Impact of HIV-1 Cellular Viral Load on the Progression of HIV-1 Disease

Leondios G. Kostrikis. Department of Biological Sciences, University of Cyprus, 75 Kallipoleos Avenue, P.O.Box 20537, CY-1678, Nicosia (Cyprus)

Background: A number of studies have identified several forms of HIV-1 DNA in untreated HIV-1-infected individuals and in patients whose plasma HIV-1 RNA load is suppressed by long-term potent antiretroviral therapy. Material and Methods: The overall aim of our studies is to establish whether the concentration of HIV-1 DNA in cells, defined as “HIV-1 cellular viral load,” has any implications in the progression of HIV-1 disease in untreated patients and whether HIV-1 cellular viral load can predict the long-term outcome of antiretroviral therapy. We measured the HIV-1 cellular viral load by using a molecular-beacon-based real-time PCR assay in untreated patients and assessed the influence of baseline HIV-1 cellular viral load levels on the progression of HIV-1 disease. Furthermore, we measured the HIV-1 cellular viral load in patients before and after effective antiretroviral therapy. Results: Among the untreated patients who progressed to AIDS, the median HIV-1 cellular viral load levels, were significantly higher compared to those who remained AIDS-free during the 16 years of follow-up. The progression rates of death and development of AIDS varied significantly by quartile distribution of cellular viral load levels. By adjusting for other parameters, the relative hazard of death and AIDS was significantly increased with higher cellular viral load levels. In patients under antiretroviral therapy, we have shown that none of the patients with an initial virological response to antiretroviral therapy and baseline HIV-1 cellular viral load levels below the median experienced a rise of HIV-1 plasma viral load. Conclusions: Our findings show that HIV-1 cellular viral load had an independent effect on the clinical outcome of HIV-1 disease and it may have important implications on the long-term success to antiretroviral therapy.