Abstract
The rates of immunologic and clinical progression are lower in patients with drug-resistant HIV compared to wild-type HIV. This difference is not fully explained by viral load. It has been argued that reductions in T cell activation and/or viral fitness might result in preserved target cells and an altered relationship between the level of viremia and the rate of CD4+ T cell loss. We tested this hypothesis over time in a cohort of patients with highly resistant HIV. Fifty-four antiretroviral-treated patients with multi-drug resistant HIV and detectable plasma HIV RNA were followed longitudinally. CD4+ T cell counts and HIV RNA levels were measured every 4 weeks and T cell activation (CD38/HLA-DR) was measured every 16 weeks. We found that the levels of CD4+ T cell activation over time were a strong independent predictor of CD4+ T cell counts while CD8+ T cell activation was more strongly associated with viremia. Using spectral analysis, we found strong evidence for oscillatory (or cyclic) behavior in CD4+ T cell counts, HIV RNA levels, and T cell activation. Each of the cell populations exhibited an oscillatory behavior with similar frequencies. Collectively, these data suggest that there may be a mechanistic link between T cell activation, CD4+ T cell counts, and viremia and lends support for the hypothesis of altered predator-prey dynamics as a possible explanation of the stability of CD4+ T cell counts in the presence of sustained multi-drug resistant viremia.
Highlights
Current therapeutic strategies for HIV-infected persons include the use of antiretroviral therapy to fully inhibit viral replication, as defined by achieving and maintaining undetectable plasma HIV RNA levels
We found that CD4+ T cell activation was most strongly associated with the CD4+ T cell counts while CD8+ T cell activation was more strongly associated with viremia
We chose a threshold of 10,000 copies of HIV RNA/mL for this study because previous data suggested that viral loads above this threshold might be associated with rapid CD4+ T cell loss
Summary
Current therapeutic strategies for HIV-infected persons include the use of antiretroviral therapy to fully inhibit viral replication, as defined by achieving and maintaining undetectable plasma HIV RNA levels. As compared to untreated disease, those who remain on a stable regimen despite the presence of drug-resistance mutations have slower rates of CD4+ T cell decline and a lower risk of progressing to AIDS and/or death [1,2,3]. This effect appears to be more strongly associated with failure of protease inhibitor-based regimens than with failure of non-nucleoside reverse transcriptase inhibitor based regimens [1,4]. Partial reduction in viral load clearly contributes to the residual benefit of therapy [5], the delayed risk of disease progression in treated versus untreated disease remains significant, even after controlling for viral load [1,2]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
