Short-cycle structured intermittent treatment of chronic HIV infection with highly active antiretroviral therapy: Effects on virologic, immunologic, and toxicity parameters

We evaluated the effect of short-cycle intermittent highly active antiretroviral therapy on HIV-specific immune responses, antiretroviral drug susceptibility, and serum cholesterol and triglyceride levels

M. Dybul

2002

Scholarcy highlights

  • Highly active antiretroviral therapy has reduced HIV mortality significantly, it is clear that prolonged treatment that maintains suppression of plasma viremia is unlikely to eradicate HIV
  • We evaluated the effect of short-cycle intermittent highly active antiretroviral therapy on HIV-specific immune responses, antiretroviral drug susceptibility, and serum cholesterol and triglyceride levels
  • In addition to a lack of increase in HIV RNA or DNA in peripheral blood mononuclear cells during up to 52 weeks of intermittent therapy, there was no change in the pool of CD4ϩ T cells harboring replication-competent HIV during 24 weeks of intermittent HAART; the median infectious units per million CD4ϩ T cells of 0.12 at enrollment was no different from the median of 0.14 at 24 weeks of structured intermittent therapy
  • Because plasma viremia was too low for standard drug susceptibility testing, we evaluated replication-competent HIV or, where that was not detected, genomic DNA from purified CD4ϩ T cells
  • The importance of strict adherence to the prescribed regimen was clear as suggested by the fact that a ‘‘drug holiday’’ for 21 days or a relatively brief interruption of HAART for 10 days rather than 7 days resulted in a significant increase in plasma viremia
  • With up to 34 cycles of 7 days on HAART followed by 7 days off of HAART, there was no clear increase in HIV replication as determined by plasma viremia and as suggested by the stable levels of HIV proviral DNA, RNA, and replication-competent virus in the peripheral
  • This proof-of-concept study has demonstrated the feasibility of reducing the amount of antiretroviral therapy patients are required to receive by 50% while maintaining suppression of HIV in peripheral blood and lymphoid tissue, preserving CD4ϩ T cell counts and reducing markers of toxicity

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