Baseline CD4+ T-cell counts predict HBV viral kinetics to adefovir treatment in lamivudine-resistant HBV-infected patients with or without HIV infection.
BACKGROUND
Coinfection with HIV and hepatitis B virus (HBV) substantially alters the course of HBV. Directly acting anti-HBV agents suppress HBV viral levels; however, the kinetics of HBV decline in mono- and coinfected persons have not been evaluated. We investigated the role of baseline CD4+ T-cell counts as a predictor of HBV response to adefovir (ADV) therapy in chronic HBV with and without HIV coinfection.


METHODS
We conducted a double-blind, randomized, placebo-controlled study of HIV-infected (n = 12) and uninfected (n = 5) chronic HBV patients treated with ADV. Five HIV uninfected patients received ADV; the HIV+ patients received ADV or placebo for a total of 48 weeks. At the end of 48 weeks, all patients received open-label ADV for an additional 48 weeks. HBV, HIV viral loads, CD4+ T-cell counts, and safety labs were performed on days 0, 1, 3, 5, 7, 10, 14, and 28 and then every 4 weeks.


RESULTS
Lower HBV slopes were observed among coinfected compared to monoinfected patients (P = .027 at 4 weeks, P = .019 at 24 weeks, and P = .045 at 48 weeks). Using a mixed model analysis, we found a significant difference between the slopes of the 2 groups at 48 weeks (P = .045). Baseline CD4+ T-cell count was the only independent predictor of HBV decline in all patients.


CONCLUSIONS
HIV coinfection is associated with slower HBV response to ADV. Baseline CD4+ T-cell count and not IL28B genotype is an independent predictor of HBV decline in all patients, emphasizing the role of immune status on clearance of HBV.
Division of Human Tissues, Office of Cell Therapy and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Rockville, MD, USA.
K J
KJ
Cortez
M A
MA
Proschan
L
L
Barrett
D G
DG
Brust
Barry
B
Weatherley
E
E
Formentini
R T
RT
Davey
H
H
Masur
M A
MA
Polis
A U
AU
Neumann And
S
S
Kottilil
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D060085:Coinfection / Q000188:drug therapy / Q000821:virology; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D006509:Hepatitis B / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007700:Kinetics; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*
D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000225:Adenine