Variations In Trim5α And Cyclophilin A Genes Among HIV-1 Elite Controllers and Non Controllers In Uganda; A Laboratory-Based Cross-sectional study

Abstract Background Tripartite Motif Containing 5 alpha (TRIM5α), a restriction factor produced ubiquitously in cells and tissues of the body plays an important role in the immune response against HIV. TRIM5α targets the HIV capsid for proteosomal destruction. Cyclophilin A, an intracellular protein has also been reported to influence HIV infectivity in a cell-specific manner. Accordingly, variations in TRIM5α and Cyclophilin A genes have been documented to influence HIV-1 disease progression. However, these variations have not been documented among Elite controllers in Uganda and whether they play a role in viral suppression remains largely undocumented. Our study focused on identifying the variations in TRIM5α and Cyclophilin A genes among HIV-1 Elite controllers and non-controllers in Uganda.Results From the sequence analysis, the rs10838525 G>A mutation in exon 2 of TRIM5α was only found among elite controllers (30%) while the rs3824949 in the 5’UTR was seen among 25% of the non-controllers. In the Cyclophilin A promoter, rs6850 was seen among 62.5% of the non-controllers and only among 10% elite controllers. Furthermore, rs17860048 in the Cyclophillin A promoter was predominantly seen among elite controllers (30%) and 12.5% non-controllers. From gene expression analysis, we noted that the respective genes were generally elevated among elite controllers, however, this difference was not statistically significant (TRIM5α p=0.6095; Cyclophilin A p=0.6389). Conclusion Variations in TRIM5α and Cyclophillin A promoter may influence HIV viral suppression. The rs10838525 SNP in TRIM5α may contribute to viral suppression among HIV-1 elite controllers. The rs6850 in the cyclophillin A gene may be responsible for HIV-1 rapid progression among HIV-1 non-controllers. These SNPs should be investigated mechanistically to determine their precise role in HIV-1 viral suppression.

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Variations In Trim5α and Cyclophilin A Genes Among HIV-1 Elite Controllers and Non Controllers in Uganda; A Laboratory-Based Cross-Sectional Study

10.21203/rs.3.rs-27470/v1 ◽

2020 ◽

Author(s):

Sharon Bright Amanya ◽

Brian Nyiro ◽

Francis Waswa ◽

Bonniface Obura ◽

Rebecca Nakaziba ◽

...

Keyword(s):

Viral Suppression ◽

Cyclophilin A ◽

Cross Sectional Study ◽

The Body ◽

Rapid Progression ◽

Elite Controllers ◽

Cross Sectional ◽

Exon 2 ◽

Hiv Viral Suppression ◽

Hiv 1

Abstract Background Tripartite Motif Containing 5 alpha (TRIM5α), a restriction factor produced ubiquitously in cells and tissues of the body plays an important role in the immune response against HIV. TRIM5α targets the HIV capsid for proteosomal destruction. Cyclophilin A, an intracellular protein has also been reported to influence HIV infectivity in a cell-specific manner. Accordingly, variations in TRIM5α and Cyclophilin A genes have been documented to influence HIV-1 disease progression. However, these variations have not been documented among Elite controllers in Uganda and whether they play a role in viral suppression remains largely undocumented. Our study focused on identifying the variations in TRIM5α and Cyclophilin A genes among HIV-1 Elite controllers and non-controllers in Uganda.Results From the sequence analysis, the rs10838525 G > A mutation in exon 2 of TRIM5α was found only among elite controllers (30%) while the rs3824949 in the 5’UTR was seen among 25% of the non-controllers. In the Cyclophilin A promoter, rs6850 was seen among 62.5% of the non-controllers and only among 10% elite controllers. Furthermore, rs17860048 in the Cyclophillin A promoter was predominantly seen among elite controllers (30%) and 12.5% non-controllers. From gene expression analysis, we noted that the respective genes were generally elevated among elite controllers, however, this difference was not statistically significant (TRIM5α p = 0.6095; Cyclophilin A p = 0.6389).Conclusion Variations in TRIM5α and Cyclophillin A promoter may influence HIV viral suppression. The rs10838525 SNP in TRIM5α may contribute to viral suppression among HIV-1 elite controllers. The rs6850 in the cyclophillin A gene may be responsible for HIV-1 rapid progression among HIV-1 non-controllers. These SNPs should be investigated mechanistically to determine their precise role in HIV-1 viral suppression.

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Variations In Trim5α And Cyclophilin A Genes Among HIV-1 Elite Controllers and Non Controllers In Uganda; A Laboratory-Based Cross-sectional Study

10.21203/rs.3.rs-26665/v1 ◽

2020 ◽

Author(s):

Sharon Bright Amanya ◽

Brian Nyiro ◽

Francis Wasswa ◽

Bonniface Obura ◽

Rebecca Nakabazi ◽

...

