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Plasma soluble factor following two decades prolonged suppressive antiretroviral therapy in HIV-1-positive males: A cross-sectional study.

ABSTRACT: Acute human immunodeficiency virus (HIV) infection is associated with a marked induction of several pathways that are linked to inflammation and CD4 T-cell depletion. Many of these processes do not fully resolve on short-term combination antiretroviral therapy (cART) (<5 years), despite complete and durable suppression of viremia. The effects of long-term (>15 years) successful antiretroviral therapy (ART) and the linkage between levels of biomarkers remain unclear. Therefore, the present study aims to assess the host plasma proteome in a well-defined clinical material from HIV-1-positive male patients on successful long-term ART (>15 years) and compared them with age-matched healthy controls and treatment-naïve male patients with viremia in a cross-sectional manner.Plasma samples were obtained from 3 categories of age-matched HIV-1-positive male patients on long-term successfully (ART, n?=?10) with a median (Interquartile range, IQR) of 19 (17-20) years, treatment-naïve patients with viremia (VP, n?=?14), and HIV-1-negative persons (HC, n?=?11). Plasma proteome was analyzed using the proximity extension assay targeting 92 factors. Statistical analyses were performed with GraphPad Prism v7, R-packages, and Qlucore Omics Explorer v3.2. Functional enrichment analysis was performed by Kyoto Encyclopedia of Genes and Genomes (KEGG), and interactions of specific molecules were identified using Path Designer integrated into Ingenuity Pathway Analysis (IPA).Group wise comparison identified 53 soluble factors, which differed between the groups (P?

SUBMITTER: Sperk M

PROVIDER: S-EPMC5805434 | biostudies-other | 2018 Feb

REPOSITORIES: biostudies-other

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Plasma soluble factor following two decades prolonged suppressive antiretroviral therapy in HIV-1-positive males: A cross-sectional study.

Sperk Maike M Zhang Wang W Nowak Piotr P Neogi Ujjwal U

Medicine 20180201 5

Acute human immunodeficiency virus (HIV) infection is associated with a marked induction of several pathways that are linked to inflammation and CD4 T-cell depletion. Many of these processes do not fully resolve on short-term combination antiretroviral therapy (cART) (<5 years), despite complete and durable suppression of viremia. The effects of long-term (>15 years) successful antiretroviral therapy (ART) and the linkage between levels of biomarkers remain unclear. Therefore, the present study ...[more]

PMID: 29384862

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Project description:The majority of potent and broadly neutralizing antibodies against HIV-1 have been isolated from untreated patients with acute or chronic infection. To assess the extent of HIV-1 specific antibody response and neutralization after many years of virologic suppression from potent combination ART, we examined antibody binding titers and neutralization of 51 patients with chronic HIV-1 infection on suppressive ART for at least three years. In this cross-sectional analysis, we found high antibody titers against gp120, gp41, and the membrane proximal external region (MPER) in 59%, 43%, and 27% of patients, respectively. We observed significantly higher endpoint binding titers for gp120 and gp41 for patients with >10 compared to ≤ 10 years of detectable HIV RNA. Additionally, we observed higher median gp120 and gp41 antibody titers in patients with HIV RNA <50 copies/mL for ≤ 5 years. 22% of patients neutralized a HIV-1 primary isolate (HIV-1(JR-FL)) and 8% neutralized a HIV-2/HIV-1 MPER chimera. Significantly greater HIV-1(JR-FL) neutralization was found among patients with >10 years of detectable HIV RNA (8/20 [40.0%] versus 3/31 [9.7%] for ≤ 10 years, p = 0.02) and a trend toward greater neutralization in patients with ≤ 5 years of HIV RNA <50 copies/mL (7/20 [35.0%] versus 4/31 [12.9%] for >5 years, p = 0.08). All patients with neutralizing activity mediated successful phagocytosis of VLPs by THP-1 cells after antibody opsonization. Our findings of highly specific antibodies to several structural epitopes of HIV-1 with antibody effector functions and neutralizing activity after long-term suppressive ART, suggest continuous antigenic stimulation and evolution of HIV-specific antibody response occurs before and after suppression with ART. These patients, particularly those with slower HIV progression and more time with detectable viremia prior to initiation of suppressive ART, are a promising population to identify and further study functional antibodies against HIV-1.

