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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060 EISSN: 1678-8060
Vol. 102, Num. 4, 2007, pp. 535-537
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Memórias do Instituto Oswaldo Cruz, Vol. 102, No. 4, 2007, pp. 535-537
The role of triple infection with hepatitis B virus, hepatitis C virus,
and human immunodeficiency virus (HIV) type-1 on CD4+ lymphocyte levels in the highly HIV infected population of North-Central
Nigeria
JC
Forbi, S Gabadi, R Alabi, HO Iperepolu, CR Pam, PE Entonu, SM Agwale+
Virology
Laboratory, Innovative Biotech-Keffi No. 1, Abdu Abubakar Street,
GRA- Keffi, PO Box 30, Keffi, Nasarawa State, Nigeria
+Corresponding
author: sagwale@innovativebiotechng.com
Received
18 July 2006
Accepted
19 March 2007
Code Number: oc07084
We
set out to determine the seroprevalence of hepatitis B and C among
human immunodeficiency virus type-1 (HIV-1) infected individuals
in North-Central Nigeria to define the influence of these infections
on CD4+ lymphocytes cells among our patients as access
to antiretroviral therapy improves across the Nigerian nation. The
CD4+ values of 180 confirmed HIV-1 infected individuals
were enumerated using a superior fluorescence-activated cell sorter
system. These patients were tested for the presence of hepatitis
B surface antigen and anti-hepatitis C virus (HCV) using third generation
enzyme-linked immunosorbent assays. Fifty (27.8%) patients had active
hepatitis B virus (HBV) infection while 33 (18.3%) tested positive
for anti-HCV antibody. Of these infections, 110 (61.1%), 37 (20.6%),
and 20 (11.1%) had HIV only, HBV/HIV-only, and HCV/HIV-only respectively.
A HBV/HCV/HIV coinfection prevalence of 7.2% (13 patients) was recorded.
Patients coinfected with HIV/HBV/HCV appeared to have lower CD4+
counts (mean = 107 cells/µl; AIDS defining) when compared to
HBV/HIV-only (mean = 377 cells/µl), HCV/HIV-only (mean = 373
cells/µl) and patients with mono HIV infection (mean = 478
cells/µl). Coinfection with HBV or HCV is relatively common
among HIV-infected patients in Nigeria and should be a big consideration
in the initiation and choice of therapy.
Key
words: human immunodeficiency virus - hepatitis B and C viruses
- Nigeria
Human
immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis
C virus (HCV) are devastating disease agents that share common modes
of transmission (Santiago-Munoz et al. 2005), therefore HIV positive
individuals are at risk of co-infection with HBV and HCV infections.
With the advent of highly active antiretroviral therapy (HAART)
regimens capable of dramatically prolonging the survival of HIV-infected
patients, the impact of co-morbid infections such as HBV and HCV
has come into focus (Petoumenos & Ringland 2005). Co-infection
with HBV or HCV increases the risk for hepatotoxicity of HAART and
likelihood of onset of an AIDS-defining illness, compared
with infection with HIV-1 alone (Greub 2000, Feld
et al. 2005). Although the HIV co-infection with HBV and/or HCV
has been recognized worldwide in individuals exposed to blood-borne
diseases, limited data are available on the extent of co-infection
and effect of these viruses on the immune system in developing countries.
Nigeria belongs to the group of countries highly endemic for viral
hepatitis (Odemuyiwa et al. 2001). Few studies have been done on
HIV, HBV, HCV separately in Nigeria but the knowledge about the
interrelationship between these viruses and their effect on the
immune system remains unclear. This study was therefore carried
out to estimate the prevalence of HBV and/or HCV seropositivity
in a cohort of people living with HIV/AIDS in North-Central Nigeria
and to investigate the effect of these viruses on CD4+
lymphocytes in the HAART era in Nigeria.
One
hundred and eighty plasma samples were randomly selected
from confirmed HIV-1 positive samples stored at _24oC
in the Virology laboratory of Innovative Biotech (IBL), Keffi, Nasarawa
State, Nigeria. These samples were collected between June and December
2005 from clients who assessed IBL services for voluntary HIV counseling
and testing or for other health needs. Before each client was bled,
informed consent was obtained in accordance with IBL and international
regulations. These samples were labeled with a serialized IBL code
number that could not be linked to individuals. As patients were
bled, a fluorescence-activated cell sorter system (Becton Dickenson
FACSCount, Canada) was used to enumerate absolute values for CD4+
cells for each sample according to manufacturers instructions. The
second CD4+ counts of clients who returned after HAART
were also enumerated. The double antibody sandwich
ShantestTM- HBsAg ELISA (Shantha Biotech Limited - India)
was used for the detection of HBsAg in plasma following manufacturers
instructions and the microplates read at a wavelength of 450 nm
using the ELISA reader (BIO-RAD 2100, version 6.1, US). Anti-HCV
antibodies were detected in plasma using the Anti-HCV-EIA-Avicenna
(Avicenna Medical Center, Russia) which is a third generation quantitative
ELISA that uses recombinant proteins and synthetic peptides derived
from core and structural regions of HCV to detect the presence of
anti-HCV in plasma samples. The test was carried out and interpreted
according to manufacturer's instructions. Demographic
data (age and gender) for participants were retrieved from coded
clients' electronic registration records maintained at IBL. To compare
the proportion of HIV positive individuals co-infected with HBV
and/or HCV, the chi-square test was used at 95% confidence level.
The analysis was done after recording the data in a Microsoft Excel
worksheet on a Windows- 98 platform.
