Effect of a fat spread enriched with medium-chain triacylglycerols and a special fatty acid-micronutrient combination on cardiometabolic risk factors in overweight patients with diabetes

<p>Abstract</p> <p>Background</p> <p>Medium-chain triacylglycerols (MCT), omega-3 polyunsaturated fatty acids (n-3-PUFA) and micronutrients may be useful for weight and cardiometabolic risk management. However, studies analyzing the effect of a combination of both in individuals at increased cardiometabolic risk are lacking. Therefore, this randomized, controlled, double-blind study investigated the effect of a fat spread enriched with two different doses of MCT and a special long-chain fatty acid-micronutrient combination on cardiometabolic risk factors in overweight diabetic patients.</p> <p>Methods</p> <p>Fifty-four patients received either a fat spread with 6 g/d MCT (MCT30%) or 1.2 g/d (MCT6%). Forty-three completed the study. Analysis was performed according to the median of MCT intake (supplemented and food-derived MCT). Clinical, anthropometric, blood, 24 h-urine parameters and dietary intake were assessed at baseline and after 12 weeks.</p> <p>Results</p> <p>Total MCT intake > 7 g/d (MCT > 7 group) significantly reduced waist circumference (WC) by 1.81 ± 2.69 cm, whereas ≤ 7 g/d MCT (MCT ≤ 7 group) increased WC by 0.32 ± 3.03 cm (p = 0.027), which was supported by a change in waist-to-height ratio (WHtR) (p = 0.018). Fasting serum triglycerides (TG) increased in both groups over time due to dietary habits. In contrast, diabetic metabolic situation and urinary albumin excretion did not alter. Urinary pH differed significantly between groups after 12 weeks.</p> <p>Conclusion</p> <p>An intake of >7 g/d MCT reduced WC in overweight diabetics, whereas the increase in the intake of fatty acids may have worsened fasting TG. Therefore, the suitability of a fat for nutrient enrichment remains to be challenged, and further studies in low-fat matrices are desirable.</p

Effect of a conventional energy-restricted modified diet with or without meal replacement on weight loss and cardiometabolic risk profile in overweight women

<p>Abstract</p> <p>Background</p> <p>Abdominal obesity, atherogenic dyslipidemia and hypertension are essential risk factors for cardiovascular diseases. Several studies showed favorable effects of weight loss in overweight subjects on cardiometabolic risk profile.</p> <p>Methods</p> <p>This open-label, randomized, controlled study investigated the effect of an energy-restricted modified diet with (MR) or without meal replacements for weight control (C) on weight loss, body composition and cardiometabolic risk profile in overweight women. Of 105 randomized participants, 87 were eligible for per protocol analysis. Anthropometric, clinical, blood, 24 h-urine parameters and dietary intake were assessed at baseline and after 12 weeks.</p> <p>Results</p> <p>Dietary intervention resulted in a significant weight loss in both groups (MR: -5.98 ± 2.82 kg; p < 0.001, C: -4.84 ± 3.54 kg; p < 0.001). However, the rate of responder (weight loss >5%) was higher in MR (77%) versus C group (50%) (p = 0.010). A significant reduction in waist circumference (WC) and body fat mass (BFM) was observed in both groups. Body cell mass (BCM) and lean body mass (LBM) decreased, while percentage of BCM of body weight increased in MR more than in C group. Systolic and diastolic blood pressure (BP) significantly decreased and to a similar extent in both groups. Total cholesterol (TC), LDL-C but also HDL-C declined significantly in both groups, while no change occurred in triglycerides.</p> <p>Conclusions</p> <p>Both dietary intervention strategies had a similar effect on weight loss and body fat distribution, but rate of responder was significantly higher in MR group. Systolic BP decreased to a similar extent in both groups. Cardiometabolic risk profile improved only partly in both groups.</p

Efficient Suppression of Minority Drug-Resistant HIV Type 1 (HIV-1) Variants Present at Primary HIV-1 Infection by Ritonavir-Boosted Protease Inhibitor-Containing Antiretroviral Therapy

