Title

Author(s)

Mother-to-child-transmission (MTCT) of human

immunodeficiency virus (HIV) in designated hospital in Hong
Kong
Chan, Wai-hung;

Citation

Issued Date

URL

Rights

2011

http://hdl.handle.net/10722/173743

Creative Commons: Attribution 3.0 Hong Kong License

Mother-to-child-transmission (MTCT) of Human Immunodeficiency

Virus (HIV) in Designated Hospital in Hong Kong

By

Chan Wai Hung

This work is submitted to

Faculty of Medicine of The University of Hong Kong
In partial fulfillment of the requirements for
The Postgraduate Diploma in Infectious Diseases, PDipID (HK)

Date: 30th June 2011

Supervisor: Professor Yuen Kwok Yung

Declaration

I, Chan Wai Hung, declare that this dissertation represents my own work and
that it has not been submitted to this or other institution in application for a
degree, diploma or any other qualifications.
I, Chan Wai Hung also declare that I have read and understand the guideline on
What is plagiarism? published by The University of Hong Kong (available at
http://www.hku.hk/plagiarism/) and that all parts of this work complies with the
guideline.

Candidate: Chan Wai Hung

Signature:
Date:

30th June 2011

Acknowledgement
I have to give my special thanks to Dr. Yau Yat Sun from Department of
Paediatrics, Queen Elizabeth Hospital who actually looks after all the infants
born from HIV infected mothers in last 10 years. Without the work of Dr. Yau,
this piece of work will not be completed and the meaningful clinical information
will not be revealed. Also I need to give thanks to Dr. Chan Lai Har Grace from
Department of Paediatrics and Dr. Li Chung Kee Patrick from Department of
Medicine, Queen Elizabeth Hospital who had pioneered the clinical care of
babies born from HIV infected mothers.
Apart from the medical professionals, the successfulness of the specialist
care provides by the designated hospital relies heavily on the contributions by the
nurse specialist Ms. Yu Pansy, social worker, dietitian, physiotherapist and
occupational therapist. The health and welfare of people living with Human
Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome
(AIDS) and their families depend upon on the hard work by the multidisciplinary
team. Their work is much appreciated.

Abstract
Background:

Mother-To-Child-Transmission

(MTCT)

of

Human

Immunodeficiency Virus (HIV) infection in developed countries are by and large

lowered to very low level by preventive and prophylactic measures including
antenatal universal screening of HIV antibody in pregnant women, antiretroviral
prophylaxis, elective caesarean sections and avoidance of breast feeding after
birth. The exact MTCT rate after commencement of the above prophylactic
measures in Hong Kong remains uncertain.
Objective: To determine the MTCT rate of a designated hospital taking care of
people living with HIV or Acquired Immunodeficiency Syndrome (AIDS) in
Hong Kong and to study the potential side effects and toxicity of antiretroviral
prophylaxis given in antenatal, intrapartum and postnatal period in newborns
born from HIV infected mothers in the designated hospital.
Methods: Retrospective descriptive study of all newborns born from HIV
infected mothers during the period of 1st January 2002 to 31st December 2010 in
the designated hospital was conducted.
Results: Total 17 infants born from HIV infected mothers are identified. It
consists of 31.5% of total number of infants born from HIV infected mothers in
Hong Kong. Only 1 was diagnosed to have HIV infection at 4 months of age.

Hence, the MTCT rate is 5.9% in the designated hospital. Serial haemoglobin
(Hb) levels and liver function (LFT) at birth of all infants; lactate only when
infants develop symptoms indicating neurologic involvement are recorded. Only
the Hb levels at birth are moderately lower than normal which indicate mild
transient marrow toxicity.
Conclusions: The MTCT rate in a designated hospital in Hong Kong is
approaching the rate in developed countries after commencement of various
preventive and prophylactic measures for prevention of MTCT in HIV infected
mothers. No significant persistent toxicity of antiretroviral prophylaxis exposure
during antenatal, intrapartum and postnatal period in infants born from HIV
infected mothers is identified. However, prolonged follow up for potential long
term teratogenic and carcinogenic effect is still suggested for such exposure.
(315 words)

