Ppediatric hiv june06


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  • If infant negative, repeat tests after 3-6 months. If infant still breastfeeding, wait until 3 months after cessation of breastfeeding to confirm final HIV status.
  • AIDS Surveillance Case Definition (Severe HIV Disease) Case surveillance definition for reporting severe HIV disease only Not for diagnosis or management of individual patients Severe HIV Disease In the absence of CD4 count All clinical stage 3 and 4 disease Where CD4 available Stage 4 disease + any CD4 count CD4<350
  • P. Carinii has been renamed P. jiroveci but the eponym PCP is retained (Emerg Infect Dis 2002;8:891
  • The first regimen must be selected with the aim of suppressing the virus replication to the maximum achievable levels in the shortest time possible. It needs also to have the quality of durability by not inducing resistance early . Its side effects must be tolerable to the patient so that the quality of life is improved.
  • didanosine + abacavir + PI/ritonavir (ddI) (ABC) (LPV/r if NFV used)
  • Ppediatric hiv june06

    1. 1. Management of HIV infected Children KMA Curriculum Module 7 June 2006
    2. 2. Objectives <ul><li>To outline the epidemiology of HIV in children </li></ul><ul><li>To describe various modes of HIV transmission to children. </li></ul><ul><li>To discuss the natural disease progression of HIV in children. </li></ul><ul><li>Outline diagnostic criteria for paediatric HIV – laboratory as well as clinical. </li></ul><ul><li>To impart knowledge on prevention and treatment of common HIV related conditions in HIV infected children </li></ul><ul><li>To describe how and when to provide antiretroviral therapy in children, , including initiation, pre-ART preparation, monitoring, when to change/withdraw ART. </li></ul>
    3. 3. Epidemiology and HIV transmission in Children Unit 1 Management of HIV infected Children
    4. 4. Epidemiology - Kenya <ul><li>1 million live births in Kenya annually </li></ul><ul><li>8% born to HIV infected mothers </li></ul><ul><li>Without PMTCT 30% of these become infected </li></ul><ul><li>About 24,000 neonates acquire HIV annually </li></ul><ul><li>About 12,000 (50%) die within first 2 years </li></ul><ul><li>HIV has had a negative impact on infant survival </li></ul>
    5. 5. Modes of HIV transmission to Children <ul><li>Mother to child transmission – 95% of paediatric infections </li></ul><ul><ul><li>Intrauterine </li></ul></ul><ul><ul><li>During delivery </li></ul></ul><ul><ul><li>During breastfeeding </li></ul></ul>
    6. 6. Mother to Child HIV Transmission 30% babies born to HIV+ women become infected through MTCT 5% intrauterine 10-20% during delivery 10-20% via breastfeeding
    7. 7. Modes of HIV transmission to Children <ul><li>Horizontal transmission - < 5% of paediatric infections </li></ul><ul><ul><li>Sexual transmission </li></ul></ul><ul><ul><li>Transfusion of blood and blood products </li></ul></ul><ul><ul><li>Exposure to other body fluids </li></ul></ul><ul><ul><li>Use of contaminated needles and other skin piercing/cutting instruments (circumcision, uvulectomy). </li></ul></ul>
    8. 8. Natural history of HIV in Children Unit 2: Management of HIV infected Children
    9. 9. Natural history – patterns of disease progression in African children <ul><li>HIV disease progresses at differing rates in children </li></ul><ul><li>Rapid progressors (25 – 30%): </li></ul><ul><ul><li>Develop AIDS and die within 1-2 years. </li></ul></ul><ul><ul><li>Disease acquired in utero or perinatally. </li></ul></ul><ul><li>Intermediate progressors (50 – 60%): </li></ul><ul><ul><li>Children who develop symptoms early in life. </li></ul></ul><ul><ul><li>Deteriorate and die by 3 to 5 years. </li></ul></ul><ul><li>Slow progressors (5 – 25%): </li></ul><ul><ul><li>Long-term survivors who live beyond 8 years of age. </li></ul></ul>
