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- Aralaguppe, SG, et al.
(författare)
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MiDRMpol: A High-Throughput Multiplexed Amplicon Sequencing Workflow to Quantify HIV-1 Drug Resistance Mutations against Protease, Reverse Transcriptase, and Integrase Inhibitors
- 2019
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- The detection of drug resistance mutations (DRMs) in minor viral populations is of potential clinical importance. However, sophisticated computational infrastructure and competence for analysis of high-throughput sequencing (HTS) data lack at most diagnostic laboratories. Thus, we have proposed a new pipeline, MiDRMpol, to quantify DRM from the HIV-1 pol region. The gag-vpu region of 87 plasma samples from HIV-infected individuals from three cohorts was amplified and sequenced by Illumina HiSeq2500. The sequence reads were adapter-trimmed, followed by analysis using in-house scripts. Samples from Swedish and Ethiopian cohorts were also sequenced by Sanger sequencing. The pipeline was validated against the online tool PASeq (Polymorphism Analysis by Sequencing). Based on an error rate of <1%, a value of >1% was set as reliable to consider a minor variant. Both pipelines detected the mutations in the dominant viral populations, while discrepancies were observed in minor viral populations. In five HIV-1 subtype C samples, minor mutations were detected at the <5% level by MiDRMpol but not by PASeq. MiDRMpol is a computationally as well as labor efficient bioinformatics pipeline for the detection of DRM from HTS data. It identifies minor viral populations (<20%) of DRMs. Our method can be incorporated into large-scale surveillance of HIV-1 DRM.
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- Ashenafi, S, et al.
(författare)
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Anemia Is a Strong Predictor of Wasting, Disease Severity, and Progression, in Clinical Tuberculosis (TB)
- 2022
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 14:16
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Tidskriftsartikel (refereegranskat)abstract
- A typical trait of chronic tuberculosis (TB) is substantial weight loss that concurs with a drop in blood hemoglobin (Hb) levels, causing anemia. In this observational study, we explored Hb levels in 345 pulmonary TB patients. They were divided into anemic or non-anemic groups which related to clinical symptoms, anthropometric measurements, and immune status. Data was obtained in a randomized controlled trial that we previously conducted using nutritional supplementation of TB patients in Ethiopia. A post hoc analysis demonstrated that anemic patients have a higher composite clinical TB score at baseline than non-anemic patients. Consequently, Hb values were significantly lower in underweight patients with moderate to severe disease and/or cavitary TB compared to normal weight patients with mild disease or non-cavitary TB. Anemia was associated with a low body mass index (BMI), low mid-upper arm circumference (MUAC), lower peripheral CD4 and CD8 T cells counts and IFN-γ levels, and a higher erythrocyte sedimentation rate (ESR). Chronic inflammation and TB disease progression appeared to be driven by elevated systemic levels of pro-inflammatory IL-6 in anemic patients. Multivariable modeling confirmed that a low Hb and a low BMI were key variables related to an unfavorable TB disease status. Although Hb levels increased with successful chemotherapy, anemic TB patients maintained a slower clinical recovery compared to non-anemic patients during the intensive phase treatment (two months). In conclusion, anemia is a strong predictor of wasting, disease severity, inflammation, and slower recovery in patients with pulmonary TB.
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- Ashenafi, S, et al.
(författare)
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Daily Nutritional Supplementation with Vitamin D₃ and Phenylbutyrate to Treatment-Naïve HIV Patients Tested in a Randomized Placebo-Controlled Trial
- 2019
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Poor nutritional status is common among human immunodeficiency virus (HIV)-infected patients including vitamin D (vitD3) deficiency. We conducted a double-blinded, randomized, and placebo-controlled trial in Addis Ababa, Ethiopia, to investigate if daily nutritional supplementation with vitD3 (5000 IU) and phenylbutyrate (PBA, 2 × 500 mg) could mediate beneficial effects in treatment-naïve HIV patients. Primary endpoint: the change in plasma HIV-1 comparing week 0 to 16 using modified intention-to-treat (mITT, n = 197) and per-protocol (n = 173) analyses. Secondary endpoints: longitudinal HIV viral load, T cell counts, body mass index (BMI), middle-upper-arm circumference (MUAC), and 25(OH)D3 levels in plasma. Baseline characteristics were detectable viral loads (median 7897 copies/mL), low CD4+ (median 410 cells/µL), and elevated CD8+ (median 930 cells/µL) T cell counts. Most subjects were vitD3 deficient at enrolment, but a gradual and significant improvement of vitD3 status was demonstrated in the vitD3 + PBA group compared with placebo (p < 0.0001) from week 0 to 16 (median 37.5 versus 115.5 nmol/L). No significant changes in HIV viral load, CD4+ or CD8+ T cell counts, BMI or MUAC could be detected. Clinical adverse events were similar in both groups. Daily vitD3 + PBA for 16 weeks was well-tolerated and effectively improved vitD3 status but did not reduce viral load, restore peripheral T cell counts or improve BMI or MUAC in HIV patients with slow progressive disease. Clinicaltrials.gov NCT01702974.
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- Missailidis, C, et al.
(författare)
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Vitamin D and Phenylbutyrate Supplementation Does Not Modulate Gut Derived Immune Activation in HIV-1
- 2019
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Dysbiosis and a dysregulated gut immune barrier function contributes to chronic immune activation in HIV-1 infection. We investigated if nutritional supplementation with vitamin D and phenylbutyrate could improve gut-derived inflammation, selected microbial metabolites, and composition of the gut microbiota. Treatment-naïve HIV-1-infected individuals (n = 167) were included from a double-blind, randomized, and placebo-controlled trial of daily 5000 IU vitamin D and 500 mg phenylbutyrate for 16 weeks (Clinicaltrials.gov NCT01702974). Baseline and per-protocol plasma samples at week 16 were analysed for soluble CD14, the antimicrobial peptide LL-37, kynurenine/tryptophan-ratio, TMAO, choline, and betaine. Assessment of the gut microbiota involved 16S rRNA gene sequencing of colonic biopsies. Vitamin D + phenylbutyrate treatment significantly increased 25-hydroxyvitamin D levels (p < 0.001) but had no effects on sCD14, the kynurenine/tryptophan-ratio, TMAO, or choline levels. Subgroup-analyses of vitamin D insufficient subjects demonstrated a significant increase of LL-37 in the treatment group (p = 0.02), whereas treatment failed to significantly impact LL-37-levels in multiple regression analysis. Further, no effects on the microbiota was found in number of operational taxonomic units (p = 0.71), Shannon microbial diversity index (p = 0.82), or in principal component analyses (p = 0.83). Nutritional supplementation with vitamin D + phenylbutyrate did not modulate gut-derived inflammatory markers or microbial composition in treatment-naïve HIV-1 individuals with active viral replication.
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