Haematological
Indices of HIV Infected Antiretroviral-naïve
Children in Port Harcourt, Nigeria
Innocent
Ocheyana
George1, Nsirimobu Ichendu
Paul1
1Department
Of Paediatrics,
University of Port Harcourt Teaching Hospital, Nigeria.
Corresponding author: Dr. I.O.
George, Department
of Paediatrics, University of Port
Harcourt Teaching
Hospital, Nigeria.
E-mail-geonosdemed@yahoo.com
Afr J Haematol
Oncol 2015;5:21-26
ABSTRACT
AIM Even
though haematological abnormalities are
common manifestations of
HIV infection, few studies on haematological
parameters in HIV-infected children have been carried out in
sub-Saharan
Africa. The aim of this study was to assess the haematological
parameters in HIV-infected antiretroviral-naïve children attending
the
Infectious Disease Clinic of the University of Port Harcourt Teaching
Hospital.
METHODS
A prospective cross-sectional study which was carried out
in children
aged 5 -16 years attending the Infectious Disease Clinic of University
of Port
Harcourt Teaching Hospital over a two year period. The
control
population was HIV negative age and sex matched children. Haematological indices and CD4+ count were done at
first visit as part of our routine workup. Patients were classified
based on
severity of their disease state in accordance with the WHO Clinical
Staging of
HIV/AIDS. The haematologic indices were
estimated by
automation and the CD4+ T lymphocytes were counted by flow cytometre.
Antibodies to HIV were confirmed by two positive Rapid Diagnostic Test.A P
value less
than 0.05 was considered significant.
RESULTS One
hundred and seven HIV infected antiretroviral naïve children were
seen during
this period. There were more females 66 (61.7%) than males 41 (38.3%).
Most 52
(48.6%) of the mothers had secondary level of education while 35
(32.7%) and 20
(18.7%) had primary and tertiary levels of education respectively. The
mean age
was 7.4±1.34
years (range, 5-16 years). Haematological
indices showed haematocrit of
26.98±0.70 (P=0.004);
lymphocyte of 57.90±56 (P=0.13) and platelet of
86.95±16.59 (P=0.01). Most 79
(73.8%) of patients had moderate to severe immunosuppression. The mean
CD4
count was 239.34±22.21 (P=0.01).
CONCLUSION
This study has demonstrated that most children with HIV infection
presented
with significant anaemia, thrombocytopenia
and
moderate to severe immunosuppression.
Keywords: Haematological parameters; HIV; Children; Sub-Saharan
Africa; Acquired
Immunodeficiency Syndrome.
INTRODUCTION
Acquired
Immune Deficiency
Syndrome (AIDS) is a multi-system disease caused by HIV, and characterised by severe impairment and
progressive damage
of both cellular and humoral immune responses. In addition to CD4
lymphocyte
cells, HIV replicates in dendritic cells and macrophages,1-3
this replication disables the immune system and can lead to life
threatening opportunistic infections.
Apart from immunological abnormalities of HIV disease,1
haematological complications have
been shown as
strong independent determinants of morbidity and mortality in
HIV-infected
individuals.4
Though
numerous complications
occur in HIV infected patients,4-6 the most common haematological abnormalities are anaemia
and neutropenia.5 These are
mostly
caused by inadequate blood cell production due to bone marrow
suppression by
HIV infection mediated by abnormal cytokine expression, alteration of
the bone
marrow microenvironment and as a complication of some of the
antiretroviral
agents.7,8Anaemia in many series have been found to occur in
20-70%
of HIV infected patients and are associated with HIV disease
progression and
subsequent increased mortality.7,9 The anaemia may be due to
chronic infection, poor nutrition, autoimmune factors, virus-associated
conditions (haemophagocytic syndrome,
parvovirus B19
red cell aplasia), or the adverse effect of drugs (zidovudine).9 Severe
forms of anaemia in these individuals is
associated with low CD4
levels and progression to AIDS10 and is one of the strongest
predictors of HIV mortality and poor responses to antiretroviral
therapy (ART).4
Neutropenia
is commonly found in
advanced stages of HIV infection after development of AIDS, and has
been
associated with certain types of antiretroviral medications used in the
treatment of HIV infection.11 Thrombocytopenia is characterised by platelet counts below
125×103/mm3,
and also frequently occurs in HIV-infected patients.12-14Anaemia
and
leukopaenia in HIV-infected
HAART-naïve patients
result in poor ART-treatment outcome and otherwise strongly predict
mortality.4,15,16
Although
haematological
complications are common features of HIV infection and AIDS, and may
have a far
reaching impact on patients’ well-being, treatment and care, few
studies on haematological parameters in
HIV-infected children have
been carried out in this sub-region. Such information for HIV-infected
children
in Port Harcourt may help to inform treatment and monitoring of
HIV-infected
individuals in this region. We therefore reviewed the haematological
indices in HIV-infected HAART-naïve Children presenting to the
University of
Port Harcourt Teaching Hospital.