Background
The natural MTCT rate of HIV infection in infants is high if there are no
preventive and prophylactic interventions. The MTCT rate in resource poor
countries ranges from 25 to 42% (1). Therefore, various protocols and
methodologies are advocated and actively studied in the last two decades in order
to control further upsurge of such transmission and hopefully abolish all MTCT.
Pediatric AIDS Clinical Trial Group (PACTG) is one of the investigating group
looks into this problem. It set up the PACTG protocol 076 since 1994 and series
of studies were conducted (2-3) and concluded that series of preventive and
prophylactic measures can bring down MTCT rate approximately to 1% to 2%
(4). The most important preventive strategy in unknown HIV status expecting
mothers is universal screening of HIV antibody in all. This measure can screen
out all asymptomatic HIV infected mothers and it is an effective and cost-saving
measure (5-7). For the HIV infected expecting mothers, three aspects of
preventive

measures

are

important

in prevention of MTCT. Firstly,

administration of antiretroviral prophylaxis during antenatal and intrapartum

period to the HIV infected mothers; and postnatally of 6 weeks course to HIV
exposed infants have vital importance (2-3). Secondly, elective caesarean section
is advocated before rupture of membrane and before the onset of labour in

mothers whose HIV RNA viral load more than 1000 copies per ml before
delivery can actually reduce MTCT. Last but not the least, complete avoidance of
breast feeding in resource adequate setting can further help in reducing MTCT as
most of the postnatal acquired infection are from the route of breast milk (8-9).
How about the scenario in Hong Kong? The very first case of HIV
infection was diagnosed in 1984. Since then, there are two designated units
providing specialist care for the people living with HIV and AIDS were set up
since 1980s. One of them is the Special Medical Service of Queen Elizabeth
Hospital (QEH) which provides in-patient as well as out-patient specialist care
for people living with HIV and AIDS. Another unit is the Special Preventive
Programme under the Department of Health provides mainly out-patient
specialist care. It locates in Kowloon Bay Integrated Treatment Centre (KBITC).
The Infectious Disease unit of Princess Margaret Hospital (PMH) joined the
KBITC to provide clinical care of people living with HIV and AIDS since 2001
(10).
Concerning the epidemiology of HIV and AIDS, the incidence was
increasing since 1984 till 1997. The incidence then has a slower rate of increase
probably due to the introduction of HAART in 1997. The incidence was then
gradually increased till 2009 with drops in incidence in two consecutive years.

Up to the first quarter of 2011, the total numbers of HIV and AIDS cases are
4935 and 1198 respectively (22). Hong Kong has low prevalence of HIV
infection and AIDS with prevalence of less than 0.1% in adult population (12-20).
The major route of transmission is sexual contact and the men having sex with
men (MSM) dominate the transmission since 2003 (12-20). MTCT is not the
major route of transmission.
Even though the MTCT is not the major route of transmission in Hong
Kong, the implication of such transmission is huge as every single infant affected
will require long term, probably life long HAART and in the long run, majority
of HIV infection from MTCT will progress into AIDS. The situation before
various preventive and prophylactic measures commenced in Hong Kong is
similar to the rest of the world, i.e. the historical data about MTCT rate. There
are total 14 cases out of 41 HIV infected mothers have MTCT during 1992 to
1999. Therefore, the MTCT rate is 34.1% before all these interventions
commenced (12). In response to the successfulness of various preventive
protocols and strategies to prevent MTCT available, Hong Kong had came up to
a consensus statement of starting universal screening of HIV antibody in all
pregnant women since September 2001 (11). This universal screening test
adopted an opt out mechanism that pregnant mothers have to actively decline

the test in order to have high uptake rate. The strategy was successful that the
coverage rate is high ranging from 96% to 98.2% from September 2001 to 2008
(12-19). However, the coverage rate dropped to 93.8% in 2009 (20), which may
be related to high influx of pregnant women from mainland China in recent few
years that the antenatal visits in Hong Kong may be very late in their pregnancies.
If the trend continues to drop, it may imply that the screening preventive measure
is failing. Six percent opt out rate already means 5280 pregnant women escape
from the screening with the yearly delivery rate of 88,000 in Hong Kong.
After the commencement of universal screening of HIV antibody in all
pregnant women, total 59 pregnant women were screened to be HIV antibody
positive in the period of September 2001 to the end of 2009 (12-20). Hence, the
mean yearly positive HIV antibody screening test is around 7 per year. After
knowing the positive HIV antibody test results, 17 out of the 59 pregnant women
decided not to continue their pregnancies, i.e. overall percentage is 28.8%. It
seems that the initial termination of pregnancies rate is higher in the first 3 years
after commencement of universal HIV antibody screening. Ten out of 24 HIV
infected mothers decided for termination of pregnancies, i.e. 41.6%, during
September 2001 to the end of 2004, while 2 out of 7 decided for termination of
pregnancies, i.e. 28.6%, in 2009. It may be explained by a better education of the

