1. HIV/AIDS and the Pediatric Patient Prepared by Kate Powis, MD Global Women’s Health Fellow Harvard Medical School Instructor

2. Presentation Objectives HIV Epidemiology HIV Epidemiology Pathophysiology Pathophysiology Presentation in the Pediatric Population Presentation in the Pediatric Population Testing Testing Clinical Staging Clinical Staging Treatment Treatment Ongoing Care Issues Ongoing Care Issues

3. 2007 AIDS Epidemic Update

5. HIV/AIDS Global Statistics 33.2 million people living with HIV/AIDS worldwide as of 2007 1 33.2 million people living with HIV/AIDS worldwide as of 2007 1 90% of HIV/AIDS infected persons live in developing countries 1 90% of HIV/AIDS infected persons live in developing countries 1 2.1 million children under age 15 were living with HIV/AIDS in 2007 2 2.1 million children under age 15 were living with HIV/AIDS in 2007 2 Globally, 1,150 of newborns are infected daily by peri-natal transmission of HIV 2 Globally, 1,150 of newborns are infected daily by peri-natal transmission of HIV 2 In 2007, 420,000 children were newly infected with HIV and 290,000 died of AIDS 2 In 2007, 420,000 children were newly infected with HIV and 290,000 died of AIDS 2 1 UNAIDS 2007 World Report 2 http://www.uniteforchildren.org/knowmore/knowmore_30104.htm

6. HIV/AIDS Global Statistics In 2007, the number of new HIV infections was 2.5 higher than the increase in the number of people receiving ARV’s 1 In 2007, the number of new HIV infections was 2.5 higher than the increase in the number of people receiving ARV’s 1 Young people aged 15-24 accounted for 40% of new HIV infections among adults aged 15 years and up in 2007 2 Young people aged 15-24 accounted for 40% of new HIV infections among adults aged 15 years and up in 2007 2 5.4 million young people aged 15-24 were living with HIV/AIDS in 2007 2 5.4 million young people aged 15-24 were living with HIV/AIDS in 2007 2 50% of infected infants will die before their second birthday 2 50% of infected infants will die before their second birthday 2 1 Report of the Secretary-General; Declaration of Commitment to HIV/AIDS and Political Declaration on HIV/AIDS: midway to the Millennium Development Goals; Sixty-second session, 1-Apr-08. 2 http://www.uniteforchildren.org/knowmore/knowmore_30104.htm

7. HIV/AIDS Statistics in Liberia Adult prevalence of HIV/AIDS in Liberia estimated to be 5.2%. 1 Adult prevalence of HIV/AIDS in Liberia estimated to be 5.2%. 1 The prevalence rate of HIV in Greater Monrovia is estimated to be 9.5% 1 The prevalence rate of HIV in Greater Monrovia is estimated to be 9.5% 1 UNICEF has not received reporting on incidence or prevalence of HIV/AIDS in the pediatric population of Liberia. 2 UNICEF has not received reporting on incidence or prevalence of HIV/AIDS in the pediatric population of Liberia. 2 1 The Basic Package of Health and Social Welfare Services, Republic of Liberia, Ministry of Health and Social Welfare. 2 http://www.unicef.org/infobycountry/liberia.html

8. Human Immunodeficiency Virus

9. Global Distribution of HIV-1 by Subtype (Clade) http://www.iavireport.org/

10. HIV-1 Particle KITSO Aids Training Program, Botswana

11. HIV Lifecycle Monini P et al, Antitumor effects of antiretroviral therapy, Nature Reviews Cancer, 4,861-875 Nov 2004.

12. Helper Function of CD4 Cells B Lymphocyte T helper cell (CD4) Macrophage Antibody secreting (plasma) cell Infected cell Cytotoxic T Lymphocyte (CD8) Killed KITSO AIDS Training Program, Botswana

13. Surrogate Markers of HIV Disease CD4 cell counts reflect the strength of the immune system. CD4 cell counts reflect the strength of the immune system. Viral load reflects the viral replication. Viral load reflects the viral replication.

