Dual therapy (DT) with boosted protease inhibitors (bPIs) plus lamivudine has been shown to be superior to bPI monotherapy in virologically suppressed patients despite previous selection of the ...lamivudine resistance M184V mutation. We compared the virological efficacy of lamivudine-based DT in patients with and without a history of M184V detection.
We retrospectively analyzed patients with HIV-RNA ≤50 copies/mL switching to DT with at least 1 previous resistance genotype in the ARCA database. Time to virological failure (VF; HIV-RNA ≥200 copies/mL or 2 consecutive HIV-RNA >50 copies/mL) and to treatment discontinuation (TD) was analyzed by survival analysis.
Four hundred thirty-six patients switching to lamivudine plus bPIs (70%) or integrase inhibitors (30%) were included. Patients with M184V (n = 87) were older, had lower nadir CD4+ cell count, longer duration of antiretroviral therapy and of virologic suppression, and higher rate of hepatitis C virus infection compared with patients without M184V. The 3-year probability of remaining free from VF was 91.9% (95% confidence interval CI, 86.6-97.2) without M184V and 87.8% (95% CI, 78.4-97.2) with M184V (
= .323). The time to TD did not differ between groups. Multivariate analysis adjusting for baseline variables differing between groups also did not detect M184V as being associated with VF or TD; however, the 3-year probability of remaining free of viral blips (isolated HIV-RNA 51-199 copies/mL) was 79.8% (95% CI, 67.8%-91.8%) with M184V vs 90.1% (95% CI, 84.0%-96.2%) without M184V (
= .016).
Previous selection of M184V did not increase the risk of VF or TD with lamivudine-based DT but was associated with a higher probability of viral blips.
The proportion of new diagnoses of HIV infection in immigrants residing in Italy raised from 11% in 1992 to 29.7% in 2018. To investigate the HIV clades circulating in this community a retrospective ...study was performed in 557 HIV-infected immigrants living in 12 Italian cities. Immigrants originated from East-Europe and Central-Asia (11.7%), North Africa and Middle East (7.3%), South and South-East Asia (7.2%), Latin America and the Caribbean (14.4%), and sub-Saharan Africa (59.4%). More than 87% of immigrants were on antiretroviral therapy (ART), although 26.6% of them were viremic. A 22.0% of immigrants had hepatitis (HBV and/or HCV) and/or tuberculosis. HIV phylogenetic analysis on sequences from 192 immigrants showed the presence of clades B (23.4%), G (16.1%), C (10.4%), A1 (9.4%), F1 (5.2%), D (1.6%) and Circulating Recombinant Forms (CRFs) (33.9%). CRF02_AG represented 72.3% of the total CRFs. Clusters between immigrants and Italian natives were also present. Drug resistance mutations to NRTI, NNRTI, and PI drug classes occurred in 29.1% of ART-treated and in 12.9% of ART-naïve individuals. These data highlight the need for tailored public health interventions in immigrants to avoid spreading in Italy of HIV genetic forms and ART-resistant variants, as well as HIV co-morbidities.
Difficulties in identifying patients at risk of clinical deterioration or death represent one of the main barriers to Palliative Care (PC) development in the community. Currently, no specific Italian ...tools aimed at identifying patients with PC needs are available. Of the different European tools available, the SPICT™ can be used easily in any kind of setting and does not include the Surprise Question. The purpose of the study was to translate, cross-culturally adapt and pre-test the Italian version of the SPICT™.
The Beaton recommendations for the cross-cultural adaptation of instruments were followed. Content validity was assessed using the Lynn method. A sample of Italian General Practitioners (GPs) assessed the SPICT-IT™ for feasibility and tested it.
