145 research outputs found
-DEPENDENCE OF THE VIBRATIONAL ZEROPOINT ENERGY IN THE PARTIALLY DEUTERATED METHYL ALCOHOLS, REVISITED
No full text1. A Serrallach, R. Mever, and Hs. H. Gunthard, J. Mol. Spec. 52, 94(1974). 2. C. R. Quade and R. D. Suenram, J. Chem. Phys. 73, 1127(1980): 81, 1054(1984).Author Institution: Department of Physics, Texas Tech UniversityThe contribution of the zeropoint energy from the 3N - 7 other vibrations to the effective potential energy for internal rotation have been calculated for eight isotopic species of methyl alcohol. The basis of the calculation is the set of force constants determined by Serrallach, Meyer, and from infrared analyses. The calculated results for are and with . These values agree favorably with the experimental results as previously determined by Quade and from analysis of the microwave torsional-rotational spectra of
Nonlinear Mixed-Effects Models for HIV Viral Load Trajectories Before and After Antiretroviral Therapy Interruption, Incorporating Left Censoring
No full textCharacterizing features of the viral rebound trajectories and identifying host, virological, and immunological factors that are predictive of the viral rebound trajectories are central to HIV cure research. In this paper, we investigate if key features of HIV viral decay and CD4 trajectories during antiretroviral therapy (ART) are associated with characteristics of HIV viral rebound following ART interruption. Nonlinear mixed effect (NLME) models are used to model viral load trajectories before and following ART interruption, incorporating left censoring due to lower detection limits of viral load assays. A stochastic approximation EM (SAEM) algorithm is used for parameter estimation and inference. To circumvent the computational intensity associated with maximizing the joint likelihood, we propose an easy-to-implement threestep method. We evaluate the performance of this method through simulation studies and apply it to data from the Zurich Primary HIV Infection Study. We find that some key features of viral load during ART (e.g., viral decay rate) are significantly associated with important characteristics of viral rebound following ART interruption (e.g., viral set point)
Clinical Significance of Extraintestinal Hafnia alvei Isolates from 61 Patients and Review of the Literature
No full textHafnia alvei is a gram-negative bacterium that is rarely isolated from human specimens and is rarely considered to be pathogenic. It has been associated with gastroenteritis, meningitis, bacteremia, pneumonia, nosocomial wound infections, endophthalmitis, and a buttock abscess. We studied 80 H. alvei isolates recovered from 61 patients within a period of 30 months. H. alvei was cultured from sites that included the respiratory tract (n = 38), the gastrointestinal tract (n = 16), and the urogenital tract (n = 12); the organism was found in blood cultures (n = 8), on central venous catheters (n = 3), and on the skin (n = 3). Only 25% of H. alvei isolates were recovered in pure cultures. Fifty-seven (93.4%) of the patients had an underlying illness. H. alvei proved to be the etiologic agent in two episodes of septicemia and in one episode of peritonitis and was probably responsible for septicemia in two other patients and pneumonia in one. All six of these patients recovered after receiving antibiotic treatment and/or standard surgical treatment, when needed. Three of these infections were nosocomial, and three were community acquired. Of the strains of H. alvei tested in our study, 100% were susceptible to netilmicin, ciprofloxacin, and imipenem; 92% were susceptible to piperacillin; 90% were susceptible to co-trimoxazole; and 88% were susceptible to ceftriaxone and ceftazidime. In this study, we found H. alvei to be a rare but significant etiologic agent of nosocomial and community-acquired infection
Proviral HIV-DNA predicts viral rebound and viral setpoint after structured treatment interruptions
No full textIn HIV-1-infected patients with long-term undetectable viraemia on highly active antiretroviral treatment (HAART), we found that pre-HAART plasma viraemia and the baseline proviral DNA level were significantly associated with the viraemia setpoint during scheduled treatment interruptions. In long-term treated patients, pre-HAART viraemia may not be available, and in these circumstances proviral DNA, measured at the time of scheduled treatment interruption, can help to identify patients likely to reach a low viraemia setpoint after treatment interruption
Drug resistance mutations during structured treatment interruptions
No full textBACKGROUND: We assessed whether treatment interruptions induce selection of mutations associated with drug resistance in the Swiss-Spanish Intermittent Treatment Trial (SSITT). Patients had been on HAART without previous failure and had undetectable viraemia for at least 6 months. Their HAART was interrupted for 2 weeks and restarted for 8 weeks. After four of these cycles, treatment was definitively interrupted at week 40. METHODS: Genotypic resistance testing was performed in 87/97 Swiss patients: in those failing treatment before week 40, at the time of first viral rebound > 500 copies/ml off treatment and preceding failure to reach RNA < 50 copies/ml after 8 weeks of re-treatment; for patients without virological failure, on the first sample with HIV-1 RNA > 1000 copies/ml after week 40. RESULTS: Mutations associated with drug resistance were detected in 9/25 (36%) patients with virological failure during the first 40 weeks and in 6/59 (10%) patients after week 40. Overall, drug resistance mutations were detected in 17% of patients, all but two with the 184V/I mutation. Among the 74 patients receiving lamivudine, the M184V/I mutation was detected in 13/74 (17.6%) patients. A wild-type codon at position 184 was detected in previous samples in all but two. The relative risk for virological failure was 2.55-fold higher in patients with the M184V/I mutation than in patients without detectable mutation (P=0.007). CONCLUSIONS: The M184V/I mutation is frequently selected during repeated treatment interruptions
Anticholinergic medication use in elderly people living with HIV and self-reported neurocognitive impairment: a prospective cohort study
No full textBACKGROUND
Anticholinergic (ACH) medications have been associated with neurocognitive impairment, particularly in the elderly. This study determined prospectively the prevalence of prescribed ACH medications and their association with self-reported neurocognitive impairment (SRNI) in elderly people living with HIV (PLWH) of the Swiss HIV Cohort Study (SHCS).
