Fatal interruption of a 3TC-containing regimen in a HIV-infected patient.
Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. B10353)
Clevenbergh P, Sellier P, Mazeron M, Cazals-Hatem D, Evans J, Cervoni J, Badsi E, Bendenoun M, Diemer M, Vincent V, Caulin C, Bergmann J Internal Medicine Dpt, Lariboisiere Hospital, Paris, France
Introduction: Ten % of HIV-infected individuals are hepatitis B virus (HBV) surface antigen-positive (HBs Ag). First line anti-HIV therapy usually contains lamivudine (3TC), a reverse transcriptase inhibitor with antiviral activity against both HIV and HBV. Interrupting 3TC can lead to severe hepatitis and death. Case report: A 58-year-old man was diagnosed HIV-HBV co-infected in 1992. HBV serology revealed HBs Ag +, HBs antibody (Ab) -, HBc Ab +, Hbe Ab + and plasma HBV DNA present. Stavudine and 3TC were begun in December 1996 with complete suppression of HIV and HBV replication. In March 1999, nevirapine was added to this regimen. In Augustus 2000, HIV genotypic resistance testing revealed mutations at positions M41L, K103N, Y181Y/C, M184V, T215Y. HBV DNA was still undetectable. HIV therapy was changed to stavudine, didanosine, indinavir. In september 2000, the patient was admitted for acute hepatic failure. Serology showed HBs Ag +, HBs Ab -, HBc IgM +, Hbe Ag +, Hbe Ab -, HBV DNA: 5.7 Meq/mL. He died the next day. A post-mortem hepatic biopsy revealed active HBV replication.
DISCUSSION: HIV and HBV use a reverse-transcriptase that is inhibited by some nucleoside or nucleotide analogues. They tend to acquire resistance mutation, a process accelerated in the context of monotherapy. Resistance mutations decrease their replicative capacity and pathogenicity. They exhibit a virologic rebound after stopping therapy or when the virus has become resistant to it, associated with manifestations ranging from clinically silent to acute infection. They establish lifelong reservoirs in the liver (HBV) and/or lymphatic system (HBV, HIV) and their eradication is elusive. The major difference is their viral dynamics, where HIV acquires resistance faster than HBV and drives treatment change. Concomitant treatment of both viruses is complicated and can be dangerous. Once 3TC had been started, when and how to stop it remain unresolved questions.
Keywords: AEGIS, Lamivudine, HIV, Acquired Immunodeficiency Syndrome, HIV Seropositivity, Reverse Transcriptase Inhibitors, Hepatitis B virus, HIV Infections, Hepatitis B e Antigens, Antiviral Agents, Hepatitis B Surface Antigens, HIV-1, Indinavir, Stavudine, HIV-1 Reverse Transcriptase, Humans, Male, immunology
