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Stefano Vella

Publications and source records attributed to Stefano Vella.

At least 19 recordsLinked to original sources
PubMed2007

Triple antiretroviral prophylaxis administered during pregnancy and after delivery significantly reduces breast milk viral load: a study within the Drug Resource Enhancement Against AIDS and Malnutrition Program.

BACKGROUND: The administration of antiretroviral therapy to lactating women could represent a possible strategy to reduce postnatal HIV transmission. In this study, we assessed the effect of antiretroviral treatment on breast milk viral load and determined plasma and breast milk drug concentrations in pregnant women receiving highly active antiretroviral therapy (HAART). METHODS: We studied 40 women receiving zidovudine, lamivudine, and nevirapine from 28 weeks of gestation to 1 month postpartum (group A) and 40 untreated pregnant women (group B). Blood and breast milk samples were collected at delivery and 7 days postpartum. RESULTS: Women in group A had received a median of 85 days of therapy before delivery. Median breast milk concentrations of nevirapine, lamivudine, and zidovudine were 0.6, 1.8, and 1.1 times, respectively, those in maternal plasma. HIV RNA levels in breast milk were significantly lower in group A than in group B (median of 2.3 vs. 3.4 log at delivery and 1.9 vs. 3.6 log at day 7; P < 0.001 for both comparisons). CONCLUSIONS: Antiretroviral drugs administered during the last trimester of pregnancy and after delivery reach levels similar to or higher than plasma concentrations in breast milk and can significantly reduce HIV RNA levels. Our data support the potential role of maternal HAART prophylaxis in reducing the risk of breast-feeding-associated transmission.

Adolescent↗
PubMed2007

Apoptosis-associated gene expression in HIV-infected patients in response to successful antiretroviral therapy.

The simultaneous expression of 19 apoptosis-related genes was analyzed by RNA-protection assay in peripheral blood mononuclear cells of HIV-infected patients before and during successful antiretroviral therapy (ART). After 12 months of therapy, the expression of the pro-apoptotic genes FAS, FAS-L, FAF-1, FADD, CASPASE-8, DR3, TRAIL, TNFR-1, TRADD, and BAX was significantly downregulated with respect to time 0, while that of BCL-2, BCL-XL, and MCL-1 was significantly upregulated. The data suggest that inhibition of cell death in HIV-positive patients under successful therapy is the result of a complex network of multifactor signaling, correlated with both death and survival of lymphocytes.

Anti-HIV Agents↗
PubMed2006

Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel.

CONTEXT: Guidelines for antiretroviral therapy are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are used. The International AIDS Society-USA panel has updated its recommendations as warranted by new developments in the field. OBJECTIVE: To provide physicians and other human immunodeficiency virus (HIV) clinicians with current recommendations for the use of antiretroviral therapy in HIV-infected adults in circumstances for which there is relatively unrestricted access to drugs and monitoring tools. The recommendations are centered on 4 key issues: when to start antiretroviral therapy; what to start; when to change; and what to change. Antiretroviral therapy in special circumstances is also described. DATA SOURCES AND STUDY SELECTION: A 16-member noncompensated panel was appointed, based on expertise in HIV research and patient care internationally. Data published or presented at selected scientific conferences from mid 2004 through May 2006 were identified and reviewed by all members of the panel. DATA EXTRACTION AND SYNTHESIS: Data that might change previous guidelines were identified and reviewed. New guidelines were drafted by a writing committee and reviewed by the entire panel. CONCLUSIONS: Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/microL and before it declines to 200/microL. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and the long-term is crucial for treatment success and must be continually reinforced.

Adult↗
PubMed2006

Development of a human immunodeficiency virus vector-based, single-cycle assay for evaluation of anti-integrase compounds.

Therapeutic strategies aimed at inhibiting human immunodeficiency virus type 1 (HIV-1) replication employ a combination of drugs targeted to two viral enzymes (reverse transcriptase and protease) and to the viral entry/fusion step. However, the high propensity of HIV-1 to develop resistance makes the development of novel compounds targeting different steps of the HIV-1 life cycle essential. Among these, integrase (IN) inhibitors have successfully passed the early phases of clinical development. By preventing integration, IN inhibitors preclude viral replication while allowing production of extrachromosomal forms of viral DNA (E-DNA). Here, we describe an improved and standardized assay aimed at evaluating IN inhibitors by taking advantage of the transcriptional activity of E-DNA produced by HIV-derived vectors in the absence of replication-competent virus. In this context, the use of the firefly luciferase gene as a reporter gene provides a rapid and quantitative measure of viral-vector infectivity, thus making it a safe and cost-effective assay for evaluating novel IN inhibitors.

