Longer HAART (tenofovir) Use Predicts Hepatitis B Clearance

Longer HAART (tenofovir) Use Predicts Hepatitis B Clearance

"HIV-HBV co-infected patients have decreased survival compared to HBV and HIV monoinfected patients.11–15 Therefore, to halt the liver damage induced by HBV is a priority in the management of HIV-HBV co-infected patients"...."More prolonged use of HBV-active HAART was associated with clearance of both HBeAg and HBsAg".......Updated HHS Treatment Guidelines recommend treating HBV+ without delay.

"Two of the seven patients with cirrhosis developed HCC as well. It has been previously reported that HIV-infected patients with viral hepatitis develop HCC at earlier age.19 Both patients had maintained persistent suppression of HBV before the diagnosis of HCC, and one of them had even cleared the HBsAg. This is a reminder of the continued need of screening with alfafetoprotein levels and liver ultrasound in these patients, even after HBsAg clearance....Higher transaminase levels before treatment was a predictor factor of diagnosis of liver cirrhosis. Although an imperfect parameter, transaminase level refl ects histological activity and it is an important factor in HBV treatment decision making....HIV-HCV-HBV tri-infection have higher risk of developing cirrhosis and have lower survival"

"For those who cleared the antigen, average time on the drugs was 4.25 years, compared with 1.676 for the others"
"Their median time of follow-up and of adherence to HBV-active HAART were 3 and 1 years, respectively. HBeAg and HBsAg cleared in 17.6% and 5.5% of patients, respectively"...."Longer time of HBV-active HAART use was found to be associated with HBeAg clearance (OR 2.66, 95% CI 1.15–6.16, p = .02) (4.0 vs. 1.7 years)."....."Longer time of HBV-active HAART use was the only identifi ed factor predicting HBsAg clearance (OR 1.54, 95% CI 1.02–2.31, p = .04) (4.25 vs. 1.67 years)."
"The findings "stress the importance of good control of the HIV and (hepatitis B) infections"
"higher (ALT) alanine aminotransferase levels before HAART initiation were associated with the diagnosis of cirrhosis during follow-up"
"In patients with elevated liver enzymes, "it is even more important to control the (hepatitis B) infection in an attempt to decrease the risks of complications,"......"Those patients should also be more closely screened for liver complications."

"Although not statistically significant, HBsAg clearance tended to occur more frequently among patients with higher baseline

CD4 counts (mean CD4 550 cells/mm3 vs. 246 cells/mm3; p = .06)."

"While without statistical significance, mean nadir CD4 counts were lower among patients experiencing liver complications (80 cells/mm3 vs. 176 cells/mm3). In like manner, active HCV-co-infection was more frequent in those with liver complications (29% vs. 8%)."


TORONTO, July 15 -- In patients with both HIV and hepatitis B, prolonged use of drugs active against both viruses improves the odds of clearing the hepatitis, researchers said.

Action Points


* Explain to interested patients that patients with both HIV and hepatitis B are at higher risk of liver complications.



* Note that this study found that longer use of antiretrovirals that are also active against hepatitis B increased the odds of clearing the infection.


In a retrospective, longitudinal study, patients who were on such highly active antiretroviral therapy (HAART) for a longer period had nearly three times the likelihood of clearing the HBeAg antigen associated with active hepatitis B, according to Marina Núñez, MD, PhD, and a colleague at Wake Forest University School of Medicine in Winston-Salem, N.C.


Those patients also had a 54% improvement in the chance of clearing the so-called surface antigen -- HBsAg -- the researchers said in the May/June issue of HIV Clinical Trials.


In addition, the researchers found that patients with higher levels of alanine aminotransferase at baseline were at a higher risk of being diagnosed with cirrhosis within a few years.


"One of the most interesting findings was the confirmation that a simple marker, such as transaminase levels before treatment, is useful in identifying patients at higher risk of developing (hepatitis B-related) complications in a few years," Dr. Núñez said in a statement.


The researchers looked at medical records of 72 patients treated at Wake Forest University Baptist Medical Center between 1990 and 2008 who had both HIV and hepatitis B.


