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Increased Circulating Levels of Growth Differentiation Factor 15 in Association with Metabolic Disorders in People Living with HIV Receiving Combined Antiretroviral Therapy.

ABSTRACT: People living with HIV (PLWH) have an increased cardiovascular risk (CVR) owing to dyslipidemia, insulin resistance, metabolic syndrome, and HIV/combination antiretroviral therapy (cART)-associated lipodystrophy (HALS). Atherosclerosis and inflammation are related to growth differentiation factor-15 (GDF15). The relationship between metabolic disturbances, HALS, and CVR with GDF15 in PLWH is not known. Circulating GDF15 levels in 152 PLWH (with HALS = 60, without HALS = 43, cART-naïve = 49) and 34 healthy controls were assessed in a cross-sectional study. Correlations with lipids, glucose homeostasis, fat distribution, and CVR were explored. PLWH had increased circulating GDF15 levels relative to controls. The increase was the largest in cART-treated PLWH. Age, homeostatic model assessment of insulin resistance 1 (HOMA1-IR), HALS, dyslipidemia, C-reactive protein, and CVR estimated with the Framingham score correlated with GDF15 levels. The GDF15-Framingham correlation was lost after age adjustment. No correlation was found between GDF15 and the D:A:D Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) score estimated CVR. CVR independent predictors were patient group (naïve, HALS-, and HALS+) and cumulated protease inhibitor or nucleoside reverse transcriptase inhibitor exposure. PLWH, especially when cART-treated, has increased GDF15 levels-this increase is associated with dyslipidemia, insulin resistance, metabolic syndrome, HALS, and inflammation-related parameters. GDF15 is unassociated with CVR when age-adjusted.

SUBMITTER: Domingo P

PROVIDER: S-EPMC8836868 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Increased Circulating Levels of Growth Differentiation Factor 15 in Association with Metabolic Disorders in People Living with HIV Receiving Combined Antiretroviral Therapy.

Domingo Pere P Mateo María Gracia MG Villarroya Joan J Cereijo Rubén R Torres Ferran F Domingo Joan C JC Campderrós Laura L Gallego-Escuredo José M JM Gutierrez María Del Mar MDM Mur Isabel I Corbacho Noemí N Vidal Francesc F Villarroya Francesc F Giralt Marta M

Journal of clinical medicine 20220122 3

<h4>Objective</h4>People living with HIV (PLWH) have an increased cardiovascular risk (CVR) owing to dyslipidemia, insulin resistance, metabolic syndrome, and HIV/combination antiretroviral therapy (cART)-associated lipodystrophy (HALS). Atherosclerosis and inflammation are related to growth differentiation factor-15 (GDF15). The relationship between metabolic disturbances, HALS, and CVR with GDF15 in PLWH is not known.<h4>Research design and methods</h4>Circulating GDF15 levels in 152 PLWH (wit ...[more]

PMID: 35160008

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Project description:BackgroundProgress toward the global target for 95% virological suppression among those on antiretroviral treatment (ART) is still suboptimal. We describe the viral load (VL) cascade, the incidence of virological failure and associated risk factors among people living with HIV receiving first-line ART in an HIV cohort in Myanmar treated by the Médecins Sans Frontières in collaboration with the Ministry of Health and Sports Myanmar.MethodsWe conducted a retrospective cohort study, including adult patients with at least one HIV viral load test result and having received of at least 6 months' standard first-line ART. The incidence rate of virological failure (HIV viral load ≥ 1000 copies/mL) was calculated. Multivariable Cox's regression was performed to identify risk factors for virological failure.ResultsWe included 25,260 patients with a median age of 33.1 years (interquartile range, IQR 28.0-39.1) and a median observation time of 5.4 years (IQR 3.7-7.9). Virological failure was documented in 3,579 (14.2%) participants, resulting in an overall incidence rate for failure of 2.5 per 100 person-years of follow-up. Among those who had a follow-up viral load result, 1,258 (57.1%) had confirmed virological failure, of which 836 (66.5%) were switched to second-line treatment. An increased hazard for failure was associated with age ≤ 19 years (adjusted hazard ratio, aHR 1.51; 95% confidence intervals, CI 1.20-1.89; p < 0.001), baseline tuberculosis (aHR 1.39; 95% CI 1.14-1.49; p < 0.001), a history of low-level viremia (aHR 1.60; 95% CI 1.42-1.81; p < 0.001), or a history of loss-to-follow-up (aHR 1.24; 95% CI 1.41-1.52; p = 0.041) and being on the same regimen (aHR 1.37; 95% CI 1.07-1.76; p < 0.001). Cumulative appointment delay was not significantly associated with failure after controlling for covariates.ConclusionsVL monitoring is an important tool to improve programme outcomes, however limited coverage of VL testing and acting on test results hampers its full potential. In our cohort children and adolescents, PLHIV with history of loss-to-follow-up or those with low-viremia are at the highest risk of virological failure and might require more frequent virological monitoring than is currently recommended.

Project description:BackgroundThe risky sexual behavior of people living with HIV/AIDS (PLWHA) may impose a risk of transmitting the disease to their partners and increase Human Immunodeficiency Virus (HIV) co-infection. This systematic review and meta-analysis aimed to determine the pooled prevalence of risky sexual behavior and associated factors among PLWHA receiving [Antiretroviral Therapy (ART)] in Ethiopia.MethodsTo identify both published and unpublished research articles, systematic searches were performed in PubMed, HINARI, Medline, Science Direct, and Google Scholar databases. The review was carried out following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline. Cross-sectional studies reporting the prevalence of risky sexual practice and its associated factors among PLWHA receiving ART in Ethiopia were included. Two authors independently extracted all necessary data using a standardized data extraction format prepared in Microsoft Excel and exported to STATA version 14 statistical software for further analyses. The Cochrane Q test statistics and I2 test were used to assess the heterogeneity of the studies. Since the included studies exhibited considerable heterogeneity, the random-effects meta-analysis model was computed to estimate the pooled prevalence of risky sexual practice which was determined by dividing the total number of PLWHA with risky sexual practice practices by the total number of PLWHA on ART in the study and multiplied by 100. Furthermore, pooled odds ratio (OR) with 95% confidence interval (CI) was determined for the association between determinant factors and risky sexual practice.ResultIn this study, 2351 articles were identified from different databases, and fifteen articles were selected for final systematic review and meta-analysis. In Ethiopia, the pooled prevalence of risky sexual practices was 43.56% (95% confidence interval (CI):35.51, 51.62). Discussion about safe sex with sexual partner/s [AOR = 0.26, 95% CI: 0.08, 0.92] and having multiple sexual partners [AOR = 1.90, 95% CI: 0.53, 6.84] were factors significantly associated with risky sexual practice in Ethiopia.ConclusionA significant proportion of respondents engaged in risky sexual practices. Multiple sexual partners and a lack of discussion about safe sex are linked to a higher prevalence of the risky sexual practice in Ethiopia. It is critical to raise awareness about safe sexual practices during health education and counselling services and to encourage clients to freely discuss safer sex practices with their sexual partner/s at their antiretroviral therapy (ART) appointments as part of their follow-up care.Protocol registrationThe protocol for this systematic review and meta-analysis was registered at PROSPERO (record ID = CRD42021274600, 25 September 2021).

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Increased Circulating Levels of Growth Differentiation Factor 15 in Association with Metabolic Disorders in People Living with HIV Receiving Combined Antiretroviral Therapy.

Publications

Increased Circulating Levels of Growth Differentiation Factor 15 in Association with Metabolic Disorders in People Living with HIV Receiving Combined Antiretroviral Therapy.

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