    10. 10. Natural history – patterns of disease progression in African children <ul><li>Slow Progressors </li></ul><ul><ul><li>Low viral loads at birth </li></ul></ul><ul><ul><li>Stable CD4 counts for 2-10 years </li></ul></ul><ul><ul><li>Growth stunting </li></ul></ul><ul><ul><li>Initial year(s) well, opportunistic infections as disease progresses </li></ul></ul><ul><ul><li>Encephalopathy rare </li></ul></ul><ul><li>Rapid Progressors </li></ul><ul><ul><li>High viral load at birth </li></ul></ul><ul><ul><li>Rapidly declining CD4 </li></ul></ul><ul><ul><li>Low Birth Weight </li></ul></ul><ul><ul><li>Chronically unwell first year </li></ul></ul><ul><ul><ul><li>Persistent or recurrent diarrhea </li></ul></ul></ul><ul><ul><ul><li>Recurrent bacterial and fungal infections </li></ul></ul></ul><ul><ul><ul><li>Severe encephalopathy before 18 months </li></ul></ul></ul>
    11. 11. Natural History – Immunological changes <ul><li>Immunologic Parameters </li></ul><ul><li>Absolute CD4 count higher in healthy children than in adults. </li></ul><ul><li>Absolute CD4 count declines steadily during the first 5 yrs in healthy children to achieve adult levels by age 6 </li></ul><ul><li>CD4 percentage does not change with age. </li></ul><ul><li>In children < 6 yr CD4 percentage is the preferred immunological parameter for monitoring disease progression. </li></ul>
    12. 12. Natural History – Immunological changes
    13. 13. Natural History – Immunological changes
    14. 14. Natural History – Viral load patterns in children <ul><li>The HIV viral load (RNA) pattern in perinatally infected infants differs from infected adults. </li></ul><ul><li>Among infants infected before the age of 1 month: </li></ul><ul><li>Viral load (RNA) levels are zero or low at birth. </li></ul><ul><li>Increase to high levels above 100,000 copies/ml by 3-6 months of age. </li></ul><ul><li>Thereafter RNA declines slowly over several years to “set point”. </li></ul>
    15. 15. Clinical signs & conditions suggestive of HIV infection in a child <ul><li>Very specific for HIV infection: </li></ul><ul><li>Oesophageal candidiasis </li></ul><ul><li>Herpes zoster (shingles) </li></ul><ul><li>Pneumocystis carinii pneumonia </li></ul><ul><li>Extrapulmonary cryptococcosis </li></ul><ul><li>Kaposi’s sarcoma </li></ul>
    16. 16. Clinical signs & conditions suggestive of HIV infection in a child <ul><li>Common in HIV, uncommon in HIV uninfected child </li></ul><ul><li>Recurrent severe bacterial infection </li></ul><ul><li>Persistent or recurrent oral thrush </li></ul><ul><li>Parotid enlargement </li></ul><ul><li>Generalized lymphadenopathy </li></ul><ul><li>Hepatosplenomegaly (non-malaria areas) </li></ul><ul><li>Persistent or recurrent fever </li></ul><ul><li>Neurologic dysfunction </li></ul>
    17. 17. Clinical signs & conditions suggestive of HIV infection in a child <ul><li>Common in both HIV+ and HIV- children </li></ul><ul><li>Otitis media - persistent or recurrent </li></ul><ul><li>Diarrhoea – persistent or recurrent </li></ul><ul><li>Severe pneumonia </li></ul><ul><li>Tuberculosis </li></ul><ul><li>Failure to thrive </li></ul><ul><li>Persistent dermatitis </li></ul>
    18. 18. Diagnosis and Staging of HIV in Children Unit 3 Management of HIV infected Children
    20. 20. Clinical Diagnosis <ul><li>IMCI definition of symptomatic HIV infection </li></ul><ul><li>Presence of 3 or more of the following: </li></ul><ul><li>TB in any parent in the last 5 years </li></ul><ul><li>Pneumonia (now or previously) </li></ul><ul><li>2 or more episodes persistent diarrhoea (>14 days) </li></ul><ul><li>Growth faltering or weight < 3 rd centile </li></ul><ul><li>(below “very low weight curve” in card </li></ul><ul><li>Enlarged lymph nodes in 2 or more of the following sites (neck, axilla, groin) </li></ul><ul><li>Oral thrush </li></ul>
    21. 21. Clinical suspicion of pediatric HIV <ul><li>Using IMCI tool one can easily identify children highly likely to have HIV infection. </li></ul>
    22. 22. Laboratory Diagnosis Child < 18 months <ul><li>Child < 18 months, HIV Ab may come from: </li></ul><ul><li>Maternal Ab passively transferred to infant </li></ul><ul><ul><li>maternal Ab may persist in her infant up to 18 months </li></ul></ul><ul><ul><li>so Ab test is +ve in ALL children born to HIV+ women, including those that are NOT infected (gives false +ve results) </li></ul></ul><ul><li>Infant generated Ab if infant is HIV infected. </li></ul><ul><li>A positive HIV Ab test at this age is therefore not diagnostic , only shows child has been HIV exposed </li></ul>
