Cardiometabolic risk factors among HIV patients on antiretroviral therapy

Kiage, James N; Heimburger, Douglas C.; Nyirenda, Christopher; Wellons, Melissa; Bagchi, Shashwatee; Hanpin, Benjamin; Koethe, John R.; Arnett, Donna K.; Kabagambe, Edmond K.

doi:10.1186/1476-511x-12-50

Cited by 35 publications

(37 citation statements)

References 38 publications

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“…Also, recently, we obtained some preliminary data indicating that exosomes from infected cells of non-T-cell origin (microglia) contain most of these cellular proteins, as well as viral proteins including Tat, Vpr, and Nef. 5 Of note, we have also observed the presence of Tat and Vpr protein in the exosomes from HIV-1-infected promyeloid OM10.1 cells but not from infected T cell lines. Our future efforts will focus on the comparison between T cell-derived and myeloid exosomes with regards to the protein contents (cellular and viral) and their functions in recipient cells.…”

Section: Discussionmentioning

confidence: 71%

See 1 more Smart Citation

Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA

Sampey

Saifuddin

Schwab

et al. 2016

Journal of Biological Chemistry

178

273

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HIV-1 infection results in a chronic illness because longterm highly active antiretroviral therapy can lower viral titers to an undetectable level. However, discontinuation of therapy rapidly increases virus burden. Moreover, patients under highly active antiretroviral therapy frequently develop various metabolic disorders, neurocognitive abnormalities, and cardiovascular diseases. We have previously shown that exosomes containing trans-activating response (TAR) element RNA enhance susceptibility of undifferentiated naive cells to HIV-1 infection. This study indicates that exosomes from HIV-1-infected primary cells are highly abundant with TAR RNA as detected by RT-real time PCR. Interestingly, up to a million copies of TAR RNA/l were also detected in the serum from HIV-1-infected humanized mice suggesting that TAR RNA may be stable in vivo. Incubation of exosomes from HIV-1-infected cells with primary macrophages resulted in a dramatic increase of proinflammatory cytokines, IL-6 and TNF-␤, indicating that exosomes containing TAR RNA could play a direct role in control of cytokine gene expression. The intact TAR molecule was able to bind to PKR and TLR3 effectively, whereas the 5 and 3 stems (TAR microRNAs) bound best to TLR7 and -8 and none to PKR. Binding of TAR to PKR did not result in its phosphorylation, and therefore, TAR may be a dominant negative decoy molecule in cells. The TLR binding through either TAR RNA or TAR microRNA potentially can activate the NF-B pathway and regulate cytokine expression. Collectively, these results imply that exosomes containing TAR RNA could directly affect the proinflammatory cytokine gene expression and may explain a possible mechanism of inflammation observed in HIV-1-infected patients under cART.

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Section: Discussionmentioning

confidence: 71%

“…However, discontinuation of therapy rapidly increases the virus burden (3,4). For reasons not well understood, patients under highly active antiretroviral therapy frequently develop various metabolic disorders and also HIV-associated neurocognitive disorders (5)(6)(7)(8)(9).…”

mentioning

confidence: 99%

Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA

Sampey

Saifuddin

Schwab

et al. 2016

Journal of Biological Chemistry

178

273

View full text Add to dashboard Cite

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“…From 602 records identified through electronic database searching, 19 records from cross‐references, and 28 417 records from the WHO International Clinical Trials Registry Platform, we excluded 560 abstracts and 11 duplicate records. Of 50 remaining full texts assessed for eligibility, 9 articles were withdrawn, leaving 41 studies that were deemed eligible for inclusion in the meta‐analyses . In total, there were 20 178 participants, with approximately twice as many ART‐exposed as there were ART‐naïve patients.…”

Section: Resultsmentioning

confidence: 99%

“…Most studies were conducted in low-and middle-income countries, including Brazil, 19,40,41,59 Cameroon, 39,42,51,57 Ethiopia, 20,30,54 Ghana, 56 India, 33,49,52,53,60 Nigeria, 32,38,55 South Africa, 17,31 Sri Lanka, 61 Thailand, 14 and Zambia. 46 However, the studies conducted in high-income countries were generally larger in size, comprising more than half of the total study population. Table 3 summarizes other characteristics of the included studies.…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

Is there sufficient evidence for a causal association between antiretroviral therapy and diabetes in HIV‐infected patients? A meta‐analysis

