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The Effectiveness of generic Highly Active Antiretroviral Therapy for the treatment of HIV infected

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Syrup 13kg. Dose of Triomune. Weight of patient (kg) Dosing of Triomune by weight. Methods ... Adherence is better with a fixed dose combination than syrups ... – PowerPoint PPT presentation

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Title: The Effectiveness of generic Highly Active Antiretroviral Therapy for the treatment of HIV infected


1
The Effectiveness of generic Highly Active
Antiretroviral Therapy for the treatment of HIV
infected Ugandan children
  • Presenter Linda Barlow-Mosha MD, MPH, FAAP
  • Makerere University- Johns Hopkins University
    Research Collaboration
  • National AIDS Conference
  • 22nd March, 2005

2
Background
  • 90 of the 2.1million HIV infected children are
    in sub-Saharan Africa (UNAIDS, 2004)
  • Uganda has approximately 143,000 children living
    with HIV and 20,000 children are infected each
    year through mother to child transmission (MTCT)
    (MOH, 2001)
  • MU-JHU research collaboration has taken care of
    over 3000 HIV infected children since 1988
  • 80 of children have died
  • Death occurred in 30,66, 75 of the children at
    1, 3, and 5 years respectively (Marum et al. July
    1996)

3
Background
  • Benefits of HAART have not yet been realized in
    resource limited countries due to
  • High cost of drugs
  • Limited infrastructure to monitor patients
  • Access has recently been increased for patients
    in the developing world through
  • Global funds
  • World Bank funds-MAP
  • PEPFAR (President Bushs Initiative)

4
HAART
  • Includes 3 to 4 drugs in combination
  • Increase pill burden, frequent dosing and life
    long therapy contribute to poor adherence
  • Fixed dose combinations have made adherence to
    therapy better
  • Most of the fixed dose combinations are in tablet
    or capsule form and not in formulations
    appropriate for young children

5
HAART in Uganda
  • Approximately 30,000 individuals on HAART
    (Ministry of Health personal communication)
  • Less 2000 are children under 15 years of age
    (Ministry of Health personal communication)
  • Majority of the children on HAART are from
    Mildmay Center and Mulago PIDC
  • Children are often left out because of
  • Lack of infant HIV diagnostic tests
  • Limited appropriate drug formulation
  • Inadequate knowledge on ARV use in children

6
Triomune
  • Generic antiretroviral drug including the fixed
    dose combination (d4T3TCNVP) manufactured by
    CIPLA, India
  • Reduced cost has made HAART more accessible
  • Clinical experience has documented satisfactory
    response to Triomune (CIPLA Ltd) (Laurent et al,
    2004)
  • Studies of Triomune in adults at JCRC document a
    decline in viral load and increase in CD4 count
    at 12 weeks into therapy (Oyugi et al, Bangkok
    2004)

7
Objectives
  • Primary Objective
  • To determine the feasibility and effectiveness of
    a generic fixed dose combination tablet
    (Triomune) in HIV infected children
  • Secondary Objectives
  • To assess adherence to Triomune among HIV
    infected children
  • To document mortality rate of the children on
    therapy

8
Methods
  • Screening
  • HIV infected children from perinatal trials at
    MU-JHU Research Collaboration and PIDC Mulago
    Hospital were screened using WHO criteria for
    antiretroviral therapy in resource limited
    settings and CD4 count/percent

9
Methods
  • Inclusion criteria
  • Symptomatic HIV positive children (WHO stage III)
  • CD4 lt 15 regardless of stage
  • CD4lt 20 with WHO clinical stage II/III
  • Adherence to 3 pre-enrollment visits
  • Caretaker willing to follow program procedures
  • ARV naïve except for PMTCT
  • Live within a 20km radius of MU-JHU

