Epidermal Nerve Fiber Density, Fat and Mitochondrial Parameters in Thai HIV+ Patients on d4T and HIV- Patients

• Number of nerves in the skin [ Time Frame: Baseline ] [ Designated as safety issue: No ]

  To compare differences in ENFD between the 4 groups

  • group 1: HIV-positive subjects on long-term d4T with symptomatic peripheral neuropathy
  • group 2: HIV-positive subjects on long-term d4T without peripheral neuropathy
  • group 3: HIV-negative subjects without peripheral neuropathy
  • group 4: HIV-positive subjects on long-term d4T with asymptomatic peripheral neuropathy
  
  
• Condition of lipoatrophy [ Time Frame: Baseline ] [ Designated as safety issue: No ]

  To compare differences lipoatrophy between the 4 groups

  • group 1: HIV-positive subjects on long-term d4T with symptomatic peripheral neuropathy
  • group 2: HIV-positive subjects on long-term d4T without peripheral neuropathy
  • group 3: HIV-negative subjects without peripheral neuropathy
  • group 4: HIV-positive subjects on long-term d4T with asymptomatic peripheral neuropathy
  
  

• Mitochondrial parameters [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  
• Intracellular concentrations of d4T triphosphate [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  
• HIV DNA in peripheral blood mononuclear cell (PBMC) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  

The range of changes in epidermal nerve fiber density (ENFD), subcutaneous fat, and mitochondrial function induced by stavudine (d4T)-based therapy is currently not known, globally or specifically in the Thai population. This study will evaluate ENFD and subcutaneous fat and peripheral blood mitochondrial parameters in 4 groups of subjects. Group 1 will include Thai HIV-positive subjects on long-term d4T treatment with symptomatic peripheral neuropathy. Group 2 will include Thai HIV-positive subjects on long-term d4T treatment without peripheral neuropathy. Group 3 will include HIV-negative subjects without peripheral neuropathy.Group 4 will include Thai HIV-positive subjects on long-term d4T treatment with asymptomatic peripheral neuropathy. Information gained from Thai HIV-positive subjects on long-term d4T treatment with and without neuropathy in this study will provide range of positive control values for subjects in the SEARCH 003 study and other studies looking at the influence of antiretroviral agents on peripheral nerve, fat, and mitochondria. Information gained from Thai HIV-negative subjects without neuropathy can be used as negative control values for subjects in the SEARCH 003 study and other studies looking at the influence of HIV or other diseases/pathogens on peripheral nerve, fat, and mitochondria.

Hypothesis

1. HIV-positive patients who have been on long-term d4T treatment with symptomatic peripheral neuropathy will have less ENFD, increased lipoatrophy, and altered mitochondrial function than those on long-term d4T treatment with asymptomatic peripheral neuropathy and those on long-term d4T treatment without peripheral neuropathy.
2. HIV-negative patients without peripheral neuropathy will have more ENFD, no lipoatrophy, and better mitochondrial function than HIV-positive patients.

The SEARCH 003 study will assess the extent of deterioration in ENFD induced by short-term (from entry to 24 weeks) d4T use and the degree of improvement following discontinuation of d4T (from week 24 to 72). However the range of changes in ENFD and in other mitochondrial parameters induced by d4T-based therapy in not known, globally or specifically in the Thai population.

This is a cross-sectional study that will enroll 25 HIV-positive subjects on long-term d4T treatment with symptomatic peripheral neuropathy, 25 HIV-positive subjects on long-term d4T treatment without peripheral neuropathy, 50 HIV-negative subjects without peripheral neuropathy and 25 HIV-positive subjects on long-term d4T treatment with asymptomatic peripheral neuropathy for a one-time assessment.