Liver Enzyme Elevation after Lamivudine (Epivir) Withdrawal in HIV-HBV Coinfected Patients

Assessment of liver enzyme elevation in HIV positive patients coinfected with hepatitis B virus (HBV) can be complicated, since increases may be attributable to multiple causes including heavy alcohol use, liver toxicity related to antiretroviral therapy (ART), immune reconstitution due to effective anti-HIV therapy, and exacerbation of HBV infection -- especially when anti-HBV therapy is discontinued.

Read more:

Antiviral Therapy May Promote Hepatitis B Virus Genotype Changes

Hepatitis B virus (HBV) is known for its ability to mutate rapidly as it replicates, which enables it to develop resistance to antiviral treatment. As reported in the November 2008 Journal of Hepatology, a team of Spanish researchers assessed the frequency of mixed HBV genotypes in people with chronic hepatitis B, as well as genotype changes during natural disease evolution and as a result of antiviral therapy.

Read more:

Advanced Liver Disease in People with HIV

As HIV positive people live longer due to effective antiretroviral therapy, liver disease has become an increasingly important cause of illness and death in this population.

In some cases, advanced liver disease in people with HIV is related to coinfection with hepatitis B or C virus (HBV or HCV), certain antiretroviral drugs are known to cause liver toxicity, and in other cases the cause of liver disease is unclear. Three presentations at the recent 9th International Congress on Drug Therapy in HIV Infection (HIV9) in Glasgow discussed end-stage liver disease (ESLD), advanced liver fibrosis, and severe portal hypertension in HIV-infected individuals.

Read more:

EASL 2008: Some HIV-HBV Coinfected Individuals Experience Delayed Response to Tenofovir (Viread)

Tenofovir (Viread), a nucleotide analog approved for HIV treatment, has also demonstrated antiviral activity in patients with chronic hepatitis B virus (HBV) infection. The aim of the present study, presented at the 43rd annual meeting of the European Association for the Study of the Liver (EASL) last week in Milan, was to evaluate the rate of primary non-response to tenofovir in treatment-experienced HIV-HBV coinfected patients.

Read more:

Boosted Atazanavir (Reyataz) and Etravirine (Intelence) Are Safe and Well-tolerated in Patients with Hepatitis B or C Coinfection

Antiretroviral therapy (ART) may cause liver toxicity, indicated by elevated liver enzymes, and studies have shown that this is more likely to occur in HIV positive individuals with hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfection. Two studies presented at the recent 9th International Congress on Drug Therapy in HIV Infection in Glasgow, Scotland, looked at the safety of 2 newer antiretroviral drugs in patients with hepatitis B or C.

Read more:

AZT (Retrovir) Ups Anemia Risk in HIV-HCV Coinfected Patients, But Rate Remains Low

Since the advent of effective antiretroviral therapy has reduced the rate of death due to opportunistic illnesses and other AIDS-related causes, liver disease has emerged as a major cause of death among HIV positive people. HIV, in turn, has also influenced rates of death among patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, according to a study published in the February 2008 Journal of Hepatology.

In this analysis, Patrick Marcellin and colleagues estimated mortality related to HCV and HBV infection in France. A random sample of 999 death certificates was obtained from among all 65,000 French death certificates in 2001 that listed HBV, HCV, hepatitis, liver disease, possible complication of cirrhosis, bacterial infection, HIV, or transplantation as causes of death. Physicians who reported these deaths were sent a questionnaire to identify how many deaths were related to HBV or HCV infection. Death rates were then estimated according to national population census data.

Results

• The estimated annual number of deaths associated with HCV was 3618 (6.1 deaths per 100,000 inhabitants).

• The estimated annual number of deaths associated with HBV was 1507 (2.5 per 100,000 inhabitants).

• The estimated number of deaths attributable to HCV was 2646 (4.5 per 100,000 inhabitants).

• The estimated number of deaths attributable to HBV was 1327 (2.2 per 100,000 inhabitants).

• In the HCV infected group, 95% had cirrhosis and 33% had hepatocellular carcinoma (HCC).

• In the HBV infected group, the rates were similar: 93% and 35%, respectively.

• 11% percent of these deaths occurred in patients with HIV coinfection.

• Deaths related to hepatitis B or C occurred at an earlier age in patients with a history of excessive alcohol consumption. 

ICAAC 2008: Efficacy of Tenofovir (Viread) plus Emtricitabine (Emtriva) in HIV-HBV Coinfected Patients

The nucleotide reverse transcriptase inhibitor tenofovir (Viread, also in the Truvada and Atripla combination pills) is widely prescribed for the treatment of HIV, and was also recently approved for chronic hepatitis B virus (HBV) infection. As described in a poster presented at the 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008), taking place this week in Washington, DC, researchers assessed the efficacy of combination therapy with tenofovir plus emtricitabine by means of a retrospective chart review.

Current guidelines recommend that HIV-HBV coinfected patients who require hepatitis B treatment should receive a combination HAART regimen that contains drugs active against both viruses. In addition to tenofovir, such agents include lamivudine (3TC, Epivir), emtricitabine (Emtriva, also in the Truvada and Atripla pills), and -- to a lesser extent -- entecavir (Baraclude).

The analysis included 31 HIV-HBV coinfected patients. 12 lamivudine-naive patients were prescribed tenofovir plus emtricitabine as part of their antiretroviral regimen; at baseline, these patients had a median HBV DNA level of 5.8 x 10(7) copies/mL. 19 treatment-experience patients who had previously failed lamivudine therapy were prescribed tenofovir plus emtricitabine after lamivudine failure; this group had a median HBV viral load of 7.6 x 10(7) copies/mL.

Results

• The median time to complete HBV suppression in the lamivudine-naive group was 466 days, compared with 877 days in the lamivudine-experienced group (P = 0.001).

• After 12 months, 60% of the lamivudine-naive patients achieved undetectable HBV DNA (< 200 copies/mL) compared with 21% in the lamivudine-experienced group (P = 0.092).

• After 24 months, 100% of the remaining lamivudine-naive patients, but only 31% of the lamivudine-experienced group, had undetectable HBV DNA (P=0.015).

• Among initially hepatitis B "e" antigen (HBeAg) positive patients, 14% in the lamivudine-naive group and 9% in the lamivudine-experienced group experienced HBeAg loss.

"HBV DNA suppression to under 200 copies/mL was achieved significantly more rapidly among treatment-naive patients," the investigators stated.

"There was a trend towards a greater proportion of naive patients with HBV suppression at 12 months, and a significantly greater proportion of naive patients were suppressed at 24 months," they added. "Loss of HBe antigen was uncommon and not significantly different between the two groups."

Based on these findings, they concluded, "Our results support the practice of initial dual therapy" in HIV-HBV coinfected patients.

New York Univ., New York, NY

10/28/08

Reference

CA Engell, RS Holzman, and JA Aberg. Efficacy of Tenofovir Plus Emtricitabine in Treatment of HIV/HBV Coinfected Patients. 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008). Washington, DC. October 25-28, 2008. Abstract V-1626.

HAART Containing Tenofovir (Viread) plus Emtricitabine (Emtriva) is Effective for HIV-HBV Coinfected Patients

Several recent studies have added to the evidence that structured interruption of antiretroviral therapy can lead to detrimental outcomes for people with HIV. The disadvantages of treatment interruption may be even more pronounced among HIV positive individuals with hepatitis B virus (HBV) coinfection, since some drugs used to treat HIV are also active against HBV, including 3TC (lamivudine; Epivir), emtricitabine (Emtriva), and tenofovir (Viread). 

Read more: