Case-Based Review

Management of Patients with HIV and Hepatitis B Coinfection

Journal of Clinical Outcomes Management. 2017 October;24(10)

Author(s):

References

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From UT Southwestern Medical Center, Dallas, TX.

Abstract

Objective: To review the literature on and provide evidence-based recommendations for management of HIV/ hepatitis B (HBV) coinfection.
Methods: Review of the literature for clinical trials, guidelines, and cohort studies on HIV/HBV disease management.
Results: HIV patients should be evaluated for viral hepatitis. Those who do not have evidence of immunity should be vaccinated and monitored for response. Those who have HIV/HBV should have additional serologies checked to evaluate for hepatitis B e antigen status and level of viremia. All HIV/HBV coinfected patients should be started on antiretroviral therapy with tenofovir-based regimens. Those with HIV/HBV and cirrhosis should be screened for hepatocellular cancer every 6 months.
Conclusion: HIV patients should be vaccinated against hepatitis B; those with coinfection should be treated for both viruses. It is important to monitor for treatment response to both HIV and HBV and liver disease complications.

Key words: incentives; reinforcement; substance abuse treatment; dissemination; implementation.

Morbidity and mortality for HIV-infected patients remain high compared to uninfected patients despite effective virologic suppression. Major contributors to illness and death among these patients include cardiovascular disease, non–AIDS-defining malignancies, and chronic liver disease, specifically viral hepatitis [1]. Hepatitis B virus (HBV) infection is one of the main causes of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) globally. Because HIV and HBV can both be acquired through injection drug use and sexual transmission, coinfection occurs frequently. The Joint United Nations Program on HIV/AIDS estimates that 10% of the 33 million HIV-positive patients worldwide have simultaneous chronic HBV infection [2].

HIV/HBV coinfection significantly impacts the natural history, progression, and mortality related to both viruses. HIV infection accelerates HBV-related liver impairment, leading to earlier cirrhosis, end-stage liver disease, and HCC. Conversely, chronic HBV does not have a considerable influence in the progression of HIV; however, antiretroviral treatment (ART) toxicities and/or HBV flares due to immune reconstitution inflammatory syndrome (IRIS) or HBV itself can lead to increased liver-related complications [3,4].

Case Patient 1

Initial Presentation and History

An asymptomatic 38-year-old man diagnosed with HIV infection 1 month ago presents for his initial visit to establish HIV care. The patient is a man who has sex with men (MSM) and is currently sexually active with multiple partners. He reports inconsistent use of condoms. One month ago he underwent routine screening and was found to be HIV-positive. At the time of diagnosis, the patient’s baseline CD4 cell count was 328 cells/µL and his viral load was 182,600 copies/mL. The patient wants to discuss the implications of his new diagnosis of HIV and recommendations for further testing and treatment. He is especially interested in HBV screening, since one of his recent partners was known to be positive. The patient has no relevant past medical history. He does not recall the details of his childhood vaccinations. He denies smoking and injection drug use but reports moderate alcohol consumption.

Physical Examination and Laboratory Testing

Physical examination is normal. Laboratory studies show normal complete blood count (CBC) and renal and liver function test results, and a baseline HIV genotype does not show resistance. Hepatitis A total antibody (anti-HAV) testing is positive, while tests for hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), antibody to hepatitis B core antigen (anti-HBc), and hepatitis C antibody (anti-HCV) are negative.

• Which screening tests for HBV should be performed in HIV-infected patients?

Routine screening of all HIV-infected patients for hepatitis A virus, HBV, and hepatitis C virus (HCV) is recommended [5]. Routine HBV screening involves obtaining serologies for HBsAg, anti-HBs, and anti-HBc. With these results, patients can be classified into categories of either active infection, immunity, or no evidence of prior exposure (Table 1).

The serologic hallmark of active HBV infection is HBsAg, which if persistent for 6 months is diagnostic of chronic HBV infection. Patients with positive HBsAg require a full evaluation, as discussed later in this review. An isolated anti-HBc test usually means past infection with subsequent loss of anti-HBs. Incidence of HBV viremia in HIV-positive patients with isolated positive anti-HBc is variable and ranges from 1% to 36% [5]. All patients without evidence of prior exposure or vaccination as well as individuals with isolated anti-HBc should be offered vaccination against HBV [6].

• How effective is HBV vaccination in the HIV population?

Vaccination

Available HBV vaccines in the United States include 2 single-agent vaccines (Recombivax HB [Merck, Whitehouse Station, NJ] and Engerix-B [GlaxoSmithKline, Research Triangle Park, NC]) as well as a combination HAV/HBV vaccine (Twinrix [GlaxoSmithKline]). For adults (age ≥ 20 years) with an immunocompromising condition such as HIV infection, current Centers for Disease Control and Prevention guidelines recommend three 40 µg/mL doses of single-agent vaccine administered at 0, 1, and 6 months (Recombivax HB), or four 40 µg/mL doses of single-agent vaccine (2 doses of 20 µg/mL administered simultaneously) at 0, 1, 2, and 6 months (Engerix-B) [7].

The immunogenicity to HBV vaccination in HIV-positive patients is decreased, reflected by lower antibody titers, waning immunity, and seroconversion rates of 18% to 65% [8–11]. Factors associated with poor response include low CD4 cell counts, detectable HIV RNA, coinfection with HCV, and the general health status of the patient [8]. Ideally, HBV vaccination should occur prior to decline in CD4 cell count below 350 cells/µL. However, guidelines do not recommend deferring vaccination since some patients with advanced HIV disease will seroconvert [6].

Anti-HBs titers should be checked 1 month after completion of the vaccine series to confirm protective antibody titers. For patients with quantitative anti-HBs levels < 10 IU/mL, a second vaccine cycle is recommended. Some specialists may defer revaccination until a sustained increase in CD4 count is achieved on ART.

Two randomized controlled trials have demonstrated that 4 doses of double-dose (40 µg/mL) vaccine generate higher anti-HBs levels than 3 doses of standard-dose (20 µg/mL) vaccine in HIV-infected adults [12,13]. Another study showed that HIV patients with CD4 counts > 350 cells/µL had better responses when immunized with double- dose vaccines on the usual 3-dose series [14]. Currently, the CDC recommends giving a double dose for either a 3-dose schedule or a 4-dose schedule. However, it remains unclear what dosing schedule to use if a patient fails to respond. Likely waiting until the CD4 cell count has increased and HIV viral load is suppressed will be important to seeing a response.