During the cross-cultural adaptation, some issues regarding semantic, experiential, idiomatic and conceptual equivalences were raised and resolved. The Scale-Content Validity Index/Ave was 0.86. Of the 907 GPs included in the sample, 71 (7.8%) agreed to test the SPICT-IT™ and to assess its feasibility. The participants provided care for 73,526 people in the community. Of these people, 1.7% (N = 1303) were identified as being in need of PC according to the SPICT-IT™. Sixty-six (93.0%) GPs stated they would use the SPICT-IT™ in their daily clinical practice.
The SPICT-IT™ demonstrated acceptable content validity. The percentage of patients identified through the SPICT-IT™ was comparable to findings from literature. The next phase of this project will investigate the impact of a proactive training programme aimed at supporting GPs in identifying patients with PC needs and delivering appropriate Primary Palliative Care (PPC).
We assess the concordance between low level HCV values obtained using the VERSANT HCV RNA 1.0 Assay (kPCR) and COBAS AmpliPrep/COBAS TaqMan HCV Quantitative Test v2.0. The correlation between the ...values obtained by the two RT-PCR assays for samples with quantifiable HCV RNA levels revealed that viral load measured by kPCR significantly correlated with that of the CAP/CTM (R=0.644, P<0.0001). The results show a good concordance (n=126/144, 87%); discordant results were mainly observed in the assessment of values below the lower limit of detection of the assays. These variations may have an impact on clinical decisions for patients on HCV triple therapy or interferon- free regimens. It is therefore recommended to monitor individual patients with the same test throughout treatment.
Recombinant vaccinia virus has been widely employed as a cancer vaccine in several clinical trials. In this study we explored, employing BALB/c mice transgenic for the rat neu oncogene, the ability ...of the recombinant vaccinia virus neu (rV-neuT) vaccine to inhibit growth of neu+ mammary carcinomas and whether the efficacy of vaccination was dependent on: (a) carcinogenesis stage at which the vaccination was initiated; (b) number of vaccinations and (c) route of delivery (systemic vs. local). BALB-neuT mice were vaccinated one, two and three times by subcutaneous (s.c.) and intramammary gland (im.g.) injection with rV-neuT or V-wt (wild-type vaccinia virus) starting at the stage in which mouse mammary gland displays atypical hyperplasia, carcinoma in situ or invasive carcinoma. We demonstrated that vaccination using rV-neuT was more effective when started at an earlier stage of mammary carcinogenesis and after three vaccinations. The im.g. vaccination was more effective than the s.c. vaccination in inhibiting mammary carcinogenesis, eliciting anti-Neu antibodies, increasing anti-Neu IgG2a/G3 isotypes and inducing antibodies able to trigger mammary tumor cells apoptosis and antibody-dependent cellular cytotoxicity. The better protective ability of rV-neuT im.g. vaccination was associated with its capacity to induce a superior degree of in vivo mammary cancer cells apoptosis. Our research suggests that intratumoral vaccination using recombinant vaccinia virus could be employed to increase the activity of a genetic cancer vaccine. This study may have important implications for the design of cancer vaccine protocols for the treatment of breast cancer and of accessible tumors using recombinant vaccinia virus.
Cardiovascular disease (CVD) is a major public health problem in developed countries with over 17 million deaths per year. In the last decade, several infectious agents rather than any single ...pathogen, including Chlamydia pneumoniae and human immunodeficiency virus (HIV), have been shown to contribute to the development of atherosclerosis and subsequent cardiovascular events by inducing systemic inflammation and/or acting directly on the vascular wall. For the first time, we evaluated C. pneumonia DNA in peripheral blood mononuclear cells from HIV patients by real-time polymerase chain reaction in order to shed light on C. pneumonia as a co-factor with HIV in the development of CVDs. C. pneumonia DNA was not detected in our virologically suppressed HIV patients (<37 copies/mL). This finding may be related to high CD4+T cell count (>500 cells/μl) found in HIV patients suggesting functional cell-mediated immunity as a fundamental mechanism for the clearance of chlamydial infection in this population. Larger studies are needed to confirm this hypothesis.
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