Barbara Ensoli

Istituto Superiore di Sanità, Roma, Latium, Italy

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Publications (135)557.01 Total impact

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    ABSTRACT: In addition to contrast human immunodeficiency virus (HIV) replication, the HIV protease inhibitors (HIV-PI) have reduced tumour incidence or clinical progression in infected patients. In this regard, we have previously shown that, independently of its anti-viral activity, the HIV-PI indinavir (IDV) directly blocks matrix metalloproteinase (MMP)-2 proteolytic activation, thus efficiently inhibiting tumour angiogenesis in vitro, in animal models, and in humans. Herein we investigated the molecular mechanism for IDV anti-angiogenic effect. We found that treatment of human primary endothelial cells with therapeutic IDV concentrations decreases the expression of membrane type (MT)1-MMP, which is the major activator of MMP-2. This occurs for both the constitutive expression of MT1-MMP and that up-regulated by angiogenic factors. In either cases, reduction of MT1-MMP levels by IDV is preceded by the inhibition of the binding of the specificity protein (Sp)1 transcription factor to the promoter region of the MT1-MMP gene in endothelial cell nuclei. As MT1-MMP is key for tumour angiogenesis, these results support the use of IDV or its derivatives in anti-cancer therapy. This is recommended by the low toxicity of the drug, and the large body of data on its pharmacokinetic.
    Angiogenesis 04/2014; · 3.97 Impact Factor
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    ABSTRACT: Little is known about the effects of Major Histocompatibility Complex (MHC) haplotypes on immunity to primate lentiviruses involving both acquired and innate immune responses. We present statistical evidence of the influence of MHC polymorphism on antiviral immunity of Mauritian cynomolgus macaques (MCM) following simian/human immunodeficiency virus SHIVSF162P4cy infection, involving the production of pro- and anti-inflammatory cytokines and α-defensins, which may modulate acquired immune responses. During the acute phase of infection, IL-10 correlated positively with viral load and negatively with CD4+T cell counts. Furthermore, α-defensins production was directly correlated with plasma viral RNA, particularly at peak of viral load. When the effects of the MHC were analyzed, a significant association between lower anti-Env binding and neutralizing antibody levels with class IB M4 haplotype and with class IA, IB M4 haplotype, respectively, was observed in the post-acute phase. Lower antibody responses may have resulted into a poor control of infection thus explaining the previously reported lower CD4 T cell counts in these monkeys. Class II M3 haplotype displayed significantly lower acute and post-acute IL-10 levels. In addition, significantly lower levels of α-defensins were detected in class IA M3 haplotype monkeys than in non-M3 macaques, in the post-acute phase of infection. These data indicate that the MHC could contribute to the delicate balance of pro-inflammatory mechanisms, particularly with regard to the association between IL-10 and α-defensins in lentivirus infection. Our results show that host genetic background, virological and immunological parameters should be considered for the design and interpretation of HIV-1 vaccine efficacy studies.
    PLoS ONE 01/2014; 9(4):e93235. · 3.73 Impact Factor
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    ABSTRACT: The p16 (p16) tumor-suppressor protein is a biomarker for activated expression of human papillomavirus oncogenes. However, data are insufficient to determine whether p16 overexpression predicts the risk for progression of low-grade cervical intraepithelial neoplasia (CIN). This study was aimed at evaluating the risk for progression to CIN2 or worse during a 3-year follow-up of an unselected series of 739 patients with CIN1 biopsy specimens tested for p16 expression. Positivity of p16 was defined as a diffuse overexpression in the basal/parabasal cell layers. Selection biases were ruled out using a control group of 523 patients with CIN1 biopsies not tested for p16 expression. Analysis was based on the ratio of progression rates. In the first year of follow-up, the 216 patients (29%) with p16-positive CIN1 had a higher progression rate (12.3%) than did the 523 patients with p16-negative CIN1 (2.2%) (rate ratio, 5.5; 95% confidence interval [CI], 2.59-11.71). In the second and third years, differences were smaller (rate ratio, 1.32 and 1.14, respectively) and not significant. The patients with p16-positive CIN1 also had a lower risk for regression to normal in the first year of follow-up (rate ratio, 0.55; 95% confidence interval, 0.42-0.71) and nonsignificant changes in the second and third years (rate ratio, 0.81 and 0.84, respectively). The patients with p16-positive CIN1 had an increased risk for progression that was concentrated in the first year of follow-up. Immunostaining of p16 could have a role in short-term surveillance of patients with CIN1. Further research should focus on midterm/long-term outcomes of p16-positive CIN1.
