Diagnosis of HIV in Infants and Children

1. Diagnosis of HIV in Infants and Children Step 3: Infant Diagnosis (Slides 1 � 75) � 90 minutes Step 3: Infant Diagnosis (Slides 1 � 75) � 90 minutes

2. 2 Learning Objectives This presentation will: Review key concepts in diagnosing HIV infection in infants and young children Review virologic and antibody tests Explain the Ethiopian algorithms for diagnosing HIV in infants and young children Describe the use of clinical criteria to identify presumed severe HIV-infection Review roles of the parent and multidisciplinary team

3. 3 Goal of Early Infant Diagnosis The primary goal of early infant diagnosis is to identify the HIV-infected child early, prior to the development of clinical disease during the first months of life. The goal is NOT to exclude infection in infants. Diagnosis should be early enough so interventions and treatment can be started To reduce pediatric mortality and morbidity To initiate ART in an infant with rapidly progressing HIV-disease

4. 4 It is important to remember Babies can acquire HIV infection during: Pregnancy Labor & delivery Breastfeeding Keeping this in mind will help you to understand infant diagnosis

5. 5 Complexities of Infant Diagnosis HIV infection is difficult to diagnosis in infants: Routine HIV antibody tests cannot be used Specialized virologic tests are necessary Clinical diagnosis requires frequent and close follow-up of the infant HIV infection is difficult to exclude in infants: Infants who breastfeed continue to be at risk for acquiring HIV infection Risk of infection continues throughout duration of breast feeding Diagnosis of infants is an ongoing process and depends on good clinical reasoning as well as laboratory results Challenges of clinical dx: ongoing education and mentoring of clinical staff, clinical staff lack confidence in their ability to use clinical sx to make diagnoses, financial/transportation difficulties for families, staffing and space limitations in MCH clinics Challenges of clinical dx: ongoing education and mentoring of clinical staff, clinical staff lack confidence in their ability to use clinical sx to make diagnoses, financial/transportation difficulties for families, staffing and space limitations in MCH clinics

6. 6 Complexities of HIV Diagnosis: Antibody Testing All infants born to HIV+ mothers will test HIV antibody positive in the first several months of life Maternal HIV antibody (IgG) is transferred across the placenta during pregnancy A positive HIV antibody test in infants <18 months of age will not distinguish whether or not the infant is HIV-infected; rather it shows that: Mother is HIV-infected Infant is at risk for HIV infection (exposed to HIV) If the child is not infected the HIV antibody fades during first 6 - 18 months of life Most uninfected infants test negative by 12 months of age All uninfected infants test negative by 18 months of age It is assumed that most of the clinical staff is aware that antibody is not useful for early infant diagnosis. This slide is just to reiterate this fact and to begin the discussion about virologic testing. In general, most infants are probably not tested by antibody if known to be born to a positive mother. Also note that most sites use rapid antibody tests rather than EIA and WB. Positive HIV antibody test will not distinguish whether or not the infant is HIV-infected. Only indicates: Mother is HIV-infected Infant is at risk for HIV infection HIV antibody fades during first 9 - 18 months of life median time in an uninfected infant is 10 months can persist until 18 months It is assumed that most of the clinical staff is aware that antibody is not useful for early infant diagnosis. This slide is just to reiterate this fact and to begin the discussion about virologic testing. In general, most infants are probably not tested by antibody if known to be born to a positive mother. Also note that most sites use rapid antibody tests rather than EIA and WB. Positive HIV antibody test will not distinguish whether or not the infant is HIV-infected. Only indicates: Mother is HIV-infected Infant is at risk for HIV infection HIV antibody fades during first 9 - 18 months of life median time in an uninfected infant is 10 months can persist until 18 months

7. 7 Antibody Detection in 77 HIV-Exposed, Uninfected Infants in South Africa 77 uninfected infants from South Africa, tested with Abbott ELISA. Non-breast feeding population. Antibody titers declined gradually during first 3 months, then rapidly thereafter 94.5% HIV antibody negative at 12 months. 100% HIV antibody negative at 15 months . Moodley D Ped Inf Dis J 1995;14:850 77 uninfected infants from South Africa, tested with Abbott ELISA. Non-breast feeding population. Antibody titers declined gradually during first 3 months, then rapidly thereafter 94.5% HIV antibody negative at 12 months. 100% HIV antibody negative at 15 months . Moodley D Ped Inf Dis J 1995;14:850

8. 8 Complexities of HIV Diagnosis: Virologic Tests Specialized virologic tests must be used HIV DNA PCR HIV RNA PCR p24 Antigen Viral Culture Two positive virologic tests = HIV infection One positive virologic test = Presumed HIV infection Most sites will be using DNA PCR. It is important to note that the sensitivity and specificity, as noted in following slide vary with the assay. Some sites may be using an �in house� assay and will be able to specify statistics for their assay. RNA PCR sensitivity and specificity parallels that of the DNA assay and can be used for infant diagnostics. Results with low copy numbers during the first months of life often cannot be substantiated on repeat testing. Most sites will be using DNA PCR. It is important to note that the sensitivity and specificity, as noted in following slide vary with the assay. Some sites may be using an �in house� assay and will be able to specify statistics for their assay. RNA PCR sensitivity and specificity parallels that of the DNA assay and can be used for infant diagnostics. Results with low copy numbers during the first months of life often cannot be substantiated on repeat testing.