Keyword(s):

Viral Suppression ◽

Sequence Data ◽

Cyclophilin A ◽

The Body ◽

Rapid Progression ◽

Nucleotide Polymorphisms ◽

Elite Controllers ◽

Cross Sectional ◽

Exon 2 ◽

Hiv 1

Abstract Background Tripartite Motif Containing 5 alpha (TRIM5α), a restriction factor produced ubiquitously in cells and tissues of the body plays an important role in the immune response against HIV. TRIM5α targets the HIV capsid for proteosomal destruction. Cyclophilin A, an intracellular protein has also been reported to influence HIV infectivity in a cell-specific manner. Accordingly, variations in TRIM5α and Cyclophilin A genes have been documented to influence HIV-1 disease progression. However, these variations have not been documented among Elite controllers in Uganda and whether they play a role in viral suppression remains largely undocumented. Our study focused on identifying the variations in TRIM5α and Cyclophilin A genes among HIV-1 Elite controllers and non-controllers in Uganda.Methods PBMCs previously collected from HIV-1 Elite controllers and non-controllers were thawed, CD4+ T cells isolated and then cultured in presence of Anti-CD3 & Anti-CD28 for 48 hours in a CO2 incubator. RNA was extracted and RT qPCR was done using QuantiTect Probe RT-PCR Kit in a Rotor gene Q real-time PCR machine. mRNA was quantified using the delta CT relative quantification method. DNA was extracted using Qiagen Blood Genomic DNA Kit, PCR amplified and sequenced the exon 2 of TRIM5α and the promoter region of the CyclophillinA gene. Sequence data were analyzed using Mutation Surveyor to identify Single Nucleotide Polymorphisms (SNPs).Results From the sequence analysis, the rs10838525 G>A mutation in exon 2 of TRIM5α was found only among elite controllers (30%) while the rs3824949 was seen among 25% of the non-controllers. In the Cyclophilin A promoter, rs6850 was seen among 62.5% of the non-controllers and only among 10% elite controllers. rs17860048 was predominantly seen among elite controllers (30%) and 12.5% non-controllers. From gene expression analysis, we noted that the respective genes were generally elevated among elite controllers, however, this difference was not statistically significant (TRIM5α p=0.6095; Cyclophilin A p=0.6389).Conclusion Variations in TRIM5α and Cyclophillin A promoter may influence HIV viral suppression. The rs10838525 SNP in TRIM5α may contribute to viral suppression among HIV-1 elite controllers. The rs6850 in the cyclophillin A gene may be responsible for HIV-1 rapid progression among HIV-1 non-controllers.

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Variations in Trim5α and Cyclophilin A genes among HIV-1 elite controllers and non controllers in Uganda: a laboratory-based cross-sectional study

Retrovirology ◽

10.1186/s12977-020-00527-z ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Sharon Bright Amanya ◽

Brian Nyiro ◽

Francis Waswa ◽

Bonniface Obura ◽

Rebecca Nakaziba ◽

...

Keyword(s):

Cyclophilin A ◽

Cross Sectional Study ◽

Elite Controllers ◽

Sectional Study ◽

Cross Sectional ◽

Hiv 1

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CCR5 promoter variants among Ugandan HIV-1 elite and viremic controllers: a laboratory ‑ based cross ‑ sectional study

10.21203/rs.3.rs-47544/v1 ◽

2020 ◽

Author(s):

Brian Nyiro ◽

Sharon Bright Amanya ◽

Rose Nabatanzi ◽

Alice Bayiyana ◽

Linda Igumba Kalazane ◽

...

