AEGiS-15IAC: Long term treatment with adefovir dipivoxil 10 mg (ADV) in patients with lamivudine-resistant (LAM-R) HBV and HIV co-infection results in significant and sustained clinical improvement.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Long term treatment with adefovir dipivoxil 10 mg (ADV) in patients with lamivudine-resistant (LAM-R) HBV and HIV co-infection results in significant and sustained clinical improvement.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. WeOrA1329)

Benhamou Y, Thibault V, Vig P, Valantin MA, Guyon P, Katlama C, Lu B, Currie G, Brosgart CL, Poynard T
GH Pitie-Salpetriere, Paris, France

BACKGROUND: ADV has shown efficacy and safety in a broad range of populations with chronic hepatitis B, including patients with LAM-R. The objective is to evaluate 4 years (192 weeks) of ADV 10 mg daily in patients with LAM-R HBV co-infected with HIV.

METHODS: Patients who entered a 1-year pilot study continued ADV for a further 3 years. ADV was added to ongoing anti-retroviral therapy (ART) including LAM (150mg bid). Patients were seen every 4 weeks (year 1) and every 12 weeks (years 2-4). At each visit, serum ALT, serum HBV DNA (Roche PCR, LLQ 2.3 log₁₀copies/mL), HBV serology, plasma HIV RNA (LLQ, 2.3 log₁₀copies/mL) and CD4 cell count were measured.

RESULTS: 35 patients enrolled, 26 completed 192 weeks of ADV. Median serum HBV DNA declined from baseline, 8.75 log₁₀copies/mL by 3.98, 4.81, 5.45 and 5.63 log₁₀copies/mL at wks 48, 96, 144 and 192. (p<0.0001). 7 patients (27%) had serumHBV DNA<LLQ at wk 192. No adefovir-associated mutations were identified at conserved sites in either HBV DNA polymerase or HIV RT performed at baseline, wk 48, 96 and 144; week 192 genotyping is in progress. Median serum ALT at week 48 (46 IU/L), 96 (31IU/L), 144 (31 IU/L) and 192 (32 IU/L were significantly decreased from baseline (53 IU/L), p =<0.001 at all time points. Two patients gained anti-HBe by week 48. No evidence of nephrotoxicity or serious adverse events related to ADV occurred during the study. Two patients died due to HCC. There were no significant changes in HIV RNA, median CD4 cell count increased from baseline (423±34 cells/mm³) to 453±46.7 cells/ mm[3] by wk 192. Conclusion Long-term treatment with ADV was well tolerated and resulted in significant and sustained reductions in serum HBV DNA and ALT. No ADV associated HBV or HIV mutations were identified. The magnitude of the reductions increased with treatment duration and no loss of suppression was seen over four years of ADV.

Keywords: AEGIS, Lamivudine, HIV Infections, Hepatitis B, Chronic, Adenine, Acquired Immunodeficiency Syndrome, HIV Seropositivity, Alanine Transaminase, DNA-Directed DNA Polymerase, adefovir, Humans

040711
WeOrA1329