Rodolfo Iuliano

Modelling and control of HIV dynamics

Various models of HIV infection and evolution have been considered in the literature. This paper considers a variant of the Wodarz and Nowak mathematical model, adding aggressiveness as a new state variable in order to quantify the strength of the virus and its response to drugs. Although the model proposed is relatively simple, simulation results suggest that it may be useful in predicting the impact of the effectiveness of therapy on HIV dynamics.

Correlation between plasma HIV-1 RNA levels and the rate of immunologic decline.

To determine the influence of HIV-1 replication on immunologic decline and clinical outcome, we quantified the HIV-1 plasma viral load in 20 patients at different times over a mean period of 10.8 months. Quantitation was performed by branched DNA signal amplification (bDNA) and p24 antigenemia. Immunologic status was assessed through beta 2-microglobulin and CD4+ cell count determinations. CD4+ cell decline was expressed as a slope of the regression line constructed by the logarithms of CD4+ cell count observations. Mean values of plasma viral load were correlated with CD4+ cell decline and mean beta 2-microglobulin levels. Significant correlation was observed between plasma viral load quantified by the bDNA technique and CD4+ cell decline. No significant correlation was observed between plasma viral load quantified by p24 antigenemia and CD4+ cell decline. A significant correlation was observed between plasma viral load and beta 2-microglobulin levels. Immunologic decline was better predicted from HIV-1 RNA levels than from the CD4+ cell count. Significantly higher plasma viral load was observed in patients who had clinical progression of HIV-1 infection. Thus, HIV-1 plasma viral load quantified by a highly reliable technique such as bDNA showed that the immunologic decline is closely related to HIV-1 RNA replication.

Human herpesvirus‐6 reactivation in a longitudinal study of two HIV‐1 infected patients

After primary infection, human herpesvirus‐6 (HHV‐6) persists in latent form and can be reactivated in immunocompromised subjects. A longitudinal study of HHV‐6 infection was carried out in two HIV‐1 seropositive patients to provide in vivo evidence of HHV‐6 reactivation. Concomitant with a significant rise of anti‐HHV‐6 IgG detected by IFA, a transient increase of HHV‐6 viral load was shown in PBLs by PCR. During HHV‐6 reactivation it was also identified either cell‐free HHV‐6 by PCR in plasma or IgM antibody titers. HHV‐6 reactivation was followed by a temporary decrease in CD4+ count and by a progressive dramatic loss of CD4+ during the following 18 months. HHV‐6 strain characterization by PCR demonstrated that first patient (MM) initially showed the B variant, followed by reactivation and persistence of the A variant, while in the second (SG) only the A variant was detected. The evidence of HHV‐6 reactivation suggests its involvement in immunologic damage underlying the disease. J. Med. Virol. 51:259–264, 1997.

In vitro Antiviral Activity of Distamycin A against Clinical Isolates of Herpes Simplex Virus 1 and 2 from Transplanted Patients

Objective(s): Herpes simplex virus (HSV) infections in immunocompromised individuals may require prolonged antiviral therapy resulting in the emergence of viral strains resistant to the currently employed antiviral drugs. Distamycin A (DA), a basic antibiotic belonging to the lexitropsin DNA minor groove binding drugs, exhibits antiviral properties. In this study we evaluated the in vitro cytotoxicity and antiviral activity of DA against HSV type 1 and HSV type 2 clinical isolates from transplanted patients and compared them with those of acyclovir (ACV) in search of alternative antiviral drugs. Methods: Viral detection and typing was performed by multiplex PCR and immunofluorescence assay; the in vitro cytotoxicity of DA and the antiviral activity of ACV and DA was evaluated respectively by neutral red uptake assay and plaque reduction assay for HSV2 isolates and fluorescence reduction assay for HSV1 isolates. Results: Tissue culture 50% cytotoxic concentration of DA was 58 µM. Tissue culture 50% inhibitory concentration values ranged from 0.16 to 7.4 µM for the ACV-sensitive and from 5.4 to 32 µM for the ACV-resistant viral strains. Conclusions: In spite of the lower activity against ACV-resistant strains, DA may be used as an antiherpetic drug.

Quantitation of HCV viraemia by branched DNA signal amplification in patients treated with α-interferon — A longitudinal study

SummaryUsing bDNA, the plasma viral load trend of HCV-infected patients undergoing IFN therapy was analyzed. Nine patients were enrolled, each assigned to one of three groups, based on IFN response as determined by ALT and AST level trend. HCV was genotyped using DEIA. Each patients clinical stage was determined by liver biopsy analysis. In nonresponding patients elevated viral loads and biochemical parameters were observed. These values were not influenced by IFN treatment. In relapsed patients the cessation of IFN treatment increased viral load; this was associated with a rise in ALT and AST values. In responders ALT and AST levels remained normal; viral load was low. Patients with elevated HCV viral load showed a worsening in their liver histology during the follow-up period. These results confirm that plasma viral load is a good marker of biochemical change and disease progression.ZusammenfassungDer Verlauf der Virämie bei mit Hepatitis C Virus (HCV) infizierten Patienten unter Therapie mit Interferon-α wurde analysiert. Neun Patienten wurden nach dem Trend der AST- und ALT-Spiegel drei Gruppen zugeordnet: Patienten, die auf eine Therapie mit Interferon α ansprachen, Patienten, die nicht ansprachen und Patienten, die ein Rezidiv entwickelten. Der HCV-Genotyp wurde mittels DEIA bestimmt. Das klinische Stadium wurde durch Leberbiopsien ermittelt. Bei Patienten, die nicht ansprachen, war die Virämie hoch, die biochemischen Parameter wiesen hohe Spiegel auf. Die Werte wurden durch die Interferon α-Therapie nicht verändert. Bei Patienten, die nach Absetzen von Interferon ein Rezidiv entwickelten, stiegen Viruslast, ALT- und AST-Werte erneut an. Bei erfolgreich Therapierten blieben die ALT- und AST-Spiegel in einem normalen Bereich. Hohe Virustiter waren mit einer Verschlechterung der Leberhistologie während der Verlaufsbeobachtung verbunden. Die Ergebnisse belegen, daß die Virustiter im Plasma ein guter Marker für die biochemischen Parameter und die weitere Krankheitsentwicklung sind.