    23. 23. Laboratory Diagnosis Child < 18 months <ul><li>Need to do Virologic test – detect HIV virus in blood </li></ul><ul><li>Various types: </li></ul><ul><li>- RNA PCR - most available, also gives viral load </li></ul><ul><li>- DNA PCR – not widely available </li></ul><ul><li>- P24 antigen (immune-complex dissociated) </li></ul><ul><li>When to do virologic test: </li></ul><ul><ul><li>Not BF: test at age 1 month repeat 3 months later </li></ul></ul><ul><ul><li>BF: wait until 3 months after cessation of BF to confirm final HIV status. </li></ul></ul>
    24. 24. Diagnosis – combining lab and clinical criteria <ul><li>May not have access to PCR as is not widely available or affordable. </li></ul><ul><li>You can still make a diagnosis in child < 18 months combining simple lab and clinical parameters. </li></ul>
    25. 25. HIV Diagnosis before age 18 mth without virologic test <ul><li>Must fulfil the following 3 criteria: </li></ul><ul><li>WHO stage 3 or 4 </li></ul><ul><li>PLUS </li></ul><ul><li>HIV ELISA positive (child or mother) </li></ul><ul><li>PLUS </li></ul><ul><li>CD4 < 25% (or CD4 count < 1500) </li></ul><ul><li>(OR TLC < 3400) </li></ul>
    26. 26. Diagnosis <ul><li>After 18 months: </li></ul><ul><li>HIV ELISA antibody test </li></ul><ul><li>By 18 months, maternal antibodies have cleared </li></ul>
    27. 27. DIAGNOSIS - summary <ul><li>In children < 18 months HIV is diagnosed by 2 positive virological tests performed on blood samples taken on 2 separate dates. </li></ul><ul><ul><li>HIV is excluded by 2 or more negative virological tests </li></ul></ul><ul><ul><li>at >age 1 month, one of which is performed at age >4 </li></ul></ul><ul><ul><li>months in a non-breastfed infant </li></ul></ul><ul><ul><li>If BF wait 3 months after cessation of BF </li></ul></ul><ul><li>Antibody tests: 2 or more antibody tests after 18 months confirm or exclude diagnosis. </li></ul>
    29. 29. Clinical Staging <ul><li>TWO international clinical staging systems: </li></ul><ul><li>World Health Organisation (WHO) </li></ul><ul><li>Four stages – 1, 2, 3, 4 </li></ul><ul><li>Centres for Disease Control (CDC) </li></ul><ul><li>Four stages – N, A, B, C </li></ul>
    30. 30. Disease Staging <ul><li>Limitations of Staging Systems </li></ul><ul><ul><li>WHO </li></ul></ul><ul><ul><ul><li>Does not include immunological </li></ul></ul></ul><ul><ul><ul><li>Does not capture some diagnoses </li></ul></ul></ul><ul><ul><li>CDC </li></ul></ul><ul><ul><ul><li>Assumes availability of advanced diagnostic technology </li></ul></ul></ul><ul><ul><ul><li>Some conditions seen in resource-limited settings not included </li></ul></ul></ul>
    31. 31. Clinical Staging Severe (AIDS) 4 C Moderate 3 B Mild 2 A Asymptomatic 1 N Stage WHO CDC
    32. 32. WHO clinical staging <ul><li>STAGES </li></ul><ul><li>1 – asymptomatic </li></ul><ul><li>2 – mildly symptomatic </li></ul><ul><li>3 – moderately symptomatic </li></ul><ul><li>4 – severely symptomatic (AIDS) </li></ul><ul><li>For use in those 12 years or under with confirmed laboratory evidence of HIV infection </li></ul>
    33. 33. WHO Clinical Staging – stage 1 <ul><li>Stage I </li></ul><ul><li>Asymptomatic </li></ul><ul><li>Persistent generalized lymphadenopathy (PGL) </li></ul><ul><li>Hepatosplenomegaly </li></ul>
    34. 34. WHO Clinical Staging - stage 2 <ul><li>Papular pruritic eruptions </li></ul><ul><li>Seborrheic dermatitis </li></ul><ul><li>Fungal nail infections </li></ul><ul><li>Angular cheilitis </li></ul><ul><li>Linear gingival erythema </li></ul><ul><li>Extensive HPV or molluscum infection (>5% of body area/face) </li></ul><ul><li>Recurrent oral ulcerations (>2 episodes/g mos) </li></ul><ul><li>Parotid enlargement </li></ul><ul><li>Herpes zoster (>1 episode/12 mos) </li></ul><ul><li>Recurrent or chronic upper respiratory infection (URI): otitis media, otorrhea, sinusitis (>2 episodes/6 mos) </li></ul>