Project description:BackgroundThe free antiretroviral therapy (ART) program in India still relies on the clinico-immunological monitoring for diagnosis of treatment failure. As the nucleoside reverse transcriptase inhibitor (NRTI) backbone is shared in first- and second-line regimens, accumulation of drug resistant mutations (DRMs) can compromise the efficacy of NRTI. This study was undertaken to describe the pattern of HIV DRMs following immunological monitoring and investigate its impact on the cycling of NRTI between first- and second-line ART.Methods and findingsThis cross-sectional study was performed at a state-sponsored ART clinic of Pune city in western India between January and June 2016. Consecutive adults receiving first-line ART with immunological failure (IF) were recruited for plasma viral load (PVL) estimation. Randomly selected 80 participants with PVL >1000 copies/mL underwent HIV drug resistance genotyping. Of these, 75 plasma sample were successfully genotyped. The median CD4 count and duration of ART at the time of failure were 98 (IQR: 61.60-153.50) cells/μL and 4.62 (IQR: 3.17-6.15) years, respectively. The prevalence of NRTI, non-NRTI, and major protease inhibitor resistance mutations were 89.30%, 96%, and 1.33%, respectively. Following first-line failure, sequences from 56.67% of individuals indicated low- to high-level resistance to all available NRTI. The proportion of sequences with ≥2 thymidine analogue mutations (TAMs) and ≥3 TAMs were 62.12% and 39.39%, respectively. An average of 1.98 TAMs per sequence were observed following IF as compared to 0.37 TAMs per sequence following targeted PVL monitoring at 12 months of ART from a prior study; this difference was significant (p<0.001).ConclusionThe option of cycling of NRTI analogues between first- and second-line regimens would no longer be effective if individuals are followed-up by immunological monitoring due to accumulation of mutations. Introduction of routine PVL monitoring is a priority for the long-term sustainability of free ART program in India.

Project description:OBJECTIVES:Antiretroviral therapy (ART) has facilitated the transition of HIV infection into a chronic disease, where adherence to medications is required along with keeping a healthy lifestyle. Therefore, an increase in physical activity has been recommended for patients with HIV in order to maintain their health status. This study looked to determine the physical activity level and its associated factors among patients with HIV receiving ART treatment. SETTINGS:Eight outpatient clinic sites across different levels of the health systems in both rural and urban settings in Hanoi and Nam Dinh, Vietnam. STUDY DESIGN AND PARTICIPANTS:A cross-sectional study was performed among 1133 patients with HIV receiving ART treatment from January to August 2013. PRIMARY AND SECONDARY OUTCOME MEASURES:Physical activity level was measured using the International Physical Activity Questionnaire (IPAQ). Socioeconomic, health-related quality of life, ART adherence and ART-related characteristics were self-reported. RESULTS:16% of participants were inactive, and 68% were reported active via health-enhancing physical activity. Rural participants reported a higher level of physical activity compared with urban participants. Participants having a longer duration of ART were less likely to be physically active. Participants who were female and self-employed, who had higher CD4 cell count, higherEuroQol - 5 dimensions - 5levels (EQ-5D-5L) index/EQ-Visual Analogue Scale, and shared their health status with their peers were more likely to have a higher IPAQ score or be physically active. A lower IPAQ score was associated with participants living in urban areas and being at the symptomatic stage. Participants having poor adherence and longer duration of ART were more likely to be physically inactive. CONCLUSION:The majority of participants who received ART were physically active. There is a need for interventions to promote physical activity among patients with HIV in urban areas and in the later ART treatment phases. Other potential interventions to increase the level of physical activity include peer support and job guidance.

Project description:BackgroundIn Ethiopia, undernutrition among women on antiretroviral therapy has been a major challenge to achieve the full impact of intervention. Twenty seven percent and 17% of reproductive age Ethiopian women are chronically malnourished and anemic, respectively. Most studies to examine risk factors have been limited to the general population and ART-naive HIV-positive women, making it difficult to generalize findings to ART-treated HIV-positive women. The objectives of this study were thus to assess nutritional status and associated factors among adult women (? 20 years) on antiretroviral therapy.MethodsFrom August to September we conducted an Institution based cross-sectional survey among 276 women on antiretroviral therapy in Humera Hospital, Tigray, Ethiopia. Data was collected using structured and standard face to face interview, anthropometric measurements, BD FACS (CD4 count machine) and Sysmex-21 (hemoglobin analyzer). Logistic regression was done using SPSS version 16 to identify factors that are associated with nutritional status.ResultsThe prevalence of under nutrition (Body mass index < 18.5 kg/m(2)) Was 42.3% (95% CI: 37.4% - 47.3%). Severe, moderate and mild under nutrition was detected on 12%, 10% and 20.3% respondents, respectively. The prevalence of wasting (percentage body weight loss >5%) was 75% (95% CI: 70.4% - 79.2%). Severe wasting was accounted for 26.9% of respondents.In the multivariate analysis, Household food insecurity [AOR = 1.85; 95%CI 1.16, 2.86], inadequate dietary diversity [AOR = 1.19; 95%CI 1.08, 1.75], anemia [AOR = 1.67; 95%CI 1.05, 2.65] and absence of nutritional support [AOR = 0.34 95%CI 0.22, 0.54) were found to be independent predictors of under-nutrition.ConclusionHIV/AIDS is associated with an increased burden of undernutrition even among ART treated women in Humera Hospital, Tigray, Ethiopia. In addition to ART among HIV positive women interventions to ameliorate poor nutritional status may be necessary in this and similar settings. Such interventions aimed at improving household food security, dietary diversity, micronutrient supplementation, proper use of therapeutic food, as well as treating oral candidiasis.