    International Journal of Gynecological Cancer 11/2013; 23(9):1663-9. · 1.94 Impact Factor
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    ABSTRACT: T cells are functionally compromised during HIV infection despite their increased activation and proliferation. Although T cell hyperactivation is one of the best predictive markers for disease progression, its causes are poorly understood. Anti-tat natural immunity as well as anti-tat antibodies induced by Tat immunization protect from progression to AIDS and reverse signs of immune activation in HIV-infected patients suggesting a role of Tat in T cell dysfunctionality. The Tat protein of HIV-1 is known to induce, in vitro, the activation of CD4(+) T lymphocytes, but its role on CD8(+) T cells and how these effects modulate, in vivo, the immune response to pathogens are not known. To characterize the role of Tat in T cell hyperactivation and dysfunction, we examined the effect of Tat on CD8(+) T cell responses and antiviral immunity in different ex vivo and in vivo models of antigenic stimulation, including HSV infection. We demonstrate for the first time that the presence of Tat during priming of CD8(+) T cells favors the activation of antigen-specific CTLs. Effector CD8(+) T cells generated in the presence of Tat undergo an enhanced and prolonged expansion that turns to a partial dysfunctionality at the peak of the response, and worsens HSV acute infection. Moreover, Tat favors the development of effector memory CD8(+) T cells and a transient loss of B cells, two hallmarks of the chronic immune activation observed in HIV-infected patients. Our data provide evidence that Tat affects CD8(+) T cell responses to co-pathogens and suggest that Tat may contribute to the CD8(+) T cell hyperactivation observed in HIV-infected individuals.
    PLoS ONE 01/2013; 8(11):e77746. · 3.73 Impact Factor
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    ABSTRACT: This short version complies with the intention expressed in the methodological introduction to the full text Italian Guidelines for the use of antiretroviral drugs and the diagnostic-clinical management of people with HIV-1 infection. By definition, this version should not be considered completely exhaustive with respect to the full text version of the Guidelines available at the website: http://www.salute.gov.it/imgs/C_17_pubblicazioni_1301_allegato.pdf.
    The New Microbiologica: official journal of the Italian Society for Medical Virology (SIVIM) 04/2012; 35(2):113-59. · 1.67 Impact Factor
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    ABSTRACT: Treatment of human immunodeficiency virus (HIV)-infected women with the highly active antiretroviral therapy (HAART) has reduced the onset of uterine cervical intraepithelial neoplasia (CIN), and halted its progression to cervical carcinoma. We and others demonstrated that the HIV protease inhibitors (HIV-PIs) used in HAART can exert direct antitumour activities also in HIV-free preclinical or clinical models. As uterine cervical carcinoma is a leading cause of death in women independently of HIV infection, herein we assessed the impact of therapeutic concentrations of HIV-PIs including indinavir (IDV), saquinavir (SQV) or ritonavir (RTV) on cells obtained from CIN or cervical carcinoma lesions of HIV-negative women. HIV-PI effects were evaluated by cell invasion, growth or toxicity assays, and by RNA, protein or zymogram analyses. Both SQV and RTV inhibited CIN cell invasion, and this was paralleled by a reduced expression and proteolytic activity of the matrix metalloproteinase (MMP)-2 and 9 in treated cells. SQV and RTV also reduced CIN cell growth rate, but did not affect the invasion or growth of cells derived from highly progressed cervical carcinoma. As MMP-2 and MMP-9 have a key role in CIN evolution into cervical carcinoma, these results support the use of SQV or RTV for the block of CIN clinical progression in either HIV-infected or uninfected patients.
