Implications of Metabolic Toxicity in Resource Limited Settings

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Implications of Metabolic Toxicity in Resource
Limited Settings

• Elly T Katabira, FRCP
• Deputy Dean - Research
• Makerere University Medical School
• 3rd IAS Conference on HIV Pathogenesis and
  Treatment.
• Rio de Janeiro, Brazil. July 26, 2005

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Outline of the Presentation

• The burden of HIV infection in resource limited
  settings
• Status of ARV use in resource limited settings
• Overview of the metabolic toxicities
• Implications of metabolic toxicity
• Diagnosis
• Patient management
• Prevention strategies
• National AIDS/HIV programs
• Conclusion

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The Burden of HIV Infection in the Developing
World

• 90 of global HIV infection found in the
  developing world
• About 70 in sub-Saharan Africa alone.
• HIV infection is the commonest cause of morbidity
  and mortality among adults
• HIV infection is among the five commonest cause
  of morbidity and mortality in children in many
  African countries

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Status of ART in Resource Limited Settings

• Number on ART still relatively very small
• 500,000 out of 25M in sub-Saharan Africa
• Major obstacles to access and use include
• Prohibitive costs of the drugs and lab services
• Inadequate knowledgeable health workers and
  communities
• Limited VCT services

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Global Response to ARVs access

• Accelerated response to increase ART in the
  developing world since 2002
• Cost effectiveness of ART now appreciated
• WHO 3 million by 2005 campaigns
• Emphasis is in sub-Saharan Africa
• Global fund for AIDS, TB and Malaria by the UN
• PEPFAR support for 14 countries from resource
  limited settings

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Implications of the Global Response

• Overwhelming pressure to put more people on ARVs
• Many too sick prone to ARV toxicity
• The need to train more health workers,
  communities and patients about ART
• Advocacy about VCT services
• Lower cadres trained to handle more complicated
  care at shorter time
• Clinical officers, nurses, pharmacy technician
• Volunteers with minimal health background

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Implications of the Global Response

• The need to improve infrastructures to cope with
  large numbers of patients on ART
• More VCT sites and equipment
• Upgrading referal centres with better diagnostics
• Quality of services is likely to be variable
  across many countries
• Metabolic toxicity prone combinations are more
  readily available e.g. Triomune
• Better alternatives too expensive

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Overview of metabolic toxicity

• Very little is known about ART related metabolic
  problems
• However, no. of reports increasing with growing
  experience
• Common problems include
• Lipodystrophy
• Lactic acidosis
• Hyperlipideamia related problems
• Insulin resistance
• Liver dysfunction

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The Implications of metabolic toxicity on Patient
Management

• Majority of patients initiated on ART are too
  sick
• In 3315 DART pts, b/l median CD4 100
• Many are on multiple drugs including herbs
• Differentiating signs and symptoms due to HIV
  disease and metabolic toxicity may be difficult
• Worse in less experienced health worker

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The Implications of metabolic toxicity on Pt
Management - 2

• Delay in diagnosis and management of the
  toxicities
• Lack of trained personnel
• Inadequate laboratory facilities
• Few labs can diagnose Lactic acidosis
• Clinical signs and symptoms often non-specific
• Erosion of patients confidence in ART
• Lipodystrophy -ve impact on pts image
• Poor adherence followed by resistance
• Effective treatment often out of reach
• Limited choices of combinations

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The Implications of metabolic toxicity on
National Programs

• As governments push for more patients on ART,
  morbidity mortality from toxicities will
  increase
• Increased demand for more training
• Pressure to invest more in lab infrastructure
• Pressure to use more expensive combinations
• Impact ART scaling up programs
• Less money available for 1st line drugs
• Fewer patients put on treatment

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Conclusion

• The burden of metabolic toxicity will grow as we
  scale up access
• The resources to identify and manage the
  toxicities is limited
• Yet there is need to minimize their negative
  impact on the ART programs
• This would need putting extra resources by
  countries themselves