    35. 35. WHO Clinical Stage 2 <ul><li>Mild conditions of the: </li></ul><ul><li>Skin - Papular pruritic eruptions, seborrheic dermatitis, fungal nail infections </li></ul><ul><li>Upper resp tract </li></ul><ul><li>Mouth </li></ul>
    36. 36. WHO Clinical Staging – Stage 3 <ul><li>Unexplained moderate malnutrition (-2SD or Z score) not responding to standard therapy </li></ul><ul><li>Unexplained persistent diarrhea (>14 days) </li></ul><ul><li>Unexplained persistent fever (intermittent or constant, > 1mo) </li></ul><ul><li>Oral candidiasis (outside neonatal period) </li></ul><ul><li>Oral hairy leukoplakia </li></ul><ul><li>Pulmonary tuberculosis </li></ul><ul><li>Severe recurrent presumed bacterial pneumonia (>2 episodes/12 mos) </li></ul>
    37. 37. WHO Clinical Staging – Stage 3 (continued) <ul><li>Acute necrotizing ulcerative gingivitis/periodontitis </li></ul><ul><li>Lymphoid interstitial pneumonitis (LIP) </li></ul><ul><li>Unexplained anemia (<8g/dL), neutropenia (<1000/mm 3 ), or thrombocytopenia (<30,000/mm 3 ) for >1 mo. </li></ul><ul><li>HIV-related cardiomyopathy </li></ul><ul><li>HIV-related nephropathy </li></ul>
    38. 38. WHO stage 4 – all ages <ul><li>Conditions where a presumptive diagnosis can be made using clinical signs or simple investigations: </li></ul><ul><li>Unexplained severe wasting or severe malnutrition not adequately responding to standard therapy </li></ul><ul><li>Pneumocystis pneumonia </li></ul><ul><li>Recurrent severe presumed bacterial infections (2 or > episodes within one year e.g. empyema, pyomyositis, bone or joint infection, meningitis, but excluding pneumonia ) </li></ul><ul><li>Chronic orolabial or cutaneous Herpes simplex infection (of more 1 month duration) </li></ul><ul><li>Extrapulmonary tuberculosis </li></ul><ul><li>Kaposi's sarcoma </li></ul><ul><li>Oesophageal Candida </li></ul><ul><li>CNS Toxoplasmosis </li></ul><ul><li>HIV encephalopathy </li></ul>
    39. 39. WHO stage 4 – all ages (continued) <ul><li>Conditions where confirmatory diagnostic testing is necessary: </li></ul><ul><li>CMV infection (CMV retinitis or infection of organ other than liver, spleen, or lymph nodes onset at age 1 month or more) </li></ul><ul><li>Cryptococcal meningitis (or other extrapulmonary disease) </li></ul><ul><li>Any disseminated endemic mycosis(e.g. extra-pulmonary Histoplasmosis, Coccidiomycosis, Penicilliosis) </li></ul><ul><li>Cryptosporidiosis </li></ul><ul><li>Isosporiasis </li></ul><ul><li>Disseminated non-tuberculous mycobacteria infection </li></ul><ul><li>Candida of trachea, bronchi or lungs </li></ul><ul><li>Acquired HIV related recto-vesico fistula </li></ul>
    40. 40. WHO – Stage 4: Child < 18 mths - when PCR testing not available <ul><li>Presumptive Stage 4 diagnosis in children less than eighteen months old where virological confirmation of infection is not available </li></ul><ul><li>Symptomatic HIV-antibody positive infant age < 18 mos with two or more of the following: </li></ul><ul><ul><li>Oral candidiasis/thrush </li></ul></ul><ul><ul><li>Severe pneumonia </li></ul></ul><ul><ul><li>Severe wasting/malnutrition </li></ul></ul><ul><ul><li>Severe sepsis </li></ul></ul><ul><ul><li>Severe immunosuppression should be suspected and ARV treatment is indicated </li></ul></ul><ul><li>CD4 values where available should be used to guide decision making CD4 below 24% requires urgent ARV treatment </li></ul><ul><li>Other factors that support the diagnosis of clinical stage 4 HIV infection in an HIV seropositive infant are recent maternal death or advanced HIV disease in mother. </li></ul>
    41. 41. Immunological Staging <ul><li>Differences in CD4 counts between adults and children </li></ul>
    42. 42. Immunological Staging Using Absolute CD4 count < 200 < 500 < 750 3: Severely immunosuppressed 200-499 500-999 750-1,499 2: Moderately immunosuppressed > 500 > 1000 > 1500 1: Not immunosuppressed 6-12 years CD4 counts 1-5 years CD4 counts < 12 months CD4 counts Immune category
    43. 43. Immunological Staging Using CD4 percentage < 15% < 15% < 15% 3: Severely immunosuppressed 15-24% 15-24% 15-24% 2: Moderately immunosuppressed > 25% > 25% > 25% 1: Not immunosuppressed 6-12 years CD4 % 1-5 years CD4 % < 12 months CD4 % Immune category