    AIDS (London, England) 02/2012; 26(8):909-19. · 4.91 Impact Factor
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    ABSTRACT: Use of Env in HIV vaccine development has been disappointing. Here we show that, in the presence of a biologically active Tat subunit vaccine, a trimeric Env protein prevents in monkeys virus spread from the portal of entry to regional lymph nodes. This appears to be due to specific interactions between Tat and Env spikes that form a novel virus entry complex favoring R5 or X4 virus entry and productive infection of dendritic cells (DCs) via an integrin-mediated pathway. These Tat effects do not require Tat-transactivation activity and are blocked by anti-integrin antibodies (Abs). Productive DC infection promoted by Tat is associated with a highly efficient virus transmission to T cells. In the Tat/Env complex the cysteine-rich region of Tat engages the Env V3 loop, whereas the Tat RGD sequence remains free and directs the virus to integrins present on DCs. V2 loop deletion, which unshields the CCR5 binding region of Env, increases Tat/Env complex stability. Of note, binding of Tat to Env abolishes neutralization of Env entry or infection of DCs by anti-HIV sera lacking anti-Tat Abs, which are seldom present in natural infection. This is reversed, and neutralization further enhanced, by HIV sera containing anti-Tat Abs such as those from asymptomatic or Tat-vaccinated patients, or by sera from the Tat/Env vaccinated monkeys. Thus, both anti-Tat and anti-Env Abs are required for efficient HIV neutralization. These data suggest that the Tat/Env interaction increases HIV acquisition and spreading, as a mechanism evolved by the virus to escape anti-Env neutralizing Abs. This may explain the low effectiveness of Env-based vaccines, which are also unlikely to elicit Abs against new Env epitopes exposed by the Tat/Env interaction. As Tat also binds Envs from different clades, new vaccine strategies should exploit the Tat/Env interaction for both preventative and therapeutic interventions.
    PLoS ONE 01/2012; 7(11):e48781. · 3.73 Impact Factor
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    ABSTRACT: Delineation of the immune correlates of protection in natural infection or after vaccination is a mandatory step for vaccine development. Although the most recent techniques allow a sensitive and specific detection of the cellular immune response, a consensus on the best strategy to assess their magnitude and breadth is yet to be reached. Within the AIDS Vaccine Integrated Project (AVIP http://www.avip-eu.org) we developed an antigen scanning strategy combining the empirical-based approach of overlapping peptides with a vast array of database information. This new system, termed Variable Overlapping Peptide Scanning Design (VOPSD), was used for preparing two peptide sets encompassing the candidate HIV-1 vaccine antigens Tat and Nef. Validation of the VOPSD strategy was obtained by direct comparison with 15mer or 20mer peptide sets in a trial involving six laboratories of the AVIP consortium. Cross-reactive background responses were measured in 80 HIV seronegative donors (HIV-), while sensitivity and magnitude of Tat and Nef-specific T-cell responses were assessed on 90 HIV+ individuals. In HIV-, VOPSD peptides generated background responses comparable with those of the standard sets. In HIV-1+ individuals the VOPSD pools showed a higher sensitivity in detecting individual responses (Tat VOPSD vs. Tat 15mers or 20mers: p≤0.01) as well as in generating stronger responses (Nef VOPSD vs. Nef 20mers: p<0.001) than standard sets, enhancing both CD4 and CD8 T-cell responses. Moreover, this peptide design allowed a marked reduction of the peptides number, representing a powerful tool for investigating novel HIV-1 candidate vaccine antigens in cohorts of HIV-seronegative and seropositive individuals.