14. AIDS Clinical Latency Acute Retroviral Syndrome Natural History of HIV-1 Infection 1-12 weeks6-10 years 1-2 years Viral Load CD4 count

15. Pathogenesis of Acute HIV-1 Infection Initial infection of CD4 lymphocytes and macrophages Initial infection of CD4 lymphocytes and macrophages Dissemination of infection to lymph nodes Dissemination of infection to lymph nodes Burst of viral replication resulting in intense viremia Burst of viral replication resulting in intense viremia Development of humoral immunity (HIV- specific antibodies) Development of humoral immunity (HIV- specific antibodies) Development of cellular immunity (HIV- specific CD4 and CD8 cells) Development of cellular immunity (HIV- specific CD4 and CD8 cells)

16. CD4 Counts and Opportunistic Infections

17. Transmission of HIV Blood Blood Semen Semen Vaginal Fluid Vaginal Fluid Breast Milk Breast Milk

18. Unique Features of HIV in the Pediatric Population Perinatal Infection Perinatal Infection –Maternal antibodies DNA PCR Infection in a developing body Infection in a developing body –Immature Immune System CD4% –Immature Liver/Kidneys ARV Dosing –Growth ARV Dosing –Immature Physiology Formulations Vulenrability of Children Vulenrability of Children –Dependence on Others Adherence KITSO AIDS Training Program, Botswan

19. Pediatric HIV Infection – Common Clinical Presentations Infectious Diseases Infectious Diseases –Respiratory Illness (PCP, Tuberculosis) –Diarrheal Diseases –Oral Candidiasis –Herpes Zoster Lymphadenopathy, Hepatomegaly, Parotitis Lymphadenopathy, Hepatomegaly, Parotitis Persistent fever Persistent fever Growth failure: Kwashiorkor, Marasmus Growth failure: Kwashiorkor, Marasmus Developmental Delay or Regression Developmental Delay or Regression Malignancies: Lymphoma, Kaposi’s sarcoma Malignancies: Lymphoma, Kaposi’s sarcoma

20. Diarrheal Illness Similar prevalence of stool pathogens between HIV infected and uninfected children. Similar prevalence of stool pathogens between HIV infected and uninfected children. Worse outcomes in HIV infected children. Worse outcomes in HIV infected children. KITSO AIDS Training, Botswana

21. Respiratory Illness Death from respiratory tract infections: Death from respiratory tract infections: –PCP: Most common pathogen in HIV- infected children below six-months of age –Acute pyogenic pneumonia and tuberculosis common in HIV-infected and uninfected children. KITSO AIDS Training, Botswana

22. Malnutrition

23. HIV Testing Rapid Tests and ELISA for patients older than 18 months Rapid Tests and ELISA for patients older than 18 months DNA PCR for patients less than 18 months DNA PCR for patients less than 18 months

24. Pediatric HIV Staging Facilitates assessment of degree of damage to the immune system Facilitates assessment of degree of damage to the immune system Dictates treatment timing and care options Dictates treatment timing and care options Prognostic Prognostic

25. Staging and Treatment Stage Treatment Plan Stage 4 Treat Stage 3 Treat unless >18 mos and CD4 > 15% or > 5 yo and CD4 > 10% or > 200 Stage 1 and 2 Only treat if CD4 available and Under 18 months: CD4 < 25% 18-59 months: CD4 <15% > 59 months: CD4 59 months: CD4 < 10% or < 200

26. Goals of Treatment Clinical: Prolong life, improve quality of life. Clinical: Prolong life, improve quality of life. Virologic: Achieve maximal suppression of viral load Virologic: Achieve maximal suppression of viral load –Viral load should drop by at least 1.0 after 3 months of treatment –Viral load should be less than 400 after 6 months of treatment Immunologic: Reverse immune system damage. Immunologic: Reverse immune system damage.

27. Pediatric Considerations in Treatment Selection Availability of a suitable formulation Availability of a suitable formulation Simplicity of dosing schedule Simplicity of dosing schedule Taste/palatability Taste/palatability Parent or caregiver HAART regimen Parent or caregiver HAART regimen

28. Treatment HIV infections requiring treatment warrant HAART. HIV infections requiring treatment warrant HAART. WHO’s recommendation for first line regimen dictates the use of two NRTI’s and one NNRTI. WHO’s recommendation for first line regimen dictates the use of two NRTI’s and one NNRTI.

