Florio Ghinelli

Therapeutic immunization with hiv-1 tat reduces immune activation and loss of regulatory t-cells and improves immune function in subjects on HAART

Although HAART suppresses HIV replication, it is often unable to restore immune homeostasis. Consequently, non-AIDS-defining diseases are increasingly seen in treated individuals. This is attributed to persistent virus expression in reservoirs and to cell activation. Of note, in CD4+ T cells and monocyte-macrophages of virologically-suppressed individuals, there is continued expression of multi-spliced transcripts encoding HIV regulatory proteins. Among them, Tat is essential for virus gene expression and replication, either in primary infection or for virus reactivation during HAART, when Tat is expressed, released extracellularly and exerts, on both the virus and the immune system, effects that contribute to disease maintenance. Here we report results of an ad hoc exploratory interim analysis (up to 48 weeks) on 87 virologically-suppressed HAART-treated individuals enrolled in a phase II randomized open-label multicentric clinical trial of therapeutic immunization with Tat (ISS T-002). Eighty-eight virologically-suppressed HAART-treated individuals, enrolled in a parallel prospective observational study at the same sites (ISS OBS T-002), served for intergroup comparison. Immunization with Tat was safe, induced durable immune responses, and modified the pattern of CD4+ and CD8+ cellular activation (CD38 and HLA-DR) together with reduction of biochemical activation markers and persistent increases of regulatory T cells. This was accompanied by a progressive increment of CD4+ T cells and B cells with reduction of CD8+ T cells and NK cells, which were independent from the type of antiretroviral regimen. Increase in central and effector memory and reduction in terminally-differentiated effector memory CD4+ and CD8+ T cells were accompanied by increases of CD4+ and CD8+ T cell responses against Env and recall antigens. Of note, more immune-compromised individuals experienced greater therapeutic effects. In contrast, these changes were opposite, absent or partial in the OBS population. These findings support the use of Tat immunization to intensify HAART efficacy and to restore immune homeostasis. Trial registration ClinicalTrials.gov NCT00751595

Suicide probability and psychological morbidity secondary to HIV infection: a control study of HIV-seropositive, hepatitis C virus (HCV)-seropositive and HIV/HCV-seronegative injecting drug users

BACKGROUND Suicide ideation and psychological morbidity among HIV-positive patients has been the object of intense research. No study has investigated this area among injecting drug users (IDUs) infected with HIV and those infected with the hepatitis C virus (HCV), which has the same patterns of transmission of the HIV and may favour HIV replication and, possibly, HIV disease progression. METHODS In order to examine the prevalence and characteristics of suicide ideation and psychological morbidity associated with HIV and HCV infection in IDUs, a sample of HIV+ (n=81), HIV-/HCV+ (n=62) and HIV-/HCV- (n=152) subjects completed the Suicide Probability Scale (SPS), The Brief Symptom Inventory (BSI) and the Hospital Anxiety and Depression Scale (HADS). RESULTS No difference was found between the groups as far as the mean scores on SPS and the risk of suicide (no-low risk category: 70.7% HIV+, 56.09% HCV+, 65.6% HIV-/HCV-). Estimated psychological morbidity (BSI) (26.9% HIV+, 27.1% HCV+, 25.4% of HIV-/HCV-) and BSI and HADS scores were comparable across the groups. CONCLUSIONS Suicide ideation, psychological morbidity and anxiety and depression symptoms seemed not to be directly influenced by HIV-serostatus. Careful assessment of psychological symptoms and suicide ideas among IDUs, as a vulnerable segment of population at risk of HIV and HCV infections, needs to be routinely carried out in clinical settings.

Incidence of malignancies in HIV-infected patients and prognostic role of current CD4 cell count: evidence from a large Italian cohort study.

The incidence of and predictors of acquired immunodeficiency syndrome-defining malignancies (ADMs) and non-ADM (NADMs) were evaluated in a large Italian cohort. The incidence of ADM and NADM was 5.0 cases per 1000 person-years of follow-up (95% confidence interval, 4.3-5.8 cases per 1000 person-years of follow-up) and 2.4 cases per 1000 person-years of follow-up (95% confidence interval, 1.9-3.1 cases per 1000 person-years of follow-up), respectively. Lower current CD4 cell count was an independent predictor of developing malignancies, with the association being stronger for ADM than for NADM.

Different patterns of HIV-1 DNA after therapy discontinuation

BackgroundBy persisting in infected cells for a long period of time, proviral HIV-1 DNA can represent an alternative viral marker to RNA viral load during the follow-up of HIV-1 infected individuals. In the present study sequential blood samples of 10 patients under antiretroviral treatment from 1997 with two NRTIs, who refused to continue any antiviral regimen, were analyzed for 16 – 24 weeks to study the possible relationship between DNA and RNA viral load.MethodsThe amount of proviral DNA was quantified by SYBR green real-time PCR in peripheral blood mononuclear cells from a selected group of ten patients with different levels of plasmatic viremia (RNA viral load).ResultsVariable levels of proviral DNA were found without any significant correlation between proviral load and plasma HIV-1 RNA levels. Results obtained showed an increase or a rebound in viral DNA in most patients, suggesting that the absence of therapy reflects an increase and/or a persistence of cells containing viral DNA.ConclusionEven though plasma HIV RNA levels remain the basic parameter to monitor the intensity of viral replication, the results obtained seem to indicate that DNA levels could represent an adjunct prognostic marker in monitoring HIV-1 infected subjects.

Invasive Aspergillosis and HIV Infection

Invasive aspergillosis was previously considered an AIDS-defining disease. However, this infection is seen only occasionally in HIV-infected patients, usually affecting patients with advanced disease. The most commonly implicated factors for invasive aspergillosis are neutropenia, granulocyte dysfunction, exposure to broad-spectrum antibacterial therapy and a long term steroid use. The diagnosis of invasive pulmonary aspergillosis is hampered by the absence of typical clinic-radiological findings. New diagnostic tests such as galactomannan testing are of limited utility for AIDS patients. Cerebral aspergillosis seems to be more prevalent in the HIV population than in other groups. Treatment of invasive aspergillosis in the context of HIV infection is similar to treatment in patients not infected with the HIV, though special attention is required for drug-drug interactions.