Prevention of
mother-to-child
transmission of HIV
What does PMTCT mean?
• Prevention of mother-to-child
transmission of HIV
• What is it about?
Lars T. Fadnes
Centre for International Health, University of Bergen
http://research.fadnes.net
Why is there a need to for PMTCT?
• HIV can be transmitted to children
• Nearly all cases can be prevented
HIV = Human immunodeficiency
virus
• The virus discovered in 1983
• Initially (1981) reports about Kaposi’s sarcoma
and Pneumocystis jiroveci pnemumonia in
special syndrome
• Retrospectively, cases seen in Central Africa
already in mid of last century
• Transmission modes: Body fluids
ABC of AIDS: BMC publishing group 2001
How does HIV transmit?
Transmission modes:
• Sexual intercourse
– Vaginal and anal
• Contaminated needles
– Intravenous drug users
– Needle stick injuries
– Injections
• Organ/ tissue donation
– Blood
– Semen
– Kidneys
– Skin, bone marrow, corneas, heart valves, tendons etc
ABC of AIDS: BMC publishing group 2001
1
Transmission modes:
Brainstorming
• Mother-to-child
– During pregnancy (In utero)
– During delivery (intrapartum)
– After birth through breastfeeding (postpartum)
• Which factors increase HIV-transmission?
• Some very few acquire it through needle stick
injuries etc
Van de Perre P, Simonon A et al, Postnatal transmission of human immunodeficiency virus type 1 from
mother to infant. A prospective cohort study in Kigali, Rwanda. N Engl J Med. 1991 Aug 29;325(9):593-8.
Infective and anti-infective properties of breastmilk from HIV-1-infected women. Lancet. 1993 Apr
10;341(8850):914-8.
ABC of AIDS: BMC publishing group 2001
Infectivity of milk
MATERNAL FACTORS-MILK
• Viral load (cell-free and cell-ssociated)
• Viral strain
• Hiv provirus increases risk
•
Infectivity of milk
INFANT FACTORS
• Oral: (rupture of mucous membranes)
– Stomatitis
– Ulcerations
– Thrush
– Pharyngitis
• GI:
– Oesophagitis
– Gastroenteritits
Protective factors:
– Lipids
– Lactoferrin
– Lysozymes
– HIV antibodies
– Cytotoxic cells
•
MATERNAL HEALTH:
• Maternal immunosuppression
– Low CD4
• Vitamin A deficiency
• Breast problems increasing white blood cells and number of virus particles in the milk:
– Cracked or bleeding nipples
– Mastitis (clinical/ sub-clinical)
– Breast abscesses
– Trush
Ref. Lehman DA, Farquhar C. Biological mechanisms of vertical human immunodeficiency virus (HIV-1)
transmission. Rev Med Virol. 2007 Nov-Dec;17(6):381-403.
Infectivity of the HIV patient
Primary HIV Asymptomatic HIV
Symptomatic
Viral load
•
•
•
Receiving solid or semi-solid food in addition to breast milk (mixed
feeding)
Low-birth weight
Poor nutritional status
Protective factors
– Antiretroviral prophylaxis
– Protective antibodies or cytotoxic CD8 cells
Ref. Lehman DA, Farquhar C. Biological mechanisms of vertical human immunodeficiency virus (HIV-1)
transmission. Rev Med Virol. 2007 Nov-Dec;17(6):381-403
Probability of transmission
1.0
0.8
CD4 count
0.6
0.4
0 mo
Highly
infective
3 mo
5-10 years
Not so
infective
Highly
infective
0.2
0.0
100
1000
10 000 100 000 1 mill
RNA copies/ml
2
Is the risk of transmission
through breastfeeding constant?
Diagnosing HIV in children
Suggestion 1: Constant risk of 0.9% per month after
the first month of life
• How can HIV be diagnosed in children?
The breastfeeding and HIV International Transmission Study Group. Late
postnatal transmission of HIV-1 in breastfed children: A meta-analyis. J
Infect Dis 2004; 189: 2154-66
• When can it be diagnosed?