9. 9 HIV DNA PCR HIV DNA PCR is a special laboratory test that detects pieces of the viral gene that are incorporated in the human blood cell By comparison, HIV Antibody testing detects the antibody that the body makes in response to the HIV virus Sensitivity of HIV DNA PCR increases with time during the first month of life The infant may have HIV infection but there may not be enough virus in the blood to detect it at birth. It becomes easier to find/detect as the infant gets a little older DNA PCR uses amplified genetic material as a probe. The commercially available Roche Amplicor HIv-1 DNA PCR test version 1.5 detects viral subtypes other than BDNA PCR uses amplified genetic material as a probe. The commercially available Roche Amplicor HIv-1 DNA PCR test version 1.5 detects viral subtypes other than B

10. 10 DNA PCR for Infant Diagnosis Trainers: Data contributed from multiple perinatal studies, primarily in the US and Europe, with formula fed populations. Include 271 HIV-infected infants. Sensitivity of DNA PCR increases substantially after the first week of life. By 28 days the sensitivity approaches 96% Sensitivity (true positives) increases during first weeks of life Sensitivity can vary with assay and laboratory; assay should be appropriate for viral subtype Theoretically, sensitivity and specificity (true positives) may vary in populations of infants receiving perinatal prevention regimens; no supportive data has been published Primarily US and European populations, subtype B populations. HIDE 90% CI 29-46 at 48 hours 76-97 at 14 d 89-98 at 28 d 7 children had negative test results after the neonatal period, the age at the last negative test ranging between 65 and 13 days. Trainers: Data contributed from multiple perinatal studies, primarily in the US and Europe, with formula fed populations. Include 271 HIV-infected infants. Sensitivity of DNA PCR increases substantially after the first week of life. By 28 days the sensitivity approaches 96% Sensitivity (true positives) increases during first weeks of life Sensitivity can vary with assay and laboratory; assay should be appropriate for viral subtype Theoretically, sensitivity and specificity (true positives) may vary in populations of infants receiving perinatal prevention regimens; no supportive data has been published Primarily US and European populations, subtype B populations. HIDE 90% CI 29-46 at 48 hours 76-97 at 14 d 89-98 at 28 d 7 children had negative test results after the neonatal period, the age at the last negative test ranging between 65 and 13 days.

11. 11 Complexities of HIV Diagnosis: Breastfed infants Breastfed infants Remain at risk for acquiring HIV infection throughout the duration of breastfeeding Most are infected in utero, intrapartum and early postpartum (by 6 weeks of age) A negative virologic test cannot reliably exclude HIV if the infant is still breastfeeding Infant must always be tested again 6-12 weeks after complete cessation of breastfeeding

12. 12 How to Approach Diagnosis of HIV Infection in Children < 18mo Know that the child is at risk for HIV infection Born to an HIV-infected woman Tests HIV-antibody positive Pay close attention to the child�s clinical status and growth pattern Use special virologic tests to identify the infected child, not to exclude infection in the exposed child Interpretation of virologic test results should ALWAYS be done in the context of the clinical presentation of the infant

13. 13 How to Use Virologic Testing Every HIV-exposed baby should have a DNA PCR test At 4-6 weeks of life or At first visit* (if >6 weeks of age) *If the child presents at 9-18 months of age screen with a rapid antibody first Why at six weeks of age? The vast majority of infants with in utero, intra-partum and early postnatal infection will be identified by 6 weeks of age Most infants have their first visit for immunizations and growth monitoring at 6 weeks You can start CTX at this visit also. The sensitivity of the DNA PCR test is > 96% Testing at this 4-6 weeks of age should identify all babies infected in during pregnancy, labor & delivery and during early breast feeding Note: if maternal HIV status is unknown screen with rapid antibody first. For infants older than 9 months of age at the first clinic visit , screen with a rapid antibody test first. If antibody is positive then perform DNA PCR. If antibody is negative and infant is still breastfeeding, repeat rapid antibody 6-12 weeks after cessation of breast feeding.Why at six weeks of age? The vast majority of infants with in utero, intra-partum and early postnatal infection will be identified by 6 weeks of age Most infants have their first visit for immunizations and growth monitoring at 6 weeks You can start CTX at this visit also. The sensitivity of the DNA PCR test is > 96% Testing at this 4-6 weeks of age should identify all babies infected in during pregnancy, labor & delivery and during early breast feeding Note: if maternal HIV status is unknown screen with rapid antibody first. For infants older than 9 months of age at the first clinic visit , screen with a rapid antibody test first. If antibody is positive then perform DNA PCR. If antibody is negative and infant is still breastfeeding, repeat rapid antibody 6-12 weeks after cessation of breast feeding.

14. 14 Diagnosing a Child Who Presents at 9-18 Months of Age Asymptomatic child Screen with HIV antibody If positive, virologic testing is indicated If negative, no virologic testing is necessary If breastfeeding, repeat antibody testing >6-12 weeks after cessation of breastfeeding Symptomatic child Screen with virologic testing If an infant presents at 9-18 months of age the choice of test will depend on the clinical presentation. For Asymptomatic infants antibody testing should be performed to identify those who have cleared maternal antibody. For symptomatic infants virologic testing should be done to confirm the presence of HIV If an infant presents at 9-18 months of age the choice of test will depend on the clinical presentation. For Asymptomatic infants antibody testing should be performed to identify those who have cleared maternal antibody. For symptomatic infants virologic testing should be done to confirm the presence of HIV

15. 15 What if the DNA PCR is Positive? If the HIV DNA PCR result is POSITIVE the baby is presumed to be HIV-INFECTED

16. 16 What if the DNA PCR is Positive? Refer the baby for HIV care & treatment Don�t wait! Start or continue cotrimoxazole Continue exclusive breastfeeding (EBF) through 6 months of age

17. 17 What should you tell the care giver if the initial PCR test is Positive? HIV has been detected in your infant�s blood This means that your child has HIV infection We will check your baby carefully and refer you and your baby to a clinic where there are doctors and nurses who are experts in taking care of children with HIV The doctors and nurses will teach you how to care for yourself and the baby so you both stay healthy Trainers: Ask participants to discuss how they will tell a care giver that the infant has HIV infectionTrainers: Ask participants to discuss how they will tell a care giver that the infant has HIV infection

18. 18 Diagnostic Algorithm for Infants < 18 months of age

19. 19 What if the DNA PCR is Negative? If the HIV DNA PCR result is NEGATIVE the baby is presumed NOT to be HIV-infected NOTE: Infants who are still breastfeeding are at continued risk for acquiring HIV infection

20. 20 What if the DNA PCR is Negative? Continue follow-up Continue cotrimoxazole (CTX) Continue exclusive breastfeeding (EBF) through 6 months of age

21. 21 What should you tell the care giver if the initial PCR test is Negative? We did not find the HIV virus in your baby�s blood Since you are breastfeeding, your baby may still get the virus from the breast milk We will have to keep checking on him/her and look for the virus until 6 weeks after s/he stops breastfeeding If he or she stays well, we will not test again until at least 6 weeks after you wean the baby from the breast If your baby gets get sick, we will repeat the special test again to check for the virus You need to keep bringing your child for check ups and continue cotrimoxazole Trainers: Ask participants to discuss how they will tell a care giver that the initial DNA PCR was negativeTrainers: Ask participants to discuss how they will tell a care giver that the initial DNA PCR was negative

22. 22 Diagnostic Algorithm for Infants < 18 months of age

23. 23 What if the Initial DNA PCR isNegative and the child is WELL? Repeat HIV testing 6-12 weeks after weaning using Rapid HIV Antibody Test NOTE: Breastfeeding babies remain at risk for acquiring HIV

24. 24 Diagnostic Algorithm for Infants < 18 months of age If the first DNA PCR is negative and the child is well , continue clinical follow-up and CTX. These infants should have rapid antibody performed at least 6 weeks after complete cessation of breastfeeding to determine their final infection status.If the first DNA PCR is negative and the child is well , continue clinical follow-up and CTX. These infants should have rapid antibody performed at least 6 weeks after complete cessation of breastfeeding to determine their final infection status.

25. 25 What if the HIV Antibody is Negative? If the HIV Antibody result is NEGATIVE the baby is presumed NOT to be HIV-infected NOTE: At this point, the baby may be discharged from the program

26. 26 What if the HIV Antibody is Positive? If the HIV antibody result is Positive and the baby is > 18 (older than) months of age the baby is presumed to be HIV-INFECTED Refer for HIV care and treatment

27. 27 What if the HIV Antibody is Positive? If the HIV antibody is positive and the baby is <18 (younger than) months of age* Repeat HIV DNA PCR NOTE: Maternal antibody can persist until 18 months of age

28. 28 Diagnostic Algorithm for Infants < 18 months of age

29. 29 What if the Initial DNA PCR is Negative but the child is ILL? If the HIV DNA result is negative, but the child develops HIV symptoms Oral thrush Pneumonia Poor growth Developmental delay Chronic diarrhea REPEAT HIV DNA PCR TESTING NOTE: Breastfeeding babies remain at risk for acquiring HIV

30. 30 Diagnostic Algorithm for Infants < 18 months of age

31. 31 What if the 2nd DNA PCR is Positive? If the HIV DNA PCR result is POSITIVE the baby is presumed to be HIV-INFECTED Refer for HIV care and treatment

32. 32 What if the 2nd DNA PCR is Negative? If the HIV DNA PCR result is NEGATIVE the baby is presumed NOT to be HIV-infected NOTE: If the baby is still breastfeeding repeat rapid HIV test > 6-12 weeks after weaning Refer the infant for further evaluation Other diseases can have similar manifestations and should be ruled out if possibleOther diseases can have similar manifestations and should be ruled out if possible

33. 33 Diagnostic Algorithm for Infants < 18 months of age Trainers note: Infant who are HIV exposed and have two negative DNA PCR tests are most likely uninfected. However if they are still breastfeeding they are at ongoing risk for HIV. They should have an antibody test at least 6 weeks after complete cessation of breastfeeding. If the second DNA PCR is negative and the infant is ill , there are several other conditions which should be ruled out. These infants need to be referred for further evaluation to determine the cause of the illnessTrainers note: Infant who are HIV exposed and have two negative DNA PCR tests are most likely uninfected. However if they are still breastfeeding they are at ongoing risk for HIV. They should have an antibody test at least 6 weeks after complete cessation of breastfeeding. If the second DNA PCR is negative and the infant is ill , there are several other conditions which should be ruled out. These infants need to be referred for further evaluation to determine the cause of the illness

34. 34 If virologic test results don�t match the clinical picture� Clinical findings can suggest the diagnosis of HIV infection even when virologic tests are negative Rapid disease progression is common in HIV-infected infants Growth failure and delay or loss of developmental milestones are seen frequently in infants with rapid progression Use CD4 to assess immunologic status Low CD4 is consistent with HIV diagnosis Other diseases can have similar manifestations and should be ruled out if possible Repeat virologic testing should be considered HIV antibody testing should be repeated at >18 months to confirm infection status.

35. 35 Summary: How to Use DNA PCR Testing Every HIV-exposed baby should have a DNA PCR test At 4-6 weeks of life* or at first visit if > 6 weeks of age# Any infant with an initial negative DNA PCR who develops signs and symptoms of HIV infection Testing prior to 4 weeks in HIV-exposed infant who is symptomatic In a baby < 18 mo who tests antibody positive 6 weeks after weaning Trainers: Note if the infant is > 9 months at the initial visit screen with a rapid antibody first.Trainers: Note if the infant is > 9 months at the initial visit screen with a rapid antibody first.

36. 36 Summary: How to Use DNA PCR Testing As Ethiopia has adopted to use single positive DNA PCR test result to enroll HIV exposed infants into HIV care/ART all such infants must have a confirmatory rapid antibody test at 18 months of age Trainers: Note if the infant is > 9 months at the initial visit screen with a rapid antibody first.Trainers: Note if the infant is > 9 months at the initial visit screen with a rapid antibody first.

37. 37 Summary: When should you repeat the DNA PCR? HIV antibody positive infant < 18 months of age with signs and symptoms of HIV infection Children < 18 months of age with a positive rapid antibody test > 6 weeks post-weaning A sick infant whose initial DNA PCR result comes as negative An infant who becomes symptomatic after an initial negative DNA PCR result

38. 38 If the Child is <18 months and Virologic Tests are not Available A presumptive diagnosis of HIV infection must be made based on clinical findings Good clinical reasoning can identify children at high risk for HIV disease & rapid progression The purpose of making a presumptive diagnosis is to initiate ART in the sick child Infants with severe manifestations of HIV infection should not be denied treatment because their diagnosis cannot be confirmed It is likely to be sometime before some sites have PCR testing for infant diagnosis. We want them to understand that sick infants still need to be treated. They will have to make a presumptive diagnosis based on clinical findings. The diagnosis will be confirmed when the child is older. Treatment should not be withheld if there is reasonable evidence that the child has HIV. Clinical algorithms are rarely more than 70% sensitive for diagnosis of HIV infection. They vary with age especially in children less than 12 months Screen with antibody to confirm HIV exposure Confirmation of HIV diagnosis should be sought as soon as possibleIt is likely to be sometime before some sites have PCR testing for infant diagnosis. We want them to understand that sick infants still need to be treated. They will have to make a presumptive diagnosis based on clinical findings. The diagnosis will be confirmed when the child is older. Treatment should not be withheld if there is reasonable evidence that the child has HIV. Clinical algorithms are rarely more than 70% sensitive for diagnosis of HIV infection. They vary with age especially in children less than 12 months Screen with antibody to confirm HIV exposure Confirmation of HIV diagnosis should be sought as soon as possible

39. 39 Presumptive Diagnosis of Severe HIV Disease in Children <18 months HIV antibody positive and Diagnosis of Stage 4 or AIDS-indicator condition (s) OR Symptomatic with = 2 of the following: Oral thrush Severe pneumonia Severe sepsis Supporting factors Recent maternal death Advanced HIV disease in the mother CD4% < 25% in infant The diagnosis should be confirmed with HIV antibody when the child reaches 18 months The distinction that needs to be made here is the following: The purpose of this algorithm is to treat very sick kids with ART. This, therefore, is an algorithm to enable treatment of these children. Other exposed children may also be infected, but since they do not �qualify� for treatment, they will need to be observed until the dx can be confirmed Also, note that there are no CD norms for sick children, if this is available at the site it can be used as additional evidence As per IMCI definition: Thrush- Creamy white to yellow soft small plaques on red or normally coloured mucosa which can often be scraped off (pseudomembranous), or red patches on tongue, palate or lining of mouth, usually painful or tender. Not responding to topical antifungal treatment. Pneumonia- Cough or difficult breathing in a child with chest indrawing, stridor or any of the IMCI general danger signs; i.e., lethargic or unconscious, not able to drink or breastfeed, vomiting, and presence or history of convulsions during current illness; responding to antibiotics. Severe sepsis- Fever or low body temperature in a young infant with any severe sign such as fast breathing, chest indrawing, bulging fontanelle, lethargy, reduced movement, not feeding or sucking breast milk, convulsions etc. Where ART has been initiated on the based on the presumptive diagnosis of severe HIV disease, efforts should be made to confirm the HIV infection as soon as possible but at the latest with HIV antibody testing at 18 months of age. Decisions on further treatment should be adjusted at that time according to clinical staging and immunologic criteria where available. The distinction that needs to be made here is the following: The purpose of this algorithm is to treat very sick kids with ART. This, therefore, is an algorithm to enable treatment of these children. Other exposed children may also be infected, but since they do not �qualify� for treatment, they will need to be observed until the dx can be confirmed Also, note that there are no CD norms for sick children, if this is available at the site it can be used as additional evidence As per IMCI definition: Thrush- Creamy white to yellow soft small plaques on red or normally coloured mucosa which can often be scraped off (pseudomembranous), or red patches on tongue, palate or lining of mouth, usually painful or tender. Not responding to topical antifungal treatment. Pneumonia- Cough or difficult breathing in a child with chest indrawing, stridor or any of the IMCI general danger signs; i.e., lethargic or unconscious, not able to drink or breastfeed, vomiting, and presence or history of convulsions during current illness; responding to antibiotics. Severe sepsis- Fever or low body temperature in a young infant with any severe sign such as fast breathing, chest indrawing, bulging fontanelle, lethargy, reduced movement, not feeding or sucking breast milk, convulsions etc. Where ART has been initiated on the based on the presumptive diagnosis of severe HIV disease, efforts should be made to confirm the HIV infection as soon as possible but at the latest with HIV antibody testing at 18 months of age. Decisions on further treatment should be adjusted at that time according to clinical staging and immunologic criteria where available.

40. 40 Diagnosing HIV in the Child >18 Months HIV antibody should be used to diagnose HIV infection in children > 18 months of age Children >18 months with positive antibody test have HIV infection A positive antibody test should be confirmed by duplicate testing A negative antibody test in children > 18 months excludes HIV infection Except in cases of continued breast feeding. Antibody should be repeated 6-12 weeks post cessation of breast feeding Trainers: Note that the antibody may be negative in a very sick childTrainers: Note that the antibody may be negative in a very sick child

41. 41 Diagnostic Algorithm for Children > 18 months of age

42. 42 Summary: When should you use HIV Antibody Tests? Children < 18 months of age Determine HIV exposure in infants born to women of unknown HIV status Exclude infection in an infant who is not breastfed or > 6 weeks post-weaning Exclude HIV infection in children > 9 months of age Children > 18 months of age Confirm HIV infection

43. 43 Early and Frequent Clinical Evaluation Close monitoring of growth and development Early identification of disease signs & symptoms Use of symptom checklist, monitor growth and development closely Listen to the parent Common illnesses can mimic symptoms of HIV-infection (growth failure, recurrent fevers, diarrheal illnesses) Cotrimoxazole prophylaxis for all HIV-exposed infants until HIV has been excluded Vaccinations, per local guidelines

44. 44 Critical Elements for Early Infant Diagnosis Remember Virologic tests should always be interpreted in the context of the clinical presentation of the child. Use your clinical judgment Don�t hesitate to question the results if they don�t make sense. Errors do occur! Are results valid? Do the results make sense given the child�s health? Is there a laboratory problem? Could there be a specimen mix-up?

45. 45 Critical Elements for Early Infant Diagnosis (2) Early and frequent clinical evaluations Good Clinical Reasoning can identify children at high risk for HIV disease & rapid progression during the first months of life Early virologic testing Good communication with family is critical: Team members should emphasize importance of: Determining HIV status Adherence to visit schedule Identifying signs and symptoms Administering Cotrimoxazole prophylaxis

46. 46 Critical Elements for Early Infant Diagnosis (3) Children who have early virologic testing must return to the clinic for results Both infants with positive and negative results Infants who are breastfeeding must be retained in care until they are weaned and a final infection status is determined Infant and children who are identified as HIV-infected will need to be linked to pediatric HIV care and treatment service Trainers: Emphasize the importance of giving results to care givers. Infants with positive results should be prioritized and brought back early for repeat confirmatory test and referral to care and treatment Infants with an initial negative result must be given results and told they need further testing to avoid a false sense of security. Trainers: Emphasize the importance of giving results to care givers. Infants with positive results should be prioritized and brought back early for repeat confirmatory test and referral to care and treatment Infants with an initial negative result must be given results and told they need further testing to avoid a false sense of security.

47. 47 Programmatic Barriers When an infant is seen at a maternal child health clinic (or other site of care), how will the clinician know that s/he is HIV-exposed? Coordination between the ANC, MCH, and CTC Use of rapid antibody to identify mothers and exposed infants if maternal HIV status is not known Routine testing of children of adults in HIV care and treatment programs Infants are not coming back for results Use appointment systems Monitor missed appointments Enhance parent education Reminders for parents and care givers Active outreach after missed visits Family education and support Trainers: Clinics need to develop protocols to maximize adherence to care, identify those who do not return, and bring patients who miss appointments back to the clinic. Trainers: Clinics need to develop protocols to maximize adherence to care, identify those who do not return, and bring patients who miss appointments back to the clinic.

48. 48 Multidisciplinary Team Provide ongoing education, support, and counseling to parent Identify problems and issues EARLY Form a bridge between parent and medical provider Provide adherence support for both mother and infant Introduce concept of infant diagnostic testing as part of PMTCT program

49. 49 Multidisciplinary Team (2) Support the decision to have early infant diagnostic testing Review results of virologic test Explain implications Explore parental understanding Explore parental concerns Review infant feeding decisions Emphasize need for ongoing care and treatment as determined by results Education Discussion and exchange Exploration of beliefs and fears about blood letting, test results, etc. Education Discussion and exchange Exploration of beliefs and fears about blood letting, test results, etc.

50. 50 Role of the Parent/caregiver Parent needs to understand: That infant diagnosis is an ongoing process The importance of early testing, frequent monitoring, and adherence to care Often the first to notice signs and symptoms Often has multiple complex roles and needs, including self-care, caretaker role for other family members, feelings about transmission of HIV to the infant Parent needs understanding and support

51. 51 Summary Clinical reasoning is critical to diagnosing infants with HIV Early virologic testing should be used to identify the infected infant at highest risk for disease progression Specialized virologic tests are used to diagnose HIV infection in a child < 18 months Virologic tests may be unreliable or unavailable, highlighting the importance of clinical evaluation The multidisciplinary team has numerous critical roles in this process The parent or caretaker is the key player, and must be educated and supported on this logistically, emotionally, socially and medically complicated path

52. 52 Case Study: Meseret 6 week old infant, Meseret, is brought to clinic for her first post-partum visit Mom delivered in a village outside of the city where her mother and sister still live She just returned home with Meseret and her 4 year old son Mom was enrolled in a PMTCT program during pregnancy What would you like to know about the baby and his family?

53. 53 Meseret was born at home without problems Mother doesn�t know birth weight, but brought Meseret to health station at 4 days of age, weighing 3 kg Mom took her sd-NVP, but the baby didn�t receive any medication. Mom didn�t tell anyone at home about her status Breastfeeding primarily but left the baby with her sisters on two occasions. During that time Meseret was fed water and maybe some milk

54. 54 Case Study: Meseret (3) Dad is away working. Mom has not disclosed her HIV status to him He comes home 1X/month and gives her money but she must work in the fields and sells produce to have enough money She uses the general water tap in the neighborhood No running water in the house What will you do next? What is usually done at a baby�s first visit?

55. 55 Case Study: Meseret (4)�Pertinent Physical Exam Physical examination is remarkable for fairly extensive oral thrush, and diffuse lymphadenopathy The baby looks a little scrawny and seems irritable What is your assessment of the child? What could be causing Meseret�s poor growth? Identify that the child is ill, growth being a particularly sensitive indicator of health status Develop a differential diagnosis with the learners to include: HIV infection Tuberculosis Inadequate caloric intake Infectious diarrhea Others? Given that this child is ill, there is an urgency to clarify infection status and consider need for ART or other treatments Make a list with the learners.. Is there other history that may be relevant? What about infant diagnostic testing? what is available at the site and what is the experience to date? Is there a reason to do a CD4 now? In general, would not recommend CD4 unless the child is known to be infected. However, if the child is symptomatic you may opt to do a CD4 now as well. Are there other laboratory studies to consider? What would you do to evaluate for tuberculosis? Identify that the child is ill, growth being a particularly sensitive indicator of health status Develop a differential diagnosis with the learners to include: HIV infection Tuberculosis Inadequate caloric intake Infectious diarrhea Others? Given that this child is ill, there is an urgency to clarify infection status and consider need for ART or other treatments Make a list with the learners.. Is there other history that may be relevant? What about infant diagnostic testing? what is available at the site and what is the experience to date? Is there a reason to do a CD4 now? In general, would not recommend CD4 unless the child is known to be infected. However, if the child is symptomatic you may opt to do a CD4 now as well. Are there other laboratory studies to consider? What would you do to evaluate for tuberculosis?

56. 56 Meseret (5): Growth Chart for Infant Girl

57. 57 Case Study: Clinical Questions Physical examination is remarkable for fairly extensive oral thrush, and diffuse lymphadenopathy The baby looks a little scrawny and seems irritable

58. 58 Case Study: Meseret (6) Mom reports that the baby has not been feeding well for several days You watch the child feed but she tires quickly and falls asleep. Mom says that this is what has been happening over the last several days She also reports occasional watery stools She says that she had a �TB� test at ANC and it was negative Her mother (the child�s grandmother) seemed to be coughing and had lost some weight, but she didn�t seem to be too sick

59. 59 Case Study: Meseret (7) You send blood for HIV DNA PCR You work with mom around enhancing feeding and arrange for the family to receive food packages You prescribe nystatin for the oral thrush The child also begins cotrimoxazole prophylaxis Mom is instructed to come back in one week to check the baby again Mom does not make the appointment the following week. What will the team do to address this missed visit? Always begin with assessment of child�s level of illness and clinician�s level of suspicion. Early diagnostic testing should be done on all infants, as per protocol. Depending on availability and reliability of test, may need to consider 1) Other ways to support the diagnosis (CD4) 2) Potential need to start ART without confirmed diagnosis if she is progressing rapidly Need to assess mom�s ability to care for child, level of anxiety about the child, food and economic resources Review with the staff the mechanism by which they would Track missed visits Classify the urgency of the visit Steps they would take to insure follow-up �letter, phone, home visit, - and who within the team is responsible for each activity Always begin with assessment of child�s level of illness and clinician�s level of suspicion. Early diagnostic testing should be done on all infants, as per protocol. Depending on availability and reliability of test, may need to consider 1) Other ways to support the diagnosis (CD4) 2) Potential need to start ART without confirmed diagnosis if she is progressing rapidly Need to assess mom�s ability to care for child, level of anxiety about the child, food and economic resources Review with the staff the mechanism by which they would Track missed visits Classify the urgency of the visit Steps they would take to insure follow-up �letter, phone, home visit, - and who within the team is responsible for each activity

60. 60 Case Study: Meseret (8)�MDT The case is discussed at the weekly multidisciplinary meeting and it is decided that the mom should be contacted immediately. Her cell number is no longer connected so the decision is made to make a home visit A peer educator and a counselor travel to the listed address. Mom is not at home but they find the baby with a neighbor. Meseret seems sick and has loud breathing What should they do?

61. 61 Case Study: Meseret (9) Mom is due to return in a short time. She usually comes home late morning to feed the baby When she arrives you escort her to the clinic with the baby Meseret is brought in to the nurse who weighs her. Breathing seems fine now, but the child weighs the same as last visit

62. 62 Meseret -Growth Chart for Infant Girl

63. 63 Case Study: Meseret (10)�Pertinent Physical Exam On examination, the thrush is still visible and lymph nodes are somewhat larger Infant diagnostic tests are not yet back. You ask the nurse to call the lab and they have no record of the sample What would you do now?

64. 64 Case Study: Meseret (11) You decide that the child does not require hospitalization but ask mom to return in two days You order: CXR CD4 count Repeat virologic testing Test Results: The CD4 is 1200, 13% DNA PCR results are not ready CXR is normal Does this child have HIV infection?

65. 65 Case Study: Meseret (12) The team decides that the child most likely has HIV infection and requires treatment Thrush Failure to thrive ( WHO Stage III) Low CD4 (<25% for infant <11months of age) What will you tell the mother? What will you do to confirm the child�s infection status? Failure to thrive � unexplained weight loss not explained by poor or inadequate feeding or other infections and not adequately responding within 2 weeks to standard management CD4 criteria for starting ART in infant < 11 months= CD4< 25% or 1500 This is an opportunity to do a role play with the team members about how to tell the family that an infant is HIV-infected. Stress certain points Infant has HIV based on clinical and immunologic criteria Use of simple language Room for questions Need for ongoing evaluation to confirm diagnosis Baby likely to do well with treatment Need for ongoing counseling and support Identify other supports to share news Trainer should stress the following: Need to check diagnostic test results to confirm infection status The diagnosis should be confirmed with virologic testing, response to treatment and/or antibody testing >18 months Failure to thrive � unexplained weight loss not explained by poor or inadequate feeding or other infections and not adequately responding within 2 weeks to standard management CD4 criteria for starting ART in infant < 11 months= CD4< 25% or 1500 This is an opportunity to do a role play with the team members about how to tell the family that an infant is HIV-infected. Stress certain points Infant has HIV based on clinical and immunologic criteria Use of simple language Room for questions Need for ongoing evaluation to confirm diagnosis Baby likely to do well with treatment Need for ongoing counseling and support Identify other supports to share news Trainer should stress the following: Need to check diagnostic test results to confirm infection status The diagnosis should be confirmed with virologic testing, response to treatment and/or antibody testing >18 months

66. 66 Case Study: Meseret (13) Meseret was continued on CTX, nystatin for thrush and started on ARVs Both initial and repeat DNA PCR results were positive when test results were finally available

67. 67 Case Study: Tsegenet Mom brings her 10 week old baby, Tsegenet, for a return visit The baby has been receiving cotrimoxazole since 4 weeks of age She is breastfeeding well and has not been sick A DNA PCR test was sent at the previous visit and mom is anxious to know the results The team discussed this family last week during the multidisciplinary meeting

68. 68 Case Study: Tsegenet (2) DNA-PCR results were positive The team talked about how to share the news with the parents What will you say to her mother when she comes to the clinic? Trainers Need to emphasize that baby should be evaluated in context of physical examination and findings of the days� visit. Also, that team needs to identify who will be part of the discussion with the mother. Most often the clinician provides the information but a counselor or nurse participates or is available for support Trainers Need to emphasize that baby should be evaluated in context of physical examination and findings of the days� visit. Also, that team needs to identify who will be part of the discussion with the mother. Most often the clinician provides the information but a counselor or nurse participates or is available for support

69. 69 Case Study: Tsegenet (3) Tsegenet appears well with a normal physical examination Growth is plotted on the 50th percentile for weight, height and head circumference She smiles, makes good eye contact, and reaches out She is EXCLUSIVELY breastfeeding

70. 70 Case Study: Tsegenet (4)�Growth Curve

71. 71 Case Study: Tsegenet (5)�Clinical Questions Given the laboratory result and the clinical findings, do you think this child is HIV-infected? How will you manage the child? What will you tell the mother? Review evidence in favor of infection � can consider making a list with learners Positive virologic test High rate of mtct in local setting Child with recent exposure may not yet be symptomatic Some infants may remain asymptomatic And evidence against infection Most infants have some symptoms, often quite severe � growth is excellent, baby is thriving Laboratory tests not always reliable Explore problems, if any, at the site with laboratory testing In some sites this may be excellent. Others have had multiple problems with reliability Emphasize that laboratory tests are not always reliable Can repeat laboratory test, Part of protocol is to confirm positive tests Always maintain high level of suspicion re: labs when they are not consistent with clinical situation The baby is thriving at this moment so you would not change clinical management Continue cotrimox Close follow-up of infant Can consider CD4 This is an opportunity to try role playing or to model what to say by asking a learner to be the mother and explaining the results to her Key Points in the exchange w/the mom: Baby is doing well, good growth and development One of the lab tests shows the baby may have HIV infection Unsure if lab test is good Need to repeat and see if it is true Review evidence in favor of infection � can consider making a list with learners Positive virologic test High rate of mtct in local setting Child with recent exposure may not yet be symptomatic Some infants may remain asymptomatic And evidence against infection Most infants have some symptoms, often quite severe � growth is excellent, baby is thriving Laboratory tests not always reliable Explore problems, if any, at the site with laboratory testing In some sites this may be excellent. Others have had multiple problems with reliability Emphasize that laboratory tests are not always reliable Can repeat laboratory test, Part of protocol is to confirm positive tests Always maintain high level of suspicion re: labs when they are not consistent with clinical situation The baby is thriving at this moment so you would not change clinical management Continue cotrimox Close follow-up of infant Can consider CD4 This is an opportunity to try role playing or to model what to say by asking a learner to be the mother and explaining the results to her Key Points in the exchange w/the mom: Baby is doing well, good growth and development One of the lab tests shows the baby may have HIV infection Unsure if lab test is good Need to repeat and see if it is true

72. 72 Case Study: Tsegenet (6) Mom returns with the baby in a month The repeat DNA PCR test is negative and the baby is still thriving What will you do?

73. 73 Case Study: Tsegenet (7)�Clinical Question Which of the following actions would you consider? Repeat DNA-PCR testing CD4 Continue cotrimoxazole Monitor closely Rapid antibody screen at 12 months Given the child�s clinical status, we would recommend the following: Close follow-up and HIV Ab testing at > 12 months or > 6 wks post weaning, whichever is later Continue CTX If the child develops symptoms, could do CD4 or repeat PCR Learners should understand that: Infant diagnosis requires clinical judgment as well as laboratory tests When laboratory tests are not consistent with the clinical picture, they should be repeated If a child becomes ill, repeat virologic testing is indicated. Given the child�s clinical status, we would recommend the following: Close follow-up and HIV Ab testing at > 12 months or > 6 wks post weaning, whichever is later Continue CTX If the child develops symptoms, could do CD4 or repeat PCR Learners should understand that: Infant diagnosis requires clinical judgment as well as laboratory tests When laboratory tests are not consistent with the clinical picture, they should be repeated If a child becomes ill, repeat virologic testing is indicated.

74. 74 Case Study: Tsegenet (8)�Case Conclusion The team was unsure about the lab tests, but decided to: Continue the CTX for now Schedule more frequent follow-up, at the same time as mom�s visits Work with the mom to continue exclusive breastfeeding till she is 6 months then introduce complementary feeds with continued breastfeeding Tsegenet is weaned at 10 months At 12 months Tsegenet tested HIV Ab negative

75. 75 Key Points Infant diagnosis can be a complex and lengthy process Early virologic testing should be used to identify the infected infant at highest risk for disease progression Specialized virologic tests are used to diagnose HIV infection in a child <18 months Two positive virologic tests confirm HIV infection in an exposed infant The presence of HIV antibody in a child >18 months defines HIV infection

76. 76 Key Points (2) Clinical reasoning is critical to diagnosing infants with HIV Virologic tests may be unreliable or unavailable, making clinical evaluation important HIV can be diagnosed without a definitive virologic test in an ill child with clinical and immunological evidence of infection The diagnosis should be confirmed with virologic testing, response to treatment and/or antibody testing >18 months The multidisciplinary team has numerous critical roles in this process The parent or caretaker is the key player, and must be educated and supported on this logistically, emotionally, socially and medically complicated path