Cell Line↗
PubMed2005

Residual viraemia in subjects with chronic HIV infection and viral load < 50 copies/ml: the impact of highly active antiretroviral therapy.

OBJECTIVE: To determine factors associated with < 2.5 copies/ml plasma HIV RNA in subjects treated with highly active antiretroviral therapy (HAART) and with viraemia < 50 copies/ml. DESIGN: Cross-sectional analysis of 84 HIV-positive patients taking HAART with plasma HIV RNA < 50 copies/ml for at least 6 months and no history of virological failure. METHODS: Current HAART therapy was based on a non-nucleoside reverse transcriptase inhibitor (NNRTI) in 66%, a protease inhibitor in 26% and nucleoside reverse transcriptase inhibitors in 7%. Viraemia levels were measured using a modified ultrasensitive Roche Amplicor HIV-1 Monitor test able to quantify plasma HIV RNA to a lower limit of 2.5 copies /ml; proviral DNA was measured with a real-time polymerase chain reaction assay. Analysis of variance and multiple logistic regression analysis were utilized to test for associations between residual replication and other variables. RESULTS: Residual HIV viraemia > 2.5 copies/ml was found in 50% of subjects; 94% of subjects had detectable proviral DNA (>or= 20 copies/10(6) peripheral blood mononuclear cells) and 21% had archived mutations. Usage of a NNRTI-based HAART was the only independent predictor of viral suppression below the cut-off value of the modified ultrasensitive assay. CONCLUSIONS: In our population, NNRTI-based HAART seems to have a stronger impact on residual replication than protease inhibitor-based HAART. This finding may be considered in therapeutic decisions such as the choice of initial HAART regimen and the interruption or simplification of treatment.

Adult↗
PubMed2005

Interleukin-15 enhances the secretion of IFN-gamma and CC chemokines by natural killer cells from HIV viremic and aviremic patients.

Several lines of evidence documented a renewed interest in the role of natural killer (NK) cells in the innate immune control of HIV infection and disease progression. To further assess the role of NK cells as target for immunotherapy in HIV infection, we evaluated the priming effect of interleukin (IL)-15 on freshly isolated human peripheral NK cells, from viremic and aviremic HIV-infected patients, measuring the production of IFN-gamma and CC chemokines. In vitro IL-15 priming induced a significant increase of IFN-gamma production in both viremic and aviremic patients. IL-15 stimulated NK cells producing CC chemokine quantities that are reported to be capable of inhibiting HIV infection and replication. This priming effect is observed both in viral suppressed patients after antiretroviral therapy, and in viremic subjects with progressive HIV infection. The combination of IL-15 plus IL-12 is the most potent costimulus for CD69 expression and production of CC chemokines by NK cells. These findings indicate that NK cells are an important target for immunotherapeutic agents and provide additional pre-clinical data supporting the great potential of IL-15 in the immune-based interventions in HIV disease.

Adult↗
PubMed2005

The global status of resistance to antiretroviral drugs.

Since 1989, the emergence of resistant human immunodeficiency virus mutants has been documented for any new antiretroviral agent introduced in the clinical setting; it is a major cause of failure of antiretroviral therapy that may ultimately compromise the antiretroviral's efficacy in the general population. In most cases, resistance is due to poor adherence by the patient and/or to low potency of the therapeutic regimen. Resistance is called "primary" if detected in treatment-naive persons and is called "acquired" when it develops in treatment-experienced persons. This latter population represents potential transmitters of resistant viruses to newly infected persons. Data about the actual prevalence of resistance are derived from studies that differ in design, sample size, geographic area, and definitions. For this reason, a limited number of surveillance programs have been established in the past, both in countries where highly active antiretroviral therapy is widely accessible and in geographic areas where it is being introduced.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Gender differences in clinical progression of HIV-1-infected individuals during long-term highly active antiretroviral therapy.

