The anti-HIV activity of entecavir: a multicentre evaluation of lamivudine-experienced and lamivudine-naive patients.
BACKGROUND
Entecavir, an antiviral with potent anti-hepatitis B virus activity, was recently shown to have anti-HIV activity in three patients and the ability to select for the lamivudine-resistant HIV polymerase mutation M184V in a patient with prior antiretroviral therapy.


OBJECTIVE
To further characterize entecavir's anti-HIV activity and identify risk factors for selection of the M184V.


METHODS
Retrospective cohort study.


METHODS
We evaluated the virological characteristics of HIV and hepatitis B virus in 17 HIV-hepatitis B virus coinfected patients (10 antiretroviral therapy-naive and seven antiretroviral therapy-experienced) prior to and during entecavir monotherapy. Descriptive statistics were used to assess changes in HIV RNA and hepatitis B virus DNA. Variables associated with development of the M184V were determined by univariate analysis.


RESULTS
Of the 17 patients, 13 (76%) demonstrated a reduction in HIV RNA by at least 0.5 log10 copies/ml. Of the remaining four patients, two had the M184V detected prior to entecavir therapy and the other two had wild-type HIV. The median reduction in HIV RNA for the cohort was 1.2 log10 copies/ml, which was similar in antiretroviral therapy-naive and antiretroviral therapy-experienced patients. The M184V mutation emerged in six patients receiving entecavir, including three antiretroviral therapy-naive patients. No other HIV mutations were consistently detected. Risk factors for the emergence of the M184V mutation were a decline in hepatitis B virus DNA (P = 0.04) and duration of entecavir use (P = 0.05).


CONCLUSIONS
Entecavir monotherapy in HIV-hepatitis B virus coinfected patients, including antiretroviral therapy-naive patients, has significant anti-HIV activity and can result in the development of the M184V variant. Entecavir should not be used in such co-infected patients without concomitant antiretroviral therapy.
Sasadeusz
Joe
J
The Alfred Hospital, Melbourne, Victoria, Australia. joe.sasadeusz@mh.org.au
Audsley
Jennifer
J
Mijch
Anne
A
Baden
Rachel
R
Caro
Jose
J
Hunter
Hermeyone
H
Matthews
Gail
G
McMahon
Moira A
MA
Olender
Susan A
SA
Siliciano
Robert F
RF
Lewin
Sharon R
SR
Thio
Chloe L
CL
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood; D004341:Drug Evaluation; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D006515:Hepatitis B virus / Q000187:drug effects / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D012307:Risk Factors
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D054303:HIV Reverse Transcriptase