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HIV/AIDS and the Pediatric Patient. Prepared by Kate Powis, MD Global Women’s Health Fellow Harvard Medical School Instructor. Presentation Objectives. HIV Epidemiology Pathophysiology Presentation in the Pediatric Population Testing Clinical Staging Treatment Ongoing Care Issues.
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HIV/AIDS and the Pediatric Patient Prepared by Kate Powis, MD Global Women’s Health Fellow Harvard Medical School Instructor
Presentation Objectives • HIV Epidemiology • Pathophysiology • Presentation in the Pediatric Population • Testing • Clinical Staging • Treatment • Ongoing Care Issues
Estimated number of people living with HIV globally, 1990–2007 40 Millions 30 Number of people living with HIV 20 10 0 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 Year This bar indicates the range 1 2007 AIDS Epidemic Update
Estimated number of adult and child deaths due to AIDS globally, 1990–2007 3.0 Millions 2.5 2.0 Number of adult and child deaths due to AIDS 1.5 1.0 0.5 0 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 Year This bar indicates the range 3
HIV/AIDS Global Statistics • 33.2 million people living with HIV/AIDS worldwide as of 20071 • 90% of HIV/AIDS infected persons live in developing countries1 • 2.1 million children under age 15 were living with HIV/AIDS in 20072 • Globally, 1,150 of newborns are infected daily by peri-natal transmission of HIV2 • In 2007, 420,000 children were newly infected with HIV and 290,000 died of AIDS2 1UNAIDS 2007 World Report 2http://www.uniteforchildren.org/knowmore/knowmore_30104.htm
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’s1 • Young people aged 15-24 accounted for 40% of new HIV infections among adults aged 15 years and up in 20072 • 5.4 million young people aged 15-24 were living with HIV/AIDS in 20072 • 50% of infected infants will die before their second birthday2 1Report 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. 2http://www.uniteforchildren.org/knowmore/knowmore_30104.htm
HIV/AIDS Statistics in Liberia • 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 • UNICEF has not received reporting on incidence or prevalence of HIV/AIDS in the pediatric population of Liberia.2 1The Basic Package of Health and Social Welfare Services, Republic of Liberia, Ministry of Health and Social Welfare. 2http://www.unicef.org/infobycountry/liberia.html
Global Distribution of HIV-1 by Subtype (Clade) http://www.iavireport.org/
HIV-1 Particle KITSO Aids Training Program, Botswana
HIV Lifecycle Monini P et al, Antitumor effects of antiretroviral therapy, Nature Reviews Cancer, 4,861-875 Nov 2004.
Helper Function of CD4 Cells Macrophage T helper cell (CD4) Cytotoxic TLymphocyte(CD8) BLymphocyte Infected cell Antibody secreting (plasma) cell Killed KITSO AIDS Training Program, Botswana
Surrogate Markers of HIV Disease • CD4 cell counts reflect the strength of the immune system. • Viral load reflects the viral replication.
Acute Retroviral Syndrome Clinical Latency AIDS Natural History of HIV-1 Infection Viral Load CD4 count 1-2 years 1-12weeks 6-10years
Pathogenesis of Acute HIV-1 Infection • Initial infection of CD4 lymphocytes and macrophages • Dissemination of infection to lymph nodes • Burst of viral replication resulting in intense viremia • Development of humoral immunity (HIV-specific antibodies) • Development of cellular immunity (HIV-specific CD4 and CD8 cells)
Transmission of HIV • Blood • Semen • Vaginal Fluid • Breast Milk
Unique Features of HIV in the Pediatric Population • Perinatal Infection • Maternal antibodies DNA PCR • Infection in a developing body • Immature Immune System CD4% • Immature Liver/Kidneys ARV Dosing • Growth ARV Dosing • Immature Physiology Formulations • Vulenrability of Children • Dependence on Others Adherence KITSO AIDS Training Program, Botswan
Pediatric HIV Infection –Common Clinical Presentations • Infectious Diseases • Respiratory Illness (PCP, Tuberculosis) • Diarrheal Diseases • Oral Candidiasis • Herpes Zoster • Lymphadenopathy, Hepatomegaly, Parotitis • Persistent fever • Growth failure: Kwashiorkor, Marasmus • Developmental Delay or Regression • Malignancies: Lymphoma, Kaposi’s sarcoma
Diarrheal Illness • Similar prevalence of stool pathogens between HIV infected and uninfected children. • Worse outcomes in HIV infected children. KITSO AIDS Training, Botswana
Respiratory Illness • 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
HIV Testing • Rapid Tests and ELISA for patients older than 18 months • DNA PCR for patients less than 18 months
Pediatric HIV Staging • Facilitates assessment of degree of damage to the immune system • Dictates treatment timing and care options • Prognostic
Goals of Treatment • Clinical: Prolong life, improve quality of life. • 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.
Pediatric Considerations in Treatment Selection • Availability of a suitable formulation • Simplicity of dosing schedule • Taste/palatability • Parent or caregiver HAART regimen
Treatment • HIV infections requiring treatment warrant HAART. • WHO’s recommendation for first line regimen dictates the use of two NRTI’s and one NNRTI.
HAART - Mechanism of Action KITSO AIDS Training - Botswana
ARVs in the Liberian Formulary NRTIs NNRTIs PIs 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)
HAART Initiation Considerations • Caregiver reliability and HIV insight • Infants under six months of age having received single dose NVP at birth. • Reproductive potential • CD4 with planned use of NVP
HAART Labs - Baseline • CD4 • Hematology • Chemistry • AST/ALT
HAART – Ongoing Labs • 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.
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. • 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.
HAART Dosing • Rechecking dosing at every visit and adjust for weight gain • Utilize WHO Pediatric Dosing Guides • Ensure dosing is a simple and convenient as possible
Changing HAART Regimens • Treatment failure • Treatment toxicity • Drug Interactions • Adherence issues secondary to tolerance
Pediatric HIV Routine Care Plan • 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.
HIV - Nutrition • All HIV infected individuals should eat energy-rich foods and increase energy intake. • Varying foods is important to ensure micronutrient intake is appropriate.
HIV and Immunizations • 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. • HIV infected children require and extra measles vaccine at 6 months of life, as well as the standard vaccine at 9 months of life.
Presentation Objectives • HIV Epidemiology • Pathophysiology • Presentation in the Pediatric Population • Testing • Clinical Staging • Treatment • Ongoing Care Issues
Additional Training Modules • HIV Prevention Programs • Case Presentations, HAART Dosing and Management • HIV and Opportunistic Infections