METHODS
A literature review was performed to identify ACH medications, which were scored 0 to 3 (higher score indicating more ACH burden). Prescriptions were reviewed in July 2019 for all SHCS participants ≥65 years old to assess the prevalence of ACH medications. Association between ACH burden and neurocognitive impairment was evaluated using the SHCS SRNI questions addressing memory loss, attention difficulties and slowing in reasoning.
RESULTS
One thousand and nineteen PLWH (82% male) with a median age of 70 (IQR = 67-74) years were included. Most participants were on ART (99%). The average number of non-HIV drugs was 5.1 ± 3.6, representing a polypharmacy prevalence of 50%. Two hundred participants (20%) were on ≥1 ACH medication, with an average ACH score of 1.7 ± 1.3. SRNI, adjusted for age, sex, CD4, nadir CD4, viral load, efavirenz use and polypharmacy, was associated with depression (OR = 4.60; 95% CI = 2.62-8.09) and a trend was observed with being on ≥1 ACH medication (OR = 1.69; 95% CI = 0.97-2.95). In a subgroup analysis of participants without depression (n = 911), SRNI was associated with the use of ≥1 ACH medication (OR = 2.51; 95% CI = 1.31-4.80).
CONCLUSIONS
ACH medication use is common in elderly PLWH and contributes to SRNI. The effect of ACH medications on neurocognitive impairment warrants further evaluation using neurocognitive tests
Increased CHIP Prevalence Amongst People Living with HIV.
No full textPeople living with human immunodeficiency virus (PLWH) have significantly increased risk for cardiovascular disease in part due to inflammation and immune dysregulation. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related acquisition and expansion of hematopoietic stem cells due to leukemogenic driver mutations, increases risk for both hematologic malignancy and coronary artery disease (CAD). Since increased inflammation is hypothesized to be both a cause and consequence of CHIP, we hypothesized that PLWH have a greater prevalence of CHIP. We searched for CHIP in multi-ethnic cases from the Swiss HIV Cohort Study (SHCS, n=600) and controls from the Atherosclerosis Risk in the Communities study (ARIC, n=8,111) from blood DNA-derived exome sequences. We observed that HIV is associated with increased CHIP prevalence, both in the whole study population and in a subset of 230 cases and 1002 matched controls selected by propensity matching to control for demographic imbalances (SHCS 7%, ARIC 3%, p=0.005). Additionally, unlike in ARIC, ASXL1 was the most commonly implicated mutated CHIP gene. We propose that CHIP may be one mechanism through which PLWH are at increased risk for CAD. Larger prospective studies should evaluate the hypothesis that CHIP contributes to the excess cardiovascular risk in PLWH
Impact of HIV-1 reverse transcriptase polymorphism F214L on virological response to thymidine analogue-based regimens in antiretroviral therapy (ART)-naive and ART-experienced patients
No full textBackground. A negative association between the polymorphism F214L and type 1 thymidine analogue ( TA) mutations (TAMs) has been observed. However, the virological response to TAs according to the detection of F214L has not been evaluated. Methods. We studied 590 patients from EuroSIDA who started TA therapy for the first time as part of potent combination antiretroviral therapy (cART) and who were tested for genotypic resistance within the past 6 months. End points were median reduction in the week 24 viral load and time to virological failure (2 consecutive VL measurements > 400 copies/mL after at least 6 months of the TA-containing cART). Results. In ART-naive patients, the prevalence of F214L was 17%. By 48 months after starting TA-based cART, the proportion of patients who experienced virological failure was 16% in patients with 214L and 36% in those with 214F (p = .03). In a multivariable Cox regression model, the relative hazard of virological failure for patients with 214L compared with those with 214F was 0.22 (95% confidence interval, 0.07-0.72). In ART-experienced patients, results were similar, and larger differences in virological response associated with the detection of 214L versus F were observed in patients with M41L/T215Y and mixed TAM profiles detected before the initiation of cART. Conclusions. This study provides evidence that the detection of polymorphism F214L is associated with a favorable virological response to TA-based cART
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