public, proper counseling of newly diagnosed HIV infected mothers by medical

and nursing staff, as well as better control of disease by HAART which turned a
deadly disease into a controllable chronic condition requires long term
medications. The public is now more acceptable for people living with HIV and
AIDS. Three HIV infected mothers lost to follow up. Total 39 HIV infected
mothers delivered babies in Hong Kong and 33 of mothers received caesarean
section as part of the preventive measure of MTCT, i.e. 84.6%. Most of the
caesarean sections are elective. Eight infants are reported to acquire HIV
infection by MTCT after commencement of universal HIV antibody screening in
all pregnant women and hence, the MTCT rate is 20.5%. However, the MTCT
rate is probably over estimated as few of the reported infants acquire HIV
infection by MTCT are retrospective reports, i.e. few of the mothers did not
know to have HIV infection before and after delivery and they only know they
are infected when their children developed symptoms or opportunistic infection
related to HIV infection. We can conclude that the exact MTCT rate remains
uncertain in Hong Kong.

10

Objective
Since the exact MTCT rate in Hong Kong remains uncertain after
commencement of universal HIV antibody screening in all pregnant women, we
conduct a retrospective descriptive study to determine the MTCT rate of HIV
infection in infants born from HIV infected mothers in the designated hospital in
Hong Kong. Therefore, we can compare the MTCT rate before and after
commencement of series of preventive and prophylactic measures in Hong Kong.
We study the potential side effects and toxicities of antiretroviral
prophylaxis exposure to infants, in which antiretroviral prophylaxis is given to
mother during antenatal and intrapartum period, as well as given to infants as
postnatal antiretroviral prophylaxis. Such exposure may post a potential long
term and potential teratogenic and carcinogenic effect on exposed infants.

11

Method
As the Special Medical Service of QEH provides specialist care to people
living with HIV and AIDS since 1980s, significant proportion of newly
diagnosed HIV infected pregnant women will be cared in QEH. Hence, majority
of the HIV infected mothers will have their delivery in QEH. All the HIV
infected mothers are managed according to the recommended clinical guidelines
on prevention of perinatal HIV transmission (21).
Since quite a significant portion of HIV infected mothers choose to have
delivery in QEH, all the infants born from HIV infected mothers will be cared by
Paediatric Infectious Diseases physician from Department of Paediatrics in QEH.
All these newborns are managed according to the clinical pathway on prevention
of MTCT according to the recommended guidelines (2-3,21).
All the newborn infants delivered in Departments of Gynaecology and
Obstetrics (O&G) in all Hospital Authority (HA) hospitals in Hong Kong are
retrieved by Clinical Data Analysis and Reporting System (CDARS) from the
period of 1st January 2002 to 31st December 2010 with the ICD9 diagnostic codes
using Contact with or exposure to HIV - V01.7, or Human immunodeficiency
antibody positive V08, or any history of using postnatal antiretroviral
prophylaxis such as oral (PO) or intravenous (IV) Zidovudine (ZDV), PO

12

Nevirapine (NVP) or PO Lamuvidine (3TC).

The number of newborn infants born from HIV infected mothers born in
HA hospitals is retrieved by CDARS. Then all the hospital records of newborn
infants born in QEH from HIV infected mothers are retrieved. The patients
records are cross checked whether they have currently or have history of follow
up in our out-patient Specialist Clinic in Special Medicine Service.
All the clinical information of all these patients is obtained. Demographic
data such as sex, gestation, birth weight, ethnic group, maternal baseline RNA
viral load and CD4 count, use of HAART solely for mothers own health either
high RNA viral load, low CD4 count, or history of opportunistic infection or
antiretroviral prophylaxis only as antenatal prophylaxis, completeness of giving
antenatal and intrapartum antiretroviral prophylaxis, completeness of giving
postnatal course of ZDV and or 3TC prophylaxis, mode of delivery and serial
RNA viral loads are collected. Potential side effects or toxicity from
antiretroviral prophylaxis were recorded as well with data include haemoglobin
(Hb) levels at birth, 4 weeks and 2 months of age, liver function test at birth and
checking lactate only when there is evidence of neurologic symptoms such as
seizure or poor oral feeding. Duration of follow up and development of all active
follow up patients are also collected.