Suggestion 2:
The risk is dependent of period of lactation
Kuhn, L et al. PLoS ONE. 2007 Dec 26;2(12):e1363
HIV testing
• Direct demonstration of virus
– PCR
– Viral culture
Limitations with indirect tests
• An open ”window” some weeks after infection
– Virus is present but not yet antibodies
Virus? Yes!
• Indirect tests (antibody tests)
– All rapid tests
– ELISA tests
– Confirmatory Western Blot
Antibodies? Not yet!
Retest later or use direct tests (or combination tests)!
• Nice test web-page:
http://wwwn.cdc.gov/dls/ila/hivtraining/video.aspx
Limitations with indirect tests
Rapid tests
• Can not be used in infants before 15 months of age
– Due to maternal antibodies
Virus? Don’t know!
Antibodies? Yes! (from mother)
Retest later or use direct tests!
Now PCR is widely used for young infants in programme settings
3
PCR
Transmission rates
• Without intervention: What is the total risk
of HIV-transmission from mother to child?
– What is the risk without any breastfeeding?
– What is the risk including breastfeeding?
MTCT risk - no interventions
Antenatal
(before
delivery)
5-10%
Increasing
with
gestational
age
Intrapartum
(during delivery)
10-20%
Highest risk
per time unit
Early
postpartum
Late
postpartum
5-10%
(first 2
months)
5-10%
(2-24
months)
Total
risk
30-45%
De Cock et al. JAMA. 2000;283:1175-1182.
Risk of remaining uninfected –
No interventions
5 10-20 10-20
% %
%
Two thirds uninfected
Out of 100 pregnant HIV+ mothers
over 60% are going to have healthy
babies
De Cock et al. JAMA. 2000;283:1175-1182.
4
Increased risk
when:
Antenatal
(before
delivery)
Intrapartum
(during delivery)
- Placental - Preterm labour
dysfunction (<34 weeks)
- Prolonged
membrane rupture
- Exposure to
maternal blood
- STIs and infections
Early
postpartum
Late
postpartum
Maternal factors:
- Maternal health
- Breast health
- Infectivity of milk
Infant factors:
- Oral and gastrointestinal factors
- Immune factors
Vertical transmission epidemiology
BMC International Health and Human Rights 2006, 6:6 (3 May 2006)
Karamagi et al
Bull World Health Organ vol.85 no.11 Genebra Nov. 2007
5
Current testing numbers:
• How can infants be fed?
– How do we normally categorise infant
feeding?
• Does it matter?
– What are regarded as more beneficial for the
children?
Towards universal access: Scaling up priority HIV/AIDS interventions in the health sector
WHO: Progress report 2010
How many child
deaths can we
prevent this year?
Gareth Jones,
Richard W Steketee,
Robert E Black,
Zulfiqar A Bhutta,
Saul S Morris, and
the Bellagio Child
Survival Study
Group
Infant feeding patterns
• Exclusive breastfeeding
•
• Predominant breastfeeding
• Complementary feeding/ partial breast-feeding/ mixed feeding
• Replacement feeding
THE LANCET • Vol 362 • July 5, 2003
Suboptimal
breastfeeding
Lancet 2008;371:243-60
Breastfeeding acknowledged
•
•
•
•
•
1933: Kwashiorkor
1966: R. Cook advocacy paper against formula feeding
1992: G K Mukasa, Uganda: Early lactation failure
Undernutrition related diseases still exist, highly avoidable
Undernutirion increases morbidity and all cause mortality
6
So why is breastfeeding so important?
The Dilemma
Lessions from the large PMTCT studies
•
Not breastfeeding – high risk of death for the infant
– Replacement feeding - increasing mortality
•
Women who need HAART for her own health should receive it
– (clinical symptoms or CD4 < 350 cells/mL)
– Need for early diagnosis in pregnancy
•
For mothers with CD4 > 350 cells/ml
– both maternal HAART and infant prophylaxis seems acceptable
•
Risk resistance for infants who become infected – depending on drug
– Nevirapine alone is unfortunate
•
Often a need to continue breastfeeding beyond 6 months to reduce death
and disease risk for the infant
•
Contextual and operational research is needed
•
Methodological and ethical challenges
BALANCE:
Risk of HIV-1
transmission through
breast milk
&
Risk of child death
through nonbreastfeeding
Prevention by:
Antenatal
(before
delivery)
- Prophylaxis
with ARV
- Treatment
with ARV
(= lower
viral load)
Intrapartum
(during delivery)
Early
postpartum
HIV transmission to children
Nevirapine + zidovudine before delivery
and nevirapine to infant post-partum
Late
postpartum
EBF
ARV treatment during
pregnancy
PEP
RF
-Prophylaxis with ARV - Prevention of new infections:
-Treatment with ARV - Maternal ARV treatment
- Infant ARV prophylaxis
-Caesarean section
- Exclusive breastfeeding
with lactation management
-Replacement feeding
-(Guidelines infant feeding)
In the future:
- Vaccine for the infant?