OBJECTIVE: To assess gender differences in the long-term clinical, virological and immunological outcomes during highly active antiretroviral therapy (HAART). METHODS: This longitudinal observational multicentre study followed 2460 HIV-infected patients who had begun a protease inhibitor-based regimen for a median period of 43 months. Outcome measures were virological suppression (< 500 copies/ml), confirmed virological rebound after suppression, and death or new AIDS-defining illness (ADI). RESULTS: At baseline, 690 female patients (28.0%) had significantly lower age, higher prevalence of heterosexual contact and lower prevalence of intravenous drug use as risk factors for HIV infection compared with males. Furthermore, females had a lower number of AIDS-defining illnesses, higher CD4 cell counts and lower viral loads. No gender differences were reported in terms of proportion of patients achieving viral suppression or exhibiting rebound after achieving viral suppression. Female patients experienced reduced clinical progression during follow-up compared with males (P = 0.008) by Kaplan-Meier analysis; however this difference was not significant in an adjusted analysis. In a multivariate model, the interaction between gender and risk factor for HIV or viral load showed that female drug users and female patients with a baseline HIV RNA viral load of 10(4)-10(5) copies/ml had a favourable clinical outcome compared with males (P = 0.035 and P = 0.015, respectively). CONCLUSION: No differences were found between genders in terms of virological and immunological outcomes during long-term HAART. Nevertheless, a lower risk of clinical progression was reported among female patients with intermediate baseline viral load than in males.

Adult↗
PubMed2005

Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort.

BACKGROUND: Whether hepatitis B (HBV) coinfection affects outcome in HIV-1-infected patients remains unclear. OBJECTIVE: To assess the prevalence of HBV (assessed as HBsAg) coinfection and its possible impact on progression to AIDS, all-cause deaths, liver-related deaths and response to highly active antiretroviral therapy (HAART) in the EuroSIDA cohort. METHODS: Data on 9802 patients in 72 European HIV centres were analysed. Incidence rates of AIDS, global mortality and liver-related mortality, time to 25% CD4 cell count increase and time to viral load < 400 copies/ml after starting HAART were calculated and compared between HBsAg-positive and HBsAg-negative patients. RESULTS: HBsAg was found in 498 (8.7%) patients. The incidence of new AIDS diagnosis was similar in HBsAg-positive and HBsAg-negative patients (3.3 and 3.4/100 person-years, respectively) even after adjustment for potential confounders: the incidence rate ratio (IRR) was 0.94 [95% confidence interval (CI), 0.74-1.19; P = 0.61]. The incidences of all-cause and liver-related mortalities were significantly higher in HBsAg-positive subjects (3.7 and 0.7/100 person-years, respectively) compared with HBsAg-negative subjects (2.6 and 0.2/100 person-years, respectively). The adjusted IRR values were 1.53 for global (95% CI, 1.23-1.90; P = 0.0001) and 3.58 for liver-related (95% CI, 2.09-6.16; P < 0.0001) mortality. HBsAg status did not influence viral or immunological responses among the 1679 patients starting HAART. CONCLUSIONS: The prevalence of HBV coinfection was 9% in the EuroSIDA cohort. Chronic HBV infection significantly increased liver-related mortality in HIV-1-infected patients but did not impact on progression to AIDS or on viral and immunological responses to HAART.

Adult↗
PubMed2005

Mode of infant feeding and HIV infection in children in a program for prevention of mother-to-child transmission in Uganda.

OBJECTIVE: To evaluate the impact of different modalities of infant feeding on HIV transmission in children in a prevention of mother-to-child transmission (PMTCT) program in an urban hospital in Uganda. METHODS: HIV-infected pregnant women in the PMTCT program at St Francis Hospital Nsambya, Kampala were offered the chance to participate in the study. Short-course antiretroviral regimens were provided and formula feeding offered free of charge for women choosing not to breastfeed. Mother-infant pairs were followed until 6 months postpartum. HIV status in children was assessed at week 6 and month 6. For the analyses, mother-infant pairs were classified into three groups according to the mode of infant feeding: exclusive formula feeding (EFF), exclusive breastfeeding (EBF) and mixed feeding (MF). RESULTS: A total of 306 children were enrolled. Transmission rates were 8.9% at week 6 (3.4% in the EFF group, 11.2% in the EBF group, 17.1% in the MF group) and 12.0% at month 6 (3.7% in the EFF group, 16.0% in the EBF group, and 20.4% in the MF group). The EBF and MF groups were associated with a significantly higher risk of HIV transmission than the EFF group. No significant risk difference was observed between the EBF and the MF groups. CONCLUSIONS: HIV transmission rates were significantly lower in formula-fed infants in comparison with both exclusively breastfed and mixed-fed infants. Transmission through breastfeeding seems to occur mainly in the first weeks after delivery.