    44. 44. CDC Immunological staging < 200 < 15% < 500 < 15% < 750 < 15% 3: Severely immunosuppressed 200-499 15-24% 500-999 15-24% 750-1,499 15-24% 2: Moderately immunosuppressed > 500 > 25% > 1000 > 25% > 1500 > 25% 1: Not immunosuppressed 6-12 years CD4 counts CD4 percentage 1-5 years CD4 counts CD4 percentage < 12 months CD4 counts CD4 percentage Immune category
    45. 45. Total Lymphocyte Count <ul><li>Where cannot perform CD4 assays, TLC provides a rough guide to level of immunosuppression. </li></ul><ul><li>This is only useful for baseline evaluation for immunosuppression. </li></ul>
    46. 47. Relationship between CD4 and Lymphocyte count (TLC) < 2300/mm 3 (< 2.3 x 10 9 /l) < 15 % 18mo-5yr < 1200/mm 3 (< 1.2 x 10 9 /l) < 15% or CD4 count < 200 6 yrs or more < 3400/mm 3 (< 3.4 x 10 9 /l) < 20 % < 18 mo Lymphocyte count/mm 3 (Lymph count/litre) CD4 Age
    47. 48. Computing CD4% <ul><li>CD4% = Absolute CD4 count per mm 3 x 100 </li></ul><ul><li>Total lymphocyte count per mm 3 </li></ul><ul><li>OR = Absolute CD4 count per litre x 100 </li></ul><ul><li>Total lymphocyte count per litre </li></ul>
    48. 49. Computing Total Lymphocyte Count <ul><li>TLC = Lymphocyte percentage per litre x 100 </li></ul><ul><li>White cell count per litre </li></ul><ul><li>TLC = Lymphocyte percentage per mm3 x 100 </li></ul><ul><li>White cell count per mm3 </li></ul>
    49. 50. HIV – Related Conditions: Prevention and Treatment Unit 4 Management of HIV infected Children
    50. 51. Vaccination concerns in child with HIV <ul><li>Broad concerns include, is the child able: </li></ul><ul><li>To mount an effective immune response to the vaccine? </li></ul><ul><li>To sustain their immune response as CD4 declines? </li></ul><ul><li>Do they require re-vaccination after CD4 is restored following successful antiretroviral therapy? </li></ul><ul><li>Safety of live vaccines - can live vaccines result in severe vaccine-associated disease in immunocompromised individuals? </li></ul>
    51. 52. World Health Organization/UNICEF recommendations For the Immunization of HIV-infected children and women of childbearing age
    52. 53. * IPV an alternative for children with symptomatic HIV ** Pending further studies *** 5 doses TT for women of child-bearing age 5 doses*** Yes Yes Tetanus toxoid No** Yes Yellow fever As for uninfected children Yes Yes Hepatitis B 6 and 9 months Yes Yes Measles 0, 6,10,14 wks Yes Yes OPV* 6,10,14 wks yes yes DPT birth no yes BCG Optimal timing of immunization Symptomatic HIV Asymptomatic HIV Vaccine
    53. 54. HIV-related Diseases <ul><li>Infections that complicate HIV disease in children include: </li></ul><ul><li>Infections that are commonly seen even in HIV uninfected children </li></ul><ul><li>Opportunistic infections </li></ul><ul><ul><li>rare in HIV negative children </li></ul></ul><ul><ul><li>more common with advancing immune compromise. </li></ul></ul>
    54. 55. HIV-related Diseases (cont) <ul><li>Other clinical problems not commonly seen in other children </li></ul><ul><ul><li>Lymphoid interstitial pneumonitis </li></ul></ul><ul><ul><li>Malignancies </li></ul></ul><ul><ul><li>HIV encephalopathy </li></ul></ul>
    55. 56. Pneumocystis Pneumonia <ul><li>Caused by a fungus, Pneumocystis jiroveci*, that is commonly found in the environment </li></ul><ul><li>Commoner under the age of 1 year and in severely immunosuppressed children </li></ul><ul><li>Clinical presentation: </li></ul><ul><ul><li>Usually less than 1 year </li></ul></ul><ul><ul><li>Tachypnoea </li></ul></ul><ul><ul><li>Dyspnoea </li></ul></ul><ul><ul><li>Low grade fever or afebrile </li></ul></ul><ul><ul><li>Cough </li></ul></ul><ul><ul><li>Hypoxemia (paO 2 < 90%) </li></ul></ul><ul><ul><li>Clear chest or fine crepitations </li></ul></ul><ul><ul><li>Poor response to standard antibiotics </li></ul></ul>
    56. 57. Investigations <ul><li>Chest X-ray: hyperinflation, diffuse infiltrates or may be normal </li></ul><ul><li>Sputum induction or nasopharyngeal aspirate, stained with Silver or Immunofluorescent stain </li></ul><ul><li>Bronchoalveolar lavage washing stained as above </li></ul>
