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Occult Hepatitis B Viremia in HIV-infected Individuals on 3TC-containing ART and Its Relationship to Immunologic Status
Debika Bhattacharya*1, D Katzenstein2, D Israelski3, L P Shen4, C Wong4, C Bush4, and R Donovan5
1David Geffen Sch of Med, Univ of California, Los Angeles, US; 2Stanford Univ, CA, US; 3San Mateo Clin AIDS Prgm, CA, US; 4Bayer Diagnostics, Berkeley, CA, US; and 5California Dept of Hlth Svcs, Richmond, US
Background: Occult hepatitis
B virus (HBV), HBV DNA in the absence of HBsAg, occurs in ~10% of untreated HIV+
individuals and is often marked by the anti-HBc alone pattern. Occult HBV
during long-term lamivudine (3TC) -containing ART may
lead to 3TC-resistant HBV in those with “cleared” HBV. Occult HBV prevalence in
HIV+ individuals on prolonged 3TC-containing ART and its
relationship to immune status is unknown. Our objective was to evaluate the presence of HBV DNA at multiple
time-points in HIV+ anti-HBc alone
individuals on 3TC-containing ART and, where HBV viremia was present, to examine
immunologic correlates.
Methods: A clinical database was
reviewed to identify patients in the San Mateo AIDS program who were anti-HBc+, but HBsAg–
and anti-HBs–, on 3TC-containing ART, and
with ≥1 annual samples. HBV DNA was detected with Bayer’s research real-time
polymerase chain reaction (RT-PCR) assay, linear range from 10 to 109
copies and a lower limit of detection of 4 copies/reaction,
in a Stratagene Mx3000P thermocycler.
Results: We analyzed 74 plasma
samples from 29 HIV+
and anti-HBc alone subjects receiving 3TC-containing ART.
Among the 29 subjects, 4 interrupted 3TC, 6 (21%) were female, and 20
(71%) had HCV infection; median entry CD4 cell count and log HIV RNA were 218
cells/mm3 and 3.3 copies/mL, respectively.
Of 29 patients, 7 (24%) had occult HBV at 1 or 2 time-points; 2 had persistent
HBV DNA while 4 lost and 3 gained HBV DNA, and all 7 in whom we detected occult
HBV were HCV+. Patients with occult HBV had lower mean entry
CD4 (130 vs 345 cells/mm3, p
<0.07), higher entry log HIV RNA (3.5
vs 3.2 copies/mL), and greater mean duration
of 3TC-containing ART (4 vs 2 years, p <.05). Loss of detectable HBV in 3
of 4 patients was associated with a median CD4 increase of 93 cells/mm3,
HIV RNA decrease of log 0.15 copies/mL,
and alanine aminotransferase
decrease of 20 IU/mL.
Conclusions: Despite 3TC-containing
ART, occult HBV was detected in 24% of HIV-infected patients with anti-HBc
alone antibodies. Occult HBV in this small cohort was associated
with HCV co-infection, immunodeficiency, and prolonged 3TC treatment. In a
few cases, loss of detectable HBV was associated with immune reconstitution and
decreased hepatic inflammation.
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