    Journal of immunological methods 09/2011; 375(1-2):46-56. · 2.35 Impact Factor
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    ABSTRACT: We have previously demonstrated that in Ova-immunized mice the increase in intra-macrophage thiol pool induced by pro-GSH molecules modulates the Th1/Th2 balance in favour of a Th1-type immune response. We show now that the same molecules can support a Th1-type over Th2-type immunity against Tat, which is an early HIV-1 regulatory protein and a Th1 polarizing immunomodulator that is increasingly considered in new anti-HIV vaccination strategies. Our results indicate that Tat-immunized mice pre-treated with the C4 (n-butanoyl) derivative of reduced glutathione (GSH-C4) or a pro-drug of N-acetylcysteine (NAC) and beta-mercaptoethylamine (MEA) (I-152), have decreased levels of anti-Tat IgG1 as well as increased levels of anti-Tat IgG2a and IgG2b isotypes suggesting a Th1-type response. Moreover, Th1-(IFN-γ and IL-2) Ag-specific cellular responses were detected by ELISPOT assay in splenocytes of the same animals as well as an increase of IL-12 levels in the plasma. These findings suggest that the Th1 immune response to HIV-1 Tat could be further polarized by these molecules. These results together with those previously reported suggest that pro-GSH molecules could be used to modulate the immune response towards different antigens and may be further exploited for inducing specific Th1 immune responses against other HIV antigens as well as other intracellular pathogens in new Tat-based vaccination protocols.
    Vaccine 08/2011; 29(40):6823-9. · 3.77 Impact Factor
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    ABSTRACT: INTRODUCTION: Kaposi's sarcoma (KS) is an angioproliferative disease that occurs in four clinical-epidemiological forms sharing the same immunological and histopathological features, suggesting common etiological and pathogenic factors. Infection with the human herpesvirus 8, cytokine- and angiogenic factor-induced growth together with an immuno-dysregulated state represent fundamental conditions for the development of this tumor. Despite the recent improvements in KS management, it remains an incurable disease. AREAS COVERED: The growing knowledge of KS biology provides multiple opportunities for the development of rational, molecularly targeted therapies. The present review summarizes the current management of KS, including local and systemic conventional therapies, and thoroughly describes the results obtained with new pathogenesis-based anti-KS treatments. EXPERT OPINION: Kaposi's sarcoma represents a paradigm of how the elucidation of disease pathogenesis can drive the development of molecularly targeted treatments. The multifactorial pathogenesis of KS has led to the evaluation of many experimental agents targeting one or more specific factors or pathways involved in the development or progression of the disease. Although targeted therapy so far represents investigational treatment, clinical evaluation of several of these agents is yielding promising results.
    Expert Opinion on Pharmacotherapy 04/2011; 12(11):1669-90. · 2.86 Impact Factor
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    The New Microbiologica: official journal of the Italian Society for Medical Virology (SIVIM) 04/2011; 34(2):109-46. · 1.67 Impact Factor
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    ABSTRACT: The role of volunteer recruitment in HIV vaccine trials has recently been considered particularly with respect to critical issues, such as motivation, psychological assessment and social impact. The preventative and therapeutic phase I trials based on the recombinant biologically active Tat vaccine candidate, sponsored in Italy by the Istituto Superiore di Sanità, included a specific centralised procedure (SCP) developed to support both the sponsor and the volunteers during trial enrolment and conduction. This process, which is an integrated, multidisciplinary, biomedical and psycho-socio-behavioural network, represented a novel and important aspect for the conduction and success of the clinical study. A specific flow of information from the sponsor to the population was developed through the SCP which started from the national announcement of the trials (through a press conference and a press release) to the enrolment of the volunteers. To this aim a telephone counselling intervention was performed to supply the scientific information translated in personalised message, allowing to select potential participants prior to the first contact with the clinical sites. Furthermore, the multi-step procedure contributed in reinforcing the motivation to participation and trial retention, providing important hints for the design of standardised enrolment procedures to be used in clinical studies. Indeed, this methodological approach, which foresees the joined participation of researchers and expert of communication, could be followed in future vaccine trials in order to improve the effectiveness of enrolment procedures.
