Dataset Information

Comparison of HIV-1 resistance profiles in plasma RNA versus PBMC DNA in heavily treated patients in Honduras, a resource-limited country.

ABSTRACT: The World Health Organization currently does not recommend the use of dried blood spot specimens for drug resistance testing in patients undergoing antiretroviral therapy (ART). Therefore, HIV-1 resistance testing using peripheral blood mononuclear cells (PBMCs) may be of value in resource-limited settings. We compared genotypic resistance profiles in plasma and PBMCs from patients failing ART in two cities of Honduras (Tegucigalpa and San Pedro Sula), a resource-limited country. One hundred patients failing ART were randomly selected from a longitudinal patient monitoring cohort. Plasma and PBMC samples without patient identifier were used for genotypic resistance testing. Sequence data were analyzed, resistance profiles were determined and compared using Stanford HIV Drug Resistance Database algorithm. Specimens with concordant resistance profiles between the two compartments were 88% (95% CI: 80.3% - 94.5 %). Nine specimens (12%, 95% CI: 6.5% - 21.3%) had discordant resistance profiles of clinical significance. Logistic regression analyses indicated that patients on triple therapy were 17.24 times more likely to have concordant drug resistance profile than those on non-triple therapies (OR=17.24, 95% CI: 3.48, 83.33), while patients with increasing number of regimens and years on ART have a decreased rate of concordance (OR = 0.59, 95% CI: 0.32, 1.09 and OR = 0.62, 95% CI: 0.43, 0.88), respectively, than those with less number of regimens and years on ART. Our results show high level of concordance between plasma and PBMC resistance profiles, indicating the possibility of using PBMCs for drug resistance testing in resources-limited settings.

SUBMITTER: Diallo K

PROVIDER: S-EPMC3316452 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comparison of HIV-1 resistance profiles in plasma RNA versus PBMC DNA in heavily treated patients in Honduras, a resource-limited country.

Diallo Karidia K Murillo Wendy E WE de Rivera Ivette Lorenzana IL Albert Jan J Zhou Zhiyong Z Nkengasong John J Zhang Guoqing G Sabatier Jennifer F JF Yang Chunfu C

International journal of molecular epidemiology and genetics 20120228 1

The World Health Organization currently does not recommend the use of dried blood spot specimens for drug resistance testing in patients undergoing antiretroviral therapy (ART). Therefore, HIV-1 resistance testing using peripheral blood mononuclear cells (PBMCs) may be of value in resource-limited settings. We compared genotypic resistance profiles in plasma and PBMCs from patients failing ART in two cities of Honduras (Tegucigalpa and San Pedro Sula), a resource-limited country. One hundred pat ...[more]

