TAF in a poorly adherent HIV/HBV coinfected patient in haemodialysis, with HIV and HBV drug resistance and few options as rescue therapy. During ART, poor adherence led to selection of drug-resistant mutants, responsible for therapeutic failure.

TAF, the novel tenofovir prodrug, may retain some level of anti-HIV activity even in the presence of K65R mutation or multiple thymidine analog mutations, because of increased cell loading of tenofovir diphosphate with TAF versus TDF observed in vitro and in vivo[1,2].

Another important issue for the management of this patient was the renal impairment. CKD in HIV-infected study participants result from a variety of mechanisms, including direct viral cell injury, host susceptibility factors, and ART adverse effects [3]. In our patient, it is conceivable that previous renal tuberculosis and potential TDF-induced nephrotoxicity led to end-stage renal disease requiring haemodialysis.

Recent studies showed that TAF compared with TDF, has a better safety profile and less impact on bone mineral density and renal parameters [4–6]. Particularly, in study participants with severe renal impairment (eGFR 15–29 ml/min) receiving TAF at 25 mg, TAF exposures were higher than those in the control group were, but lower than the exposures in nonrenal impaired study participants on TDF-based regimens. In study participants with severe renal damage, TAF at 25 mg provided a tenofovir area under the concentration versus time curve 10–40% lower than that from historical TDF-based tenofovir exposures in study participants with normal renal function. Therefore, in study participants with renal disease TAF administration does not require dose modification [7–10].

To our knowledge, this is the first report on the use of TAF in a HIV/HBV coinfected patient under haemodialysis. In this patient with HIV and HBV drug resistance and limited therapeutic options, introducing TAF led to HIV and HBV viral suppression, without significant side-effects. Of course, TAF safety in this particular setting has to be confirmed by further studies.

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Acknowledgements

Conflicts of interest

There are no conflicts of interest.

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