60-80% not HIV-infected
10-20%
5%
10-20%
Anteduringmanagement
through
If optimal
natal
delivery
BF
HIV-positive
7
Historical background with implications for infant
Gradually
feeding counselling
PRE HIVidentification
1980
better insight
on
preventional
strategies
and infant
feeding
HIVidentification
1982/3
ACTION
UNICEF GOBI FFF:
Unicef’s
WHO
campaigns in
1980s including
breastfeeding
promotion and
improved
feeding
1990
1992-94
2000
BFHI
IMCI
Breastfeeding
hospital/
health
initiative
Integrated
management of
childhood
infections
2010
Guidelines
more similar for
HIV-exposed
and unexposed
Counsellors and counselling
• Science and recommendations under continuous changes
– Feasibility of updating personnel
– Resistance - belief in old knowledge (Risk of breast milk)
• Societal and psychological dimensions with PMTCT programmes
• PMTCT-programmes have prohibitive elements (Thorsen, V.2008)
• Lack of empowerment – lack of drugs (Blysatd, A & Moland, KM 2009)
• Nutrition under-prioritised (Chopra, M. 2005+2008)
• Providing formula (South-Africa) (Coutsoudis, A. 2008)
• Difficulties for counsellors and mothers
Mother’s choice - disclosure, rejection and stigma
Counsellors burden (Fadnes 2010, Leshabari, S. 2006+2007)
Counsellors and counselling
• Science and recommendations under continuous changes
– Feasibility of updating personnel
– Resistance - belief in old knowledge (Risk of breast milk)
• Societal and psychological dimensions with PMTCT programmes
• PMTCT-programmes have prohibitive elements (Thorsen, V.2008)
• Lack of empowerment – lack of drugs (Blysatd, A & Moland, KM 2009)
• Nutrition under-prioritised (Chopra, M. 2005+2008)
• Providing formula (South-Africa) (Coutsoudis, A. 2008)
• Difficulties for counsellors and mothers
Mother’s choice - disclosure, rejection and stigma
Counsellors burden (Fadnes 2010, Leshabari, S. 2006+2007)
Guidelines and
Recommendations
Frequent reports on Infant feeding and HIV
• 2003: HIV and infant feeding: Framework for
priority action
• 2004: HIV and infant feeding: Guidelines for
decision-makers
• 2005: HIV and infant feeding counselling From
research to practice
• 2006 guidelines on HIV and IF and PMTCT
• 2009: New guidelines: more use of PMTCT
medicines
HIV and IF
Guidelines and
recommendations
• Key principle 1: Balancing HIV prevention
with protection from other causes of child
mortality
from WHO 2010
8
HIV and IF
• Key principle 2: Integrating HIV
interventions into maternal and child
health services
HIV and IF
• Key principle 3: Setting national or subnational recommendations for infant
feeding in the context of HIV
HIV and IF
• Key principle 4: Informing mothers known
to be HIV-infected about infant feeding
alternatives
HIV and IF
• Key principle 5: Providing services to
specifically support mothers to
appropriately feed their infants
HIV and IF
• Key principle 6: Avoiding harm to infant
feeding practices in the general population
9
HIV and IF
HIV and IF
• Key principle 7: Advising mothers who are
HIV uninfected of whose HIV status is
unknown
• Key principle 8: Investing in improvements
in infant feeding practices in the context of
HIV
HIV and IF
Use of ARV
• Recommendation 1: Ensuring mothers
receive the care they need
• Recommendation 1: In women with
confirmed HIV serostatus, initiation of ART
for her own health is recommended when
– CD4 <350 cells/mm3 or
– WHO clinical stage 3 or 4
– Throughout pregnancy, delivery and continue
thereafter
Use of ARV
• Recommendation 3: In pregnant women in
need of ART for their own health, the
preferred first-line ART regimen
HIV and IF
• Recommendation 2: Which breastfeeding
practices and for how long
– Many settings
– AZT + 3TC + NVP/EFV.
