Care of HIV-Infected Infants and Children

1. 1 Care of HIV-Infected Infants and Children

2. 2 Learning Objectives Understand the goals of care for HIV-infected infants and children Describe reasons for close follow-up Demonstrate appropriate use of the major components of routine care for HIV-infected infants & children Categorize disease stage Prescribe PCP prophylaxis Perform tuberculosis screening Evaluate ARV eligibility Schedule pediatric visits as per ICAP protocols Antiretroviral therapy is discussed in a different training module

3. 3 Model of care Family-centered HIV primary care Multidisciplinary team Maximize health & prevent disease progression Prevent early death Prevent OI Maximize growth and development Reduce hospitalization rate Reduce frequency of intercurrent illnesses ICAP Goals for Care of HIV-Infected Infants & Children ICAP tries to combine best practice and care for the individual participant with a public health approach to HIV care. For the infected child, the goal is to maintain maximal health. This includes: Prevent early death and opportunistic infections, reducing hospitalization rate, reduce frequency of intercurrent illnesses, maximizing growth and development. This will be accomplished with the components of care listed above.ICAP tries to combine best practice and care for the individual participant with a public health approach to HIV care. For the infected child, the goal is to maintain maximal health. This includes: Prevent early death and opportunistic infections, reducing hospitalization rate, reduce frequency of intercurrent illnesses, maximizing growth and development. This will be accomplished with the components of care listed above.

4. 4 Background: HIV Disease in Children Rapid disease course compared with adults Bimodal distribution of disease manifestations >30% with rapid disease progression Majority with symptoms by 12 months 50% mortality by 24 months <5% long term nonprogressors In the original study by Stephen Blanche in 1990, he described a bimodal distribution of disease manifestations. One third of 94 children developed early onset of OI. Survival rate was 48% at 3 years. (Blanche AJDC 1990;144:1210) However, the European cohort in 1997 studied 392 children from two prospective European cohorts. The early severe form of HIV disease affects approximately 20% of infants, and after 6 years, 75% of infected children are still alive. This was published in 1997 before the widespread use of protease inhibitors. (JAIDS 14:442. 1997). In Malawi, Taha reported a mortality rate of 340/1000 person years of observation in infected children compared with 46/1000 person years in exposed uninfected children. By 32 months of age none of the severely immunosuppressed children had survived.In the original study by Stephen Blanche in 1990, he described a bimodal distribution of disease manifestations. One third of 94 children developed early onset of OI. Survival rate was 48% at 3 years. (Blanche AJDC 1990;144:1210) However, the European cohort in 1997 studied 392 children from two prospective European cohorts. The early severe form of HIV disease affects approximately 20% of infants, and after 6 years, 75% of infected children are still alive. This was published in 1997 before the widespread use of protease inhibitors. (JAIDS 14:442. 1997). In Malawi, Taha reported a mortality rate of 340/1000 person years of observation in infected children compared with 46/1000 person years in exposed uninfected children. By 32 months of age none of the severely immunosuppressed children had survived.

5. 5 Common Clinical Manifestations Infancy and early childhood - rapid progression poor growth/failure-to-thrive/weight loss pneumonia (PCP & TB) encephalopathy recurrent, severe infections diarrhea Older children poor growth recurrent infections lymphoid interstitial pneumonia (LIP) dermatitis Clinical manifestations vary considerably

6. 6 HIV Causes Increased Mortality in Children This graph is from Newell et al. Lancet 2004 shows estimated unadjusted mortality for HIV infected and uninfected children. HIV infected children have a higher probability of death compared to non HIV infected children. .This graph is from Newell et al. Lancet 2004 shows estimated unadjusted mortality for HIV infected and uninfected children. HIV infected children have a higher probability of death compared to non HIV infected children. .

7. 7 3 year old with HIV encephalopathy, Failure-To-Thrive, Recurrent Infections This child has multiple problems secondary to HIV. He has severe failure-to-thrive. He has had recurrent infections. He has failed to gain milestones, can�t walk or talk. He is often uncomfortable and in great discomfort without a clear etiology for his pain. This child has multiple problems secondary to HIV. He has severe failure-to-thrive. He has had recurrent infections. He has failed to gain milestones, can�t walk or talk. He is often uncomfortable and in great discomfort without a clear etiology for his pain.

8. 8 11 year old with Varicella Zoster This is an eleven year old with severe advanced HIV and a history of previous PCP and encephalopathy. This is an eleven year old with severe advanced HIV and a history of previous PCP and encephalopathy.

9. 9 Background: HIV Disease in Children (con�t) HIV during infancy = primary infection Acquisition of HIV can occur in utero Intrapartum postnatally through breast feeding Very high viral load; peak at 6-12 weeks of life Maturing/developing immune system of the newborn Unlike adults, infection in infants can occur at three time points as reviewed earlier. Timing of transmission doesn�t necessarily affect disease progression. One can consider pediatric infection during infancy to be a primary infection as most have very recent exposure. Viral loads during the first year of life are very high. They are often undetectable or at low levels at birth, rise quickly during the first weeks of life and peak at 6-12 weeks. Additionally, this infection takes place in the context of an immature immune system. Infants are relatively immunocompromised and generally develop immune response during the first months/year of life. Timing of infection was mentioned during the module on the care of the exposed infant. It may require reiteration in this section. In utero infection is generally defined as positive virology within 48 hours of birth. Intrapartum is usually defined as negative at birth (within 48 hours), but subsequently virology positive. Differentiating intrapartum from postnatal through breast feeding is difficult especially as it appears that the highest risk of transmission occurs during the earliest period of breast feeding. HIV during infancy can be considered a primary infection as most children are infected immediately prior to, during or after delivery. Compared with adults, HIV RNA viral loads are very high and generally peak during the first 6-12 weeks of life. In general viral loads are relatively low during the first weeks of life, often undetectable particularly in infants with intrapartum infection. They increase rapidly during the first six months of life and then slowly decrease over the next several years in untreated infants. There is no biologic set point equivalent to the adult set point seen with primary infection. It is important to keep in context that, compared with adults, infants have a maturing immune system. They are relatively unprotected against many pathogens and are infected at a time of significant immunologic vulnerability.Unlike adults, infection in infants can occur at three time points as reviewed earlier. Timing of transmission doesn�t necessarily affect disease progression. One can consider pediatric infection during infancy to be a primary infection as most have very recent exposure. Viral loads during the first year of life are very high. They are often undetectable or at low levels at birth, rise quickly during the first weeks of life and peak at 6-12 weeks. Additionally, this infection takes place in the context of an immature immune system. Infants are relatively immunocompromised and generally develop immune response during the first months/year of life. Timing of infection was mentioned during the module on the care of the exposed infant. It may require reiteration in this section. In utero infection is generally defined as positive virology within 48 hours of birth. Intrapartum is usually defined as negative at birth (within 48 hours), but subsequently virology positive. Differentiating intrapartum from postnatal through breast feeding is difficult especially as it appears that the highest risk of transmission occurs during the earliest period of breast feeding. HIV during infancy can be considered a primary infection as most children are infected immediately prior to, during or after delivery. Compared with adults, HIV RNA viral loads are very high and generally peak during the first 6-12 weeks of life. In general viral loads are relatively low during the first weeks of life, often undetectable particularly in infants with intrapartum infection. They increase rapidly during the first six months of life and then slowly decrease over the next several years in untreated infants. There is no biologic set point equivalent to the adult set point seen with primary infection. It is important to keep in context that, compared with adults, infants have a maturing immune system. They are relatively unprotected against many pathogens and are infected at a time of significant immunologic vulnerability.

