Evidence of long-term suppression of hepatitis B virus DNA by tenofovir as rescue treatment in patients coinfected by HIV.
BACKGROUND
The efficacy of long-term hepatitis B virus (HBV) treatment with tenofovir (TDF) in relation to lamivudine (LMV) resistance in HIV patients failing on LMV deserves further investigations.


METHODS
HIV-HBV coinfected patients were selected, provided that LMV was included in the first highly active antiretroviral therapy regimen and TDF was subsequently introduced.


RESULTS
Forty HIV-HBV patients were included, 25 had undetectable HBV DNA on LMV and 15 were failing on LMV treatment. Three cases of triple 173V + 180M + 204V HBV reverse transcriptase (rt) mutants were identified, as well as several mutations or polymorphisms in the surface antigen gene at positions possibly correlating with vaccine escape. A new mutation (rtl233V) was found in one adefovir-naive patient. In 10 patients, uninterrupted TDF treatment led to a sustained treatment response for a median of 160 (interquartile range 111-189) weeks. Two patients underwent intermittent treatment with TDF and LMV, responding any time TDF was reintroduced. In one patient, TDF without LMV provided treatment response. One patient did not respond to TDF because of low treatment adherence. One patient infected with the triple rt mutant did not respond to entecavir, but TDF was successful as rescue.


CONCLUSIONS
Combination therapy with TDF was effective against HBV mutant viruses resistant to LMV and provided sustained control of HBV replication over long-term follow-up, even after entecavir failure. Moreover, suppression of HBV vaccine escape variants could provide important benefits from a public health perspective.
Institute for Infectious and Tropical Diseases, University of Brescia, Brescia, Italy.
Eugenia
E
Quiros-Roldan
Alessandra
A
Calabresi
Giuseppe
G
Lapadula
Valeria
V
Tirelli
Silvia
S
Costarelli
Giuliana
G
Cologni
Serena
S
Zaltron
Massimo
M
Puoti
Giampiero
G
Carosi
Carlo
C
Torti
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000097:blood*; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy*; D006514:Hepatitis B Surface Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D009154:Mutation; D063065:Organophosphonates / Q000627:therapeutic use*; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D000068698:Tenofovir; D013997:Time Factors; D016896:Treatment Outcome; D014779:Virus Replication
D019380:Anti-HIV Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000068698:Tenofovir; D012194:RNA-Directed DNA Polymerase; D000225:Adenine