    AIDS Care 03/2011; 23(8):939-46. · 1.60 Impact Factor
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    ABSTRACT: HIV native Tat and V2 loop-deleted Env (EnvΔV2) proteins already proved safe and immunogenic in phase I clinical testing as single vaccine components. Further, a phase II vaccine trial with Tat showed intensification of the therapeutic effects of HAART in successfully treated HIV-infected individuals. Here a pilot study assessed the immunogenicity and protective efficacy of an HIV/AIDS vaccine based on the combination of Tat and EnvΔV2 proteins in cynomolgus macaques against homologous intrarectal challenge with 35 MID(50) (monkey infectious dose 50) of an R5 simian-human immunodeficiency virus (SHIV(SF162P4cy)). Upon challenge, three of four macaques immunized with Tat and EnvΔV2, and two of three monkeys immunized with EnvΔV2 alone were protected from infection. In contrast, all three control animals, which had been either administered with the adjuvants only or left untreated, and an additional monkey immunized with Tat alone became systemically infected. Protection of the macaques vaccinated with EnvΔV2 or Tat/EnvΔV2 correlated with higher peak titers of pre-challenge neutralizing antibodies obtained during the immunization period (between 70 and 3 weeks before challenge) and with anti-Env V3 loop binding antibodies assessed 3 weeks before challenge. Compared to EnvΔV2 alone, the Tat and EnvΔV2 combined vaccine elicited faster antibody responses (IgM) with a trend, early in the vaccination schedule, after the second immunization including EnvΔV2, towards broader anti-Env IgG epitope specificity and a higher ratio of neutralizing to Env-binding antibody titers. As the number of immunizations increased, vaccination with EnvΔV2 approached the immune response assessed after two inocula with the Tat/EnvΔV2 combined vaccine, even though some differences remained between groups, as indicated by anti-Env IgG epitope mapping. In fact, three weeks before challenge, plasma IgG of animals in the EnvΔV2 group showed a trend towards stronger specificity for the V1 loop and V5 loop-C5 regions of Env, whereas the Tat/EnvΔV2 group displayed an overall higher reactivity for epitopes within the Env V3 loop throughout the immunization period. Although differences in terms of protection rate were not found between the EnvΔV2 or Tat/EnvΔV2 vaccination groups in this pilot study, vaccination with Tat/EnvΔV2 appeared to accelerate the induction of potentially protective antibody responses to Env. In particular, antibodies to the Env V3 loop, whose levels at pre-challenge correlated with protection, were already higher early in the vaccination schedule in monkeys immunized with Tat/EnvΔV2 as compared to EnvΔV2 alone. Further studies including larger vaccination groups and fewer immunizations with these two vaccine candidates are needed to confirm these findings and to assess whether the Tat/EnvΔV2 vaccine may afford superior protection against infection.
    Vaccine 02/2011; 29(16):2918-32. · 3.77 Impact Factor
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    ABSTRACT: Kaposi's sarcoma (KS) is a vascular tumor frequently occurring in Human Immunodeficiency Virus- (HIV-) 1-infected individuals. Our previous work indicated that the angiogenic fibroblast growth factor (FGF)-2 and the Tat protein of HIV-1, both expressed in KS lesions of HIV-infected patients, synergize at inducing angioproliferative, KS-like lesions in mice. Here we show that the development of angioproliferative lesions promoted in mice by combined Tat and FGF-2 associates with an increase in the levels of expression of the antiapoptotic Bcl-2 protein. Upregulation of Bcl-2 expression by combined FGF-2 and Tat occurs also in vitro, and this protects human primary endothelial cells from programmed cell death. As Bcl-2 is expressed in human KS lesions in a fashion paralleling the progression of the disease, these findings suggest a molecular mechanism by which Tat and FGF-2 cooperate in KS maintenance and progression in HIV-infected individuals.
    International journal of vascular medicine 01/2011; 2011:452729.
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    ABSTRACT: Human immunodeficiency virus protease inhibitors (HIV-PIs), such as indinavir and saquinavir, have been shown to block angiogenesis and tumor cell invasion and to induce tumor cell apoptosis and growth arrest, respectively, both in vitro and in vivo. These findings have suggested that HIV-PIs or their analogues can be used as antitumor drugs. To this regard, indinavir and saquinavir were assessed for their ability to inhibit in vivo the growth of highly prevalent human tumors, such as lung, breast, colon and hepatic adenocarcinomas. We show here that both HIV-PIs significantly inhibited the growth of all adenocarcinomas tested in the mice model. This was not mediated by effects on proteasome-dependent cell growth arrest or on apoptosis but by the block of angiogenesis and matrix metalloproteinase activity. Accordingly, therapeutic steadystate concentrations of indinavir or saquinavir were highly effective in inhibiting invasion of tumor cells in vitro. In contrast, growth arrest was induced only by high concentrations of saquinavir that are not reached or are only transiently present in plasma of treated patients, likely through a proteasome-mediated mechanism. These data suggest that HIV-PIs or their analogues, characterized by a better biodistribution and lower toxicity, may represent a new class of antitumor drugs capable of targeting both matrix metalloproteinases and the proteasome for a most effective antitumor therapy.