10. 10 Trainers- the point to make here is that viral load starts low and quickly increase during the first months of life to very high values. This is similar to adults who were recently infected. 80 African children who were infected with HIV-1. The solid line connects the mean values of the individual data points. The vertical bars represent the 95% CI of the means. For children who were infected peripartum/early postnatally HIV-1 RNA viral load was below the cutoff level in the first sample around birth, rose rapidly to 6 log10 copies/ml at day 45 and month 3, then gradually declined by 12 months of age, and then stabilized. Similar pattern was seen for children infected in utero/peripartum: Definitions: In utero � DNA PCR within 48 hours In utero/peripartum � positive within 3 weeks, no early sample at 48 hours. Peripartum/early postnatal � 1 positive DNA PCR at day 45, but negative before Late postnatal though breastfeeding - negative at day 45, then subsequent positive. In an earlier analysis by Abrams, et al, virus load was highly associated with imminent vulnerability to AIDS and death during the first 18 months of lifeTrainers- the point to make here is that viral load starts low and quickly increase during the first months of life to very high values. This is similar to adults who were recently infected. 80 African children who were infected with HIV-1. The solid line connects the mean values of the individual data points. The vertical bars represent the 95% CI of the means. For children who were infected peripartum/early postnatally HIV-1 RNA viral load was below the cutoff level in the first sample around birth, rose rapidly to 6 log10 copies/ml at day 45 and month 3, then gradually declined by 12 months of age, and then stabilized. Similar pattern was seen for children infected in utero/peripartum: Definitions: In utero � DNA PCR within 48 hours In utero/peripartum � positive within 3 weeks, no early sample at 48 hours. Peripartum/early postnatal � 1 positive DNA PCR at day 45, but negative before Late postnatal though breastfeeding - negative at day 45, then subsequent positive. In an earlier analysis by Abrams, et al, virus load was highly associated with imminent vulnerability to AIDS and death during the first 18 months of life

11. 11 Background: HIV Disease in Children (con�t) Multiple factors influence rate of disease progression: Maternal advanced disease Maternal vital status Timing of transmission (peripartum vs. late) Genetic susceptibility Virus characteristics Multiple factors appear to influence the rate of disease progression in children including maternal advanced disease, genetic profile of the child and perhaps the mother, characteristics of the virus (SI vs NSI) and immunologic profile of the child (thymus dysfunction). Additionally, exposure to perinatal ZDV has been associated with more rapid disease progression. And in some studies, infants infected in utero have had worse disease course than those with intrapartum exposure.Multiple factors appear to influence the rate of disease progression in children including maternal advanced disease, genetic profile of the child and perhaps the mother, characteristics of the virus (SI vs NSI) and immunologic profile of the child (thymus dysfunction). Additionally, exposure to perinatal ZDV has been associated with more rapid disease progression. And in some studies, infants infected in utero have had worse disease course than those with intrapartum exposure.

12. 12 Background: HIV Disease in Children (con�t) Also from Newell et al. Please note that mother�s death, mother�s CD4 count < 200, and early acquisition of the virus seem to increase mortality for HIV infected children. Trainers - This is to emphasize that lower maternal CD4+ cell count, and early acquisition of HIV-infection, is associated with worse clinical outcome or �bad events�Also from Newell et al. Please note that mother�s death, mother�s CD4 count < 200, and early acquisition of the virus seem to increase mortality for HIV infected children. Trainers - This is to emphasize that lower maternal CD4+ cell count, and early acquisition of HIV-infection, is associated with worse clinical outcome or �bad events�

13. 13 Background: HIV Disease in Children (con�t) Likelihood of disease progression is associated with child�s: CD4 count HIV-1 RNA copy number When looking at a child with HIV infection, CD4 and HIV RNA appear to be the best predictors of the likelihood of disease progression presently or in the near future. When looking at a child with HIV infection, CD4 and HIV RNA appear to be the best predictors of the likelihood of disease progression presently or in the near future.

