HIV. Transmission modes. Transmission modes in children. Prevention of mother-to-child transmission of HIV. HIV identified in 1983

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1 Prevention of mother-to-child transmission of HIV HIV identified in 1983 HIV 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 Lars Thore Fadnes Centre for International Health 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 Aug 29;325(9): Infective and anti-infective properties of breastmilk from HIV-1-infected women. Lancet Apr 10;341(8850): ABC of AIDS: BMC publishing group

2 Transmission risk of HIV related to maternal HIV stage Primary HIV Asymptomatic HIV Symptomatic Viral load CD4 count 0 3 months 5-10 years 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 Highly infective Less infective Highly infective 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 Nov-Dec;17(6): 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 Nov-Dec;17(6): 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? Direct demonstration of virus PCR Viral culture Indirect tests (antibody tests) All rapid tests ELISA tests Confirmatory Western Blot HIV testing More about testing: 2

3 Rapid tests PCR Transmission rates Without intervention: What is the total risk of HIVtransmission 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 3

4 Mortality from all causes Estimated 13% of 8 million child deaths could be prevented with optimal breastfeeding Particularly in low-income settings Jones G et al: How many child deaths can we prevent this year? Lancet % of deaths avoided with promotion of exclusive breastfeeding Bhutta ZA et al: What works? Interventions for maternal and child undernutrition and survival. Lancet The Dilemma BALANCE: 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 or other treatment? To mother? To child? What will you say? HIV transmission to children 60-80% not HIV-infected Nevirapine + zidovudine before delivery and nevirapine to infant postpartum EBF PEP ARV treatment during RF pregnancy Risk of HIV-1 transmission through breast milk & Risk of child death through nonbreastfeeding 5% 10-20% 10-20% Antenatal delivery If optimal during management through BF 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 breastfeeding/ mixed feeding Necessary to give more than breast milk after 6 months of age 4

5 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): G8 Amming og legemidler 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 Guidelines and recommendations on infant feeding in the context of HIV from WHO 2010 Contextual and operational research is needed Methodological and ethical challenges Key principles on HIV and infant feeding Recommendation 1 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 In women with confirmed HIV serostatus, initiation of ART for her own health is recommended when CD4 <350 cells/mm 3 or WHO clinical stage 3 or 4 Throughout pregnancy and continue thereafter 5

6 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 of 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. 6

7 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? 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)? NO Is it possible to reduce HIV-transmission from mother-to-child to less than 1%? 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? Is it possible to test children for HIV before they are 6 months? 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? Does WHO have good advices for everything? Almost 7

8 Questions and comments 8