Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons

We show in human immunodeficiency virus-positive persons that the coronary artery disease effect of an unfavorable genetic background is comparable to previous studies in the general population, and comparable in size to traditional risk factors and antiretroviral regimens known to increase cardiovascular ris

Kin of coauthorship in five decades of health science literature

Family background-kinship-can propagate careers. The evidence for academic nepotism is littered with complex associations and disputed causal inferences. Surname clustering, albeit with very careful consideration of surnames'' flows across regions and time periods, can be used to reflect family ties. We examined surname patterns in the health science literature, by country, across five decades. Over 21 million papers indexed in the MEDLINE/PubMed database were analyzed. We identified relevant country-specific kinship trends over time and found that authors who are part of a kin tend to occupy central positions in their collaborative networks. Just as kin build potent academic networks with their own resources, societies may do well to provide equivalent support for talented individuals with fewer resources, on the periphery of networks

Robust supervised and unsupervised statistical learning for HIV type 1 coreceptor usage analysis

Human immunodeficiency virus type 1 (HIV-1) isolates differ in their use of coreceptors to enter target cells. This has important implications for both viral pathogenicity and susceptibility to entry inhibitors, recently approved or under development. Predicting HIV-1 coreceptor usage on the basis of sequence information is a challenging task, due to the high variability of the envelope. The associations of the whole HIV-1 envelope genetic features (subtype, mutations, insertions-deletions, physicochemical properties) and clinical markers (viral RNA load, CD8(+), CD4(+) T cell counts) with viral tropism were investigated, using a set of 2896 (659 after filter, 593 patients) sequence-tropism pairs available at the Los Alamos HIV database. Bootstrapped hierarchical clustering was used to assess mutational covariation. Univariate and multivariate analysis was performed to assess the relative importance of different features. Different machine learning (logistic regression, support vector machines, decision trees, rule bases, instance based reasoning) and feature selection (filter and embedded) methods, along with loss functions (accuracy, AUC of ROC curves, sensitivity, specificity, f-measure), were applied and compared for the classification of X4 variants. Extra-sample error estimation was assessed via multiple cross-validation and adjustments for multiple testing. A high-performing, compact, and interpretable logistic regression model was derived to infer HIV-1 coreceptor tropism for a given patient [accuracy = 92.76 (SD 3.07); AUC = 0.93 (SD 0.04)]

Detection of HLA-B*57:01 by real-time PCR: implementation into routine clinical practice and additional validation data.

Aim:HLA-B*57:01 status needs to be determined before initiating abacavir therapy. We developed a pharmacogenetic real-time (Q)-PCR screening test using two sets of sequence specific primers. This test has been implemented into routine clinical practice. Materials & methods: HIV-infected patients admitted at our University Hospital were thus genotyped using the above mentioned test. A panel of 80 DNA samples with a known genotype were used to characterize Q-PCR conditions using different master mixes. Results: A total of 353 patients were genotyped, detecting 15 (4.25%) HLA-B*57:01 positive carriers. Among the negative patients, 17.2% were treated with abacavir without any hypersensitivity reaction. Using different Q-PCR master mixes, significantly lower cutoff Ct values were found, thus new analytical settings are provided. Conclusion: The pharmacogenetic test developed in our laboratory for the fast screening of HLA-B*57:01 can be successfully implemented into routine clinical practice. All 16 sequences (including an additional six) currently known for the HLA-B*57:01 allele are detected by sequence specific primers used in this test. The Brilliant II SYBR(\uae) Green QPCR MM (Stratagene) can safely replace the master mix originally used to develop the test

Relationship between self-reported adherence, antiretroviral drug concentration measurement and self-reported symptoms in patients treated for HIV-1 infection