Of the
180 samples, 83 were from males and 97 from females. The age range
of the patients in this study was 20-64 years. The seroprevalence
of HIV/hepatitis viruses and the distribution of disease burden
are as follows: HIV only = 61.1%; HBV/HIV only = 20.6%, HCV/HIV
only = 11.1%, and HIV/HBV/HCV = 7.2%. The gender distribution and
ages of the infected individuals are as shown: 110 HIV only (57
males: 53 females; mean age = 32 and 20 years respectively); 37
HIV/HBV (21 males: 16 females; mean age = 29 and 25 years respectively);
20 HIV/HCV (13 males: 7 females; mean age = 37 and 30 years respectively);
13 HIV/HBV/HCV (7 males: 6 females; mean age = 43 and 31 years respectively).
The CD4+ profile was not different from either the HBV
(range = 5 to 523 CD4+ cells/µl , mean = 377 CD4+
cells/µl) or HCV (range = 46 to 791 CD4+ cells/µl,
mean 373 CD4+ cells/µl) coinfected individual. On
the other hand, CD4+ count values in HBV/HCV/HIV coinfected
patients were poorer (range = 4 to 442 CD4+ cells/µl,
mean = 107 CD4+ cells/µl). The mean CD4+
count value for patients infected with HIV only was 478 CD4+
cells/µl (range = 8 to 755 CD4+ cells/µl).
Thirty-seven patients enrolled for HAART (nevirapine 200 mg, lami-vudine
150 mg, stavudine 40 mg, and nutrilite dietary supplement) during
the period under review. The CD4+ counts for 14 clients
were enumerated four months post-antiretroviral therapy (ART). There
was an average increase of 128 (range = 22 to 586) CD4+
cells in all the category of patients. However, there was a post
ART decline of 133 CD4+ cells in a 35 years old female
client coinfected with HIV and HCV infections.
HAART
has transformed HIV/AIDS from a uniformly fatal illness into a manageable
chronic infection and has been shown to be able to restore CD4+
cells in HIV infected patients (Rathbun et al. 2006). The gains
of HAART could be compromised by coinfection with hepatitis viruses
as they are known to have adverse effects on the prognosis of HIV
and hepatitis infections (Feld et al. 2005). Consequently, increased
attention has to be paid on coinfection of hepatitis viruses and
HIV especially in the developing countries like Nigeria where these
groups of viruses are endemic. In this study, 20.6% of HIV infected
individuals were coinfected with HBV. Our study correlates with
a recent study in Jos (Uneke et al. 2005), that recorded that 25.9%
of HIV-infected individuals were HBsAg seropositive. This study
therefore confirms the endemicity of HBV infection and increased
infection in HIV infected individuals. This calls for the need to
strengthen the HBV vaccination program in Nigeria which is known
to be able to considerably reduce the incidence of HBV infections.
The average CD4+ count values for this group was 377
cells/µl which is lower than that for HIV mono-infection recorded
(mean = 478 cells/µl). The natural history of HBV is known
to be complicated by HIV-co-infection but the effect of HBV on the
outcome of patients infected with HIV-1 is controversial (Rockstroh
2006). The reasons for the CD4+ decline is not clear
but it is known that there is an imbalance in peripheral blood T-lymphocyte
subsets and turbulence in cellular immunity in the patients with
chronic hepatitis B (Tian et al. 2005). Also, lamivudine resistant
mutations in HBV treatment have adverse effects on treatment response
in HIV infected individuals coinfected with HBV.
We also
found an HCV seroprevalence rate of 11.1% in the group of HIV-1
infected individuals sampled. Previous studies in Nigeria had reported
an overall HCV prevalence of 2.9% among blood donors in Rivers state
of Nigeria (Kaote et al. 2005). Agwale et al. (2004), had recorded
an HCV seroprevalence rate of 8.2% among HIV infected Nigerians.
There is a clear indication of increased HCV infection in HIV infected
individual in Nigeria. It is known that HIV/HCV coinfected individuals
accelerate rapidly to end-stage liver disease, AIDS defining clinical
event and death (Greub 2000, Monga et al. 2001). Unfortunately at
this time, no effective vaccine has been developed against HCV infection.
We also report a case of a 35 years old female client coinfected
with HIV and HCV who virologically failed therapy (CD4+
decline from 199 to 66) after four months on HAART. We also record
that, the rate of increase in CD4+ cells post-HAART does
not change in HIV and hepatitis coinfection but HCV appears to hinder
virological response to therapy. Although there have been case reports
of clearance of HCV viraemia after initiation of HAART (Ranieri
et al. 2003), majority of available data indicates that HAART results
in net increase in HCV viraemia (Chung et al. 2002). We have recorded
that 7.2% of individual do have triple coinfection with HIV/HBV/HCV.
As far as we know, this is the first report of HIV, HBV, and HCV
triple combination coinfections in the same individuals in Nigeria.
The CD4+ values of these group was significantly poorer
(mean = 107 cells/µl: AIDS defining) when compared with individuals
who have HIV infection alone (mean = 478 cells/ µl). Triple
coinfected individuals are more likely to present with lower CD4+
counts and therefore reduced host immunity. Triple coinfection is
therefore a growing problem in Nigeria and needs careful attention
owing to its adverse effects on HIV treatment response.
We have
demonstrated that co-infection of HIV and hepatitis viruses (HBV
and/or HCV) is on the increase in Nigeria and appears to decrease
the CD4+ counts of patients who are coinfected especially
with triple coinfection of HIV, HBV, and HCV. Treatment of either
hepatitis virus is complex because of pharmacokinetic interactions
with components of HAART regimens. Thus, the phenomenon of HIV and
hepatitis viruses coinfection is a cause for concern. The medical
community in Nigeria therefore needs to be alert to this phenomenon
as smart treatment options would need to be instituted in such individuals
if treatment is to be meaningful.
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Copyright 2007 Instituto Oswaldo Cruz - Fiocruz
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