10
Methods
  • Exclusion criteria
  • AST/ALT greater than 5 times normal
  • Serum Creatinine gt 1.7mg/dl if older than 2yrs
  • Serum Creatinine gt1.2mg/dl if under 2yrs
  • Hemoglobin lt 7.0 g/dl
  • Absolute neutrophil count (ANC) lt250/mm
  • Hypersensitivity to Nevirapine
  • (Weight lt13kg)

11
Methods
12
Methods
  • Data collection
  • Baseline
  • CBC
  • CD4/CD4 abs
  • Viral Load
  • Liver function test
  • Renal function test
  • Weight/Height/Head Circumference/Age
  • Physical exam

13
Methods
  • Data collection
  • Follow up 2 years
  • CBC, CD4/CD4 abs, and viral load every 12 wks
  • Liver function test at 2 wks, then annually
  • Weight/Height/Age, Physical exam, and Pill counts
    at all routine visits
  • Preliminary data after 36 weeks on therapy will
    be presented

14
Results
  • Total number screened 155 HIV infected children
  • 69 enrolled and initiated on Triomune
  • 55 remain on Triomune (d4T/3TC/NVP)
  • 14 switched to AZT/3TC/NVP or EFV and d4T/3TC/EFV
  • 8 due to weight lt13kg
  • 4 due to hypersensitivity to NVP
  • 1 hepatitis
  • 1 thrombocytopenia
  • 4 deaths

15
Results
  • At Enrollment
  • Mean age 5yrs (1-14yrs)
  • 55 female
  • 45 male
  • 91 of the participants lt 3rd percentile expected
    weight for age (underweight)
  • 62 of the participants lt 5th percentile expected
    height for age (stunted)
  • 55 of the participants were stage II and 20
    Stage III
  • 26 of participants had CD4 lt 5, 35 between
    5-10 and 32 between 10-15

16
Results
17
RESULTSCD4 VS BASELINE, 12, 24, 36 Weeks
CD4 Percent
36wks
24wks
12wks
Baseline
18
RESULTSVIRAL LOAD VS BASELINE, 12, 24, 36 Weeks
Baseline
VIRAL LOAD
12WKS
BASELINE
24WKS
36wks
24wks
12wks
19
Results
  • 36 weeks after therapy
  • 84 (16/19) of children have CD4 gt 15
  • 71 (12/17) of children have undetectable viral
    load (lt400copies/ml)
  • Of the children with detectable viral loads 4/5
    had poor/fair adherence to syrups
  • However all 5 children with detectable viral
    loads were exposed to single-dose Nevirapine
  • All 5 children with detectable viral load had
    baseline viral loads gt750,000

20
Results
  • 4/5 of the children with detectable viral loads
    had a rebound effect

21
Results
  • All 5 children with detectable viral loads showed
    an immunologic response to therapy

22
Results
  • Adherence rate 95 in 90 of the children
  • All children with poor adherence were on syrups
  • Side effects
  • skin rash - 6 (4/69)
  • hepatitis - 1 (1/69)
  • Mortality rate is 6 (4/69)
  • 2 children had an initial CD4 count less than1
  • 3 children were severely immuno-suppressed or WHO
    stage III
  • Causes of death include toxoplasmosis, malaria,
    and pneumonia

23
Conclusions
  • The use of fixed dose combination in HIV infected
    children is feasible and effective
  • Triomune lead to a significant increase in CD4
    count and a decrease in viral load during the
    initial 36 weeks of therapy
  • Adherence is better with a fixed dose combination
    than syrups
  • We are still monitoring the effect of single dose
    Nevirapine on response to future NVP containing
    HAART regimens

24
Acknowledgments
  • Elisabeth Glaser Pediatric AIDS Foundation
  • International Leadership Award
  • Dr. Phillipa Musoke Department of Pediatrics,
    Makerere University Mulago / MU-JHU Research
    Collaboration
  • Study Staff MU-JHU Research Collaboration
  • P. Ajuna, M. Luttajumwa, B. Musoke, J. Walabyeki,
    M. Owor, M. Mubiru, M.G. Nalubega, M. Namawejje
  • Caretakers of all the children
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