RESUMO
The efficacy of entecavir for patients with hepatitis B virus/human immunodeficiency virus coinfection has not been fully elucidated. Here we examined a patient coinfected with both viruses in whom entecavir-resistant hepatitis B virus appeared. The 60-year-old Japanese male with the coinfection received antiretroviral therapy including lamivudine. The therapy initially suppressed replication of both viruses, followed by reactivation of the hepatitis B virus alone by 2 years of therapy. He subsequently received entecavir therapy in addition to the antiretroviral regimen. After entecavir administration, the hepatitis B virus DNA level was slightly reduced, but then increased after 6 months of entecavir therapy. In the sequencing analysis of hepatitis B virus, no drug resistance-associated amino acid substitutions were observed in the reverse transcriptase (rt) domain before antiretroviral therapy. The lamivudine-resistant amino acid substitutions at rt173, rt180 and rt204 were detected before entecavir administration, and further the entecavir-resistant rt202 substitution was observed after 6 months of entecavir therapy. The full-length hepatitis B sequences showed that the viral strain derived from the patient belonged to genotype H. In summary, this report describes a patient with hepatitis B virus/human immunodeficiency virus coinfection who received entecavir therapy in addition to an antiretroviral regimen and showed the early emergence of entecavir-resistance hepatitis B virus. In entecavir therapy for patients infected with both viruses, great care should be taken with respect to the emergence of entecavir-resistant hepatitis B virus, especially in patients with pre-existing lamivudine-resistant virus.
RESUMO
Although it has not caused overt renal damage in clinical trials, tenofovir disoproxil fumarate (TDF) has been associated with renal dysfunction in isolated cases. The objective of this study was to assess the TDF concentration with use of the glomerular filtration rate (GFR) and blood urea nitrogen (BUN) level. Serum creatinine (used to calculate GFR), BUN, and plasma TDF trough values were measured in 51 patient volunteers at pretreatment and post-treatment time points. The post-treatment GFR (post_GFR) and the difference between the pretreatment and post-treatment BUN levels (dif_BUN) were strongly related to TDF concentration. A piecewise multiple regression technique was applied to the nonlinear TDF distribution, revealing a significant association of the post_GFR and dif_BUN values with TDF concentration (P=0.002 and P= 0.003, respectively). Post_GFR values below 125 mL/min/1.73 m(2) and/or dif_BUN values below -3 mg/dL are predicted to cause a marked increase in the TDF concentration. The relationship between TDF and BUN is a new finding. Knowledge of the pretreatment and post-treatment serum creatinine and BUN levels is important for the safe clinical administration of TDF.
