RESUMO
Hepatitis B virus (HBV) molecular profiles were determined for 44 patients who were infected with human immunodeficiency virus (HIV) type 1 and had antibodies to the hepatitis B core antigen (anti-HBc), with and without other HBV serological markers. In this population, 70% of the patients were under lamivudine treatment as a component of antiretroviral therapy. HBV DNA was detected in 14 (32%) patients. Eight out of 12 (67%) HBsAg positive samples, 3/10 (30%) anti-HBc only samples, and 3/22 (14%) anti-HBs positive samples were HBV DNA positive. HBV DNA loads, measured by real time polymerase chain reaction, were much higher in the HBsAg positive patients (mean, 2.5 x 10(9) copies/ml) than in the negative ones (HBV occult infection; mean, 2.7 x 10(5) copies/ml). Nine out of the 14 HBV DNA positive patients were under lamivudine treatment. Lamivudine resistant mutations in the polymerase gene were detected in only three patients, all of them belonging to the subgroup of five HBsAg positive, HBV DNA positive patients. A low mean HBV load (2.7 x 10(5) copies/ml) and an absence of lamivudine resistant mutations were observed among the cases of HBV occult infection.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/complicações , HIV-1/genética , Vírus da Hepatite B/imunologia , Hepatite B/diagnóstico , Lamivudina/uso terapêutico , Adulto , Brasil , DNA Viral/análise , Farmacorresistência Viral/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Hepatite B/complicações , Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Reação em Cadeia da Polimerase , Fatores de Risco , Carga ViralRESUMO
Hepatitis B virus (HBV) molecular profiles were determined for 44 patients who were infected with human immunodeficiency virus (HIV) type 1 and had antibodies to the hepatitis B core antigen (anti-HBc), with and without other HBV serological markers. In this population, 70 percent of the patients were under lamivudine treatment as a component of antiretroviral therapy. HBV DNA was detected in 14 (32 percent) patients. Eight out of 12 (67 percent) HBsAg positive samples, 3/10 (30 percent) anti-HBc only samples, and 3/22 (14 percent) anti-HBs positive samples were HBV DNA positive. HBV DNA loads, measured by real time polymerase chain reaction, were much higher in the HBsAg positive patients (mean, 2.5 Î 10(9) copies/ml) than in the negative ones (HBV occult infection; mean, 2.7 Î 10(5) copies/ml). Nine out of the 14 HBV DNA positive patients were under lamivudine treatment. Lamivudine resistant mutations in the polymerase gene were detected in only three patients, all of them belonging to the subgroup of five HBsAg positive, HBV DNA positive patients. A low mean HBV load (2.7 Î 10(5) copies/ml) and an absence of lamivudine resistant mutations were observed among the cases of HBV occult infection.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/complicações , HIV-1 , Vírus da Hepatite B/imunologia , Hepatite B/diagnóstico , Lamivudina/uso terapêutico , Brasil , DNA Viral/análise , Farmacorresistência Viral/genética , Ensaio de Imunoadsorção Enzimática , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B/complicações , Mutação/genética , Reação em Cadeia da Polimerase , Fatores de Risco , Carga ViralRESUMO
BACKGROUND: Lamivudine inhibits replication of both human immunodeficiency virus (HIV) and hepatitis B virus (HBV) and is commonly used as part of antiretroviral therapy. The main limitation in the use of lamivudine is resistant mutation selection. Most of these mutations affect the YMDD motif of the HBV DNA polymerase. The resistance occurs through M550V or M550I aminoacid replacements. The M550V variation may be accompanied by L526M mutation, notably in HIV-HBV co-infected patients. The aim of this study was to investigate mutations associated with lamivudine resistance in a hemodialysis patient chronically co-infected with HIV-1 and HBV, who was submitted to several antiretroviral treatments. METHODS: HBV isolates derived from three blood samples collected at different times of antiretroviral therapies with and without lamivudine, were titred and submitted to nucleotide sequencing. RESULTS: HBV isolate derived from a sample collected in 1999 during an antiretroviral treatment with lamivudine showed the lamivudine resistant double mutation (L526M, M550V). However, no mutation associated with lamivudine resistance was observed in the HBV genome derived from the sample collected during a period of treatment without lamivudine (2001). After reinstitution of lamivudine (2002), the predominant HBV population exhibited a rare triple mutation (V519L, L526M, M550V), which has previously been associated with an in vitro reduction of virus antigenicity (escape mutant). HBV DNA was detected at high levels (108-109 copies/ml) in the three blood samples. CONCLUSIONS: Reintroduction of lamivudine as part of antiretroviral treatment in a patient who had developed lamivudine resistant HBV strains favored the predominance of an HBV isolate with reduced antigenicity. The absence of hepatitis acute exacerbation in this patient may be correlated to the absence of significant variations of the viral load, which was independent of the presence of mutations in the HBV DNA polymerase.