Nduka

Stranges

Kimani

et al. 2017

Diabetes Metabolism Res

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The association of antiretroviral therapy (ART) with diabetes is inconsistent and varies widely across primary epidemiological studies. A comprehensive and more precise estimate of this association is fundamental to establishing a plausible causal link between ART and diabetes. We identified epidemiological studies that compared mean fasting plasma glucose (FPG) concentrations and proportions of diabetes and metabolic syndrome between HIV-infected patients naïve and exposed to ART. Mean difference in FPG concentrations and odds ratios of diabetes and metabolic syndrome were pooled using random-effects meta-analyses. Data on 20 178 participants from 41 observational studies were included in the meta-analyses. Mean FPG concentrations (Pooled mean difference: 4.66 mg/dL; 95% confidence interval [CI], 2.52 to 6.80; 24 studies) and the odds of diabetes (Pooled odds ratios: 3.85; 95% CI, 2.93 to 5.07; 10 studies) and metabolic syndrome (Pooled odds ratios: 1.45; 95% CI, 1.03 to 2.03; 18 studies) were significantly higher among ART-exposed patients, compared to their naïve counterparts. ART was also associated with significant increases in FPG levels in studies with mean ART duration ≥18 months (Pooled mean difference: 4.97 mg/dL; 95% CI, 3.10 to 6.84; 14 studies), but not in studies with mean ART duration <18 months (Pooled mean difference: 4.40 mg/dL, 95% CI, -0.59 to 9.38; 7 studies). ART may potentially be the single most consistent determinant of diabetes in people living with HIV worldwide. However, given the preponderance of cross-sectional studies in the meta-analysis, the association between ART and diabetes cannot be interpreted as cause and effect.

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“…Although HIV remains the leading cause of death among adults in sub‐Saharan Africa, the burden of cardiovascular disease (CVD) is substantial and growing , due both to the increasing prevalence of CVD risk factors (CVDRF) such as hypertension , diabetes mellitus , and tobacco smoking , and to the persistence of infectious and congenital causes of heart disease . People living with HIV (PLWH) are at higher risk for CVD compared to the general population , given the effects of HIV replication on inflammatory and coagulation markers as well as the increased risk of hyperlipidemia and diabetes mellitus associated with some antiretroviral drugs .…”

Section: Introductionmentioning

confidence: 99%

A time‐motion study of cardiovascular disease risk factor screening integrated into HIV clinic visits in Swaziland

et al. 2018

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IntroductionScreening of modifiable cardiovascular disease (CVD) risk factors is recommended but not routinely provided for HIV‐infected patients, especially in low‐resource settings. Potential concerns include limited staff time and low patient acceptability, but little empirical data exists. As part of a pilot study of screening in a large urban HIV clinic in Swaziland, we conducted a time‐motion study to assess the impact of screening on patient flow and HIV service delivery and exit interviews to assess patient acceptability.MethodsA convenience sample of patients ≥40 years of age attending routine HIV clinic visits was screened for hypertension, diabetes, hyperlipidemia and tobacco smoking. We observed HIV visits with and without screening and measured time spent on HIV and CVD risk factor screening activities. We compared screened and unscreened patients on total visit time and time spent receiving HIV services using Wilcoxon rank‐sum tests. A separate convenience sample of screened patients participated in exit interviews to assess their satisfaction with screening.ResultsWe observed 172 patient visits (122 with CVD risk factor screening and 50 without). Screening increased total visit time from a median (range) of 4 minutes (2 to 11) to 15 minutes (9 to 30) (p < 0.01). Time spent on HIV care was not affected: 4 (2 to 10) versus 4 (2 to 11) (p = 0.57). We recruited 126 patients for exit interviews, all of whom indicated that they would recommend screening to others.ConclusionProvision of CVD risk factor screening more than tripled the length of routine HIV clinic visits but did not reduce the time spent on HIV services. Programme managers need to take longer visit duration into account in order to effectively integrate CVD risk factor screening and counselling into HIV programmes.

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Cardiometabolic risk factors among HIV patients on antiretroviral therapy

Cited by 35 publications

References 38 publications

Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA

Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA

Is there sufficient evidence for a causal association between antiretroviral therapy and diabetes in HIV‐infected patients? A meta‐analysis

A time‐motion study of cardiovascular disease risk factor screening integrated into HIV clinic visits in Swaziland

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