METHODS
This was a prospective cross-sectional study which was
carried out in
children aged 5 -16 years attending the
Infectious Disease Clinic of
University of Port Harcourt Teaching Hospital( UPTH) over a two year period (from January 2013 -
December 2014). One hundred and seven HIV infected antiretroviral
naïve
children were seen during this period. Patient demographic data were
documented
(gender, age, parents’ educational status and occupation). The
control
population was age and sex matched children who were HIV negative. Haematological indices and CD4+ count were done at
first visit as part of our routine workup to assess the disease status
and the
need for antiretroviral therapy. Patients were classified based on
severity of
their disease state in accordance with the World Health Organization
(WHO)
Clinical Staging of HIV/AIDS.
The haematologic indices
were estimated by automation
and the CD4+ T lymphocytes were counted by flow cytometre.
Antibodies to HIV were confirmed by two positive
Rapid
Diagnostic Tests (RDT). Erythrocyte sedimentation rate (ESR)
measurement
was carried out using Westergreen method
as described
by Dacie& Lewis.17 Two ml
of blood was
diluted in 0.5 ml of trisodium citrate
solution. The Westergreen pipette was
filled to a zero mark and mounted
on the Westergreen stand for one hour for
the red
cells to sediment with the aid of gravitational force. Then the column
of the sedimented red cells was read at
exactly 1 hour and results
were recorded in mm/hr. Ethical clearance was obtained from the Ethics
Committee of UPTH. Parents gave a written informed consent.
Statistical
analyses were performed using SPSS v.18 (SPSS, Chicago, Illinois, USA).
Student
t-test where appropriate were used. A p-value less than 0.05 was
considered significant.
RESULTS
One hundred and seven HIV
infected antiretroviral naïve children were seen during this
period. There were
more females 66 (61.7%) than males 41 (38.3%). Demographic features
(Table1)
showed that most 52 (48.6%) of the mothers had secondary level of
education
while 35 (32.7%) and 20 (18.7%) had primary and tertiary levels of
education
respectively. The mean age was 7.4 ±1.34
years (range, 5-16
years). Haematological indices obtained
when compared
with age and sex matched controls are shown in Table
2. The mean haematocrit, leucocyte
and
platelet levels were significantly lower than the control. The mean
erythrocyte
sedimentation rate (ESR) was higher among controls (p=0.31). The WHO
Clinical
Staging System showed that 70 (65.4%) symptomatic patients were in
advanced
disease stages (3 and 4) while 37 (34.6%) patients were in stages 1 and
2. Most
(79, 73.8%) of the patients had moderate to severe immunosuppression
(Table 2).
The mean CD4 count was 239.34±22.21 (P=0.01).
Table
1. Demographic and Baseline Characteristics of
Antiretroviral-naïve Children at Presentation |
Table
2. The Haematologal and CD4+ Cell Count
Findings of HIV naïve Children at the Time of Diagnosis |
DISCUSSION
HIV infection is known to cause varied degrees of
immuno-depression in
man and this has massive haematologic
concerns.