Background. Selection of preexisting minority variants of drug-resistant human immunodeficiency virus type 1 (HIV-1) can lead to virological failure in patients who receive antiretroviral therapy (ART) with low genetic resistance barriers. We studied treatment response and dynamics of minority variants during the first weeks of ART containing a ritonavir-boosted protease inhibitor (PI) and 2 nucleoside reverse-transcriptase inhibitors (NRTIs), which is a regimen with a high genetic resistance barrier. Methods. Plasma samples obtained prior to initiation of ART from 109 patients with primary HIV infection and samples obtained during viral decay during early ART from 17 of these 109 patients were tested by allelespecific polymerase chain reaction for K103N and M184V variants. Results. K103N and/or M184V mutations were detected in 15 (13.8%) of 109 patients prior to ART asminority variants. No selection of these variants was observed within the first weeks of ART in 7 of 15 patients with preexisting drug resistance mutations, nor was any selection observed in 10 patients without preexisting drug resistance mutations. Most patients received ART immediately after diagnosis of HIV-1 infection, showed a rapid decrease in viral load, and experienced sufficient suppression of viremia for ⩽48 months. Conclusions. Minority variants, in particular viruses harboring the M184V mutation, were efficiently suppressed in patients with acute infection who received a ritonavir-boosted PI and 2 NRTIs (most regimens included lamivudine). Under this high genetic resistance barrier regimen, the M184V was not further selecte

Reappearance of Minority K103N HIV-1 Variants after Interruption of ART Initiated during Primary HIV-1 Infection

BACKGROUND: In the Zurich Primary HIV infection study (ZPHI), minority drug-resistant HIV-1 variants were detected in some acutely HIV-1-infected patients prior to initiation of early antiretroviral therapy (ART). Here, we investigated the reappearance of minority K103N and M184V HIV-1 variants in these patients who interrupted efficient early ART after 8-27 months according to the study protocol. These mutations are key mutations conferring drug resistance to reverse transcriptase inhibitors and they belong to the most commonly transmitted drug resistance mutations. METHODOLOGY/PRINCIPAL FINDINGS: Early ART was offered to acutely HIV-1-infected patients enrolled in the longitudinal prospective ZPHI study. Six patients harboring and eleven patients not harboring drug-resistant viruses at low frequencies prior to ART were included in this substudy. Minority K103N and M184V HIV-1 variants were quantified in longitudinal plasma samples after treatment interruption by allele-specific real-time PCR. All 17 patients were infected with HIV-1 subtype B between 04/2003 and 09/2005 and received LPV/r+AZT+3TC during primary HIV-1 infection (PHI). Minority K103N HIV-1 variants reappeared after cessation of ART in two of four patients harboring this variant during PHI and even persisted in one of those patients at frequencies similar to the frequency observed prior to ART (<1%). The K103N mutation did not appear during treatment interruption in any other patient. Minority M184V HIV-1 variants were detected in two patients after ART interruption, one harboring and one not harboring these variants prior to ART. CONCLUSION: Minority K103N HIV-1 variants, present in acutely HIV-1 infected patients prior to early ART, can reappear and persist after interruption of suppressive ART containing two nucleoside/nucleotide analogue reverse transcriptase inhibitors and a ritonavir-boosted protease inhibitor. TRIAL REGISTRATION: Clinicaltrials.gov NCT00537966

Characterization of Human Immunodeficiency Virus Type 1 (HIV-1) Diversity and Tropism in 145 Patients With Primary HIV-1 Infection

Viral diversity during primary HIV-1 infection (PHI) relating to transmission mode, HIV-1 subtypes, and viral tropism was revisited. Varying mucosal barriers were not associated with differences in diversities of founder populations. CXCR4-using viruses are present during PHI but remain exceptional case

Prevalence of HIV-1 drug resistance mutations in proviral DNA in the Swiss HIV Cohort Study, a retrospective study from 1995 to 2018

BACKGROUND: Genotypic resistance testing (GRT) is routinely performed upon diagnosis of HIV-1 infection or during virological failure using plasma viral RNA. An alternative source for GRT could be cellular HIV-1 DNA. OBJECTIVES: A substantial number of participants in the Swiss HIV Cohort Study (SHCS) never received GRT. We applied a method that enables access to the near full-length proviral HIV-1 genome without requiring detectable viraemia. METHODS: Nine hundred and sixty-two PBMC specimens were received. Our two-step nested PCR protocol was applied to generate two overlapping long-range amplicons of the HIV-1 genome, sequenced by next-generation sequencing (NGS) and analysed by MinVar, a pipeline to detect drug resistance mutations (DRMs). RESULTS: Six hundred and eighty-one (70.8%) of the samples were successfully amplified, sequenced and analysed by MinVar. Only partial information of the pol gene was contained in 82/681 (12%), probably due to naturally occurring deletions in the proviral sequence. All common HIV-1 subtypes were successfully sequenced. We detected at least one major DRM at high frequency (≥15%) in 331/599 (55.3%) individuals. Excluding APOBEC-signature (G-to-A mutation) DRMs, 145/599 (24.2%) individuals carried at least one major DRM. RT-inhibitor DRMs were most prevalent. The experienced time on ART was significantly longer in DRM carriers (P = 0.001) independent of inclusion or exclusion of APOBEC-signature DRMs. CONCLUSIONS: We successfully applied a reliable and efficient method to analyse near full-length HIV-1 proviral DNA and investigated DRMs in individuals with undetectable or low viraemia. Additionally, our data underscore the need for new computational tools to exclude APOBEC-related hypermutated NGS sequence reads for reporting DRMs

