Transcript Serologic Markers and Molecular Epidemiology of HBV in an HIV

Serologic markers and molecular epidemiology of
HBV from an HIV infected cohort from Cameroon
Tshifhiwa Magoro1, Emmaculate Nongpang2, Lufuno Mavhandu1,
Roland Ndip2, Helen Kimbi2, Pascal Bessong1
1HIV/AIDS
and Global Health Research Programme, Department of
Microbiology, University of Venda, Thohoyandou, South Africa
2Department of Parasitology, Faculty of Science, University of Buea,
Buea, Cameroon
Background and rationale
• Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) are
of global public concern. Despite the availability of a safe and efficient
HBV vaccine.
• The results of HBV infection varies widely among infected patients,
response to antiviral treatment and disease progression may differ
depending on the genotype of a patient (Singh et al., 2009).
It is imperative to determine HBV genotypes to identify patients at
great risk for disease progression to cirrhosis and the risk of HCC.
Background and rationale
• Occult HBV infection (presence of HBV DNA in the absence of
HBsAg).
• Guidelines for the use of antiretroviral agents in HIV/HBV co-infected
patients recommend combination therapy with a tenofovir (TDF) Plus
lamivudine (3TC) or Emtricitabine.
• The majority of HIV-HBV co-infected patients therefore receive an
anti-HBV lamivudine monotherapy that has been shown to lead to
frequent emergences of drug resistance.
• This study was aimed at investigating the prevalence, genotypes, and to
assess HBV Lamivudine resistance mutations in a Cameroon HIV
infected population.
STUDY DESIGN
Study site and study participants
Study population
Outpatient clients of
the Baptist Health
Centre, Mutengene,
Cameroon.
The centre offers HIV
treatment.
Yoke
Ekona
Idenau
Mutengeni
Limbe
Laboratory procedures
Ethical
consideration
Sample
n=455
Serology
HBsAg
seropositive
Isolation of
DNA
DNA
amplification
Plasma
HBsAg
seronegative
Sequencing
HBeAg
AntiHBc
AntiHBs
Occult
infection
Genotyping
Drug
resistance
mutation
Results and discussion
Prevalence of hepatitis B virus serological markers in 455 study participants in Cameroon.
Why are children still infected?
• In subjects below the age of 15 years (1-14), 20.9% (9/43) of them were
reactive for HBsAg. Of which 44.4% (4/9) were reactive for HBeAg
(indicating high levels of infectiousness in this subset of
participants).
• However, those who were found to be infected in the same age group, it
might be due to vaccine escape mutants or did not receive the vaccine at all
or they did not respond to HBV vaccine.
• 31.3% (5/16) of subjects reactive for HBeAg were women of child-bearing
age. Vertical transmission is frequently observed in women with HBeAg.
Epidemiological risk factors and HBsAg seropositivity (univariate analysis)
Occult HBV infection
• Occult HBV infection was assessed in samples with a negative HBsAg
serology, regardless of their anti-HBc and anti-HBs serology.
• The prevalence of occult HBV infection was 6.5% (20/310).
• 35% (7/20) of the samples which showed occult HBV DNA, were also
negative for anti-HBc and anti-HBs markers.
• In most countries, blood is screened for HBsAg; however the techniques
used vary widely. A study from Ghana showed that using particle
agglutination or dipstick tests, 46 and 29% of viremic patients were
missed, respectively.
Why only a fraction of HBsAg positive patients were
positive for HBV DNA?
• HBV DNA was successfully amplified in 45.7% (48/105) of the HBsAg
positive patients.
HBsAg is a marker of active infection, so we expected to find HBV DNA in such patients
Genotypes
Two major genotypes:
Genotype E
HBV genotype E
(n=33; 71.7 %);
HBV genotype A
(n=13; 28.3 %).
Genotype A
Lamivudine mutations
Several mutations were observed in the polymerase region of seven
patients only [ 15.2 % (7/46) ].
ETV-entecavir
TBV-telbivudine
FTC-emtricitabine
Note: Samples in RED- Lamivudine naïve
Samples in Black- Lamivudine experienced as part of HIV treatment
No mutations that can code for resistance to tenofovir and adenofovir were detected
Limitations
• Sample size
• HBV vaccination history were not recorded during sample
collection.
• HBV viral load
• Measuring the level of protection (anti-HBs plasma levels of ≥10
IU/ml).
Conclusion and recommendations
• The present study demonstrates that HBV infection is endemic in the study
population, with genotype E dominating and HBV genotypic resistance to
lamivudine exists in the studied population.
• The results also highlight the importance of screening for HBV resistance
before HIV treatment.
• This data can contribute to the development of policies for screening
programmes in Cameroon.
• The study also illustrated the need for occult HBV detection to be
implemented even if anti-HBc and anti-HBs were negative especially in an
endemic area, such as Cameroon.
Acknowledgements
• We are grateful to the study participants.
• University of Venda- funding.
• National Research Foundation.
• The entire team of HIV/AIDS and Global Health Research Programme
at the University of Venda.
THANK YOU!!
NDO LIVHUWA!!
NDA TENDA!!