HIV mother-to-child HIV identified in 1983 transmission of HIV - - PDF document

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Prevention of mother-to-child transmission of HIV

Lars Thore Fadnes Centre for International Health http://presentations.fadnes.net/PMTCT

HIV

• HIV identified in 1983
• AIDS syndrome described in 1981
• Kaposi’s sarcoma, Pneumocystis jiroveci

pnemumonia and wasting often combined

• Retrospectively, cases of HIV seen in Central

Africa already around 1930

• Around 33 million cases globally (2009)

ABC of AIDS: BMC publishing group 2001

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

Transmission modes in children

• Mother-to-child

– During pregnancy (In utero) – During delivery (intrapartum) – After birth through breastfeeding (postpartum)

• 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

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Transmission risk of HIV related to maternal HIV stage

Viral load CD4 count Primary HIV Asymptomatic HIV Symptomatic 3 months 5-10 years Highly infective Less infective Highly infective

Factors related with mother-to-child transmission of HIV

MATERNAL FACTORS-MILK

• Viral load (cell-free and cell-ssociated)
• Viral strain
• Hiv provirus increases risk
• 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

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 milk

INFANT FACTORS

• Oral/ gastrointestinal (integrity of mucous membranes)

– Stomatitis, oral thrush – Ulcerations – Pharyngitis, oesophagitis – Gastroenteritits

• Receiving solid or semi-solid food in addition to breast milk during

the first months (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

Case: Faith

• HIV positive parents
• 4 months old child with growth failure

(WLZ -3) and fungal infection gastrointestinal – Is it likely to be HIV? – How can HIV be diagnosed in children? – If HIV is diagnosed, what about treatment – If HIV is diagnosed, what about breastfeeding?

Diagnosing HIV in children

• How can HIV be diagnosed in children?
• When can it be diagnosed?

HIV testing

• Direct demonstration of virus

– PCR – Viral culture

• Indirect tests (antibody tests)

– All rapid tests – ELISA tests – Confirmatory Western Blot

• More about testing:

http://wwwn.cdc.gov/dls/ila/hivtraining/video.aspx

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Rapid tests

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?

• A. Less than 10% of the children?
• B. 10%-20 of the children?
• C. 20%-40 of the children?
• D. 40%-60 of the children?
• E. Above 60 of the children?

Is it better to avoid breastfeeding?

Breastfeeding has benefits related to

Morbidity

• Less infections (diarrhoea, pneumonia, otitis media etc)
• Less allergies and auto-immune diseases
• Better growth

Health aspects in adult life Probably slightly better cognitive outcomes Reduced risk of child deaths

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Mortality from all causes

Estimated 13% of 8 million child deaths could be prevented with

• ptimal breastfeeding
• Particularly in low-income settings
• Jones G et al: How many child deaths can we prevent this

year? Lancet 2003.

8% of deaths avoided with promotion of exclusive breastfeeding

• Bhutta ZA et al: What works? Interventions for maternal and

child undernutrition and survival. Lancet 2008.

The Dilemma

BALANCE: Risk of HIV-1 transmission through breast milk & Risk of child death through non- breastfeeding

Case: Rachel

• Mother from Mali testing HIV-positive for

HIV just before delivery. No clinical symptoms of HIV

• What about breastfeeding?
• What about antiretroviral medicines
• r other treatment?
• To mother?
• To child?
• What will you say?

HIV transmission to children

10-20% during delivery

10-20% through BF

60-80% not HIV-infected

5% Ante- natal

ARV treatment during pregnancy Nevirapine + zidovudine before delivery and nevirapine to infant post- partum EBF PEP RF

If optimal management HIV-positive

Infant feeding patterns

• Exclusive breastfeeding and

predominant breastfeeding

• Relatively low risk of HIV-transmission
• Positive effect on respiratory infections and

risk of several diseases

• Not beneficial after around 6 months of age
• Complementary feeding/ partial breast-

feeding/ mixed feeding

• Necessary to give more than breast milk after

6 months of age

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Case: Mary

• Mother testing negative for HIV

with diabetes mellitus type II and hypertension

• Has been prescribed atenolol

and metformin by family doctor

• Child 1 month and

breastfeeding and ask whether breastfeeding is safe?

• What will you say?

Case: Mary

• Atenolol has low protein binding and is excreted in high

proportion into breast milk

• Unfortunate effect on child

– Metoprolol or propranolol are safer options

• Metformin is relatively safe when breastfeeding

Breastfeeding is safe when changing atenolol into e.g. metoprolol or propranolol

• Lactation Medicine on ToxNet (NLM):

http://toxnet.nlm.nih.gov/cgi-bin/sis/search G8 Amming og legemidler http://legemiddelhandboka.no/ https://www.tryggmammamedisin.no

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

Guidelines and recommendations on infant feeding in the context of HIV

from WHO 2010 Key principles on HIV and infant feeding

• Balancing HIV prevention with protection from other causes of child mortality
• Ensuring mothers receive the care they need
• Integrating HIV interventions into maternal and child health services
• Setting specific recommendations

– Feasibility, affordability, acceptability, safety, sustainability

• Providing necessary balanced information
• Support mothers to appropriately feed their infants
• Avoiding harm to infant feeding practices in the general population

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 and continue thereafter

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Use of ARV

• Preferred first-line ART regimen

– AZT + 3TC + NVP/EFV. – TDF + 3TC (or FTC) + NVP/EFV Recommendation 2

• Which breastfeeding practices and for how long

– Many settings

• Exclusive breastfeeding for 6 months with antiretroviral

prophylaxis or maternal antiretroviral therapy

• 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

Recommendation 3

• When mothers decide to stop

breastfeeding

– avoid abrupt weaning

Recommendation 4

• What to feed infants when mothers stop or

avoid breastfeeding

– Safe and adequate replacement feeds to enable normal growth and development

• Alternatives during first 6 months:

– Commercial infant feeding formula – Exressed, heat treated breast milk

– Home-modified animal milk is not recommended as a replacement first six months of life

Recommendation 5

• Infants born to HIV-infected women

receiving ART for their own health should receive

– daily AZT or NVP from birth until 6 weeks

• f age

Recommendation 6

• 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.

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Recommendation 7

• 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

Recommendation 8

• 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.

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

• Is it scientific agreement that exclusive breastfeeding is much better than

predominant breastfeeding (e.g. in terms of HIV-transmission)? – NO

• Is mixed feeding associated with higher HIV-transmission than exclusive

breastfeeding? – YES

• Are more than 50% of the children born to HIV-positive mothers in low-

income countries infected with HIV if no protective measures are taken (no interventions)? – NO

• Is it possible to reduce HIV-transmission from mother-to-child to less than

1%? – YES

• Had the HIV-virus been identified in 1980?

– NO

Quiz

• 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? – YES

• Is it possible to test children for HIV before they are 6 months?

– YES

• Can rapid antibody tests be used when testing children for HIV

before 6 months? – NO

• Is maternal viral load an important factor in respect to

transmission of mother-to-child transmission? – YES Does WHO have good advices for everything? – Almost

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Questions and comments