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

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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
• 3rd IAS Conference
• July 27, 2005

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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
• Death occurred in 30,66, 75 of the children at
  1, 3, and 5 years respectively (Marum et al. July
  1996)

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Background

• Benefits of HAART have not yet been fully
  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)

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HAART in Uganda

• Approximately 64,000 individuals on HAART
  (Ministry of Health,2005)
• lt 4000 are children under 15 years of age
  (Ministry of Health,2005)
• Majority of the children on HAART are in a few
  clinics
• Children are often left out because of
• Lack of infant HIV diagnostic tests
• Limited appropriate drug formulation
• Inadequate knowledge on ARV use in children

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Triomune

• Fixed dose combination (d4T3TCNVP) - CIPLA
• Reduced cost has made HAART more accessible
• Clinical experience has documented satisfactory
  response (Laurent et al, 2004)
• In Uganda a study in adults documented a decline
  in viral load and increase in CD4 count at 12
  weeks into therapy (Oyugi et al, Bangkok 2004)
• Most of the fixed dose combinations available are
  in tablet or capsule form and not in formulations
  appropriate for young children

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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

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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

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Methods

• Data collection
• Baseline
• CBC, CD4/CD4 abs,Viral Load
• Liver function test and Renal function test
• Follow up 2 years
• CBC, CD4/CD4 abs, and viral load every 12 wks
• Adherence assessment by self report and pill
  counts at all routine visits
• Plasma storage for later NVP resistance testing
• Sub-study for NVP pharmacokinetic (n20)
• Preliminary data after 48 weeks on therapy will
  be presented

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Results

• Total number screened 164 HIV infected children
• 90 enrolled
• 81 given Triomune (d4T/3TC/NVP) as 1st line
  regime
• 72 remain on Triomune
• 14 are on alternative regimens
• 8 due to weight lt13kg
• 4 due to hypersensitivity to NVP
• 1 hepatitis
• 1 virologic failure
• 4 deaths

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Results

• At Enrollment
• Median age 5yrs (1-14yrs)
• 48 female
• 96 lt 3rd percentile expected weight for age
• 67 lt 5th percentile expected height for age
• 60 WHO stage II and 16 WHO stage III
• 26 with CD4 percent lt 5
• 67 with CD4 percent between 5-15

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Results
Baseline n 90 12 wks n 78 24 wks n 52 36 wks n25 48 wks n23
Median CD4 9 (0.2-22) 17 (1-41) plt0.0001 23 (7-44) plt0.0001 27 (8-58) plt0.0001 32 (10-76) plt0.0001
Median Viral Load (copies/mL) Non-detectable lt400copies/ml 284,391 (150-gt750,000) 121 (0-gt750,000) plt0.0001 141 (0-133,469) plt0.0001 190 (0-140,418) plt0.0001 190 (0-416,941) plt0.0001
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Results
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ResultsViral Load vs Baseline, 12, 24,36, 48
Weeks
Baseline
VIRAL LOAD
12wks
12wks
24wks
36wks
48wks
12wks
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Results

• 48 weeks after therapy
• 96 (22/23) of children have CD4 gt 15
• 83 (19/23) of children have undetectable viral
  load (lt400copies/ml)
• 42 (8/19) of the children with undetectable
  viral loads were NVP exposed at birth
• Adherence rate 95 in 90 of the children
• Majority of children with poor adherence were on
  syrups

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Results- Toxicity and Mortality

• Side Effects
• skin rash - 4 (4/90)
• hepatitis - 1 (1/90)
• Mortality rate is 4 (4/90)
• 2/4 children had an initial CD4 count less than
  1
• 3/4 children were severely immuno-suppressed or
  WHO stage III
• Causes of death include toxoplasmosis, malaria,
  and pneumonia

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Results

• Treatment Failure
• Defined as viral load gt400 copies/ml at 48 wks
• The 4 children with detectable viral loads
• history of poor/fair adherence to syrups
• exposure to single-dose Nevirapine at birth
• baseline viral loads gt750,000 copies/ml
• viral rebound effect

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Results- Treatment Failure

• 1/4 children with detectable viral loads has also
  shown immunologic failure to therapy

Baseline CD4 12wk CD4 24wk CD4 36wk CD4 48wk CD4
A 11.1 31.8 27.4 32.1 32.5
B 7.1 14.4 15.5 20.5 31.8
C 2.2 7.8 12.4 14.5 9.9 (4.5 at 60wk)
D 13.2 21.1 30.6 34.8 39.2
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Conclusions

• The use of fixed dose combination in HIV infected
  children is feasible and effective
• Triomune led to a significant increase in CD4
  count and a decrease in viral load during the
  initial 48 weeks of therapy
• Adherence is better with a fixed dose combination
  than syrups
• We are still monitoring the effect of single-dose
  Nevirapine exposure on response to future NVP
  containing HAART regimens

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Acknowledgments

• Elizabeth Glaser Pediatric AIDS Foundation
• International Leadership Award (ILA)
• Dr. Phillipa Musoke Department of Pediatrics,
  Makerere University Mulago / MU-JHU Research
  Collaboration, Recipient of ILA
• Program Staff MU-JHU Research Collaboration
• P. Ajuna, M. Luttajumwa, B. Musoke, J. Walabyeki,
  M. Owor, M. Mubiru, M.G. Nalubega, M. Namawejje,
  E. Babirekere
• MU-JHU Research Collaboration
• Children and their caretakers

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Thank You