124 research outputs found
Switching to boosted protease inhibitor plus a second antiretroviral drug (dual therapy) for treatment simplification: a multicenter analysis
No full textTo assess the role of drugs used in dual therapy (DT), as cART simplification, over the risk of treatment failure
Interpretation systems for genotypic drug resistance of HIV-1
No full textGenotypic assays are widely used tools for determining human immunodeficiency virus type 1 (HIV-1) drug resistance and for guiding treatment changes in patients failing antiretroviral therapy. Several systems have been developed to interpret the complex influence of key amino acid substitutions of the enzymes targeted by therapy on the phenotypic susceptibility or clinical response to available antiretroviral agents. This overview identifies 21 systems giving an interpretation on how amino acid substitutions affect phenotypic drug susceptibility or clinical activity of anti-HIV-1 agents. There was substantial variability in the mechanisms underlying the interpretations, the nature of the systems, their intended use, the source type of their knowledge base, and their update and output. Most of the systems could be accessed for free on the internet, functioned as rule-based algorithms updated by experts and at least partially based on literature evidence, and offered an automated report through a software. Nevertheless, the rule base was not always clarified. An update of the rules and the clinical validation of the systems are presented to help in the critical evaluation of their possible use. Importantly, only 8 systems were intended for clinical use and 5 of these had at least partially undergone clinical validation
Combining epidemiological and genetic networks signifies the importance of early treatment in HIV-1 transmission
No full textInferring disease transmission networks is important in epidemiology in order to understand and prevent the spread of infectious diseases. Reconstruction of the infection transmission networks requires insight into viral genome data as well as social interactions. For the HIV-1 epidemic, current research either uses genetic information of patients' virus to infer the past infection events or uses statistics of sexual interactions to model the network structure of viral spreading. Methods for a reliable reconstruction of HIV-1 transmission dynamics, taking into account both molecular and societal data are still lacking. The aim of this study is to combine information from both genetic and epidemiological scales to characterize and analyse a transmission network of the HIV-1 epidemic in central Italy.We introduce a novel filter-reduction method to build a network of HIV infected patients based on their social and treatment information. The network is then combined with a genetic network, to infer a hypothetical infection transmission network. We apply this method to a cohort study of HIV-1 infected patients in central Italy and find that patients who are highly connected in the network have longer untreated infection periods. We also find that the network structures for homosexual males and heterosexual populations are heterogeneous, consisting of a majority of 'peripheral nodes' that have only a few sexual interactions and a minority of 'hub nodes' that have many sexual interactions. Inferring HIV-1 transmission networks using this novel combined approach reveals remarkable correlations between high out-degree individuals and longer untreated infection periods. These findings signify the importance of early treatment and support the potential benefit of wide population screening, management of early diagnoses and anticipated antiretroviral treatment to prevent viral transmission and spread. The approach presented here for reconstructing HIV-1 transmission networks can have important repercussions in the design of intervention strategies for disease control
Cardiovascular risk score change in HIV-1-infected patients switched to an atazanavir-based combination antiretroviral regimen.
No full textBACKGROUND: We aimed to establish whether the limited impact of atazanavir on the plasma lipid profile could translate into a reduction in the predicted cardiovascular risk in antiretroviral (ARV)-experienced patients switching to an atazanavir-containing regimen. METHODS: HIV-1-infected treatment-experienced patients, switched to atazanavir for whatever reason and without prior major cardiovascular events, were selected and followed for at least 1 month. An individual cardiovascular risk score (10-year risk of major cardiovascular events) based on validated events and measurable risk factors in Italian cardiovascular cohorts was calculated using software available online. RESULTS: A total of 197 patients were selected for inclusion in the study. After switching to atazanavir, the mean changes from pre-switch to last available measurement were -6.5% (P<0.001) for total cholesterol, -1.7% (P=0.029) for high-density lipoprotein (HDL) cholesterol, -11.3% (P<0.001) for non-HDL cholesterol and -8.6% (P<0.001) for triglycerides. The crude cardiovascular risk score was reduced from 3.43 to 3.38% (P=0.51); the analysis normalized by age showed a reduction from 3.43 to 3.14% (P<0.001). Subsets of patients with high baseline total cholesterol or triglycerides showed more marked reductions. CONCLUSIONS: A treatment switch to atazanavir caused significant reductions in plasma lipids and a modest but significant reduction in the normalized-for-age cardiovascular risk score. Efforts should be made to concomitantly reduce the other preventable cardiovascular risk factor
Increased ophthalmic artery resistance index is associated with cognitive impairment in HIV-infected patients.
No full textOBJECTIVES:
Despite the introduction of combined antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HANDs) remains high. Aim of the study was to investigate the potential relationship between ophthalmic artery resistance index (OARI), a marker of subclinical cerebrovascular disease, and cognitive performance.