Adult↗
PubMed2005

Clinical outcome after 4 years follow-up of HIV-seropositive subjects with incomplete virologic or immunologic response to HAART.

The duration of the clinical, virologic, and immunologic response to HAART, is not well defined. In this observational multi-center study 2,143 patients were enrolled classified according to virologic suppression (<500 cp/ml) and immune recovery (>100 CD4+ cells/mul from baseline) at month 12 of HAART as complete responders, virologic only responders, immunologic only responders and non-responders. Kaplan Meyer curves, multivariate and politomous regression analysis were used. Complete responders patients were 781 (36.4%), immunologic only responders 441 (20.6%), virologic only responders 336 (15.7%), and non-responders 585 (27.3%). Using multivariate analysis, being antiretroviral-naive increased the probability of having both a virologic only or a complete response and reduced the probability of an immunologic only response (P < 0.001 for all tests). Older age was associated directly with a virologic only response and inversely associated with an immunologic only response (P = 0.027 and P = 0.035, respectively). Using politomous analysis, patients baseline HIV-RNA level more than 5 log cp/ml had a 1.9-fold higher probability of an immunologic response than of a complete response (P = 0.001). After 4 years, the clinical progression rate was six times greater in non-responders, 1.9 times greater in virologic only responders, and 2.3 times greater in immunologic only responders than for responders. However, patients with virologic only response or with immunologic only response had a significantly reduced risk for clinical progression than non-responders (P < 0.001). After 4 years of HAART, the risk of clinical progression in patients with immunologic only or virologic only response is low but still higher than in complete responder patients.

Adult↗
PubMed2005

Association between cellular human immunodeficiency virus DNA level and immunological parameters in patients with undetectable plasma viremia level during highly active antiretroviral therapy.

The association between human immunodeficiency virus (HIV) DNA load and immunologic parameters was investigated in 163 HIV-infected patients with undetectable plasma viremia during highly active antiretroviral therapy (HAART). Patients with HIV DNA below the 25th percentile (133 copies/10(6) peripheral blood mononuclear cells) had higher pre-HAART (P = 0.001) and current (P = 0.005) CD4 counts and a prolonged duration of treatment (P = 0.001). At adjusted analysis, prolonged duration of treatment was independently associated with lower (P = 0.006) and undetectable (P < 0.001) HIV DNA values.

Adult↗
PubMed2004

Causes of death in HIV infection: the key determinant to define the clinical response to anti-HIV therapy.

Studies have shown an increased risk of new AIDS/death among injecting drug users (IDU) starting highly active antiretroviral therapy (HAART). Of 3872 patients starting HAART in the EuroSIDA study, 819 were IDU (21.2%). During 14 769 person-years of follow-up, 499 patients progressed to new AIDS/death. Compared with homosexual individuals, IDU had an increased incidence of new AIDS/death, but only for non-HIV deaths. There is an urgent need to define and standardize causes of death in observational studies.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Treatment for adult HIV infection: 2004 recommendations of the International AIDS Society-USA Panel.