• Exclusive breastfeeding for 6 months with ART prophylaxis
or maternal HAART
– TDF + 3TC (or FTC) + NVP/EFV
• Appropriate complementary feeding together with continued
breastfeeding for their next months with ART prophylaxis or
maternal HAART
• Only stop breastfeeding when nutritionally adequate and safe
diet without breast milk can be provided
10
HIV and IF
• Recommendation 3: When mothers decide
to stop breastfeeding
– Avoid abrupt weaning
HIV and IF
• Recommendation 4: What to feed infants
when mothers stop breastfeeding
– Safe and adequate replacement feeds to
enable normal growth and development
• Alternatives:
– Commercial infant feeding formula
– Exressed, heat treated
– Home-modified animal milk is not recommended as a
replacement first six months of life
Use of ARV
• Recommendation 4: Infants born to HIVinfected women receiving ART for their
own health should receive
– for breastfeeding infants: daily NVP from birth
until 6 weeks of age
– for non-breastfeeding infants: daily AZT or
NVP from birth until 6 weeks of age
HIV and IF
• Recommendation 5: Conditions needed to safely
formula feed
– safe water and sanitation
– caregiver can reliably provide sufficient infant formula
milk to support normal growth and development
– can prepare it cleanly and frequently enough to
reduce risk of diarrhoea and malnutrition
– family is supportive of this practice
– caregiver can access health care that offers
comprehensive child health services
– ALL ARE REQUIRED to recommend formula feeding
Use of ARV
• Recommendation 5: All children born to
HIV-positive mothers who are not in need
of ART for their own health should have
an effective ARV prophylaxis
– started from as early as 14 weeks gestation or
as soon as possible when women present late
in pregnancy, in labour or at delivery.
HIV and IF
• Recommendation 6: Heat-treated, expressed
breast milk
– HIV-positive mothers may consider expressing and
heat-treating breast milk as an temporary feeding
strategy
• when low birth weight or otherwise ill in the neonatal period
and unable to breastfeed; or
• When the mother is unwell and temporarily unable to
breastfeed or has a temporary breast health problem such as
mastitis
• To assist mothers to stop breastfeeding
• If antiretroviral drugs are temporarily unavailable.
11
HIV and IF
• Recommendation 7: When the infant is
HIV-infected
– strongly encouraged to exclusively breastfeed
for the first 6 months of life and continue
breastfeeding as for the general population
New guidelines summed up
• Antiretroviral therapy and prophylaxis has
got an important role
– prolonged therapy during breastfeeding
• Emphasising the importance of treating
mother when she needs treatment
• More setting specific approach to adapt
the guidelines to the settings
Quiz
1.
Is it scientific agreement that exclusive breastfeeding is much better than
predominant breastfeeding (e.g. in terms of HIV-transmission)?
1.
NO
2.
Is mixed feeding associated with higher HIV-transmission than exclusive
breastfeeding?
1.
YES
3.
Are more than 50% of the children born to HIV-positive mothers in lowincome countries infected with HIV if no protective measures are taken (no
interventions)?
1.
NO
4.
Is it possible to reduce HIV-transmission from mother-to-child to less than
1%?
1.
YES
5.
Had the HIV-virus been identified in 1980?
1.
NO
Quiz
1.
Does kwashiorkor mean ‘the sickness the baby gets when the
new baby comes’ reflecting on the development of the condition
in an older child who has been weaned from the breast when a
younger sibling comes?
1. YES
2.
Is it possible to test children for HIV before they are 6 months?
1. YES
3.
Can rapid antibody tests be used when testing children for HIV
before 6 months?
1. NO
4.
Is maternal viral load an important factor in respect to
transmission of mother-to-child transmission?
1. YES
–
Does WHO have good advices for everything?
Almost
12
Questions and comments
13