Influence of HIV on Tenofovir Response in Chronic HBV
Background: HIV worsens the natural history of chronic hepatitis B virus (HBV) infection. Suppression of HBV replication slows progression of liver damage. Information about the influence of HIV on response to tenofovir in HIV/HBV-coinfected patients is scarce.
Methods: All individuals with persistent HBsAg+ at four clinics in Spain were identified. Information from the subset that initiated tenofovir therapy was examined.
Results: A total of 176 patients with chronic hepatitis B were evaluated, of whom 138 (78.4%) were coinfected with HIV. Prior lamivudine exposure was extensive in both groups, and nearly half of HBV viremic patients harboured drug resistance mutations. Most patients took tenofovir coformulated along with emtricitabine (Truvada). Of 101 HBV viremic patients at the time of beginning tenofovir (78 with HIV coinfection and 33 with HBV alone), a similar proportion achieved undetectable HBV-DNA at weeks 24, 48 and 96 of tenofovir therapy. Interestingly, HIV/HBV-coinfected patients with positive HBeAg showed a lower response than HBeAg-negatives. In multivariate analysis, however, baseline serum HBV-DNA was the only predictor of virological response to tenofovir.
Conclusion: The antiviral efficacy of tenofovir is similar in HIV/HBV-coinfected and HBV-monoinfected patients, achieving undetectable HBV-DNA nearly 90% of patients at week 96 of therapy. Baseline serum HBV-DNA is the major determinant of time-trends in virological response, with no significant influence of HBeAg, drug resistance mutations nor coinfection with hepatitis C or delta viruses.
Over two billion people have been infected with the hepatitis B virus (HBV) worldwide, being 350 million chronic carriers, and therefore at a risk for complications of progressive liver disease. Due to shared sexual and blood-borne routes of transmission, the prevalence of chronic hepatitis B is particularly high in HIV-positive individuals. Overall, 4–10% of HIV-infected persons have chronic hepatitis B. HIV worsens the natural history of HBV infection, increasing the rate of chronification following exposure, enhancing HBV replication and accelerating liver disease progression. Interestingly, effective therapy for HIV may improve HBV outcomes in coinfected individuals, largely throughout immune-mediated mechanisms.
As several nucleos(t)ide analogues display activity against both HIV and HBV, many HIV/HBV-coinfected individuals have been treated for HBV for long periods. Sometimes it has been done inadvertently, ignoring that the HIV patient was positive for HBsAg. Tenofovir displays the most robust and prolonged anti-HBV activity regardless of prior lamivudine exposure, largely as a result of its unique high barrier to resistance. Conversely, lamivudine therapy selects for HBV resistance in 25–65% of patients treated for 1–5 years. This rate is further increased in HIV/HBV-coinfected individuals. On the basis of this information, current antiretroviral treatment guidelines recommend the inclusion of tenofovir along with either emtricitabine or lamivudine as part of any triple combination regimen prescribed to HIV/HBV-coinfected patients. Herein, we examine longitudinal serum HBV-DNA in a large population of chronic hepatitis B patients on long-term tenofovir therapy, comparing HBV-monoinfected and HIV/HBV-coinfected individuals.
Abstract and Introduction
Abstract
Background: HIV worsens the natural history of chronic hepatitis B virus (HBV) infection. Suppression of HBV replication slows progression of liver damage. Information about the influence of HIV on response to tenofovir in HIV/HBV-coinfected patients is scarce.
Methods: All individuals with persistent HBsAg+ at four clinics in Spain were identified. Information from the subset that initiated tenofovir therapy was examined.
Results: A total of 176 patients with chronic hepatitis B were evaluated, of whom 138 (78.4%) were coinfected with HIV. Prior lamivudine exposure was extensive in both groups, and nearly half of HBV viremic patients harboured drug resistance mutations. Most patients took tenofovir coformulated along with emtricitabine (Truvada). Of 101 HBV viremic patients at the time of beginning tenofovir (78 with HIV coinfection and 33 with HBV alone), a similar proportion achieved undetectable HBV-DNA at weeks 24, 48 and 96 of tenofovir therapy. Interestingly, HIV/HBV-coinfected patients with positive HBeAg showed a lower response than HBeAg-negatives. In multivariate analysis, however, baseline serum HBV-DNA was the only predictor of virological response to tenofovir.
Conclusion: The antiviral efficacy of tenofovir is similar in HIV/HBV-coinfected and HBV-monoinfected patients, achieving undetectable HBV-DNA nearly 90% of patients at week 96 of therapy. Baseline serum HBV-DNA is the major determinant of time-trends in virological response, with no significant influence of HBeAg, drug resistance mutations nor coinfection with hepatitis C or delta viruses.
Introduction
Over two billion people have been infected with the hepatitis B virus (HBV) worldwide, being 350 million chronic carriers, and therefore at a risk for complications of progressive liver disease. Due to shared sexual and blood-borne routes of transmission, the prevalence of chronic hepatitis B is particularly high in HIV-positive individuals. Overall, 4–10% of HIV-infected persons have chronic hepatitis B. HIV worsens the natural history of HBV infection, increasing the rate of chronification following exposure, enhancing HBV replication and accelerating liver disease progression. Interestingly, effective therapy for HIV may improve HBV outcomes in coinfected individuals, largely throughout immune-mediated mechanisms.
As several nucleos(t)ide analogues display activity against both HIV and HBV, many HIV/HBV-coinfected individuals have been treated for HBV for long periods. Sometimes it has been done inadvertently, ignoring that the HIV patient was positive for HBsAg. Tenofovir displays the most robust and prolonged anti-HBV activity regardless of prior lamivudine exposure, largely as a result of its unique high barrier to resistance. Conversely, lamivudine therapy selects for HBV resistance in 25–65% of patients treated for 1–5 years. This rate is further increased in HIV/HBV-coinfected individuals. On the basis of this information, current antiretroviral treatment guidelines recommend the inclusion of tenofovir along with either emtricitabine or lamivudine as part of any triple combination regimen prescribed to HIV/HBV-coinfected patients. Herein, we examine longitudinal serum HBV-DNA in a large population of chronic hepatitis B patients on long-term tenofovir therapy, comparing HBV-monoinfected and HIV/HBV-coinfected individuals.
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