CONTEXT: Substantial changes in the field of human immunodeficiency virus (HIV) treatment have occurred in the last 2 years, prompting revision of the guidelines for antiretroviral management of adults with established HIV infection. OBJECTIVE: To update recommendations for physicians who provide HIV care regarding when to start antiretroviral therapy, what drugs to start with, when to change drug regimens, and what drug regimens to switch to after therapy fails. DATA SOURCES: Evidence was identified and reviewed by a 16-member noncompensated panel of physicians with expertise in HIV-related basic science and clinical research, antiretroviral therapy, and HIV patient care. The panel was designed to have broad US and international representation for areas with adequate access to antiretroviral management. STUDY SELECTION: Evidence considered included published basic science, clinical research, and epidemiological data (identified by experts in the field or extracted through MEDLINE searches using terms relevant to antiretroviral therapy) and abstracts from HIV-oriented scientific conferences between July 2002 and May 2004. DATA EXTRACTION: Data were reviewed to identify any information that might change previous guidelines. Based on panel discussion, guidelines were drafted by a writing committee and discussed by the panel until consensus was reached. DATA SYNTHESIS: Four antiretroviral drugs recently have been made available and have broadened the options for initial and subsequent regimens. New data allow more definitive recommendations for specific drugs or regimens to include or avoid, particularly with regard to initial therapy. Recommendations are rated according to 7 evidence categories, ranging from I (data from prospective randomized clinical trials) to VII (expert opinion of the panel). CONCLUSION: Further insights into the roles of drug toxic effects, drug resistance, and pharmacological interactions have resulted in additional guidance for strategic approaches to antiretroviral management.

Adult↗
PubMed2004

Predictors of immunological failure after initial response to highly active antiretroviral therapy in HIV-1-infected adults: a EuroSIDA study.

BACKGROUND: Factors that determine the immunological response to highly active antiretroviral therapy (HAART) are poorly defined. OBJECTIVE: Our aim was to investigate predictors of immunological failure after initial CD4(+) response. METHODS: Data were from EuroSIDA, a prospective, international, observational human immunodeficiency virus (HIV) type 1 cohort. RESULTS: Of 2347 patients with an increase in CD4(+) cell count >or=100 cells/microL within 6-12 months of the initiation of HAART, 550 (23%) subsequently experienced immunological failure (CD4(+) count less than or equal to the pre-HAART value). The incidence of failure was 11.6 incidences/100 person-years of follow-up (95% confidence interval [CI], 10.2-13.4) during the first 12 months and decreased significantly over time (P<.0001). Independent predictors of immunological failure were pre-HAART CD4(+) cell count (per 50% higher; relative hazard [RH], 2.05; 95% CI, 1.83-2.31; P<.0001), time-updated virus load (per 1 log(10) higher; RH, 1.77; 95% CI, 1.64-1.92; P<.0001), and HIV-1 risk behavior (P=.047 for a global comparison of risk groups). CONCLUSION: The risk of immunological failure in patients with an immunological response to HAART diminishes with a longer time receiving treatment and is associated with pretreatment CD4(+) cell count, ongoing viral replication, and intravenous drug use.

Adult↗
PubMed2004

Inverse correlation between CD8+ lymphocyte apoptosis and CD4+ cell counts during potent antiretroviral therapy in HIV patients.

OBJECTIVES: We have addressed the relationships between inhibition of CD4+ and CD8+ cell apoptosis and CD4+ cell recovery in HIV patients undergoing potent antiretroviral therapy (PART) by correlating apoptosis levels with virological and immunological parameters detected over a long-term period in HIV patients undergoing therapy. PATIENTS AND METHODS: Twenty-two HIV-1-infected patients undergoing PART were enrolled in a long-term, open longitudinal study. Data derived from 17 patients with successful response to therapy (TS; median time of follow-up 36 months, range 24-36 months) were used for correlation studies. Apoptosis was evaluated after short-term culture of peripheral blood lymphocytes by flow cytometry analysis of isolated nuclei or of annexin V/CD4, annexin V/CD8 double-stained cells. RESULTS: Sustained, noticeable levels of apoptosis inhibition in peripheral blood mononuclear cells were measured, in the long-term, in 16 of the 17 TS patients. Levels of total cell apoptosis correlated with levels of CD8+ apoptotic cells more significantly than with levels of CD4+ apoptotic cells. In addition, CD4+ cell counts were correlated inversely with levels of CD8+ apoptotic cells in a highly significant fashion, but not with levels of CD4+ apoptotic cells. CONCLUSIONS: Our data indicate that the increase of CD4+ lymphocytes in HIV patients, as a consequence of successful response to PART, may be related to changes in apoptosis level occurring in the CD8+, and not in the CD4+, cell compartment.

Adult↗