Correspondence

Tenofovir Disoproxil Fumarate in Patients with HIV and Lamivudine-Resistant Hepatitis B Virus

N Engl J Med 2003; 348:177-178January 9, 2003

Article

To the Editor:

Mutations in the YMDD (tyrosine, methionine, aspartate, aspartate) motif of the DNA polymerase resulting in phenotypic hepatitis B virus (HBV) resistance to lamivudine monotherapy have been observed after two years in 50 percent of patients coinfected with the human immunodeficiency virus (HIV).1 Adefovir dipivoxil has been shown to be effective for lamivudine-resistant HBV infection in HIV-coinfected patients.2 Tenofovir disoproxil fumarate, a nucleotide reverse-transcriptase inhibitor, is active against HIV and has in vitro activity against wild-type and lamivudine-resistant HBV.3,4

We examined the efficacy and safety of tenofovir disoproxil fumarate, at a dose of 300 mg given once daily, in HIV-coinfected patients with lamivudine-resistant HBV infection. The study was approved by our institutional review board, and all the patients provided written, informed consent. Paired t-tests were used to assess changes from base line. Twelve men (mean [±SE] age, 44.1±3.6 years) who were coinfected with HIV and HBV and whose regimen included lamivudine (150 mg given twice daily) had tenofovir disoproxil fumarate added to their regimen. They were evaluated at 4, 8, 12, and 24 weeks. The patients were serum-positive for HBV DNA for a median of 30 months (range, 10 to 34) before the administration of tenofovir disoproxil fumarate was initiated. Ten patients had documented HBV polymerase mutations (rtM204V/rtL180M in eight and rtM204I/rtL180M in two). Serum HBV DNA and plasma HIV RNA levels were assessed by the polymerase chain reaction (Roche Amplicor; sensitivity, 2.6 and 2.3 log₁₀ copies per milliliter, respectively). From base line to week 24, serum HBV DNA levels decreased in all the patients (P=0.003) (Figure 1Figure 1Serum Levels of HBV DNA in 12 HIV-Coinfected Patients Who Received Tenofovir Disoproxil Fumarate in Addition to Lamivudine for 24 Weeks.). None of the patients had loss of hepatitis B e antigen or seroconversion to anti–hepatitis B e. Sequencing at week 24, performed in four patients, revealed base-line mutations but no new mutations in domain B or C of the polymerase. The CD4 cell count at base line (mean, 440±66 cells per cubic millimeter) had increased by 77±27 cells per cubic millimeter at week 24 (P=0.016). The levels of HIV RNA and serum alanine aminotransferase did not change significantly during the study. The tenofovir disoproxil fumarate was generally well tolerated. One patient, who had polycystic kidney disease, withdrew at week 12 because of an increase in his serum creatinine level (from 2.8 mg per deciliter at base line to a maximum of 4.5 mg per deciliter, without a change in the serum levels of potassium, phosphorus, or bicarbonate). After the administration of tenofovir disoproxil fumarate was discontinued, serum creatinine and serum HBV DNA returned to their pretreatment levels.

These preliminary, 24-week data suggest that 300 mg of tenofovir disoproxil fumarate given once daily may be effective for the treatment of lamivudine-resistant HBV infection in HIV-coinfected patients. Larger studies that evaluate a longer duration of treatment will be necessary to assess the extent and durability of the responses.

Yves Benhamou, M.D., Ph.D.
Roland Tubiana, M.D.
Vincent Thibault, M.D.
Groupe Hospitalier Pitié–Salpêtrière, 75013 Paris, France
ybenhamou@teaser.fr

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