HIV-1 dynamics at different time scales under antiretroviral therapy

We exploit a model that considers three compartments: blood plasma (BP), lymphoid tissue-interstitial spaces (LT-IS), and follicular dendritic cells (FDC), for the HIV-1 dynamics under the application of highly active antiretroviral therapy (HAART) which allowed us to unravel distinct viral dynamics occurring in short- (2 days), middle- (21 days), and long-term (183 days) time scales. The different time scales are determined by the viral clearance rate, the ratio of productively infected CD4⁺ T cells to chronically infected cells, and the dissociation rate of HIV-1 complexes from FDC. This generates a scenario in which, after an initial transient stage, the viral BP dynamics decouples and becomes governed by the lymphoid tissue (LT) dynamics; in a later stage, a new decoupling occurs in which the LT-IS dynamics is slaved to that of the FDC dynamics. We observed an initial increase in the viremia after HAART in a patient who did not receive protease inhibitors (PI). By means of the above-mentioned model we were able to highlight the relevant parameters which need to be estimated at three different time scales after HAART.     

Proteomic analysis of serum cytokine levels in response to highly active antiretroviral therapy (HAART)

A 30-cytokine protein microarray was used to screen for cytokine profile changes in HIV-infected patients in response to highly active antiretroviral therapy (HAART). Serum cytokines showing significant changes were confirmed by enzyme immunoassay. Monokine induced by gamma-interferon (MIG) and interferon-inducible protein-10 (IP-10) levels significantly decreased after 24 weeks of HAART. Protein microarrays are useful for initial screening of novel cytokine expression. Further studies are needed to elucidate the role of MIG and IP-10 in response to HAART.     

Une radiothérapie interne contre l’infection au VIH, la dernière pièce du puzzle ?

Although highly active antiretroviral therapy (HAART) has succeeded in many cases in suppressing ongoing viral replication, the HIV-infected cells are not eradicated by this therapy. In this article, the author proposes a new treatment protocol based on administration of radiophosphorus 32 (³²P) with HAART combination. The proposed new protocol consists of the following steps: HAART keeps viral replication below the level of detection. Then, ³²P is administered for the removal of the “residual disease”. By its beta emission, incorporated ³²P to viral RNA or proviral DNA may kill free virions and productively infected cells, reactivates latently infected cells and makes them vulnerable to immune competent cells and antiretroviral therapy. This new combination may exhibit synergistic interactions between virostatic effects of antiretroviral molecules and radiobiological effect of internal radiotherapy and provide a new tool to purge the viral reservoirs.