Background: The aim of the study was to explore relationships between self-reported adherence, antiretroviral drug concentration measurement (TDM) and self-reported symptoms. Methods: We systematically administered to human immunodefi ciency (HIV)-infected outpatients a questionnaire evaluating measures of self-reported adherence (missing doses during last week, deviations from the prescribed timing of therapy, self-initiated discontinuations for > 24 or 48 h, exhausting drugs and present sense of how patients are taking therapy) and a panel of referred symptoms (a symptom score was built summing self-reported scores for each listed symptom). We selected patients who completed the questionnaire and also had a TDM (mainly reflecting adherence in the past few days or weeks), thus comparing these two tools as measures of adherence. Results: A total of 130 patients (64.6% males, median age 44 years, 76.2% with HIV RNA < 50 copies/ml, median CD4 540 cells/μl) were included. Mean self-reported adherence (on a 0 - 100 visual analogue scale) was 80% (standard deviation, 18.7). Drug concentration was subtherapeutic in 16 patients (12.3%), of which 7 (5.4%) had undetectable drug levels (< 0.05 mg/L). Of these last seven patients, five (71.4%) reported an adherence below 80%. In a multivariable analysis, females and patients with undetectable drug levels (mean change - 18.43%, 95% confidence intervals (CIs) - 31.83 to - 5.03, p = 0.007) showed a lower self-reported adherence, while those with HIV RNA < 50 copies/ml showed a higher adherence. Lower self-reported adherence (odds ratio 0.62 per 10% increase, 95% CI = 0.43 - 0.89, p = 0.009) and longer time from last drug intake were independently related to the development of undetectable drug levels. We also found that a higher symptom score was associated with a lower self-reported adherence and with a higher proportion of undetectable drug levels. Conclusions: Self-reported adherence and TDM showed a correlation and seemed to be comparable tools for adherence estimation. Self-reported symptoms were associated with lower adherence and undetectable drug levels. © 2015 Informa Healthcare

Liver fibrosis is associated with cognitive impairment in HIV-positive patients

Introduction: The aim of our study was to investigate the potential relationship between liver fibrosis (LF) and cognitive performance in HIV+ patients. Materials and Methods: We performed a cross-sectional cohort study by consecutively enrolling HIV+ patients during routine outpatient visits at two clinical centres in Italy. Subjects with decompensated liver disease were excluded. All subjects underwent a comprehensive neuropsychological battery exploring memory, attention, psychomotor speed and language; cognitive impairment was defined as at least two abnormal [1.5 SD below the mean for appropriate norms] cognitive domains. LF was explored by calculating FIB4 index; in a subgroup of patients, LF was also assessed by transient elastography. Factors associated with cognitive impairment were investigated by logistic regression models. Results: A total of 413 patients [77% males, median age 46 (IQR 39–52), 17% with past AIDS-defining events, 19% past IDU, 3% with diabetes, 94% on cART, 90% with HIV RNA <50 copies/mL, 18% co-infected with HCV] were enrolled. Seventeen patients (4%) had FIB4 >3.25 and 14/129 (3%) had liver stiffness >14KPa. Forty-seven patients (11%) were diagnosed with cognitive impairment. At multivariate analyses patients with FIB4 >1.45 showed a higher risk of cognitive impairment in comparison with those with lower values (OR 2.19, 95% CI 1.02–4.72; p=0.044) after adjusting for education (OR 0.79, 95% CI 0.71–0.88; p<0.001), past IDU (OR 1.69, 95% CI 0.67–4.23; p=0.264), diabetes (OR 2.35, 95% CI 0.62–8.86; p=0.207), HIV RNA <50 copies/mL (OR 0.47, 95% CI 0.19–1.14; p=0.095) and HCV co-infection (OR 0.88, 95% CI 0.33–2.39; p=0.807). Analyzing any single cognitive domain, a higher risk of abnormal psychomotor speed was associated with fibroscan score >14KPa in comparison with fibroscan score <7KPa (OR 285.07; 95% CI 2.42–33574.06; p=0.020) after adjusting for education (OR 0.54, 95% CI 0.31–0.92; p=0.024), age (for 10 years increase) (OR 2.03, 95% CI 0.55–7.53; p=0.288), past IDU (OR 4.43, 95% CI 0.35–7.57; p=0.526), HIV RNA <50 copies/mL (OR 0.01, 95% CI 0.00–0.18; p=0.003), HIV history (for 1 year increase) (OR 0.96, 95% CI 0.83–1.12; p=0.641), CD4 cells count at nadir (OR 1.10, 95% CI 0.56–2.16; p=0.779), and HCV co-infection (OR 0.06; 95% CI 0.00–1.93; p=0.113). Conclusions: In HIV-infected patients higher LF, estimated through non-invasive methods, is associated to a higher risk of cognitive impairment

Total cellular HIV-1 DNA decreases after switching to raltegravir-based regimens in patients with suppressed HIV-1 RNA