During follow-up, 64 (or 88.9%) of the patients had HAART containing drugs active against hepatitis B, including tenofovir (Viread), lamivudine (3TC), or emtricitabine (Emtriva).


Most patients took at least two active drugs during follow-up, but 11.1% took only one antiretroviral with hepatitis B activity.


Six out of 34 patients positive for HBeAg (or 17.6%) cleared the antigen, the researchers found. The only factor that was associated with HBeAg clearance was long use of the medications.


For those who cleared the antigen, the average use of antihepatitis medications was 4.0 years, compared with 1.7 for those who did not. The difference yielded an odds ratio of 2.66, with a 95% confidence interval from 1.15 to 6.16, which was significant at P=0.02.


And 5.5% of the patients cleared the HBsAg antigen. Again the only factor predicting clearance was longer use of hepatitis B-active HAART.


For those who cleared the antigen, average time on the drugs was 4.25 years, compared with 1.676 for the others, yielding an odds ratio of 1.54, with a 95% confidence interval from 1.02 to 2.31, which was significant at P=0.04.


Finally, higher alanine aminotransferase levels before HAART initiation were associated with the diagnosis of cirrhosis during follow-up -- the odds ratio was 1.02, with a 95% confidence interval from 1.002 to 1.03, which was significant at P=0.02.


The findings "stress the importance of good control of the HIV and (hepatitis B) infections," Dr. Núñez said.


In patients with elevated liver enzymes, "it is even more important to control the (hepatitis B) infection in an attempt to decrease the risks of complications," she said. "Those patients should also be more closely screened for liver complications."


The study had a number of limitations including its retrospective nature, small sample size, predominantly African-American male population, late diagnosis of HIV, indeterminant duration of hepatitis B infection, and radiologic rather than histologic diagnosis of cirrhosis.


The study was supported by the 2008 Medical Student Summer Research Training Program, supported through grants from the NIH Health, Wake Forest University School of Medicine Departments, Centers, and Institutes, and private gifts.


The researchers made no disclosures.


Primary source: HIV Clinical Trials

Source reference:

Lee, T Núñez, M "Longer duration of HBV-active antiretroviral therapy is linked to favorable virological outcome in HIV-HBV co-infected patients" HIV Clin Trials 2009; 10 (3).
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Longer Duration of HBV-Active Antiretroviral Therapy is Linked to Favorable Virological Outcome in HIV-HBV Co-infected Patients

Tsan Lee1, Marina Núñez2


1 Wake Forest University School of Medicine, Winston Salem, North Carolina, USA

2Division on Infectious Disease, Department on Internal Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA

Abstract


Background: HBV-HIV co-infection is associated with increased liver-related morbidity and mortality. Herein we analyzed HBV-related virologic and clinical outcomes in HBV-HIV patients in the HAART era. Methods: HBsAg positive HIV-infected patients followed at a US academic center between 1990 and 2008 were assessed in a retrospective and longitudinal study. Factors associated with HBsAg and/or HBeAg clearance and with advanced liver disease were evaluated using logistic regression.
Results: 72 patients were evaluated. Their median time of follow-up and of adherence to HBV-active HAART were 3 and 1 years, respectively. HBeAg and HBsAg cleared in 17.6% and 5.5% of patients, respectively. More prolonged use of HBV-active HAART predicted clearance of HBeAg (odds ratio [OR] 2.66, 95% CI 1.15–6.16, p = .02) and of HBsAg (OR 1.54, 95% CI 1.02–2.31, p = .04). Patients clearing HBsAg tended to have higher baseline CD4 (mean CD4 counts: 550 vs. 246 cells/mm3; p = .06). Rate of diagnosis of liver-related complications and death were 24.6/1,000 and 10.5/1,000 patient-years, respectively. Higher ALT levels before HAART initiation were associated with the diagnosis of cirrhosis during follow-up (OR 1.02, 95% CI 1.002–1.03, p = .02).
Conclusions: Prolonged use of HBV-active HAART favors HBsAg and HBeAg clearance in HIV-HBV co-infected patients. Those with higher ALT levels at presentation have higher risk of being diagnosed with cirrhosis during the first few years of follow-up.