Time-to-effect guided pulmonary vein isolation utilizing the third-generation versus second generation cryoballoon: One year clinical success

Background: The second-generation cryoballoon (CB2) provides effective and durable pulmonary vein isolation (PVI) associated with encouraging and reproducible clinical outcome data. The latest- -generation cryoballoon (CB3) incorporates a 40% shorter distal tip, thus allowing for an increased rate of PVI real-time signal recording and facilitating individualized ablation strategies taking the time-to- -effect (TTE) into account. However, whether this characteristic translates into favorable clinical success has not been evaluated yet. Herein was investigated 1-year clinical success after CB3 in comparison to CB2 based-PVI. Methods: One hundred and ten consecutive patients with paroxysmal or short-standing persistent atrial fibrillation (AF) underwent CB2 (n = 55 patients) -or CB3 (n = 55 patients) -based PVI. The freeze-cycle duration was set to TTE + 120 s if TTE could be recorded, otherwise a fixed freeze-cycle duration of 180 s was applied. Results: A total of 217/218 (99%, CB3) and 217/217 (100%, CB2) pulmonary veins (PV) were successfully isolated. The real-time PVI visualization rate was 69.2% (CB3) and 54.8% (CB2; p = 0.0392). The mean freeze-cycle duration was 194 ± 77 s (CB3) and 206 ± 85 s (CB2; p = 0.132), respectively. During a median follow-up of 409 days (interquartile range [IQR] 378–421, CB3) and 432 days (IQR 394–455, CB2) 73.6% (CB3) and 73.1% of patients (CB2) remained in stable sinus rhythm after a single procedure (p = 0.806). Conclusions: A higher rate of real-time electrical PV recordings was seen using the CB3 as compared to CB2. There was no difference in 1-year clinical follow-up

Genetic diversity from proviral DNA as a proxy for time since HIV-1 infection.

HIV-1 RNA genetic diversity predicts time since infection which is important for clinical care and research. It's unclear, however, whether proviral DNA genetic diversity sampled under suppressive antiretroviral therapy can be used for this purpose. We tested whether proviral genetic diversity from NGS sequences predicts time since infection and recency in 221 people with HIV-1 with known infection time. Proviral diversity was significantly associated with time since infection (p<5*10-07, R2 up to 25%) and predictive of treatment initiation during recent infection (AUC-ROC up to 0.85). This shows the utility of proviral genetic diversity as a proxy for time since infection

Using viral diversity to identify HIV-1 variants under HLA-dependent selection in a systematic viral genome-wide screen.

The pathogenesis of HIV-1 infection is governed by a highly dynamic, time-dependent interaction between the host and the viral genome. In this study, we developed a novel systematic approach to assess the host-virus interaction, using average pairwise viral diversity as a proxy for time since infection, and applied this method to nearly whole viral genome sequences (n = 4,464), human leukocyte antigen (HLA) genotyping data (n = 1,044), and viral RNA load (VL) measurements during the untreated chronic phase (n = 829) of Swiss HIV Cohort Study participants. Our systematic genome-wide screen revealed for 98 HLA/viral-variant pairs a signature of immune-driven selection in the form of an HLA-dependent effect of infection time on the presence of HIV amino acid variants. Of these pairs, 12 were found to have an effect on VL. Furthermore, 28/58 pairs were validated by time-to-event analyses and 48/92 by computational HLA-epitope predictions. Our diversity-based approach allows a powerful and systematic investigation of the interaction between the virus and cellular immunity, revealing a notable subset of such interaction effects. From an evolutionary perspective, these observations underscore the complexity of HLA-mediated selection pressures on the virus that shape viral evolution and pathogenesis