Hepatitis B virus
(HBV) genotype A1 infection is associated with poor virological control and the
rapid emergence of drug resistance among people living with HIV who are starting
antiretroviral therapy in Malawi in the absence of tenofovir, investigators report in the online edition of
Clinical Infectious Diseases.
The study looked at people starting
HIV therapy between 2007 and 2009. Antiretroviral therapy (ART) consisted of
fixed-dose lamivudine, stavudine and nevirapine. This meant that lamivudine was the
only drug in their combination which was active against hepatitis B.
proportion of HIV-1 infected patients … were at risk of progressive liver
fibrosis and excess mortality due to poorly controlled HBV co-infection,”
comment the investigators. “Suboptimal HBV suppression and emergence of
resistance was most evidence in subjects that tested HBeAg-positive and had HBV
viral load at treatment initiation.”
proportion of people living with HIV have hepatitis B virus co-infection. HIV increases hepatitis B virus
replication and the risk of liver-related disease, especially in the context of
low CD4 counts and high hepatitis B viral load.
recommend that everyone living with HIV should be intensively screened for hepatitis B and that people with hepatitis B co-infection should receive antiretroviral
therapy that includes two drugs with activity against both HIV and hepatitis B,
typically tenofovir with emtricitabine or lamivudine.
Hepatitis B is
highly prevalent in sub-Saharan Africa. However, few people living with HIV in
the region are screened for hepatitis B and ART is usually initiated without
knowledge of co-infection status. This is especially concerning as, until
recently, the only drug with hepatitis B activity used in HIV treatment combinations in
the region was lamivudine; hepatitis B monotherapy with this drug is associated with
the rapid emergence of drug resistance.
Hepatitis B virus genotype A1 is
unique to Africa and some investigators have proposed that it is associated
with a relatively benign disease course.
To see if this was
the case, investigators monitored hepatitis B levels among people living with HIV in
Malawi who had hepatitis B genotype A1 co-infection and who received ART that included
lamivudine as the only hepatitis B-active drug. Follow-up lasted for up to twelve
months. A variety of sequencing techniques were used to detect hepatitis B
A total of 1117
people started therapy during the study period and 12% tested HBsAg-positive.
Half of these patients were HBeAg-positive. HBeAg-positive status
was associated with higher HBV DNA detection rates (p = 0.0014), an increased
likelihood of having HBV DNA levels above 2000 iu/ml (p = 0.0006) and higher HBV
DNA levels (p < 0.001).
three-quarters of patients (72%) were retained in care six months after
starting HIV treatment and 41% were still in care after twelve months.
At the last
follow-up, 96% of patients had achieved an undetectable HIV viral load (below
40 copies/ml). Half the people with hepatitis B co-infection achieved HBV DNA suppression below 14 iu/ml; half the patients with persistent
HBV DNA levels achieved HBV RNA suppression.
"HBV outcomes were
poor among HBeAg-positive patients,” note the authors. “HBV DNA levels initially
declined by 4.5 log10 iu/ml, then rebounded, coinciding with the
rapid emergence of resistance.”
Use of the Sanger
sequencing technique showed that none of the people with HIV and hepatitis B co-infection had HBV
resistance associated mutations at baseline. However, prevalence was 8% after
six months of follow-up, increasing to 33% at the twelve-month follow-up
interval. The incidence of resistance was 34 per 100 person-years.
revealed a higher prevalence of HBV resistance-associated mutations. Prevalence
was zero at baseline, 19% six months after starting ART and 35% after twelve
months of follow-up.
Sanger and deep sequencing results showed that HBV resistance rates were
significantly higher in HBeAg-positive patients compared to HBeAg-negative patients (49%
vs 4%, p < 0.0001). Higher baseline HBV DNA was also associated with the
emergence of resistance (p < 0.0001).
“Our data provide clear evidence in support of
the motion that HBsAg testing should be introduced as part of routine HIV care
in sub-Saharan Africa in order to guide ART selection and early adoption of
tenofovir, and to identify patients that require follow-up for liver disease,”
conclude the authors.