13

Results
There are total 54 infants born from HIV infected mothers in O&G
Departments of all HA hospitals of which 17 is from QEH. It accounts for 31.5%
of all infants. Since the current available data from SPP surveillance reports is
only up to 2009, we have shorten the study period from 1st January 2002 to 31st
December 2009 and we still have total 43 infants from all O&G Departments of
all HA hospitals of which 14 is from QEH. It accounts for 32.6% of all infants.
There is discrepancy from data by SPP and data retrieved by CDARS as
there are 5 more infants identified by CDARS. They are probably infants from
mothers who are known to have HIV infection that they are not picked up by the
universal HIV antibody screening.
The exact MTCT rate of infants born from HIV infected mothers in HA
hospitals cannot be arrived because the lack of information on whom has
subsequent HIV infection or not. But from the data available in QEH, there is
only 1 case of infants developed HIV infection despite the adequate preventive
and prophylactic measures. Hence, the MTCT rate of infants born from HIV
infected mothers in QEH is 5.9%.
Demographic data is unremarkable. There are 8 male infants and 9 female
infants. The mean gestation is 37 weeks 4 days. There are 2 premature deliveries.

14

One prematurity delivery was born at 34 weeks 5 days and another at 35 weeks 2
days. All gestations are below 39 weeks as majority of infants were delivered by
earlier elective caesarean sections. The mean birth weight is 2.76 kg with the
range of 1.5 kg to 3.31 kg. Large proportion of infants is from non-Chinese
origin. Eleven out of 17 is non-Chinese which accounts for 64.7%. Various ethnic
groups are involved including Africans, Nepalese, Filipinos, Indonesians and
Thai.
Maternal viral data shows the mean RNA viral load before delivery is 493
copies per ml with the range from undetectable to 1681 copies per ml. The mean
maternal CD4 count before delivery is 465 with the range from less than 200 to
694.
Four out of 17 mothers received HAART for their own health either for
low CD4 count or opportunistic infection such as Pneumocystis jirovercii
infection (PCP) which consists of 23.5% of HIV infected mothers. Two of these
4 mothers are from universal HIV antibody screening and 2 are from women who
are known to have HIV infection. There are 4 mothers are known to have HIV
infection and 2 of them do not need any HAART before this pregnancy.
There are 16 out of 17 caesarean sections, i.e. 94.1% have caesarean
sections to further lower MTCT risk. Only one was delivered vaginally. In this

15

particular case, it was premature delivery and HIV infection was diagnosed
during labour by point of care test (POCT) of HIV antibody. All newborn infants
received formula feeding and none has started breast feeding.
Concerning the potential side effects and toxicities of antiretroviral
prophylaxis exposure in infants, haematologic and biochemical parameters are
collected. The mean Hb level at birth is 16.7 g/dL with the range from 13.5 to
20.9 g/dL. Five out of 17 (29.4%) has neonatal anaemia with Hb level less than
15 g/dL. The mean Hb level at 4 weeks is 11.1 g/dL with the range from 9.5 to
14.4 g/dL. The mean Hb level at 2 months is 11.3 g/dL wit range from 10.5 to
12.5 g/dL. One infant received transfusion of pack cells at 3 weeks of age
because of sepsis that he required IV antibiotics. Haemoglobin level dropped to
10 g/dL and hence, transfusion of pack cells was given once.
Liver function tests at birth are all normal. The mean Alanin Transaminase
(ALT) is 14 IU/L with the range from 8 to 30 IU/L. Only 4 infants had checked
lactate level. One infant developed neonatal seizure after taking 1 week course of
combination antiretroviral prophylaxis (ZDV and 3TC), hence, lactate was
checked. Another 3 infants had checked lactate because of poor feeding and one
had unstable temperature and poor feeding. The mean lactate level is 3.27
mmol/L and the range is from 0.9 to 5.5 mmol/L. Two had high lactate at the first

16

start but then was all normalized on repeating lactate.

The mean duration of follow up is 2.9 years. Three lost to follow up as 2
had returned to their original countries before 1st birthday. Another probably
emigrated to another country as the mother is an African refugee. All infants have
normal development upon the last follow up. One patient has small head and
perimembranous ventricular septal defect but his development is normal.

17

Discussion
The MTCT rate of infants born from HIV infected mothers in the
designated hospital in Hong Kong is 5.9%. The MTCT rate is actually
approaching that of the reported best scenario in the literature. It is much better
than the rate before any preventive and prophylactic measures (34.1%) ten to
twenty years ago (12). However, the overall MTCT rate in Hong Kong with
shorter period is still high, up to 20.5% (12-20). It is probably an over estimation
because few cases are reported retrospectively.
In our series, the only infant contracted the HIV infection is mainly
because the mother did not turn up for medical assessment after the HIV
antibody result was known. With repeated efforts, the mother finally returned for
assessment and HAART was only started 1 week before delivery. Then the
intrapartum and postnatal antiretroviral prophylaxis commenced according to the
clinical pathway. However, the infant had high RNA viral load at birth up to 4190
copies per ml. The subsequent RNA viral loads were persistently high and it was
already more than 50,000 copies per ml at 4 months. Hence, confirmatory test by
Western blot at 4 months showed that he has HIV infection. HAART was started
at 6 months of age.
Though we have a significant drop in MTCT rate in our designated