Project description:BackgroundDefining the association of non-AIDS-defining events with inflammation and immune activation among human immunodeficiency virus (HIV)-infected persons with antiretroviral therapy (ART)-associated virological suppression is critical to identifying interventions to decrease the occurrence of these events.MethodsWe conducted a case-control study of HIV-infected subjects who had achieved virological suppression within 1 year after ART initiation. Cases were patients who experienced non-AIDS-defining events, defined as myocardial infarction, stroke, non-AIDS-defining cancer, non-AIDS-defining serious bacterial infection, or death. Controls were matched to cases on the basis of age, sex, pre-ART CD4(+) T-cell count, and ART regimen. Peripheral blood mononuclear cells and plasma specimens obtained at the visit before ART initiation (hereafter, baseline), the visit approximately 1 year after ART initiation (hereafter, year 1), and the visit immediately preceding the non-AIDS-defining event (hereafter, pre-event) were analyzed for activated CD4(+) and CD8(+) T cells, plasma interleukin 6 (IL-6) level, soluble tumor necrosis factor receptor I (sTNFR-I) level, sTNFR-II level, soluble CD14 level, kynurenine-to-tryptophan (KT) ratio, and D-dimer level. Conditional logistic regression analysis was used to study the association between biomarkers and outcomes, with adjustment for potential confounders.ResultsHigher IL-6 level, sTNFR-I level, sTNFR-II level, KT ratio, and D-dimer level at year 1 were associated with the occurrence of a non-AIDS-defining event. Significant associations were also seen between non-AIDS-defining events and values of these biomarkers in specimens obtained at baseline and the pre-event time points. Effects remained significant after control for confounders. T-cell activation was not significantly related to outcomes.ConclusionsInterventional trials to decrease the incidence of non-AIDS-defining events among HIV-infected persons with virological suppression should consider targeting the pathways represented by these soluble markers. Clinical Trials Registration. NCT00001137.

Project description:BackgroundAdherence to antiretroviral therapy (ART) remains the main predictor of sustained HIV virologic suppression for people with HIV (PWH). Mail-order pharmacy services are often offered to patients as an alternative option to traditional pharmacy services. Some payers mandate ART to be dispensed from specific mail-order pharmacies regardless of patient choice complicating ART adherence for patients affected by social disparities. Yet, little is known about patient perspectives regarding mail-order mandates.MethodsEligible patients of the HIV program at University of Nebraska Medical Center with experience receiving ART from both a local and mail-order pharmacy were invited to complete a 20-question survey with three core sections: experiences/perspectives on local and mail-order pharmacy settings; pharmacy attributes rankings; and pharmacy preference. Paired t-tests and Mann-Whitney tests were used to compare the agreement scores of pharmacy attributes.ResultsSixty patients (N = 146; 41.1%) responded to the survey. Mean age was 52 years. Most were male (93%) and White (83%). The majority of participants were on ART for HIV treatment (90%) and 60% were using mail-order pharmacies for their prescription services. Significant scoring differences (p<0.05) were observed for all pharmacy attributes favoring local pharmacies. Refilling ease was the most important attribute noted. More respondents (68%) preferred local pharmacies versus mail-order pharmacies. Payer associated mail-order pharmacy mandates were experienced by 78% with half believing the mandates impacted their medical care negatively.ConclusionsIn this cohort study, respondents preferred local pharmacies compared to mail-order pharmacy for ART prescription services and noted ease of refilling as the most important pharmacy attribute. Two-thirds of respondents believed mail-order pharmacy mandates negatively affected their health. Insurance payers should consider the removal of mail-order pharmacy mandates to allow patient choice of pharmacy, which may help remove barriers to ART adherence and improve long-term health outcomes.

Dataset Information

Plasma soluble factor following two decades prolonged suppressive antiretroviral therapy in HIV-1-positive males: A cross-sectional study.

Publications

Plasma soluble factor following two decades prolonged suppressive antiretroviral therapy in HIV-1-positive males: A cross-sectional study.

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