    57. 58. PCP Treatment <ul><li>Cotrimoxazole I.V (or oral if IV not available) </li></ul><ul><ul><li>Trimethoprim (TMP): 4 mg/kg/dose qid </li></ul></ul><ul><ul><li>Sulphamethoxazole (SMX): 20mg/kg/dose qid </li></ul></ul><ul><ul><li>OR </li></ul></ul><ul><li>IV Pentamidine 4mg/kg/day OD </li></ul><ul><li>Duration of treatment: 3 weeks </li></ul><ul><li>Add prednisone 2mg/kg for 7-14 days in severely ill children (taper off) </li></ul>
    58. 59. Prevention of PCP <ul><li>PCP prevented by cotrimoxazole </li></ul><ul><li>Co-trimoxazole prophylaxis </li></ul><ul><ul><li>All children born to HIV infected women should receive CTZ prophylaxis from age of 6 weeks till HIV is ruled out. </li></ul></ul><ul><ul><li>Those confirmed to be HIV infected should continue CTZ prophylaxis indefinitely. </li></ul></ul><ul><ul><li>Dose 25mg SMX / 5mg TMP per kg o.d. (30mg cotrimoxazole/kg o.d.) </li></ul></ul>
    59. 60. Candidiasis <ul><li>Oral candidiasis a frequent OI </li></ul><ul><li>May extend to oesophagus and disseminate when CD4 severely depressed </li></ul><ul><li>Oesophageal candidiasis assoc with difficulty in swallowing/dysphagia </li></ul>
    60. 61. Treatment of Candidiasis <ul><li>Oral thrush: </li></ul><ul><li>Clotrimazole mouth paint 10-20 drops p.o qid 7 days (after feeds) or until thrush clears. </li></ul><ul><li>Or clotrimazole 10 mg troches (older children only) </li></ul><ul><li>Or: </li></ul><ul><li>0.25%-0.5% gentian violet solution </li></ul><ul><li>2% miconazole gel, 2.5 ml (young child) or 5 ml (older child) two times a day </li></ul>
    61. 62. Treatment of Candidiasis <ul><li>Oesophageal candidiasis: </li></ul><ul><li>Oral ketoconazole , 3-6mg/kg/day for 7 days OR </li></ul><ul><li>Oral fluconazole 3-6 mg/kg/day for 2-3 weeks or until resolution of symptoms. </li></ul>
    62. 63. Antiretroviral Therapy in Children Unit 5 Management of HIV infected Children
    63. 64. Antiretroviral Therapy <ul><li>Will cover the following: </li></ul><ul><li>Indications for ART initiation </li></ul><ul><li>National ART Regimens </li></ul><ul><li>Monitoring </li></ul><ul><li>Indications for change or withdrawal of ART </li></ul><ul><li>National second line regimens </li></ul><ul><li>ART and tuberculosis </li></ul>
    64. 65. Criteria for ART Initiation <ul><li>There are two broad criteria to consider prior to ART initiation </li></ul><ul><li>Medical criteria </li></ul><ul><li>Psychosocial criteria </li></ul>
    65. 66. Criteria for ART Initiation <ul><li>Medical criteria </li></ul><ul><li>WHO stage 3 or 4 disease (irrespective of CD4 counts or %). </li></ul><ul><li>Low CD4 count or percentage as follows (irrespective of WHO stage): </li></ul><ul><ul><li>Child < 18 months – CD4 < 25% or absolute CD4 count < 1500 </li></ul></ul><ul><ul><li>Child 18 months to 5 years – CD4 < 15% or absolute CD4 count < 500 </li></ul></ul><ul><ul><li>Child older than 5 years – CD4 < 15% or absolute CD4 count < 200 </li></ul></ul><ul><li>Recurrent hospitalizations (> 2 admissions in previous year) for HIV-related disease, or prolonged hospitalization (> 4 weeks) in previous year. </li></ul>
    66. 67. Criteria For ART Initiation <ul><li>Psychosocial criteria </li></ul><ul><li>An identifiable parent or guardian who is able to understand the regimen, and consistently administer the child’s medication. </li></ul><ul><li>Adolescent – disclosure of HIV diagnosis before ART initiation recommended where possible </li></ul><ul><li>Ability to regularly attend the HIV clinic appointments. </li></ul><ul><li>Sustainable long-term access to antiretroviral drugs (either through programs providing ART, or financially able to purchase ARV drugs). </li></ul>
    67. 68. Preparing a Child for ART <ul><li>Prior to initiating ART, the following preparations should take place </li></ul><ul><li>Medical Preparation </li></ul><ul><li>Counseling Preparation </li></ul>