18

hospital after commencement of preventive and prophylactic measures, the

overall MTCT rate in Hong Kong is still on high side. We think that the overall
MTCT rate is exaggerated but it still shows that we can have further
improvement. For example, we can further increase the coverage rate so that
more asymptomatic HIV infected mothers can be identified. In the surveillance
reports from SPP under DH, there is significant opt out in 2009 (20). We have
to watch out for further trend on the coverage rate. The stringent approach on the
antiretroviral prophylaxis and strict follow on the clinical pathway of infants
born from HIV infected mothers have vital importance on the outcome.
Antiretroviral exposure is well known for its haematologic and liver
toxicity (23). In our study to investigate the haemotologic toxicity of
antiretroviral exposure, nearly one third of the infants have neonatal anaemia at
birth. However, it is only a transient event that Hb levels returns to normal within
4 weeks. Haemoglobin has a physiological trough at 2 months of age in normal
infants but the Hb level at 2 months does not show significant anaemia. All Hb
levels are more than 10 g/dL at 2 months. In contrast to reports that antiretroviral
has persistent effects on haemopoietic progenitor cells with persistent anaemia,
we do not have similar finding in this aspect (24). In this study, it does not show
any significant abnormal liver function during this period.

19

Antiretoviral therapy has the potential to cause mitochondrial dysfunction

and may present lactate acidosis (25). The result of lactate levels does not show
significant lactate acidosis. However, we do have a case of neonatal seizure
which may be related to combination use of antiretroviral therapy. We switched
to single agent ZDV after that incidence according to PACTG Protocol 076. Then
there is no more infants develop neonatal seizure since then. Even there is no
evidence of long term side effects from antiretroviral exposure so far,
antiretroviral exposure may have teratogenic and carcinogenic effect especially
in in-utero exposure (26). Hence, prolonged follow up for any possible
terotogenic and carcinogenic effects should be continued.
There is one drawback for our study that we have patients load of slightly
less than one third of all Hong Kong cases which may not be so representative
for the whole Hong Kong scene. However, it is still a sizable portion of patients
in Hong Kong.

20

Conclusion
The MTCT rate of HIV infection in infants born from HIV infected
mothers in the designated hospital in Hong Kong is 5.9% after commencement of
universal HIV antibody screening test in all pregnant women. Antiretroviral
prophylaxis exposure to infants causes transient neonatal anaemia but no
significant mitochondrial dysfunction.
Despite the fact that antiretroviral prophylaxis is relatively safe in adults,
we have to look out for long term potential teratogenic and carcinogenic effects
in particular in-utero exposure. We recommend prolonged follow up should be
offered.
The successfulness of preventive and prophylactic measures for prevention
of MTCT in HIV relies on experienced Infectious Disease Physician to look after
mothers HIV infection and offer adequate HAART; experienced Obstetricians to
administer intrapartum antiretroviral prophylaxis and performing elective
caesarean sections; experienced Paediatric Infectious Diseases Physician
administering postnatal antiretroviral prophylaxis, advise on complete avoidance
of breast feeding and managing Paediatric HIV infection; and most importantly
the multidisciplinary team management of patients and families.

21

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24

(17) HIV Surveillance Report 2006 Update, Special Preventive Programme,

Department of Health, Hong Kong, December 2007. Available at
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25

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26

Tables and figures

Figure 1: Break down of yearly number of HIV infected mothers,
termination of pregnancy and vaginal delivery from 2005 to 2009

12
10
8

TOP
CS
NSD

6
4
2
0
2005

2006

2007

2008

2009

Table 1: Demographic data of infants and maternal baseline viral load and
CD4 count
Sex
Ethnic group

Gestation
Birth weight
Maternal

viral

Male:Female

8:9

Chinese:Non-Chinese

11:6

Mean

Range

37 wk 4 d

34 wk 5 d 38 wk 4 d

2.76 kg

1.5 3.31 kg

493 cps/ml

UD 1681 cps/ml

27

load
Maternal

CD4

465

< 200 - 694

count
UD Undetectable, cps/ml copies per ml,
Table 2: Haematologic and liver function parameters of infants
Mean

Range

Hb (g/dL) at birth

16.7

13.5 20.9

Hb (g/dL) at 4 weeks

11.1

9.5 14.4

Hb (g/dL) at 2 months

11.3

10.5 12.5

14

8 - 30

LFT (IU/L) at birth

28