Background The integrase inhibitor raltegravir has been used to intensify antiretroviral therapy in patients with undetectable plasma HIV-1RNA, resulting in variable perturbation of HIV-1 nucleic acids levels in peripheral blood. Objectives We aimed at monitoring residual plasma HIV-1RNA and total cellular HIV-1DNA in virologically suppressed patients switching to raltegravir-based regimens. Study design Fifty-eight subjects on protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens, with plasma HIV-1RNA levels &lt;40 copies/ml for ≥6 months and CD4 counts &gt;200&nbsp;cells/μl for ≥12 months were enrolled. Thirty-four patients were from the treatment simplification RASTA randomized study switching standard therapy to a raltegravir-based regimen (RASTA group), while 24 continued a PI or NNRTI based-regimen (controls). Residual plasma HIV-1RNA (5-40&nbsp;copies/mL) and HIV-1DNA were assessed at 0, 24 and 48 weeks. Results At week 0 (W0), HIV-1DNA was detected in all patients while at W48 it was detectable in 82.4% of the RASTA group vs 100% of controls (p&nbsp;=&nbsp;0.03). There was a significant decline of HIV-1DNA at W48 in the RASTA group (mean change from baseline −0.21 [95% CI −0.41; −0.01] log10 copies/106 CD4; p&nbsp;=&nbsp;0.03) but not in controls. Ultrasensitive HIV-1RNA was detectable at baseline in 50% of RASTA group vs 67% of controls and at W48 in 32.4% vs 42%, respectively. No differences were found between HIV-1RNA levels at baseline and W48 within and between groups. Conclusions Switching successful therapy to raltegravir-based regimens may be associated with a decrease of the HIV-1 reservoir, as measured by peripheral blood cellular HIV-1DNA levels

Prevalence of osteoporosis and predictors of low BMD in a cohort of HIV-1-infected patients in Rome: features of a population at high risk

Introduction: Ageing of HIV-infected patients led to an increasing rate of osteopenia and osteoporosis. The cause is multifactorial, including virus activity, drug toxicity and host factors. The aim of our analysis is to quantify this issue according to our department experience and to evaluate predictors of low BMD. Materials and Methods: HIV-1-infected patients, on stable HAART, were consecutively enrolled in this cross-sectional study and underwent DEXA. We analyzed the prevalence and evaluated predictors of low BMD in our population. Results: We collected data from 208 patients, 148 of whom were male, with 49 years median age (IQR 24.1–68.3). About 39% of patients were heterosexuals, 33.7 MSM and 12.5% were IDU, 40.4% were smokers. Caucasians were 93.3%, and 13.9% were co-infected with HCV virus. Around 6.7% of patients were on their first HAART regimen and all of them started TDF. Their median time of HAART exposure was 1.17 years (IQR 0.8–1.6). Conversely, median time of HAART exposure of multi-experienced patients was 8.5 years (IQR 3.1–12.0). We stratified DEXA results for patients on first-line regimen versus multi-experienced one. We found that 42.9% of patients on first-line HAART had low BMD of lumbar spine and 7.1% had osteoporosis. Regarding the multi-experienced group of patients, lumbar spine osteopenia was observed in 36.6% of patients and 15.5% of them had osteoporosis. Median age of patients with low BMD of lumbar spine was 45.6 (IQR 24.1–68.3) for patients on first-line regimen and 49.8 years for multi-experienced (IQR 44.2–54.0) regimen. We found similar data for BMD of hip, but no patients in the first group had hip osteoporosis. We also analyzed predictors of low BMD in our population. MSM patients showed a 3.4-fold higher risk to have osteoporosis of lumbar spine (OR 3.41, CI 1,105–9,269, p=0.03). As expected, we found that non-Caucasian patients had 13.5-fold higher risk to have osteoporosis of the hip (OR 13.52, CI 1.5–122.7, p=0.02). Exposure to HAART was also evaluated, but no predictors were found. Conclusions: Our data confirm how osteoporosis is highly prevalent and occurs earlier in HIV-infected patients. Antiretrovirals play a crucial role. In our experience loss of BMD can occur within a year of treatment, when almost half of our patients starting TDF had a low BMD. MSM patients have a higher risk to develop spine osteoporosis and non-Caucasian patients are more likely to have hip osteoporosis. We remark the importance of BMD assessment for HIV-infected patients especially during their first months of treatment