    68. 69. Preparing a Child for ART (2) <ul><li>Medical Preparation </li></ul><ul><li>Baseline tests to check haematological, liver and kidney function: </li></ul><ul><ul><li>Full blood count (resources limited, do Hb) </li></ul></ul><ul><ul><li>Liver function tests (resources limited, do alanine transaminase or ALT) </li></ul></ul><ul><ul><li>Renal function tests (resources limited, do serum creatinine) </li></ul></ul><ul><li>Do baseline CD4 if possible </li></ul><ul><li>Do baseline viral load (RNA PCR – this is optional if resources limited) </li></ul>
    69. 70. Preparing a Child for ART (3) <ul><li>Medical Preparation (continued) </li></ul><ul><li>Baseline clinical assessment including weight, height, surface area. </li></ul><ul><li>If current TB suspected, investigate for TB (If TB confirmed, consider delaying ART initiation) </li></ul><ul><li>Initiate co-trimoxazole prophylaxis (as in module 5) </li></ul><ul><li>Treat any inter-current illnesses </li></ul>
    70. 71. Prior to starting ARV in children <ul><li>Start in haste, repent at leisure!! </li></ul><ul><li>Starting ART is never an emergency </li></ul><ul><li>Take time to counsel, prepare, educate the family </li></ul><ul><li>Counsel the caregiver on: </li></ul><ul><li>Cost – drugs, monitoring tests, food security </li></ul><ul><li>Adherence to therapy – strict time scheduling </li></ul><ul><li>Support, support, support. Child can’t do it alone. </li></ul><ul><li>Older child – disclosure to child </li></ul><ul><li>Do careful social assessment of family situation prior to starting therapy. </li></ul>
    71. 72. Goals of ARV Therapy <ul><li>Maximal and durable suppression of HIV replication. </li></ul><ul><li>Restoration and preservation of immune function. </li></ul><ul><li>Reduce HIV related Morbidity & Mortality. </li></ul><ul><li>Improve quality of life. </li></ul>
    72. 73. Special Considerations for Children and ARVs <ul><li>Choose drugs that: </li></ul><ul><li>Do not have to be timed around meals </li></ul><ul><li>Have acceptable taste </li></ul><ul><li>Suspensions/syrups are stable at room temperature if patient does not own a refrigerator. </li></ul><ul><li>Children older than 6 years may take tablet and capsule formulations </li></ul><ul><li>Some capsule formulations may be opened and capsule content mixed with food or drink. </li></ul><ul><li>Some chewable tablets may be crushed and mixed with food or drink. </li></ul>
    73. 74. Types of Antiretroviral Drugs <ul><li>Nucleoside reverse transcriptase inhibitors (NRTI) </li></ul><ul><li>Non-nucleoside reverse transcriptase inhibitors (NNRTI) </li></ul><ul><li>Protease inhibitors (PI) </li></ul>
    74. 75. Kenya national recommended 1st line ART in children <ul><li>Always give three drugs (triple therapy). </li></ul><ul><li>National first line regimen – use 2 nucs and 1 non-nuc </li></ul><ul><li>Age < 3 years </li></ul><ul><li>Zidovudine (ZDV) + Lamivudine (3TC) + Nevirapine (NVP) </li></ul><ul><li>Age > 3 years </li></ul><ul><li>ZDV + 3TC + Efavirenz (EFV) or NVP. </li></ul><ul><li>These can be taken with or without food, taste is acceptable, and all are stable at room temperature. </li></ul><ul><li>If child very anaemic, ZDV may be substituted by stavudine (D4T) </li></ul>
    75. 76. First line regimen in NVP-exposed child <ul><li>Child exposed to single dose nevirapine for PMCT may have NVP resistant virus. Avoid non-nucs in their 1 st line regimen </li></ul><ul><li>AZT (or d4T) + 3TC + Kaletra </li></ul>
    76. 77. ART and Tuberculosis <ul><li>Rifampicin interacts with nevirapine and most protease inhibitors </li></ul><ul><li>If possible, complete anti-TB therapy before ART initiation. </li></ul><ul><li>If child too sick to wait, and anti-TB therapy must be given with ART use the following regimen: </li></ul><ul><li>Child < 3 yr – Replace NVP with abacavir. After completing anti-TB therapy revert to NVP </li></ul><ul><li>Child > 3 yr – Two NRTIs with efavirenz </li></ul>
    77. 78. Dosages of ARV drugs <ul><li>Many are calculated using surface area </li></ul><ul><li>S.A = sq root of ([wt x ht] / 3600) </li></ul><ul><li>Others calculated using weight for age </li></ul><ul><li>Failure to compute dosage correctly leads to under- or over-dosing </li></ul><ul><li>Suboptimal dose – resistance </li></ul><ul><li>Overdose – toxicity </li></ul>
