Long-term Effects of Highly Active Anti-Retroviral Therapy on HIV-Infected Children
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Observational

Summary: 
      This study will use the NIH-sponsored Women and Infants Transmission Study (WITS) and the
      Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection
      (P2C2) HIV-infected pediatric cohorts to determine how left ventricular (LV) function
      (particularly fractional shortening and contractility) and structure (particularly wall
      thickness and mass) are affected by cumulative intensity of exposure to highly active
      anti-retroviral therapy (HAART).
    

Detailed description: 
      BACKGROUND:

      HIV-infected children are often given HAART to reduce HIV-associated disease. The long-term
      effects and toxicities associated with this chronic therapy in children are unknown, but
      severe cardiotoxicity has been suggested in animal models.

      DESIGN NARRATIVE:

      The P2C2 HIV-infected pediatric cohort received non-HAART regimens in various intensities.
      Yet, this cohort has exhibited persistent and significant depression of LV contractility
      compared to uninfected children (after 5 years of follow-up). These same echocardiographic
      measures have proven to be independently predictive of mortality. Most of the children in the
      WITS HIV-infected pediatric cohort have been exposed to HAART at varying times and at varying
      regimen intensities. By assessing LV structure and function, with the same echocardiographic
      protocol in the WITS cohort as was used previously in the P2C2 cohort, the study will be able
      to determine the incremental effects of HAART and non-HAART regimens on LV structure and
      function. The study will also test the hypothesis that HAART exposure results in impaired
      mitochondrial function that results in cardiomyopathy. This will be assessed by comparing the
      parameters of LV structure and function that define cardiomyopathy to the frequency of
      mitochondrial DNA mutations in cells from these same patients. A nested-case-control study
      design of mitochondrial mutations will be used to assess the relationship between HAART,
      mitochondrial compromise, and LV structure and function. Treatment intensity for both HAART
      and non-HAART regimens will be captured through a cumulative score based on an existing
      8-point ordinal scale. Intensity will be measured at three points in time: 1) in utero; 2)
      during the first year of life; and 3) after the first year of life. Analysis of the
      longitudinal echocardiographic and mitochondrial data will provide valuable information about
      dose intensity and the comparative impact of HAART versus less aggressive drug regimens. It
      will also provide information on the impact of therapy during different stages of child
      development. Similar longitudinal data on viral load and duration of HIV will enable the
      investigators to control for the effects of HIV infection on cardiovascular toxicity. The
      findings will help determine the need for cardiovascular follow-up, prevention, and
      therapeutic trials.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Study participants will be children perinatally infected with HIV who were enrolled in the
        Women and Infants Transmision Study (WITS).

        This cohort will be compared to the historical Pediatric Pulmonary and Cardiovacular
        Complications Study (P2C2 HIV) cohort of perinatally HIV-infected children not exposed to
        HAART.
      
Biospecimen description: 
      Peripheral blood mononuclear cells (PBMCs) were collected from the WITS cohort to investigate
      the presence of mitochondrial DNA (mtDNA) mutations.