PMID: 22493752

Similar Datasets

Project description:BackgroundWith the phase-out of stavudine (d4T), change to first-line regimens with zidovudine (AZT) or tenofovir (TDF) in resource-limited settings (RLS) might increase risks of cross-resistance to nucleos(t) ide reverse transcriptase inhibitors (NRTI). This would restrict the scope of switching to the World Health Organisation (WHO)-recommended standard second-line combinations (SLC) without HIV drug resistance (HIVDR)-testing in routine clinical practice.MethodsAn observational study was conducted among 101 Cameroonian patients (55.4% male, median [IQR] age 34 [10-41] years) failing first-line antiretroviral therapy (ART) in 2016, and stratified into three groups according to NRTIs exposure: exposure to both thymidine analogues AZT "and" D4T (group-A, n = 55); exposure to both TDF and AZT "or" D4T (group-B, n = 22); exposure solely to D4T (group-C, n = 24). Protease-reverse transcriptase HIVDR was interpreted using the HIVdb penalty scores (≥60: high-resistance; 20-59: intermediate-resistance; < 20: susceptible). The acceptable threshold for potential-efficacy was set at 80%.ResultsThe median [IQR] CD4, viral RNA, and time on ART, were respectively 129 [29-466] cells/μl, 71,630 [19,041-368,000] copies/ml, and 4 [2-5] years. Overall HIVDR-level was 89.11% (90/101), with 83.2% harbouring M184 V (high-level 3TC/FTC-resistance) and only 1.98% (2/101) major HIVDR-mutations to ritonavir-boosted protease-inhibitors (PI/r). Thymidine-analogue mutations (TAMs)-1 [T215FY (46.53%), M41 L (22.77%), L210 W (8.91%)], with cross-resistance to AZT and TDF, were higher compared to TAMs-2 [D67N (21.78%), K70R (19.80%), K219QE (18.81%)]. As expected, K65R was related with TDF-exposure: 0% (0/55) in group-A, 22.72% (5/22) group-B, 4.17% (1/24) group-C (p = 0.0013). The potential-efficacy of AZT vs. TDF was respectively 43.64% (24/55) vs. 70.91% (39/55) in group-A (p = 0.0038); 63.64% (14/22) vs. 68.28% (15/22) in group-B (p = 1.0000); and 37.50% (9/24) vs. 83.33% (20/24) in group-C (p = 0.0032). CRF02_AG was the prevailing subtype (63.40%), followed by CRF11.cpx (8.91%), A1 (7.92%), G (5.94%); without any significant effect of the subtype-distribution on HIVDR (92.2% in CRF02_AG vs. 83.8% in non-AG; p = 0.204).ConclusionFirst-line ART-failure exhibits high-level NRTI-resistance, with potential lower-efficacy of AZT compared to TDF. Significantly, using our 80% efficacy-threshold, only patients without NRTI-substitution on first-line could effectively switch to SLC following the WHO-approach. Patients with multiple NRTI-substitutions (exposed to both thymidine-analogues and TDF) on first-line ART would require HIVDR-testing to select active NRTIs for SLC.

Project description:The pathological mechanisms that lead to the onset and reactivation of celiac disease (CD) remain largely unknown. While gluten free diet (GFD) improves the intestinal damage and associated clinical symptoms in majority of cases, it falls short of providing full recovery. Additionally, late or misdiagnosis is also common as CD presents with a wide range of symptoms. Clear understanding of CD pathogenesis is thus critical to address both diagnostic and treatment concerns. We aimed to study the molecular impact of short gluten exposure in GFD treated CD patients, as well as identify biological pathways that remain altered constitutively in CD regardless of treatment. Using RNAseq profiling of PBMC samples collected from treated CD patients and gluten challenged patient and healthy controls, we explored the peripheral transcriptome in CD patients following a short gluten exposure. Short gluten exposure of just three days was enough to alter the genome-wide PBMC transcriptome of patients. Pathway analysis revealed gluten-induced upregulation of mainly immune response related pathways, both innate and adaptive, in CD patients. We evaluated the perturbation of biological pathways in sample-specific manner. Compared to gluten exposed healthy controls, pathways related to tight junction, olfactory transduction, metabolism of unsaturated fatty acids (such as arachidonic acid), metabolism of amino acids (such as cysteine and glutamate), and microbial infection were constitutively altered in CD patients regardless of treatment, while GFD treatment appears to mostly normalize immune response pathways to "healthy" state. Upstream regulator prediction analysis using differentially expressed genes identified constitutively activated regulators relatively proximal to previously reported CD associated loci, particularly SMARCA4 on 19p13.2 and CSF2 on 5q31. We also found constitutively upregulated genes in CD that are in CD associated genetic loci such as MEF2BNB-MEF2B (BORCS8-MEF2B) on 19p13.11 and CSTB on 21q22.3. RNAseq revealed strong effects of short oral gluten challenge on whole PBMC fraction and constitutively altered pathways in CD PBMC suggesting important factors other than gluten in CD pathogenesis.