14. 14 Likelihood of Developing AIDS Within 12 MonthsBy Age and CD4+ Percentage in HIV-Infected Children Receiving No Therapy or Zidovudine Monotherapy The prognostic value of CD4+ T cell percentage and HIV RNA copy number was assessed in a large individual patient meta-analysis that incorporated clinical and laboratory data from 17 pediatric studies and included 3,941 HIV-infected children receiving either no therapy or only zidovudine monotherapy. The analysis looked at the short-term (12 month) risk of developing AIDS or death in a population of infected children receiving no therapy or only zidovudine monotherapy, based on the child�s age and selected values of CD4+ T cell percent and HIV RNA copy number at baseline. This figure depicts age-associated one-year risk for developing AIDS as a function of CD4+ cell percentage. The one-year risk of AIDS is <10% for children over age one year who have CD4+ cell percentage >25%. However, infants during the first year of life experience proportionately higher risks. For example, comparing a one year old child with CD4+ T cell percentage of 25% to a five year old child with the same CD4+ T cell percentage, there is an approximate 4-fold increase in the risk of AIDS from 3.1% in the 5 year old to 12.8% in the one year old. However, all age groups demonstrate rapid increases in risk as CD4+ cell percentage decreases below 15-20%. The prognostic value of CD4+ T cell percentage and HIV RNA copy number was assessed in a large individual patient meta-analysis that incorporated clinical and laboratory data from 17 pediatric studies and included 3,941 HIV-infected children receiving either no therapy or only zidovudine monotherapy. The analysis looked at the short-term (12 month) risk of developing AIDS or death in a population of infected children receiving no therapy or only zidovudine monotherapy, based on the child�s age and selected values of CD4+ T cell percent and HIV RNA copy number at baseline. This figure depicts age-associated one-year risk for developing AIDS as a function of CD4+ cell percentage. The one-year risk of AIDS is <10% for children over age one year who have CD4+ cell percentage >25%. However, infants during the first year of life experience proportionately higher risks. For example, comparing a one year old child with CD4+ T cell percentage of 25% to a five year old child with the same CD4+ T cell percentage, there is an approximate 4-fold increase in the risk of AIDS from 3.1% in the 5 year old to 12.8% in the one year old. However, all age groups demonstrate rapid increases in risk as CD4+ cell percentage decreases below 15-20%.

15. 15 Likelihood of Developing AIDS Within 12 MonthsBy Age and HIV-1 RNA Log10 Copy Number in HIV-Infected Children Receiving No Therapy or Zidovudine Monotherapy This is the same analysis by Dunn and colleagues in the HIV Pediatric Prognostic Markers Collaborative Study. Analyses were performed for age-associated risk in the context of plasma RNA levels. The risk of clinical progression to AIDS dramatically increases when HIV RNA exceeds 100,000 copies (5.0 log10 copies)/mL; at lower values, only older children show much variation in risk However, the relationship between plasma virus and risk approached a more linear association than for CD4+ percentage, resulting in more difficulty in assigning risk thresholds. At any given level of HIV RNA, infants under age 1 year were at higher risk of progression than older children, although these differences were less striking than observed for the CD4+ percentage data. This is the same analysis by Dunn and colleagues in the HIV Pediatric Prognostic Markers Collaborative Study. Analyses were performed for age-associated risk in the context of plasma RNA levels. The risk of clinical progression to AIDS dramatically increases when HIV RNA exceeds 100,000 copies (5.0 log10 copies)/mL; at lower values, only older children show much variation in risk However, the relationship between plasma virus and risk approached a more linear association than for CD4+ percentage, resulting in more difficulty in assigning risk thresholds. At any given level of HIV RNA, infants under age 1 year were at higher risk of progression than older children, although these differences were less striking than observed for the CD4+ percentage data.

16. 16 Maximize health & prevent disease progression By providing: HIV Primary Care Frequent Monitoring OI prophylaxis Nutritional Assessment & Management Management of Disease Manifestations Psychosocial Support ARV Treatment Family-centered care Multidisciplinary Team Approach How Will We Meet the Goals for Care ?

17. 17 History (past, interim, parental concerns) Nutrition Evaluation Developmental assessment Physical Examination Laboratory Evaluation Staging/Classification OI Prophylaxis ARV Eligibility Assessment & Plan Components of Routine Care for the HIV-Infected Child The components of care for the HIV-infected child parallel those of the exposed baby with some exceptions. Rather than focusing on surveillance for disease, we are being attentive to evidence of disease progression in the infected child. Children will also be categorized by level of illness at each visit, monitored with CD4 counts and assessed for ARV eligibility. We will only highlight the aspects of care that differ from those of the exposed baby. The components of care for the HIV-infected child parallel those of the exposed baby with some exceptions. Rather than focusing on surveillance for disease, we are being attentive to evidence of disease progression in the infected child. Children will also be categorized by level of illness at each visit, monitored with CD4 counts and assessed for ARV eligibility. We will only highlight the aspects of care that differ from those of the exposed baby.

18. 18 Why is History Important? Develop clinical profile for older children entering the program Identify changes in health status since last visit Identify changes in home setting that may affect child�s health

19. 19 Past Medical History Newly enrolled older children HIV-related illnesses Hospitalizations Medications (ARV, OI prophylaxis) The majority of children entering the program are likely to be infants born to newly enrolled moms. However, older siblings and other family members will also enter the program as well. These children, by definition, will be HIV-infected. It is essential to collect as much information as possible about their disease course to determine their level of illness and disability. Also, children with established disease may require a more comprehensive evaluation upon entry into the program compared with those known since birth. For example, the following case.The majority of children entering the program are likely to be infants born to newly enrolled moms. However, older siblings and other family members will also enter the program as well. These children, by definition, will be HIV-infected. It is essential to collect as much information as possible about their disease course to determine their level of illness and disability. Also, children with established disease may require a more comprehensive evaluation upon entry into the program compared with those known since birth. For example, the following case.

20. 20 Lymphoid Interstitial Pneumonitis For example, this six year old child entered care at age 4. He had a history of chronic cough and recurrent upper respiratory infections. He was noted to markedly clubbed. On x-ray, he was diagnosed with LIP, lymphoid interstitial pneumonitis. For example, this six year old child entered care at age 4. He had a history of chronic cough and recurrent upper respiratory infections. He was noted to markedly clubbed. On x-ray, he was diagnosed with LIP, lymphoid interstitial pneumonitis.

21. 21 6 year old with severe distal clubbing secondary to chronic pneumonia These are changes seen in the distal extremities in chronic conditions often associated with low oxygen to the lungs and/or liver disease.These are changes seen in the distal extremities in chronic conditions often associated with low oxygen to the lungs and/or liver disease.

22. 22 Interim History New health problems Signs & symptoms checklist HIV-related illness Medications Dosing Frequency Adherence The interim history is often more complicated in the infected child compared with the uninfected child. Many child will have episodes of recurrent infection and nonspecific illnesses often requiring medical management. These symptoms should be recorded. All diagnoses should also be elicited and noted. This may be somewhat difficult if the child has been seen by another physician or care provider who does not participate in the program. This is an opportunity to emphasize the need for communication within the health system and the need for the parent to use the ICAP program for all of the child�s medical problems.. The other important part of the history is the report of medication adherence. Children are likely to be receiving a number of medications including prophylaxis, ARV, vitamins and treatments for intercurrent illnesses. Providers should routinely ask about adherence to medication and barriers to adherence. This will be reviewed extensively elsewhere in the training, but it should be part of the routine history each time the child is evaluated. Focus on particular barriers that may be encountered by the child compared with the adult � palatability. Also, remember that most children will also be taking meds other than ARV.The interim history is often more complicated in the infected child compared with the uninfected child. Many child will have episodes of recurrent infection and nonspecific illnesses often requiring medical management. These symptoms should be recorded. All diagnoses should also be elicited and noted. This may be somewhat difficult if the child has been seen by another physician or care provider who does not participate in the program. This is an opportunity to emphasize the need for communication within the health system and the need for the parent to use the ICAP program for all of the child�s medical problems.. The other important part of the history is the report of medication adherence. Children are likely to be receiving a number of medications including prophylaxis, ARV, vitamins and treatments for intercurrent illnesses. Providers should routinely ask about adherence to medication and barriers to adherence. This will be reviewed extensively elsewhere in the training, but it should be part of the routine history each time the child is evaluated. Focus on particular barriers that may be encountered by the child compared with the adult � palatability. Also, remember that most children will also be taking meds other than ARV.


24. 24 Routine Nutritional Evaluation At every visit: Nutrition and feeding history Weigh, measure and examine child Use growth curves to monitor growth pattern Any child who is not thriving needs extensive nutritional history Nutrition history: Some people use a 3 day written diet diary instead of the recall. This is usually reserved for children who have problems. A dietary recall can also help identify those individuals who are making poor food choices, and can serve as an opportunity to discuss more healthy options Trainer- You can ask the participants to construct a list of questions to ask sores in the mouth. pain or difficulty in chewing or swallowing. what the stool looks like, color and consistency, smell and amount. Are they greasy?- (malbsorption) Ask about food availability and choices Nutrition history: Some people use a 3 day written diet diary instead of the recall. This is usually reserved for children who have problems. A dietary recall can also help identify those individuals who are making poor food choices, and can serve as an opportunity to discuss more healthy options Trainer- You can ask the participants to construct a list of questions to ask sores in the mouth. pain or difficulty in chewing or swallowing. what the stool looks like, color and consistency, smell and amount. Are they greasy?- (malbsorption) Ask about food availability and choices

25. 25 Why Use Growth Curves? Easy and systematic way to follow changes in growth over time for an individual child Weight, height and head circumference should be plotted at regular intervals Monthly for HIV infected infants Quarterly for older HIV-infected children

26. 26 Weight-for-Age, Height-for-AgeBoy & Girl Growth Charts As an example, here are the weight-for-age and length-for-age charts As an example, here are the weight-for-age and length-for-age charts

27. 27 How to Use and Interpret a Growth Curve Measure and weigh child using same methodology at each visit Using age and sex appropriate charts, plot measurement (weight, height, head circumference) on the vertical against age on the horizontal axis. Compare growth point with previous points Assess growth percentile There are different charts for younger and older children (< and > 36 months) The percentiles speak to the general population. There are different charts for younger and older children (< and > 36 months) The percentiles speak to the general population.

28. 28 Weight for Height This child weighs 7.2kg at 6 months of age. She is in the 50% for weight. That means that 50% of the children of the same age in the community where the growth data were collected are heavier than this child. This child weighs 7.2kg at 6 months of age. She is in the 50% for weight. That means that 50% of the children of the same age in the community where the growth data were collected are heavier than this child.

29. 29 Failure-to-Thrive The failure to sustain a normal velocity of weight and/or height growth during the first 3 years of life Can be quantified using growth curves May be indication: Of HIV disease in exposed infant For ARV treatment in infected infant/child Of ARV treatment failure in child on therapy Trainers-Remember to point out that this may be a reason to begin ARV�s since this is included in the ICAP criteria for starting ARV. Insure that HIV status is confirmed and that no easily treatable diagnoses are the reason. It will be important to try to assess the reason for this failure to grow: intake, vs absorption or losses.Trainers-Remember to point out that this may be a reason to begin ARV�s since this is included in the ICAP criteria for starting ARV. Insure that HIV status is confirmed and that no easily treatable diagnoses are the reason. It will be important to try to assess the reason for this failure to grow: intake, vs absorption or losses.


31. 31 Developmental Assessment At every visit Ask about the infant�s development Simple questions should focus on four critical developmental domains; cognitive, motor, language, and social. This can be done through observation during the physical exam or asking the parent The developmental checklist may be helpful. Delayed acquisition of developmental milestones or loss of previously acquired skills can be the first sign of HIV encephalopathy.


33. 33 Physical Examination At every visit Perform careful physical examination Initial exam should be comprehensive including examination of all organ systems Identify any HIV related physical findings; thrush, lymphadenopathy, organomegaly, dermatitis,encepatholpathy etc Subsequent exams can be guided by findings on the symptom/sign checklist


35. 35 Which Laboratory Tests Need To Be Done? Complete Blood Count CD4 number and percent As noted earlier, immune status is predictive of disease progression in HIV-infected infants and children. ICAP will support monitoring of CD4 at 6 month intervals. CD4 is also used to classify children using the new WHO criteria. And, as shown earlier, it is predictive or disease progression. ICAP does not to support the use of viral load for assessing and monitoring patients enrolled in the program. As noted earlier, immune status is predictive of disease progression in HIV-infected infants and children. ICAP will support monitoring of CD4 at 6 month intervals. CD4 is also used to classify children using the new WHO criteria. And, as shown earlier, it is predictive or disease progression. ICAP does not to support the use of viral load for assessing and monitoring patients enrolled in the program.

36. 36 Selected Centiles for CD4 Count by Age, Europe CD4 counts and percentages in healthy infants are quite high at birth and during the first year of life. There is a natural decline in the CD4 number and percent over the first years of life. Therefore, all measures of CD4 in children must be taken in the context of the normal range. T Lymphocyte subsets were measured in 459 uninfected, HIV-exposed children in Europe. CD4, CD8 and ALC rise after birth, peak at 6-9 months and then decline towards adult values. Trainers- point out that the arrow shows the CD4 count on the 50th percentile at 12months which is 2800.CD4 counts and percentages in healthy infants are quite high at birth and during the first year of life. There is a natural decline in the CD4 number and percent over the first years of life. Therefore, all measures of CD4 in children must be taken in the context of the normal range. T Lymphocyte subsets were measured in 459 uninfected, HIV-exposed children in Europe. CD4, CD8 and ALC rise after birth, peak at 6-9 months and then decline towards adult values. Trainers- point out that the arrow shows the CD4 count on the 50th percentile at 12months which is 2800.

37. 37 Selected Centiles for CD4% by Age, Europe Trainers- emphasize that CD4 percent also declines steadily from birth. So, at age 3 years, the 50th percentile for CD% is 40%Trainers- emphasize that CD4 percent also declines steadily from birth. So, at age 3 years, the 50th percentile for CD% is 40%

38. 38 NEW WHO Classification of HIV Associated Immunodeficiency This is the newly proposed WHO immunologic classification of HIV associated immunodeficiency. Measurement of the CD4 percentage is more valuable in children < 5 years since this is subject to less variation.This is the newly proposed WHO immunologic classification of HIV associated immunodeficiency. Measurement of the CD4 percentage is more valuable in children < 5 years since this is subject to less variation.


40. 40 Why is Clinical Staging Important? Assess disease severity

41. 41 Clinical Staging of Pediatric HIV/AIDS Old WHO clinical stages; I-III Doesn�t capture many disease manifestations Doesn�t include measures of immunologic status New WHO clinical and immunological staging Four clinical disease categories; asymptomatic, mild, advance and severe Immunologic staging by severity uses CD4 percent/count Age adjusted categories; < 11mo, 12-35 mo, 36-59 mo and >5 yrs WHO has developed a 4 stage system for pediatrics in their new guidelines to be consistent with the adult guidelines. Final revision will be put out in 2005/2006. WHO has developed a 4 stage system for pediatrics in their new guidelines to be consistent with the adult guidelines. Final revision will be put out in 2005/2006.

42. 42 New WHO classification of HIV associated clinical disease This is the new WHO proposed pediatric clinical staging for HIV.This is the new WHO proposed pediatric clinical staging for HIV.

43. 43 New WHO staging < 15 Years Old

44. 44 New WHO Staging < 15 Years Old (con�t)

45. 45 New WHO Staging < 15 Years Old (con�t)

46. 46 Elias Elias is 12 months old with HIV infection. He has had no major illnesses or hospitalizations. He has bilateral cervical, inguinal and axillary adenopathy, persistent oral and genital candidiasis, and is being treated for his 4th episode of otitis media. His growth is at the 10th percentile. What WHO Stage is Elias?

47. 47

48. 48 New WHO Clinical Staging System for Elias Stage I Asymptomatic, PGL Stage II HSM, Papular Pruritic Eruptions, Extensive HPV, Extensive Molluscum, Fungal Nail Infections, Recurrent Oral Ulcers, Parotid Enlargement, Zoster, Recurrent or Chronic URTIs Stage III Moderate unexplained/unresponsive malnutrition, unexplained persistent diarrhea or fever, Oral Candidiasis, Pulmonary TB, Unexplained Anemia/Neutropenia/ Thrombocytopenia, Severe Recurrent Bacterial Pneumonia Stage IV Severe wasting, PCP, Extrapulmonary TB, severe bacterial infections (Pyomyositis, Empyema, Osteomyelitis, Meningitis) KS, CNS toxoplasmosis, HIV Encephalopathy, Cryptosporidiosis, Isosporiasis, cerebral or B-cell Lymphoma, Candida of Esophagus, Trachea, Bronchi, Lung Elias meets criteria for stage 3 by new WHO criteriaElias meets criteria for stage 3 by new WHO criteria

49. 49 WHO Staging for Elias New WHO staging Stage III (Advanced)

50. 50 Selam Selam is 7 years old with HIV infection. She�s been hospitalized twice, once with bad pneumonia and once with shingles. She has had diarrhea off and on for 4 months. She is less than the 5th percentile for weight, but no old data is available for comparison. On examination she is thin and small with no other abnormalities noted. How would you stage her by WHO criteria? Trainers-ask them to stage by the system they are using at the site. Trainers-ask them to stage by the system they are using at the site.

51. 51 New WHO Clinical Staging System for Selam Stage I Asymptomatic, PGL Stage II HSM, Papular Pruritic Eruptions, Extensive HPV, Extensive Molluscum, Fungal Nail Infections, Recurrent Oral Ulcers, Parotid Enlargement, Zoster, Recurrent or Chronic URTIs Stage III Moderate unexplained/unresponsive malnutrition, unexplained persistent diarrhea or fever, Oral Candidiasis, Pulmonary TB, Unexplained Anemia/Neutropenia/ Thrombocytopenia, Severe Recurrent Bacterial Pneumonia Stage IV Severe wasting, PCP, Extrapulmonary TB, severe bacterial infections (Pyomyositis, Empyema, Osteomyelitis, Meningitis) KS, CNS toxoplasmosis, HIV Encephalopathy, Cryptosporidiosis, Isosporiasis, cerebral or B-cell Lymphoma, Candida of esophagus, trachea, bronchi or lung Selam would meet criteria for new WHO stage III. Since we do not have old growth data, we can�t assess if she has severe wasting or failure-to-thrive.Selam would meet criteria for new WHO stage III. Since we do not have old growth data, we can�t assess if she has severe wasting or failure-to-thrive.

52. 52 WHO Staging for Selam New WHO staging Stage III (Advanced)

53. 53 Clinical staging should be performed at every visit Trainers: Remind participants that staging cannot regress � e.g., a child who is ever Stage 4 will always be Stage 4. In this case, formal clinical staging is not required at every visit (since it will not change) � but careful clinical assessment is, clearly, required at every visit. Trainers: Remind participants that staging cannot regress � e.g., a child who is ever Stage 4 will always be Stage 4. In this case, formal clinical staging is not required at every visit (since it will not change) � but careful clinical assessment is, clearly, required at every visit.


55. 55 Why is OI Prophylaxis Important? Prevent disease progression Prevent morbidity and mortality

56. 56 Prophylaxis with cotrimoxazole

57. 57 PCP Cases in Children, NYC This graph shows the Cumulative AIDS-defining Conditions among 2,172 person with AIDS born to HIV-infected mothers reported to NYC DOH, by year of diagnosis. Between 1987 and 1993 there were 60-80 cases of PCP in children yearly, primarily occurring in infants during the first 2-3 months of life. PHS guidelines published in 1995 recommended routine prophylaxis of all HIV-exposed infants. The increased recognition of HIV-exposed children, widespread use of bactrim in exposed infants and the decreased rate of transmission has resulted in a significant decline in PCP cases. Only 8 cases were reported in 1998 in NYC. Fewer than 10 cases have been reported annually since that time. None were reported in 2002. [ FYI -The 39 AIDS defining conditions diagnosed in 2002: 29 CD4 <200, 3 esophageal candidiasis, 2 MAC, 1 HIV encephalopathy, 1 brain lymphoma, 1 PML, 1 extrapulmonary TB, 1 wasting syndrome. NO PCP. ] This graph shows the Cumulative AIDS-defining Conditions among 2,172 person with AIDS born to HIV-infected mothers reported to NYC DOH, by year of diagnosis. Between 1987 and 1993 there were 60-80 cases of PCP in children yearly, primarily occurring in infants during the first 2-3 months of life. PHS guidelines published in 1995 recommended routine prophylaxis of all HIV-exposed infants. The increased recognition of HIV-exposed children, widespread use of bactrim in exposed infants and the decreased rate of transmission has resulted in a significant decline in PCP cases. Only 8 cases were reported in 1998 in NYC. Fewer than 10 cases have been reported annually since that time. None were reported in 2002. [ FYI -The 39 AIDS defining conditions diagnosed in 2002: 29 CD4 <200, 3 esophageal candidiasis, 2 MAC, 1 HIV encephalopathy, 1 brain lymphoma, 1 PML, 1 extrapulmonary TB, 1 wasting syndrome. NO PCP. ]

58. 58 Cotrimoxazole prophylaxis in Zambian Children The CHAP trial was a randomized placebo-controlled trial of 541 HIV infected children in Zambia which showed that the use of CTX decreased mortality by 43 %, decreased hospitalizations by 23 % and did not result in any increase adverse drug effects. The graph shows mortality in the cotrimoxazole group and the placebo group, at a median follow-up of 19 months, mortality in the CTX group was 28% compared to 42% in the placebo group. The CHAP trial was a randomized placebo-controlled trial of 541 HIV infected children in Zambia which showed that the use of CTX decreased mortality by 43 %, decreased hospitalizations by 23 % and did not result in any increase adverse drug effects. The graph shows mortality in the cotrimoxazole group and the placebo group, at a median follow-up of 19 months, mortality in the CTX group was 28% compared to 42% in the placebo group.

59. 59 ICAP Guidelines for Cotrimoxazole Prophylaxis All HIV-infected infants < 12 months of age, and All HIV-infected infants and children with: Clinical features suggestive of HIV/AIDS and /or Prior PCP pneumonia and/or Evidence of immune dysfunction including: CD4 percent < 15% and or In children 1-5 years CD4count < 500 In children 6 + years CD4count <200 Trainers- note ICAP guidelines for cotrimoxazole prophylaxis will be revised to be consistent with the new WHO guidelines once these are published. Trainers- note ICAP guidelines for cotrimoxazole prophylaxis will be revised to be consistent with the new WHO guidelines once these are published.

60. 60 Prophylaxis Regimens Cotrimoxazole Suspension Recommended dosing is based on 4mg/kg of the trimethoprim portion once each day Use weight band chart for dosing Toxicities* include rash fever bone marrow suppression (neutropenia) *infrequent in infants Missed dose can be given next day. ICAP recommends once daily dosing Missed dose can be given next day. ICAP recommends once daily dosing

61. 61 Cotrimoxazole Prophylaxis for Infants and Children Dosing Recommendations: 4 mg/kg per day

62. 62 Tuberculosis in Infants & Children

63. 63 Background: Tuberculosis Most common opportunistic infection among HIV-infected patients in Africa, SE Asia Leading cause of AIDS-related deaths worldwide 1/3 of all AIDS-related deaths are due to TB Can be prevented by: Treatment of latent TB infection (preventive therapy) Use of antiretroviral therapy Among persons with advanced HIV, antiretroviral therapy decreases the rate of active TB disease The point of these slides is to highlight the special issues around children and to suggest using TST screening for HIV-infected children.The point of these slides is to highlight the special issues around children and to suggest using TST screening for HIV-infected children.

64. 64 Special Issues for Children High rates of co-infection (HIV and TB) Zambia: 69% hospitalized with clinical TB test HIV+ Cote d�Ivoire: 23.4% Johannesburg: 42% Higher risk of progression from latent to TB disease compared with adults Associated with severe complications Meningitis Miliary TB Due primarily to diagnostic problems, the degree of co-infection is not well documented. However, it is certain that the rate is quite high. Due primarily to diagnostic problems, the degree of co-infection is not well documented. However, it is certain that the rate is quite high.

65. 65 Special Issues for Children (con�t) Difficult to diagnose Limited yield of diagnostic procedures: poor sputum production low yield of gastric aspiration sputum induction and bronchoscopy not routinely used Multiple varied clinical manifestations Overlap with other HIV disease manifestations Impact of BCG vaccination on Tuberculin Skin Testing (TST) Limited sensitivity of TST in HIV-infected children M. TB is difficult to diagnose in children. There are multiple reasons as noted above. There is often a combination of despair and laissez-faire re: M. TB. It is so common that providers are often unwilling to make special efforts to diagnose and treat. In this section we are try to build an argument for use of TST to diagnose latent infection in HIV-infected children.M. TB is difficult to diagnose in children. There are multiple reasons as noted above. There is often a combination of despair and laissez-faire re: M. TB. It is so common that providers are often unwilling to make special efforts to diagnose and treat. In this section we are try to build an argument for use of TST to diagnose latent infection in HIV-infected children.

66. 66 Impact of BCG Vaccination WHO estimates 79% of population vaccinated Given at birth or during newborn period Thought to prevent severe TB complications in young children, i.e. disseminated disease and meningitis Can result in reactive TST No reliable method to distinguish �true-positive� TST caused by M. tuberculosis infection from �false-positive� TST caused by BCG vaccination

67. 67 Rates of Developing Active TB among HIV-Infected Persons in Africa by TST status Trainers-this slide is to emphasize that TST identifies individuals at higher risk for development of active TB. This is in the context of settings in which BCG is generally universally given.Trainers-this slide is to emphasize that TST identifies individuals at higher risk for development of active TB. This is in the context of settings in which BCG is generally universally given.

68. 68 TST Survey in Children, Botswana Trainers-This study suggests that the impact of BCG on TST results is not as significant as most believe. TST was planted and read in 783 children, aged 3-60 months in Botswana. Despite BCG, the vast majority were TST-negative. Prevalence of TST positivity related to: Contact with person with active TB disease Larger number of TB contacts Children with BCG vaccine twice as likely to have TST =5mm Prevalence of TST positivity (=10mm) not associated with BCG scar.Trainers-This study suggests that the impact of BCG on TST results is not as significant as most believe. TST was planted and read in 783 children, aged 3-60 months in Botswana. Despite BCG, the vast majority were TST-negative. Prevalence of TST positivity related to: Contact with person with active TB disease Larger number of TB contacts Children with BCG vaccine twice as likely to have TST =5mm Prevalence of TST positivity (=10mm) not associated with BCG scar.

69. 69 TST Reaction Size 6 Months after BCG, Peru In this study in Peru, 6 months after vaccination, 99% of children exhibited a BCG scar. Mean TST reaction size 6 months after vaccination was 2.9mm +/- 0.3mm. Only 3 children had TST > 10 mm and all had TB contact at home. So, once again, TST contact is the primary factor related to TST positivity.In this study in Peru, 6 months after vaccination, 99% of children exhibited a BCG scar. Mean TST reaction size 6 months after vaccination was 2.9mm +/- 0.3mm. Only 3 children had TST > 10 mm and all had TB contact at home. So, once again, TST contact is the primary factor related to TST positivity.

70. 70 Conclusions � Impact of BCG In a setting of universal BCG Positive TST is strongly associated with TB exposure TST reaction is not associated with presence of BCG scar Interpret TST the same whether BCG has been given or not

71. 71 Special Issues for Children (con�t) Difficult to diagnose Limited yield of diagnostic procedures: poor sputum production low yield of gastric aspiration sputum induction and bronchoscopy not routinely used Multiple varied clinical manifestations Overlap with other HIV disease manifestations Impact of BCG vaccination on Tuberculin Skin Testing (TST) Limited sensitivity of TST in HIV-infected children M. TB is difficult to diagnose in children. There are multiple reasons as noted above. There is often a combination of despair and laissez-faire re: M. TB. It is so common that providers are often unwilling to make special efforts to diagnose and treat. In this section we are try to build an argument for use of TST to diagnose latent infection in HIV-infected children.M. TB is difficult to diagnose in children. There are multiple reasons as noted above. There is often a combination of despair and laissez-faire re: M. TB. It is so common that providers are often unwilling to make special efforts to diagnose and treat. In this section we are try to build an argument for use of TST to diagnose latent infection in HIV-infected children.

72. 72 TST Testing in HIV-Infected Children with Tuberculosis Disease N %TST+ 4 US reports 22 >10mm 21% South Africa (I) 11 >15mm 55% Ethiopia 58 >10mm 21% South Africa (II) 52 >5mm 17% While TST positivity may be related to BCG, many children with HIV and TB will test TST negative secondary to immune suppression. This is a compilation of studies of TST in children with HIV & tuberculosis. All children were diagnosed with TB disease. No clear predictors of TST+ Positive TST was unrelated to BCG, CD4, nutritional status Each study defined TST positivity differently as noted above. While TST positivity may be related to BCG, many children with HIV and TB will test TST negative secondary to immune suppression. This is a compilation of studies of TST in children with HIV & tuberculosis. All children were diagnosed with TB disease. No clear predictors of TST+ Positive TST was unrelated to BCG, CD4, nutritional status Each study defined TST positivity differently as noted above.

73. 73 Perform routine surveillance to identify HIV-infected children with TB infection Ensure appropriate management of TB exposure, infection and disease Prevent disease progression for those with latent infection (LTBI) INH protective efficacy is ~ 90% in adherent children without known HIV infection Identify and treat active TB disease - EARLY Why Screen Children for Tuberculosis? Trainers-We want to build the argument that there is value to TST testing despite (1) BCG (false positive); (2) poor immune response in infected children (false negative)Trainers-We want to build the argument that there is value to TST testing despite (1) BCG (false positive); (2) poor immune response in infected children (false negative)

74. 74 Isoniazid (INH) reduces active TB rate by 60% among patients with positive TST (> 5 mm) Trainers- We want to emphasize that the use of INH in HIV-infected individuals with +TST significantly reduces the rate of TB. Trainers- We want to emphasize that the use of INH in HIV-infected individuals with +TST significantly reduces the rate of TB.

75. 75 Tuberculosis Screening Targeted history at each evaluation Symptom checklist Inquire about household contacts with TB In order to establish risk to infant/child In order to make sure those with TB in the household are appropriately treated Tuberculin Skin Testing (TST) Children with positive symptom screen or clinical findings consistent with TB Household contacts of adult with TB disease Annually for all children with HIV infection beginning at 1 year of age TST has two purposes in children: To identify children with mtb infection To diagnose MTB disease in conjunction with other findings, radiologic and clinicalTST has two purposes in children: To identify children with mtb infection To diagnose MTB disease in conjunction with other findings, radiologic and clinical

76. 76 4 year old with history of contact, PPD positive, and no symptoms. Abnormalities were identified on routine chest film after history of contact and +TST. Hilar adenopathy and infiltrate/atelectasis in the left upper lobe. 4 year old with history of contact, PPD positive, and no symptoms. Abnormalities were identified on routine chest film after history of contact and +TST. Hilar adenopathy and infiltrate/atelectasis in the left upper lobe.

77. 77 TST Placement and Reading Intradermal placement of .1 ml 5TU PPD Read 2-3 days after placing test by trained worker or health care provider Feel for induration Color change without induration is not included in measurement Use a ruler or calipers Document exact size (mm) of reaction = 5 mm induration considered positive in an HIV-infected child Trainers-Stress the importance of reading by trained professional. Parent reading is not adequate. 10mm considered �positive� in healthy children.Trainers-Stress the importance of reading by trained professional. Parent reading is not adequate. 10mm considered �positive� in healthy children.

78. 78 Positive TST (>5mm) Exclude active TB as per local and national guidelines Symptom checklist and physical exam Chest X-ray when available For TB disease Follow local and national guidelines For LBTI INH (10-15mg/kg, maximum 300 mg) daily for 6 months Vitamin B6 generally not given to children unless: severe malnutrition � breast feeding infant AIDS � pregnant adolescent ICAP recommends treating all children < 3 years of age in household with adult with TB disease. B6 levels are generally adequate in routine multivitamins.ICAP recommends treating all children < 3 years of age in household with adult with TB disease. B6 levels are generally adequate in routine multivitamins.

79. 79 Summary: TB Screening Perform routine surveillance to identify HIV-infected children with TB infection Ensure INH treatment for children found to have latent TB infection Prevent disease progression for those with latent infection (LTBI) Early identification and treatment of active TB disease Always inquire about any active TB household contacts Ensure adherence with treatment for TB disease (preferably through DOT) and adherence with treatment of LTBI


81. 81 New WHO Criteria for ART Eligibility WHO has updated guidelines on ARV eligibility. This will be discussed in further detail in the ARV lecture.WHO has updated guidelines on ARV eligibility. This will be discussed in further detail in the ARV lecture.

82. 82 NEW WHO Recommendations for Initiating ART in Infants and Children The new WHO recommendations on initiating ART in children divides them into two groups: Less than 18 months and Older than 18 months. In children < 18 months of age: ART should be initiated in children with WHO stage III and IV irrespective of CD4 value In children with Stage II disease treat if CD4 percentage or count OR total lymphocyte count is at or below threshold value to initiate ART. In children with Stage I Disease treat if CD4 count or percentage is at or below threshold value to initiate ART. If CD4 is not available do not treat . In children > 18months: Initiate ART in all children with stage IV irrespective of CD4 In children with Stage III treat all if there is no CD4 available. Where CD4 is available; for children with TB, LIP, OHL, thrombocytopenia ART initiation may be deferred if the CD4 is above the threshold value to initiate ART. In children with Stage II disease treat if CD4 percentage or count OR total lymphocyte count is at or below threshold value to initiate ART. In children with Stage I Disease treat if CD4 count or percentage is at or below threshold value to initiate ART. If CD4 is not available do not treat . The next table shows the age related immunologic markers for initiating ART.The new WHO recommendations on initiating ART in children divides them into two groups: Less than 18 months and Older than 18 months. In children < 18 months of age: ART should be initiated in children with WHO stage III and IV irrespective of CD4 value In children with Stage II disease treat if CD4 percentage or count OR total lymphocyte count is at or below threshold value to initiate ART. In children with Stage I Disease treat if CD4 count or percentage is at or below threshold value to initiate ART. If CD4 is not available do not treat . In children > 18months: Initiate ART in all children with stage IV irrespective of CD4 In children with Stage III treat all if there is no CD4 available. Where CD4 is available; for children with TB, LIP, OHL, thrombocytopenia ART initiation may be deferred if the CD4 is above the threshold value to initiate ART. In children with Stage II disease treat if CD4 percentage or count OR total lymphocyte count is at or below threshold value to initiate ART. In children with Stage I Disease treat if CD4 count or percentage is at or below threshold value to initiate ART. If CD4 is not available do not treat . The next table shows the age related immunologic markers for initiating ART.

83. 83 NEW WHO Recommendations for Initiating ART in Infants and Children According to Age Related Immunologic markers These are the new WHO age related immunological markers for infants and children. These immunological markers supplement clinical staging ART should be initiated at these cut-off levels regardless of clinical stage since a drop of CD4/TLC below these levels significantly increases the risk of mortality. These are the new WHO age related immunological markers for infants and children. These immunological markers supplement clinical staging ART should be initiated at these cut-off levels regardless of clinical stage since a drop of CD4/TLC below these levels significantly increases the risk of mortality.

84. 84 Determining whether a children is eligible for ARV Treatment should be done at every visit. We will review ARV eligibility more extensively during the ARV module. However, by the end of each routine visit with the HIV infected child, the clinician should determine whether the child is eligible for treatment based on clinical criteria and, when labs are available, based on CD4. We will review ARV eligibility more extensively during the ARV module. However, by the end of each routine visit with the HIV infected child, the clinician should determine whether the child is eligible for treatment based on clinical criteria and, when labs are available, based on CD4.


86. 86 Assessment & Plan Synthesize components of evaluation Diagnose and manage complications Order laboratory studies Refer for counseling/support groups Follow-up appointment These are the final stages of the visit, assessing the child and arranging follow-up for routine care as well as acute illness management.These are the final stages of the visit, assessing the child and arranging follow-up for routine care as well as acute illness management.

87. 87 Ages 0-6 months 6-24 months >24 months Symptomatic Asymptomatic Receiving ARV What is the Follow-up Schedule for the HIV-Infected Child?

88. 88 Maximize health & prevent disease progression By providing: HIV Primary Care Frequent Monitoring Growth and Nutritional Assessment Developmental Assessment OI prophylaxis Management of Disease Manifestations Psychosocial Support ARV Treatment/ Adherence Support Family-centered setting Multidisciplinary Team Approach Summary of ICAP Goals for Care

Care of HIV-Infected Infants and Children

Care of HIV-Infected Infants and Children

Presentation Transcript

Disclosure of HIV to Perinatally Infected Children and Adolescents

Diagnosis of HIV in Infants and Children

Scale up of HIV-related prevention, diagnosis, care and treatment for infants and children

Diagnosis of HIV Infection in Infants and Children

FOSTER MOTHERS OF HIV-INFECTED CHILDREN

Providing Care for HIV-Infected Women

Roles of Protease Inhibitors for HIV-infected Children

Adults and Children Newly Infected With HIV in 2008

Reproductive Health and Preconception Care of HIV-Infected Women

DOH Guidelines and HIV infected Health Care Workers

Outcomes of HIV-infected & HIV-exposed children who become LTFU

CHER Trial: Early Antiretroviral Therapy and Mortality Among HIV-Infected Infants

Linking HIV-infected infants to survival

FOSTER MOTHERS OF HIV-INFECTED CHILDREN

HIV/HBV coinfection in HIV-infected children

Providing Dental Care For Infants And Children

5 Benefits of Chiropractic Care for Infants and Children

Skin and Mucosal Lesions in HIV-Infected Children

Common neurological diseases in HIV-infected children

Digestive Tract Diseases in HIV-infected Children

PDF/READ❤ Osteology of Infants And Children

Care of HIV-Infected Infants and Children