METHODS:
We performed a cross-sectional cohort study by consecutively enrolling HIV-infected patients during routine outpatient visits. All subjects underwent a comprehensive neuropsycological battery and ultrasonographic assessment of OARI. Patients were classified as cognitively impaired if they showed decreased cognitive function involving at least two ability domains. OARI was considered abnormal if above 0.72 at left or right side. Factors associated with cognitive performance were evaluated by linear and logistic regression analysis.
RESULTS:
A total of 116 patients [78.4% males, median age 44 years (IQR 37-49), 13.8% with past AIDS-defining events, median CD4 482 cells/μL (IQR 352-690), 79.3% with HIV RNA <20 copies/mL] were enrolled. A hundred-thirteen (97.4%) subjects were on cART of which 88.5% on current regimen from one year. Fifty-four (46.6%) patients were classified as cognitively impaired. ROC curves indicated that the most discriminant left and right OARI values for predicting a mild cognitive impairment were >0.72 (AUC = 0.73, sensitivity 61.8%, specificity 81.4%, p < 0.001) and >0.71 (AUC = 0.72, sensitivity 69.1%, specificity 71.2%, p < 0.001), respectively. Multivariate analysis showed that OARI >0.72 (OR 4.7, p = 0.001) was independently associated with increased risk of cognitive impairment. Moreover, education (β = -0.18, p = 0.005), Zung depression score (β = +0.05, p = 0.021) and an abnormal OARI (β = +1.46, p = 0.002) were independently associated with an increased number of pathological performances. Evaluating separately each cognitive domain, an abnormal OARI confirmed an independent association with lower performance in attention and executive functions (p = 0.003) and in psychomotor speed (p = 0.010).
CONCLUSIONS:
Increased OARI was associated with lower cognitive performance in HIV-infected patients. These findings suggest a potential role of subclinical cerebrovascular disease in the pathogenesis of HAND
Viro-immunological efficacy and tolerability of dolutegravir-based regimens compared to regimens based on other integrase strand inhibitors, protease inhibitors, non-nucleoside reverse transcriptase inhibitors in patients with acute HIV-1 infection: a multicenter retrospective cohort study
No full textOBJECTIVES:
This study aims to compare the tolerability and viro-immunologic efficacy of dolutegravir-based regimens (DTG group) with regimens based on EVG, RAL, PI, NNRTI (NODTG group) in patients with acute HIV-1 infections (AHI).
METHODS:
All patients diagnosed with AHI between 2015 and 2017, who started ART in 5 different centers in Italy, were included and followed-up to 30th April 2018. AHI was defined by the presence of the positive p24 antigen with negative or indeterminate western blot.
RESULTS:
Forty-three patients were enrolled: 20 on DTG, 23 in NODTG. Nine patients (20.9%), 4 in DTG and 5 in NODTG group, were prescribed a four-drug regimen. In the cohort, 81.4% were Italian and 83.7% males with a median age of 41 years (IQR 31-48). The median time elapsed between HIV diagnosis and ART initiation was 12 days [IQR 5-28]. Seven patients harbored a virus with transmitted mutations at baseline (16.2%), all in DTG group (p=0.005). All patients achieved HIV-RNA undetectable at the end of follow up except two subjects, of whom one had 57 copies and one was lost to follow-up. In Kaplan-Meier analysis, time to virologic suppression was not different between the two groups (log rank: p= 0.7155). After achieving virologic suppression, four patients stopped first ART due to toxicity: 2 on DTG, 2 on EVG for neurological and gastrointestinal toxicity, respectively.
CONCLUSION:
In our setting, ART in AHI is started very early. DTG showed a good viro-immunologic efficacy even when NRTI transmitted mutations were present. DTG interruption rarely occurred.
Copyright © 2019. Published by Elsevier B.V
Cardiovascular risk factors and carotid intima-media thickness are associated with low cognitive performance in HIV-infected patients
No full textHIV Med. 2012 Sep 21. doi: 10.1111/j.1468-1293.2012.01044.x. [Epub ahead of print]
Cardiovascular risk factors and carotid intima-media thickness are associated with lower cognitive performance in HIV-infected patients.
Fabbiani M, Ciccarelli N, Tana M, Farina S, Baldonero E, Di Cristo V, Colafigli M, Tamburrini E, Cauda R, Silveri M, Grima P, Di Giambenedetto S.
SourceInstitute of Clinical Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy.
Abstract
OBJECTIVES: The aim of the study was to investigate the relationship between metabolic comorbidities, cardiovascular risk factors or common carotid intima-media thickness (cIMT) and cognitive performance in HIV-infected patients.
