Drug resistant HIV strains often develop in patients who have taken anti-HIV drugs for an
extended time. However, these drug resistant HIV strains do not always cause an increase in
the level of HIV in the blood. This study will explore why some patients with drug
resistant virus continue to have low viral loads.
Despite the emergence of high level drug resistance in HIV-infected patients on stable
antiretroviral therapy, plasma HIV RNA levels generally remain below the pretherapy viral
load "set-point". The virologic and immunologic determinants of this lower steady state
level of viremia have not been defined. Preliminary data indicate that: 1) drug resistant
variants have reduced replicative capacity and pathogenic potential; 2) drug resistant
viremia is associated with reduced T cell activation and turnover compared to wild-type
viremia; and 3) patients with low level drug resistant viremia often have HIV-specific CD4
cells that are absent in patients with higher levels of viremia. This study will
investigate whether the emergence of a poorly fit, drug resistant variant results in the
generation of an effective HIV-specific CD4 cell response and if this response contributes
to the establishment of a lower steady state level of viremia.
Participants in this study will be followed for 2 years or until antiretroviral therapy is
modified or discontinued. Study visits will occur every 2 months, for a total of 14 visits.
Study visits will include a patient interview and blood tests to measure the breadth and
magnitude of the HIV-specific CD4 and CD8 cell responses as a function of viral load, viral
replicative capacity, drug resistance phenotype, T cell turnover, and thymic function.
- HIV-infected for at least 6 months prior to study entry
- Documented pretherapy or off-therapy viral load of more than 10,000 copies/ml on at
least 2 occasions or more than 20,000 copies/ml on at least 1 occasion
- At least a 70% reduction in plasma HIV RNA levels from pretherapy baseline
- Stable highly active antiretroviral therapy (HAART) regimen for at least 4 months
prior to study entry
- HIV viral load of 200 to 10,000 copies/ml for 3 months prior to study entry
- CD4 count greater than 100 cells/mm3 and a nadir CD4 count less than 500 cells/mm3
- Virologic failure as defined by DHHS guidelines on at least one HAART regimen prior
to the study entry HAART regimen
- Documented adherence to antiretroviral therapy
- Two major resistance mutations to at least two antiretroviral drug classes
- Significant toxicity on current HAART regimen