The
mean haematocrit was significantly lower
than the control in
this study. Anaemia is a very common
finding in
patients with HIV infection, particularly in individuals with more
advanced HIV
disease. In a study of patients receiving no myelosuppressive
therapies, 8% of asymptomatic HIV-seropositive patients, 20% of those
with
symptomatic middle-stage HIV disease, and 71% of those with Centers for
Disease
Control (CDC)-defined AIDS were anaemic.18 Also a study of
serum immunoreactive erythropoietin in
HIV-infected patients in various
stages of illness showed that levels of the hormone failed to rise
commensurately with increasing anemia, suggesting that insufficient
amounts of
erythropoietin may be one cause of anaemia
in this
setting.19 Other studies have suggested that soluble factors
in the
serum of HIV-infected patients may inhibit haematopoiesis,
or that direct HIV infection of marrow progenitor cells may play a role
in
producing anaemia and other haematologic
abnormalities associated with HIV infection.20 Infection
with Mycobacterium
avium complex (MAC) is another common
cause of anaemia in advanced HIV disease.21
Zidovudine
(AZT) therapy is probably the most common cause of anaemia
in HIV-infected patients. In the original phase II clinical trial that
demonstrated the efficacy of AZT in patients with advanced HIV disease,
statistically significant reductions in haemoglobin
levels occurred in 34% of subjects receiving AZT (1,200 mg per day)
following 6
weeks of therapy.22Antierythrocyte antibodies produce a
positive
direct antiglobulin test in approximately
20% of
HIV-infected patients with hypergammaglobulinemia.23
Association of HIV
infection with thrombocytopenia was long ago recognized.24 References
of a few cases and their description in the literature indicate that
patients
might have AIDS rather than simple HIV infection, though more
speculations
would be unscientific. We observed
that the mean platelet count was significantly reduced (P < 0.05),
when
compared with the controls. According to Sullivan, 25 it
may be as a
result of increased platelet destruction or decreased platelet
production in
subjects not on ART. This may tend to affect the normal haemostasis
such that
the individual becomes predisposed to bleeding tendency.
We found slightly elevated mean lymphocyte count in our
patients when
compared with the control (P=0.13). In
HIV infection, an elevated lymphocyte
count is not commonly part of the natural history of the infection.
When it is
found, efforts should be undertaken to discover its etiology and
clinical
consequences in a specific way. The most common finding in HIV
infection over
time is actually lymphopenia. A recent
review
attributed this to different phenomena over the natural history of the
infection.26 Early in HIV infection, there is viral
destruction of
selected memory T-cell populations, followed by a combination of
profound
increases in overall memory T-cell turnover, damage to the thymus and
other
lymphoid tissues, and ultimately, physiologic limitations in peripheral
T-cell
renewal. If lymphocytosis is evident, there should be concern regarding
concomitant HTLV-1 infection, which is often seen in certain groups in
specific
geographic areas.27
The
CD4 count is an indicator of
immune status and stage of HIV infection. Most (79,
73.8%) of the children in the study group presented with
moderate to
severe degrees of immunosuppression as their CD4 counts were
significantly less
500 cells/mm3. This is in keeping with other studies
worldwide.
5,28,29 The
hallmark of HIV-1 infection is progressive depletion of the CD4
helper-inducer
subset of lymphocytes. The underlying disorder affects the patient's
cell-mediated immunity,
resulting in absolute lymphopenia and
reduced
subpopulations of helper T lymphocytes (CD4+). Moreover, before a
complete
clinical manifestation of the disease occurs, its prodrome,
"pre-AIDS", is frequently characterized by unexplained chronic
lymphadenopathy (swollen lymph glands which likely indicate hyperstimulated
antibody mediated immunity] or leukopenia involving helper T
lymphocytes [low
CD4 counts). This leads to the severe immune deficiency of the patient
and suggests
that a
specific subset of T-cells could be a primary target for an infectious
agent.30
Varying degrees of leucopenia
has been
reported in children with HAART-naïve HIV infection and often
neutropenia
occurs.9,31,32
The mean leucocyte count in our study was
within normal limits but varied significantly (P<0.05) with that of
the
control population. Circulating antineutrophil
antibodies have
been implicated in some cases, also multiple drugs used for treatment
or
prophylaxis for opportunistic infections may be incriminated. Though
our
patients were HAART-naïve some were on prophylaxis for Pneumocystis jiroveci pneumonia and this may have
contributed to the low levels of leucocytes observed in our study.
Neutropenia,
as observed in our report, is commonly reported among HIV infected
individual
in sub-Saharan Africa. 33-35 This may be due to HIV suppression of bone marrow
resulting in abnormal granulopoesis. And
anti-granulocyte antibodies have been described in HIV-infected persons.36
CONCLUSION
Haematologic
manifestations
are common in HIV-infected patients. Significant numbers of patients
show anaemia, leucopenia and
thrombocytopenia. This presupposes
that patients with HIV infection should be investigated and treated for
haematological abnormalities to reduce the
morbidity of the
patient.
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