    78. 79. Clinical Monitoring <ul><li>Clinical response – anthropometry, physical exam at every visit </li></ul><ul><ul><li>Symptoms improving, static, deteriorating? </li></ul></ul><ul><ul><li>Growth (weight, height) </li></ul></ul><ul><ul><li>General well-being </li></ul></ul><ul><li>Clinical signs of specific adverse effects (depend on class of drugs) </li></ul>
    79. 80. Laboratory Monitoring <ul><li>Response to therapy </li></ul><ul><ul><li>CD4 every 6 months (expect rise within 6 months) </li></ul></ul><ul><ul><li>Viral load at baseline, month 3 then every 6 months if affordable (aim at 5-fold drop by 8-12 weeks) </li></ul></ul><ul><li>Adverse effects </li></ul><ul><ul><li>FBC, SGPT/ALT at baseline, month 1, then 3 monthly or as appropriate </li></ul></ul><ul><ul><li>Others (lipids, glucose etc) as appropriate for toxicity or inter-current illnesses </li></ul></ul>
    80. 81. When to change or stop ART <ul><li>1. Toxicity – replace only the offending drug </li></ul><ul><li>2. Treatment failure – replace all 3 drugs </li></ul><ul><li>3. Poor adherence – if cannot rectify, withdraw ART </li></ul>
    81. 82. When to change ART <ul><li>Toxicity – replace offending agent only with equivalent drug </li></ul><ul><li>Hb < 7gm/dl </li></ul><ul><li>Platelets < 49,000 </li></ul><ul><li>Neutrophils < 250 </li></ul><ul><li>Bilirubin 3-7x upper normal </li></ul><ul><li>SGPT 10x upper normal </li></ul><ul><li>Amylase, lipase: 2-3x upper normal </li></ul><ul><li>Neuropathy, severe dermatitis </li></ul><ul><li>Lipoatrophy, pancreatitis </li></ul>
    82. 83. Indications for change of therapy – treatment failure <ul><li>FIRST CHECK ADHERENCE!! </li></ul><ul><li>Clinical indications </li></ul><ul><li>Progressive neurodevelopmental deterioration </li></ul><ul><li>Growth failure </li></ul><ul><li>Disease progression – move from one stage to next </li></ul>
    83. 84. Indications for change of therapy – treatment failure <ul><li>Immunological indications </li></ul><ul><li>For kids with CD4 below 15%, decline of ≥ 5 percentile points </li></ul><ul><li>Rapid decline in absolute CD4 count (loss of > 1/3 of CD4 cells in < 6 months) </li></ul>
    84. 85. Indications for change of therapy – treatment failure <ul><li>Virological indications </li></ul><ul><li>Persistent increase in viral load (confirmed by 2 tests) </li></ul>
    85. 86. Second line therapy – factors to consider <ul><li>Change ALL 3 DRUGS. </li></ul><ul><li>Include a Protease inhibitor. </li></ul><ul><li>Replace the NRTIs with two new NRTIs </li></ul><ul><li>Replace the NNRTI with a PI </li></ul><ul><li>IF initial problem was adherence to therapy, must address this first. If can’t best to just withdraw therapy altogether </li></ul>
    86. 87. Kenya national recommended 2 nd line ART in children <ul><li>First line </li></ul><ul><li>ZDV/3TC/NVP or EFV </li></ul><ul><li>d4T/3TC/NVP or EFV </li></ul><ul><li>ZDV/3TC/Kaletra </li></ul><ul><li>Second line </li></ul><ul><li>ddI/ABC/LPV/r or ddI/ABC/NFV </li></ul><ul><li>ddI/ABC/LPV/r or NFV </li></ul><ul><li>ddI/ABC/PI/ritonavir </li></ul>
    87. 88. When To Stop/withdraw ART. <ul><li>ART should be withdrawn in the following situations: </li></ul><ul><li>Severe adverse effects (lactic acidosis) </li></ul><ul><li>Intolerability, inability to take drugs. </li></ul><ul><li>Poor adherence </li></ul><ul><li>Interruption of drug supply </li></ul><ul><li>Patients wish. </li></ul>
    88. 89. Adherence Issues to Consider <ul><li>Children depend upon adults to administer drugs </li></ul><ul><li>Adherence may be affected by stage of development (spitting, vomiting, running away) </li></ul><ul><li>Providers need to teach families techniques of giving medicine to young children </li></ul><ul><ul><li>Use of syringe for measurement and administration </li></ul></ul><ul><ul><li>Crushing of meds </li></ul></ul><ul><ul><li>Mixing in fruit juice, other foods </li></ul></ul><ul><ul><li>Opening of capsules </li></ul></ul><ul><ul><li>Repeat dose if vomited </li></ul></ul>