Advances in the Management of Viral Hepatitis B in HIV-Coinfected Patients

[Guest guest]

http://www.medscape.com/viewarticle/554156?src=mp

14th Conference on Retroviruses and Opportunistic Infections

Selection from: CROI 2007 - Key Challenges in HIV: Metabolic Complications

and Adverse Effects; HIV/Hepatitis Coinfection; and Clinical Pharmacology

Advances in the Management of Viral Hepatitis B and Hepatitis C Infection in

HIV-Coinfected Patients - CROI 2007 CME

V. Soriano, MD, PhD

Disclosures

Introduction

This year's Conference on Retroviruses and Opportunistic Infections (CROI)

convened in Los Angeles, California, and drew nearly 4000 attendees, 45% of

whom were from abroad. The opening ceremony coincided with the Academy

Awards ceremony in Hollywood. In light of the number of abstracts on viral

hepatitis infection in people with HIV coinfection -- 75 out of 1100

abstracts in total -- there is no doubt that HIV-viral hepatitis coinfection

should have merited at least 1 at CROI.

Hepatitis B Virus Infection

The HBV Genome

The hepatitis B virus (HBV) genome is composed of 4 overlapping genes that

encode a number of complex and multifunctional proteins. Of interest, part

of the polymerase gene overlaps the gene that encodes the HBV surface

antigen (HBsAg) protein. It is not surprising that long-term antiretroviral

therapy directed against HBV reverse transcriptase (RT) can lead to the

selection of drug resistance mutations that may affect the antigenicity of

the overlapping HBsAg protein (Figure 1). In the other direction, HBV

vaccination or the use of hepatitis B immunoglobulin as prophylaxis may

select for envelope mutations that affect the polymerase (Figure 2).

Figure 1. Overlapping surface antigen (S) and polymerase genes in HBV.

Figure 2. Mutations in HBV reverse transcriptase (RT) and HBsAg. Adapted

from Sheldon et al.[1] with permission.

Characteristics of Drug-Resistant HBV

Spanish and Australian researchers examined 71 individuals with chronic

hepatitis B infection who were exposed to anti-HBV agents for longer than 12

months and who were currently experiencing virologic failure.[1] Fifty-two

of these individuals were coinfected with HIV. The study investigators found

a significant segregation of HBV genotypes. Genotype A was more prevalent in

HBV/HIV-coinfected patients (38/52), whereas genotype D was the most common

in HBV-monoinfected persons (10/19) (P < .01). Of interest,

lamivudine-associated resistance mutations in HBV were present in more than

half of all patients and were more common in HBV/HIV-coinfected than in

HBV-monoinfected individuals. In the multivariate analysis, this observation

was mainly driven by the characteristic genotype distribution.

Remarkably, 3 coinfected patients harbored HBV strains with the RT triple

mutant V173L + L180M + M204V, which results in diminished HBsAg antibody

binding.[2] The public health implications of these findings suggest that

the selection of certain HBV drug-resistance mutations may result in altered

HBsAg, thereby creating HBV strains that can evade or escape from the immune

responses generated by vaccines and/or failure to be recognized by serologic

tests for HBsAg, explaining the phenomenon of " occult " hepatitis B.

Possible Anti-HIV Activity of Entecavir?

Entecavir is one of the antiviral agents most recently approved for treating

HBV. The drug label specifically states that it lacks anti-HIV activity at

the approved recommended doses. In a rather surprising late-breaker

presentation, researchers from s Hopkins University reported on 3

HBV/HIV-coinfected individuals who were exposed to entecavir in the absence

of antiretroviral therapy.[3] All showed about a 1-log10 decline in plasma

HIV-RNA and 1 developed the M184V mutation in HIV, suggesting that entecavir

has activity against HIV. The study investigators also reported that in

vitro experiments provided additional support that entecavir shows anti-HIV

activity, although the data were somewhat controversial and virologists from

the company that markets the drug replied that their data do not support the

investigators' findings.[4] It is intriguing that HIV drug resistance

information was not reported for the other 2 HBV/HIV-coinfected patients

exposed to entecavir and that the 1 individual who harbored the M184V

mutation in HIV had been exposed in the past to lamivudine. Clearly, further

data are needed before it can be concluded that entecavir is not appropriate

for the treatment of HBV in HIV-infected individuals who do not require

antiretroviral therapy, as is recommended in current guidelines (Figure

3)[5,6]

Figure 3. Preferred anti-HBV agents for the treatment of HBV in HIV-infected

patients based on whether they also require treatment of their HIV

infection.

Supported by an independent educational grant from Bristol-Myers Squibb

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