    International Journal of Cancer 01/2011; 128(1):82-93. · 6.20 Impact Factor
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    ABSTRACT: The redox state of the cysteine-rich region of the HIV Tat protein is known to play a crucial role in Tat biological activity. In this article, we show that Tat displays two alternative functional states depending on the presence of either one or three reduced sulphydryl groups in the cysteine-rich region, respectively. Using different approaches, a disulfide pattern has been defined for the Tat protein and a specific DTT-dependent breaking order of disulfide bonds highlighted. The Tat redox state deeply influences macrophage protein uptake. Immunoistochemistry analysis shows that the oxidized protein does not enter cells, whereas partially reduced protein reaches the cytosol and, to a limited extent, the nucleus. Finally electrophoretic analysis shows Tat high-molecular weight multi-aggregation, resulting in the loss of biological activity. This is due to strong electrostatic and metal-binding interactions, whereas Tat dimerization involves metal-binding interactions as well as disulfide bond formation.
    Molecular and Cellular Biochemistry 12/2010; 345(1-2):105-18. · 2.33 Impact Factor
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    ABSTRACT: The effects of the challenge dose and major histocompatibility complex (MHC) class IB alleles were analyzed in 112 Mauritian cynomolgus monkeys vaccinated (n = 67) or not vaccinated (n = 45) with Tat and challenged with simian/human immunodeficiency virus (SHIV) 89.6P(cy243.) In the controls, the challenge dose (10 to 20 50% monkey infectious doses [MID(50)]) or MHC did not affect susceptibility to infection, peak viral load, or acute CD4 T-cell loss, whereas in the chronic phase of infection, the H1 haplotype correlated with a high viral load (P = 0.0280) and CD4 loss (P = 0.0343). Vaccination reduced the rate of infection acquisition at 10 MID(50) (P < 0.0001), and contained acute CD4 loss at 15 MID(50) (P = 0.0099). Haplotypes H2 and H6 were correlated with increased susceptibility (P = 0.0199) and resistance (P = 0.0087) to infection, respectively. Vaccination also contained CD4 depletion (P = 0.0391) during chronic infection, independently of the challenge dose or haplotype.
    Journal of Virology 09/2010; 84(17):8953-8. · 5.08 Impact Factor
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    ABSTRACT: HIV continues to spread at high rates in sub-Saharan Africa. In particular, Swaziland is one of the countries most affected by the HIV/AIDS pandemic. Monitoring of HIV infection in Swaziland is being made by periodical investigations on HIV prevalence in pregnant women. However, knowledge of proportion of recent HIV infections is important for epidemiologic purposes to assess HIV transmission patterns. To evaluate the proportion of recent HIV infections among pregnant women and its change overtime and to analyze factors associated with recent HIV infection in Swaziland. HIV-positive sera from pregnant women were collected during the 2004 and 2006 National HIV Serosurveys conducted in Swaziland and tested for the HIV antibody avidity, in order to identify recent HIV infections. Socio-demographic and clinical information was also collected. A multivariate analysis was conducted to assess the association between recent HIV infection and socio-demographic and clinical factors. A total of 1636 serum samples were tested for HIV antibody avidity. The overall proportion of recent infections was 13.8%, with no significant difference between 2004 and 2006 (14.6% vs. 13.1%, P>0.05, respectively). At the multivariate analysis, the younger age [14-19 vs. >or=20 years; adjusted odds ratio (aOR) 2.17, 95% CI: 1.45-3.24], as well as being at first pregnancy (1 vs. >or=2; aOR 1.61, 95% CI: 1.10-2.35) was independently associated with recent HIV infection. This study shows no significant difference in the proportion of recent infections between 2004 and 2006 and suggests that young women and women at their first pregnancy are currently high-risk groups for HIV acquisition, highlighting the importance of developing targeted youth programmes to reduce the spread of HIV infection in the country.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 07/2010; 48(3):180-3. · 3.12 Impact Factor
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    ABSTRACT: The activity of telomerase, a ribonucleoprotein maintaining the length of chromosome ends (telomeres) to levels allowing cells to replicate indefinitely, is undetectable in normal, differentiated cells, is present at low levels in some activated cell types (including endothelial cells) and it is highly expressed by tumor cells. Kaposi's sarcoma (KS), the most frequent tumor in Acquired Immune Deficiency Syndrome (AIDS) patients (AIDS-KS), arises as a disorder of new blood vessel formation (angiogenesis), but it may evolve into an aggressive cancer, characterized by the proliferation and invasion of spindle-shaped, endothelial-like cells (KS cells, KSC). Here we report that primary KSC express low telomerase levels which are strongly enhanced by KS initiation and progression factors including the inflammatory mediators interleukin (IL)-1beta, tumor necrosis factor (TNF)alpha and interferon (IFN)gamma, the angiogenic basic fibroblast growth factor (bFGF) and the Tat protein of Human Immunodeficiency Virus (HIV)-1. Noteworthy, the increase of telomerase activity promoted by these molecules parallels the induction of KSC growth and invasion. These preliminary in vitro findings encourage measuring telomerase activity in AIDS-KS lesions in order to survey the clinical progression of the disease.
    Oncology Reports 07/2010; 24(1):219-23. · 2.30 Impact Factor
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    ABSTRACT: The genetic diversity of HIV-1 strains circulating among HIV-1-infected South Africans was investigated in a cohort of 420 individuals enrolled as part of the AIDS Vaccine Integrated Project (AVIP) study. Representative samples (10%) were randomly selected from treatment-naive participants. Viral RNA was extracted for reverse transcriptase-initiated amplification and population-based sequencing of partial pol (encompassing protease and reverse transcriptase) and full-length integrase. Overall, HIV-1 sequences confirmed that 97.1% and 96.9% were HIV-1 subtype C in pol and integrase, respectively. Two participants were infected with unique A1/C and C/A1 recombinants in pol/integrase. Further pol sequence analysis identified mutation patterns associated with high level resistance to NNRTIs in two participants, whereas no primary mutations conferring resistance to integrase inhibitors were detected. The predominance of HIV-1 subtype C in South African populations is therefore confirmed in the AVIP cohort finalized for testing preventive or therapeutic vaccines against HIV-1 infection.
    AIDS research and human retroviruses 06/2010; 26(6):705-9. · 2.18 Impact Factor

Publication Stats

3k Citations
557.01 Total Impact Points

Institutions

  • 1998–2012
    • Istituto Superiore di Sanità
      • Laboratory of Virology
      Roma, Latium, Italy
  • 2010–2011
    • Università degli Studi di Urbino "Carlo Bo"
      • Department of Biomolecular Science
      Urbino, The Marches, Italy
    • University of the Witwatersrand
      • Department of Molecular Medicine and Haematology
      Johannesburg, Gauteng, South Africa
  • 2006–2010
    • University of Rome Tor Vergata
      Roma, Latium, Italy
  • 2006–2009
    • University of Padova
      Padua, Veneto, Italy
  • 2008
    • National Institutes of Health
      • Branch of Vaccine
      Bethesda, MD, United States
  • 2001–2008
    • Universita degli studi di Ferrara
      • • Department of Life Sciences and Biotechnologies
      • • Department of Morphology, Surgery and Experimental Medicine
      • • Sezione di Microbiologia
      Ferrara, Emilia-Romagna, Italy
  • 2005–2007
    • National Cancer Institute (USA)
      • Vaccine Branch
      Maryland, United States
    • Amedeo Avogadro University of Eastern Piedmont
      Alessandria, Piedmont, Italy
  • 2002–2007
    • Sapienza University of Rome
      • • Department of Clinical Medicine
      • • Laboratory of Virology
      Roma, Latium, Italy