The
researchers, from Johns Hopkins School of Medicine, described their data in more
detail in the June 21, 2007 issue of the New England Journal of Medicine.
The
investigators observed that entecavir led to a consistent 1 log10 decrease in
HIV-1 RNA in 3 individuals with HIV-HBV coinfection, indicating that the drug
was active against HIV. In the report, these patients and the details of their
case histories were described in full.
Patient
1: a 31-year-old
man with HIV-HBV coinfection who tested positive for HIV in 1990. In 2000, he
received AZT (Retrovir), 3TC, and nevirapine (Viramune), taking these drugs intermittently
for less than 1 year. In February 2002, his CD4 cell count was 596 cells/mm3 and
his plasma HIV RNA level was 14,602 copies/mL. These levels remained stable for
the next 4 years without therapy. In March 2006, he started entecavir for chronic
hepatitis B. At that time, his HIV RNA level was 34,088 copies/mL and his CD4
count was 574 cells/mm3. In the first 2 months after starting entecavir, his HBV
DNA level decreased from 9.60 to 3.95 log10 IU/mL, while his HIV RNA level also
decreased by approximately 1 log10 to 2193 copies/mL and his CD4 count increased
to 634 cells/mm3. After 12 months on therapy, his HIV RNA slowly rose from its
nadir to 13,345 copies/mL, while his HBV DNA remained at its nadir.
Patient
2: a 24-year-old
man diagnosed as HIV positive in February 2003. Although acute HBV infection developed
in March 2005, his HIV infection did not meet the criteria for antiretroviral
therapy. His HIV viral load ranged from 40,000 to 60,000 copies/mL and his CD4
cell counts were generally greater than 500 cells/mm3. In February 2006, he started
entecavir for the treatment of chronic hepatitis B. After 1 month, his HIV RNA
decreased 1.23 log10, from 40,273 to 2347 copies/mL, and his CD4 count rose from
490 to 568 cells/mm3. His HBV DNA level also decreased while receiving entecavir.
Given the concern about the activity of entecavir against HIV, his treatment was
switched to tenofovir (Viread), emtricitabine, and efavirenz (Sustiva) after 45
days of treatment with entecavir.
Patient
3: a 46-year-old
man with HIV-HBV coinfection who became HIV positive in the 1980s. In 1993, he
received AZT monotherapy, followed by AZT plus 3TC intermittently between 1997
and 2004. Before he received this regimen, his HIV viral load was 30,075 copies/mL
and his CD4 cell count was 375 cells/mm3. From September 2005 to February 2006,
he received pegylated interferon alfa-2a (Pegasys) to treat chronic hepatitis
B, but had a poor response. In August 2006, he began entecavir monotherapy for
hepatitis B. When entecavir was initiated, he had an HIV RNA level of 55,451 copies/mL
and a CD4 count of 399 cells/mm3. After 2 months on entecavir, his HIV RNA level
decreased 0.85 log10 to 7797 copies/mL with a rise in CD4 count to 480 cells/mm3.
His HIV viral load remained below baseline after 7 months of entecavir monotherapy,
while his HBV DNA level decreased from to 1.99 log10 IU/mL.
After
noticing this phenomenon in patients, the researchers decided to look for supportive
in vitro evidence that entecavir inhibits HIV-1 replication. They also discussed
their laboratory methods and findings in detail in the present report.
Detailed
analysis showed that in 1 of the 3 patients, entecavir monotherapy led to an accumulation
of HIV variants with the 3TC-resistance mutation, M184V. In vitro experiments
showed that M184V also confers resistance to entecavir.
In conclusion,
the authors wrote, "Until more is known about HIV-1-resistance patterns and
their selection by entecavir, caution is needed with the use of entecavir in persons
with HIV-1 and HBV coinfection who are not receiving fully suppressive antiretroviral
regimens."
07/13/07
References
MA
McMahon, BL Jilek, TP Brennan, and others. The HBV Drug Entecavir - Effects on
HIV-1 Replication and Resistance. New England Journal of Medicine 356(25):
2614-2621. June 21, 2007.
MS
Hirsch. Entecavir Surprise. New England Journal of Medicine 356(25): 2641-2643.
June 21, 2007.