29. HAART - Mechanism of Action KITSO AIDS Training - Botswana

30. NRTIs NNRTIsPIs Nucleoside Reverse Non-Nucleoside Reverse Protease Inhibitors Transcriptase Inhibitors Transcriptase Inhibitors AZT (Zidovudine) EFV (Efavirenz) LPV/r (Kaletra) 3TC (Lamivudine) NVP (Nevirapine) NFV (Nelfinavir) d4T (Stavudine) IDV (Indinavir) ddI (Didanosine) ABC (Abacavir)* RTV (Ritonavir) (TZV) (AZT+3TC+ABC) (TZV) (AZT+3TC+ABC) ARVs in the Liberian Formulary

31. WHO HAART Recommendation 1 st Line Regimen 2 nd Line Regimen ZDV or d4T ABC PlusPlus 3TCDDI PlusPlus NVP or EFV KAL or NFV or SQV

32. HAART Initiation Considerations Caregiver reliability and HIV insight Caregiver reliability and HIV insight Infants under six months of age having received single dose NVP at birth. Infants under six months of age having received single dose NVP at birth. Reproductive potential Reproductive potential CD4 with planned use of NVP CD4 with planned use of NVP

33. HAART Labs - Baseline CD4 CD4 Hematology Hematology Chemistry Chemistry AST/ALT AST/ALT

34. HAART – Ongoing Labs Viral load should be obtained every three months in the pediatric patient. Viral load should be obtained every three months in the pediatric patient. CD4 count/% should be performed at 3, 6 and 12 months post initiation. If >350 cells or 30% for one year, then annual testing thereafter unless new WHO clinical stage III or IV disease, virolgic failure or medication adherence issues are noted. CD4 count/% should be performed at 3, 6 and 12 months post initiation. If >350 cells or 30% for one year, then annual testing thereafter unless new WHO clinical stage III or IV disease, virolgic failure or medication adherence issues are noted.

35. HAART – Ongoing Labs Hematology: If on AZT at 4 and 12 weeks post initiation, then annually or when clinically warranted. Otherwise annually or when clinically warranted. Hematology: If on AZT at 4 and 12 weeks post initiation, then annually or when clinically warranted. Otherwise annually or when clinically warranted. AST/ALT: If on NVP-based HAART, 2, 4 and 12 weeks post initiation and therefter as clinically indicated. AST/ALT: If on NVP-based HAART, 2, 4 and 12 weeks post initiation and therefter as clinically indicated. Glucose/Cholesterol/Triglycerides: Annually for PI based regimens. Glucose/Cholesterol/Triglycerides: Annually for PI based regimens.

36. HAART Dosing Rechecking dosing at every visit and adjust for weight gain Rechecking dosing at every visit and adjust for weight gain Utilize WHO Pediatric Dosing Guides Utilize WHO Pediatric Dosing Guides Ensure dosing is a simple and convenient as possible Ensure dosing is a simple and convenient as possible

37. Changing HAART Regimens Treatment failure Treatment failure Treatment toxicity Treatment toxicity Drug Interactions Drug Interactions Adherence issues secondary to tolerance Adherence issues secondary to tolerance

38. Pediatric HIV Routine Care Plan Pediatric HIV patients should be evaluated every three months, or sooner for acute illnesses or issue of adherence. Pediatric HIV patients should be evaluated every three months, or sooner for acute illnesses or issue of adherence. Disclosure with progressive education about HIV status, need for lifetime medications, and significance of adherence greatly improves compliance in the pediatric population. Disclosure with progressive education about HIV status, need for lifetime medications, and significance of adherence greatly improves compliance in the pediatric population.

39. HIV - Nutrition All HIV infected individuals should eat energy-rich foods and increase energy intake. All HIV infected individuals should eat energy-rich foods and increase energy intake. Varying foods is important to ensure micronutrient intake is appropriate. Varying foods is important to ensure micronutrient intake is appropriate.

40. HIV and Immunizations Children with HIV or suspected HIV who are asymptomatic should received all appropriate vaccinations, including BCG and Yellow Fever. Children with HIV or suspected HIV who are asymptomatic should received all appropriate vaccinations, including BCG and Yellow Fever. Immunizations should be given as early as possible after the recommended age of the vaccine. Immunizations should be given as early as possible after the recommended age of the vaccine. HIV infected children require and extra measles vaccine at 6 months of life, as well as the standard vaccine at 9 months of life. HIV infected children require and extra measles vaccine at 6 months of life, as well as the standard vaccine at 9 months of life.

41. Presentation Objectives HIV Epidemiology HIV Epidemiology Pathophysiology Pathophysiology Presentation in the Pediatric Population Presentation in the Pediatric Population Testing Testing Clinical Staging Clinical Staging Treatment Treatment Ongoing Care Issues Ongoing Care Issues

42. Additional Training Modules HIV Prevention Programs HIV Prevention Programs Case Presentations, HAART Dosing and Management Case Presentations, HAART Dosing and Management HIV and Opportunistic Infections HIV and Opportunistic Infections

43. Thank you for your participation!