Project description:BackgroundDespite the undisputed benefits of breastfeeding, infants might become exposed to xenobiotics that could be excreted into breast milk following maternal exposure. This study was conducted to assess breastmilk cadmium levels among lactating women in Palestine, a resource-limited country. Estimated daily intake (EDI) of cadmium via breastmilk was also calculated and predictors of high breastmilk cadmium levels and high infant exposure via breastmilk were identified.MethodsThis multicenter study was conducted using a descriptive-analytical design. The lactating women were recruited from different maternity and public health clinics in all regions of Palestine. Demographic variables and exposure to sources of cadmium were collected in an interviewer-administered questionnaire. Foremilk samples (about 5 mL) were collected in polyethylene tubes using the hand-expression technique. The breast milk samples were collected in the period between December 2020 and March 2021. A pre-validated method using inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify breastmilk cadmium levels. EDI values were calculated from the quantified breastmilk cadmium levels.ResultsBreastmilk samples were obtained from 256 lactating women. The mean breastmilk cadmium level was 0.34 (SD: 0.33) μg / L and the mean EDI of cadmium via breastmilk was 0.059 (SD: 0.058) µg / kg per body weight / day. Breastmilk cadmium levels were quantified in 92.6% of the breastmilk samples. Of the breastmilk samples, 13 (5.1%) had cadmium levels above those reported as "normal" by the World Health Organization (WHO). Multiple linear regression showed that higher breastmilk cadmium levels and higher EDI were predicted by being a smoker, living in a refugee camp, living close to an industrial area, living close to disposal of wastes, living close to paint shops, living in a house with peeling / chipping paint, frequent use of cosmetics, frequent use of hair dyes, and not using vitamins.ConclusionThe breastmilk cadmium levels and infant exposure were predicted by maternal exposure to sources of cadmium. The findings reported in this study are valuable to antenatal and postnatal healthcare service providers. More studies are needed to plan and implement measures to reduce breastmilk cadmium levels and infants' exposure to cadmium via breastmilk.

Project description:BackgroundIn resource-limited countries, access to specialized health care services such as dermatology is limited. Clinical decision support systems (CDSSs) offer innovative solutions to address this challenge. However, the implementation of CDSSs is commonly associated with unique challenges. VisualDx-an exemplar CDSS-was recently implemented in Botswana to provide reference materials in support of the diagnosis and management of dermatological conditions. To inform the sustainable implementation of VisualDx in Botswana, it is important to evaluate the intended users' perceptions about the technology.ObjectiveThis study aims to determine health care workers' acceptance of VisualDx to gauge the feasibility of future adoption in Botswana and other similar health care systems.MethodsThe study's design was informed by constructs of the Technology Acceptance Model. An explanatory, sequential, mixed methods study involving surveys and semistructured interviews was conducted. The REDCap (Research Electronic Data Capture; Vanderbilt University) platform supported web-based data capture from March 2021 through August 2021. In total, 28 health care workers participated in the study. Descriptive statistics were generated and analyzed using Excel (Microsoft Corp), and thematic analysis of interview transcripts was performed using Delve software.ResultsAll survey respondents (N=28) expressed interest in using mobile health technology to support their work. Before VisualDx, participants referenced textbooks, journal articles, and Google search engines. Overall, participants' survey responses showed their confidence in VisualDx (18/19, 95%); however, some barriers were noted. Frequently used VisualDx features included generating a differential diagnosis through manual entry of patient symptoms (330/681, 48.5% of total uses) or using the artificial intelligence feature to analyze skin conditions (150/681, 22% of total uses). Overall, 61% (17/28) of the survey respondents were also interviewed, and 4 thematic areas were derived.ConclusionsParticipants' responses indicated their willingness to accept VisualDx. The ability to access information quickly without internet connection is crucial in resource-constrained environments. Selected enhancements to VisualDx may further increase its feasibility in Botswana. Study findings can serve as the basis for improving future CDSS studies and innovations in Botswana and similar resource-limited countries.

Dataset Information

Comparison of HIV-1 resistance profiles in plasma RNA versus PBMC DNA in heavily treated patients in Honduras, a resource-limited country.

Publications

Comparison of HIV-1 resistance profiles in plasma RNA versus PBMC DNA in heavily treated patients in Honduras, a resource-limited country.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets