86 research outputs found
Microglial nodular encephalitis and ventriculoencephalitis due to cytomegalovirus infection in patients with AIDS: two distinct clinical patterns
No full textInterruption of highly active antiretroviral therapy in HIV clinical practice: results from the I.Co.N.A study
No full textCancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: The D:A:D study
No full textBackground: The association between combination antiretroviral therapy (cART) and cancer risk, especially regimens containing protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs), is unclear. Methods: Participants were followed from the latest of D:A:D study entry or January 1, 2004, until the earliest of a first cancer diagnosis, February 1, 2012, death, or 6 months after the last visit. Multivariable Poisson regression models assessed associations between cumulative (per year) use of either any cART or PI/NNRTI, and the incidence of any cancer, non-AIDS-defining cancers (NADC), AIDS-defining cancers (ADC), and the most frequently occurring ADC (Kaposi sarcoma, non-Hodgkin lymphoma) and NADC (lung, invasive anal, head/neck cancers, and Hodgkin lymphoma). Results: A total of 41,762 persons contributed 241,556 person-years (PY). A total of 1832 cancers were diagnosed [incidence rate: 0.76/100 PY (95% confidence interval: 0.72 to 0.79)], 718 ADC [0.30/100 PY (0.28-0.32)], and 1114 NADC [0.46/100 PY (0.43-0.49)]. Longer exposure to cART was associated with a lower ADC risk [adjusted rate ratio: 0.88/year (0.85-0.92)] but a higher NADC risk [1.02/year (1.00-1.03)]. Both PI and NNRTI use were associated with a lower ADC risk [PI: 0.96/year (0.92-1.00); NNRTI: 0.86/year (0.81-0.91)]. PI use was associated with a higher NADC risk [1.03/year (1.01-1.05)]. Although this was largely driven by an association with anal cancer [1.08/year (1.04-1.13)], the association remained after excluding anal cancers from the end point [1.02/year (1.01-1.04)]. No association was seen between NNRTI use and NADC [1.00/year (0.98-1.02)]. Conclusions: Cumulative use of PIs may be associated with a higher risk of anal cancer and possibly other NADC. Further investigation of biological mechanisms is warranted
Low prevalence of primary mutations associated with drug resistance in antiviral-naive patients at therapy initiation
No full textObjective: To assess the prevalence of mutations in the reverse-transcriptase (RT) and protease (PR) region in a cohort of chronically-infected HIV-positive patients requiring highly active antiretroviral therapy (HAART). Methods: The study included 347 patients enrolled in the Italian Cohort of Antiretroviral Naive patients (I.CO.NA) who had to initiate HAART. The whole PR-region, and aminoacids 1-320 of RT-region were sequenced from plasma samples at baseline. Results: Median CD4-lymphocytes and HIV-RNA at baseline were 231 × 106 cells/l and 4.89 log10 copies/ml; 307 of 347 (88.5%) patients carried no mutations in the RT region, whereas 40 (11.5%) carried one or more mutations associated with resistance to nucleoside-RT inhibitor (NRTI) (7.8%), or non-nucleoside-RTI (NNRTI) (4.9%), with four patients carrying mutations to both classes. Among mutations associated with high-level resistance to RTI, T215Y was found in only two patients, M184V in two cases, T69D and T215C in other two cases (one each), and K103N in only one patient, for a total of six patients (one carrying both T215Y and M184V) (1.7%). Seventy-six patients (21.9%) carried no mutations in the PR region, whereas 271 (78.1%) had one or more mutations. Primary mutations associated with substantial resistance to protease inhibitors were found in only five of 347 patients (1.4%) (M46V/L, 154V, V82A/I); all the other patients carried only secondary mutations (L10F/I/V, M361, L63P, A71T/V, V771). Conclusions: Prevalence of mutations associated with high-level resistance to antiretroviral drugs is low in HIV-infected patients with long-term infection. This suggests no preclusion in principle to any antiretroviral drug at the time of decision of the first therapeutic regimen
Prevalence of pol Gene Mutations in a Cohort of Antiretroviral-Naive Patients: Correlation with HIV RNA and CD4 Count at the Time of Genotypic Testing
No full textImpact of highly active antiretroviral therapy on the presenting features and outcome of patients with acquired immunodeficiency syndrome-related Kaposi sarcoma
No full textBACKGROUND. The objective of the current study was to evaluate the impact of highly active antiretroviral therapy (HAART) on clinical characteristics of presentation and the natural history of Kaposi sarcoma (KS) in patients already receiving HAART at the time of KS diagnosis. METHODS. The authors conducted a retrospective cohort study comparing epidemiologic, clinical, and outcome data for 160 patients who were naive to HAART at the time of KS diagnosis (KS-naive) with the corresponding data for 51 patients already receiving HAART at the time of KS diagnosis (KS-HAART). The analysis included all patients with a diagnosis of KS since January 1996 within two Italian cohorts of patients with human immunodeficiency virus. RESULTS. Immunologic and virologic status at the time of KS diagnosis were significantly more favorable in the KS-HAART group than in the KS-naive group. The frequency of cutaneous involvement was similar in both groups, but cutaneous disease was more indolent among KS-HAART patients, with 1 anatomic site of involvement in 9 patients (21%) and less than 10 lesions in 26 patients (60%), compared with 16 patients (12%; P = 0.06) and 47 patients (34%; P = 0.01), respectively, in the KS-naive group. A smaller proportion of KS-HAART patients presented with visceral disease (24% vs. 39%; P = 0.06); in particular, gastrointestinal tract involvement was significantly less frequent among KS-HAART patients (14%) compared with KS-naive patients (28 %; P = 0.05). Median survival was not reached in either group, and the 3-year survival rates of KS-HAART patients (64%) and KS-naive patients (78%) were not significantly different. CONCLUSIONS. The data from the current study indicate that KS exhibits a less aggressive presentation in patients already receiving HAART compared with patients who are naive to HAART at KS diagnosis. Natural history and outcome do not appear to be influenced by the initiation of HAART before development of KS
Sexual behaviour of heterosexual individuals with HIV infection naïve for antiretroviral therapy in Italy .
No full text
Primary HIV-1 resistance in recently and chronically infected individuals of the Italian Cohort Naive for Antiretrovirals
No full textThe risk of acquiring HIV-1 drug resistance at time of infection has become a public health problem following the widespread use of antiretroviral drugs in developed countries. Although a number of studies have reported data regarding the prevalence of HIV-1 primary resistance in developed countries over the past years, limited knowledge is available regarding the proportion of mutations related to drug resistance in antiretroviral naive subjects with chronic HIV-1 disease. In this study, we evaluated the prevalence of mutations in the reverse-transcriptase (RT) and protease region both in a representative group of recently HIV-1 infected subjects (n=68) and a cohort of chronically-infected HIV-positive patients (n=347) enrolled in the Italian Cohort of Antiretroviral Naive patients (I.CO.NA.). In recently infected individuals, the overall prevalence of mutations for nucleoside RTI (NRTIs) was 10/68 (14.7%). The distribution of mutations by calendar year were 0, 1 in 1996, 9, 3 in 1997 and 1, 0 in 1998 for NRTIs and protease inhibitors (Pls) respectively. Thymidine associated mutations were identified in six subjects (8.8%), five of whom had one mutation [41L, 70K (n=2), 215Y] and one had two mutations (67N+219Q). Four subjects (5.9%) showed the changes associated with resistance to lamivudine (184V or 118I). No non nucleoside-RTI (NNRTI) mutations were present in the study period. Primary Pls mutations (two 46L and two 82I) were present in four subjects (5.9%). Of note, mutations related to resistance to more than one class of antiretrovirals were present in one (1.5%). Among patients with chronic infection a large proportion (88.5%) carried no mutations in RT region, 11.5% individuals carried one or more mutations associated with resistance to NRTI (7.8%), or NNRTI (4.9%), with 4 patients carrying mutations to both classes. Among mutations associated with high-level resistance to RTI, T215Y was found in only 2 patients, M184V in 2 cases, T69D in another case, and K103N in only 1 patient, for a total of 6 patients (one carrying both T215Y and M184V) (1.7%). Primary mutations associated with substantial resistance to Pls were found in only 5/347 patients (1.4%); all the other patients carried only secondary mutations. Prevalence of mutations associated with high-level resistance to antiretroviral drugs is stable in recently infected individuals and low in patients with established HIV infection. The potential impact of transmitted mutations on the response to first regimen in individuals carrying transmitted mutations needs to be assessed by perspective studies
Formulation and implicit numerical integration of a kinematic hardening model for unsaturated soils
No full textThis is the peer reviewed version of the following article: Monforte, L. and Rouainia, M. (2025), Formulation and Implicit Numerical Integration of a Kinematic Hardening Model for Unsaturated Soils. Int J Numer Anal Methods Geomech., 49: 514-540. https://doi.org/10.1002/nag.3878, which has been published in final form at https://onlinelibrary.wiley.com/doi/abs/10.1002/nag.3878. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.Currently, our understanding of material-scale deterioration resulting from meteorologically induced variations in pore water pressure and its significant impact on infrastructure slopes is limited. To bridge this knowledge gap, we have developed an extended kinematic hardening constitutive model for unsaturated soils that refines our understanding of weather-driven deterioration mechanisms in heterogeneous clay soils. This model has the capability of predicting the irrecoverable degradation of strength and stiffness that has been shown to occur when soils undergo wetting and drying cycles. The model is equipped with a fully coupled and hysteretic water retention curve and a hysteretic loading–collapse curve and has the capability to predict the irrecoverable degradation of strength and stiffness that occurs during cyclic loading of soils. Here, we employ a fully implicit stress integration technique and give particular emphasis to deriving a consistent tangent operator, which includes the linearisation of the retention curve. The proposed algorithm is evaluated for efficiency and performance by simulating various stress and strain-driven triaxial paths, and the accuracy of the integration technique is evaluated through the use of convergence curves.The authors express their sincere gratitude to Professor Antonio Gens for fruitful discussion at the beginning of the research. Prof David Toll and Dr Marti Lloret-Cabot generously provided their valuable feedback in the framework of a programme grant.
The authors wish to thank the Engineering and Physical Sciences Research Council (EPSRC) for funding through the programme Grant ACHILLES (EP/R034575/1). The first author is grateful for the financial support received from the Spanish Ministry of Science and Innovation, MCIN/AEI/ 10.13039/501100011033 through research project PID2023-149935OB-I00.Peer ReviewedPostprint (author's final draft
- …