METHODS: Asymptomatic HIV-infected subjects were consecutively enrolled during routine out-patient visits at two clinical centres. All patients underwent an extensive neuropsychological battery and assessment of metabolic comorbidities and cardiovascular risk factors. Moreover, cIMT was assessed by ultrasonography. Cognitive performance was evaluated by calculating a global cognitive impairment (GCI) score obtained by summing scores assigned to each test (0 if normal and 1 if pathological).
RESULTS: A total of 245 patients (median age 46 years; 84.1% with HIV RNA < 50 copies/mL; median CD4 count 527 cells/μL) were enrolled in the study. Cardiovascular risk factors were highly prevalent in our population: the most frequent were dyslipidaemia (61.2%), cigarette smoking (54.3%) and hypertension (15.1%). cIMT was abnormal (≥ 0.9mm) in 31.8% of patients. Overall, the median GCI score was 2 [interquartile range (IQR) 1-4]; it was higher in patients with diabetes (P = 0.004), hypertension (P = 0.030) or cIMT ≥ 0.9 mm (P < 0.001). In multivariate analysis, it was confirmed that diabetes (P = 0.007) and cIMT ≥ 0.9 mm (P = 0.044) had an independent association with lower cognitive performance. In an analysis of patients on combination antiretroviral therapy (cART), abacavir use was independently associated with a better cognitive performance (P = 0.011), while no association was observed for other drugs or neuroeffectiveness score.
CONCLUSIONS: Diabetes, cardiovascular risk factors and cIMT showed a strong association with lower cognitive performance, suggesting that metabolic comorbidities could play a relevant role in the pathogenesis of HIV-associated neurocognitive disorders in the recent cART era.
© 2012 British HIV Associatio
Baseline CD4+ T-cell count and cardiovascular risk factors predict the evolution of cognitive performance during 2-year follow-up in HIV-infected patients
No full textBACKGROUND:
The aim of our study was to better understand the dynamics between cardiovascular risk factors and immunological parameters in the evolution of cognitive performance in HIV+ patients.
METHODS:
We conducted a prospective longitudinal study, consecutively enrolling asymptomatic HIV+ subjects during routine outpatient visits at two clinical centres. At baseline and after 2 years, all patients underwent a comprehensive neuropsychological battery. Common carotid intima-media thickness (cIMT) was also measured.
RESULTS:
A total of 150 patients completed the study (77% males, median age 46 years, 20% with past AIDS-defining events, 95% on cART, 88% with HIV-RNA<50 copies/ml). After a 2-year follow-up, there was no difference in the proportion of patients with cognitive impairment (32% versus 33% at baseline; P=1.00). However, a significantly worse memory performance was observed (z score mean change -0.51, sd 1.05; P=0.001). At multivariate analysis, baseline dyslipidaemia (OR 2.7, 95% CI 1.1, 7.1; P=0.037) showed a significant association with a higher risk of memory impairment at 2-year follow-up, while higher baseline CD4(+) T-cell count (OR 0.80 per 100 cells/μl higher; 95% CI 0.66, 0.97; P=0.026) was found to be a protective factor, adjusting for the presence of a memory impairment at baseline. When the analysis was restricted to patients who did not change antiretroviral therapy during the study period (n=109), baseline cIMT (OR 14.6 per 0.1 mm higher; 95% CI 1.1, 189.9; P=0.041) also emerged as an independent risk factor for memory impairment at 2-year follow-up.
CONCLUSIONS:
Immunological parameters and cardiovascular risk factors are independently associated with the evolution of cognitive status in HIV+ patients
Declining prevalence of HIV-1 drug resistance in treatment-failing patients: a clinical cohort study.
No full textOBJECTIVES: A major barrier to successful viral suppression in HIV type 1 (HIV-1)-infected individuals is the emergence of virus resistant to antiretroviral drugs. We explored the evolution of genotypic drug resistance prevalence in treatment-failing patients from 1999 to 2005 in a clinical cohort. PATIENTS AND METHODS: Prevalence of major International AIDS Society-USA HIV-1 drug resistance mutations was measured over calendar years in a population with treatment failure and undergoing resistance testing. Predictors of the presence of resistance mutations were analysed by logistic regression. RESULTS: Significant reductions of the prevalence of resistance to all three drug classes examined were observed. This was accompanied by a reduction in the proportion of treatment-failing patients. Independent predictors of drug resistance were the earlier calendar year, prior use of suboptimal nucleoside analogue therapy, male sex and higher CD4 levels at testing. CONCLUSIONS: In a single clinical cohort, we observed a decrease in the prevalence of resistance to all three examined antiretroviral drug classes over time. If this finding is confirmed in multicentre cohorts it may translate into reduced transmission of drug-resistant virus from treated patients
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