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Rapid Progression ◽

Elite Controllers ◽

Promoter Polymorphisms ◽

Novel Mutations ◽

Cross Sectional ◽

Study Objective ◽

Hiv Progression ◽

Hiv 1

Abstract Background Mechanisms for HIV control among HIV-1 elite and viremic-controllers are not fully understood. In Uganda, Studies have reported individuals who without Antiretroviral therapy have the inherent ability to control HIV progression to AIDS for a period of greater than 5 years. However, reasons for this phenotype are not understood. The study objective was to determine the distribution of CCR5 co-receptor on CD4+ T-cells and its associated promoter variants among HIV-1 elite and viremic-controllers. Methods We isolated CD4+T-cells from PBMCs using EasySep CD4+ T-cell negative selection kit, and stimulated them with anti-CD3 and anti-CD28 for 48 hours. To quantify CCR5 expression, we performed immune-phenotyping using flow cytometry. CCR5 promoter polymorphisms were determined through sanger sequencing. The Kruskal–Wallis and the Mann-Whitney test were used to compare differences in the percentages of CCR5+ CD4+ T-cells and the differences in CCR5 densities on CD4+ T-cells respectively. p values < 0.05 were considered significant. Results The percentage of CCR5+CD4+ T-cells was higher among the non-controllers compared to the controllers although, the difference was not statistically significant; elite and viremic-controllers (p=0.9173), viremic and non-controllers (0.0702), elite and non-controllers (0.6010). Of significance was the CCR5 densities on CD4+ T-cells, which were significantly higher among non-controllers relative to the controllers; elite and viremic-controllers (p=3048), viremic and non-controllers (P=0.0312), elite and non-controllers (P=0.0210) From the sequence analysis, the rs1799987A>G mutation was found among elite (71%) and viremic-controllers (61%), while the -2459A/A and rs41469351C>T mutation were among the non-controllers (57%). This study also identified two novel mutations 1070T>G and 785A>G among the elite controllers (14.3%). Conclusion Rs1799987 SNP highly detected among the elite and viremic controllers may be associated with reduced CCR5 densities on CD4+ T-cells while higher frequency of -2459 A/A and rs41469351 SNP among non-controllers may be associated with increased CCR5 densities on CD4+ T-cells. Thus Rs1799987 SNP may be responsible for the delayed HIV progression among elite and viremic controllers, while -2459A/A and rs41469351 SNP may be responsible for the rapid progression of HIV among non-controllers. In vitro studies are needed to study the effect of the two novel mutations 1070T>G and 785A>G among elite-controllers.

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333. Weight Gain Among HIV-Infected Patients in Southern India on Treatment with Integrase Strand Transfer Inhibitor-based Antiretroviral Therapy

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.406 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S177-S177

Author(s):

Rifa Khan ◽

Amrose Pradeep ◽

Chithra Devaraja ◽

Bala Krishnan

Keyword(s):

Weight Gain ◽

Viral Suppression ◽

Opportunistic Infections ◽

Oral Candidiasis ◽

Cross Sectional Study ◽

Strand Transfer ◽

Median Viral Load ◽

Cross Sectional ◽

Initiation Of Therapy ◽

Hiv 1

Abstract Background Addition of integrase strand transfer-inhibitors (mainly dolutegravir) has strengthened anti-retroviral therapy (ART), to sustain viral suppression in HIV-1 and 2-infected patients. For judicious use in the future, we examine weight gain in ART-naïve, and those exposed to INSTI-based regimens as first, second, and third-line ART. Methods We undertook a retrospective cross-sectional study of patients initiated on INSTI-based regimens from 15 January 2017 to 22 December 2018 (n = 333). Descriptive statistical analyses were performed using STATA 15.1. Cross-tabulation and stratification were conducted to measure the strength of association. A linear regression model was used to study the increase in weight per unit of time. Results 331 patients are infected with HIV-1 and 2 with HIV-2. 66% are male, median age= 38 years (IQR 31–44). Median CD4 count at INSTI initiation was 226 cell/cubic mL (IQR 87–395). Median viral load at initiation of INSTI-based therapy was log104.768 copies/mL (IQR 2.9—5.63). Most common opportunistic infections were pulmonary tuberculosis (n = 97), oral candidiasis (n = 84), and herpes zoster (n = 44). Median hemeoglobin was 12gm% (IQR 10.5–13.8). 39% were initiated on TDF+3TC+DTG and 32% were initiated on TDF+FTC+DTG. 74% experienced weight gain; average increase was 3.69 Kg (SD 3.56) at 3 months. 19.5% gained >4 kg; median BMI at initiation of therapy was 22.56 kg/m2 (IQR 19.8–25.1) and 25.4 kg/m2 (IQR 22.5–28.7) at an average of 9.5 months post initiation of dolutegravir-based ART. 70% of ART naïve (n = 73) experienced weight gain; 17.8% gained 8.36 kg at 9 months. Higher weight gain was observed in patients with opportunistic infections. Association with gender (OR = 0.9 95%, CI 0.54 -1.5; P = 0.70) and age (OR=0.9, 95% CI 0.97–1.01;P = 0.71) was not significant. Weight gain was positively correlated with time (r=+1); predicted increase in weight per 0.1 months after initiation of INSTI-based regimen (F=4.62, P = 0.032). Conclusion Access and adherence to INSTI have positively influenced viral suppression of HIV-infection.To ensure the prevention of obesity and apt use of ART for malnourished patients, it is imperative to monitor weight gain in patients who are initiated on INSTI-based regimens. Further research to study the mechanism of weight gain is warranted. Disclosures All authors: No reported disclosures.

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Association between Short Hours of Sleep and Overweight/Obesity in Mexican Adolescent Population: A School-Based Cross-Sectional Study

Healthcare ◽

10.3390/healthcare9080939 ◽

2021 ◽

Vol 9 (8) ◽

pp. 939

Author(s):

Ana Fresan ◽

Alma Delia Genis-Mendoza ◽

María Lilia López-Narváez ◽

Tania Guadalupe Gómez-Peralta ◽

Daniela Georgina Aguilar-Velázquez ◽

...

Keyword(s):

Cross Sectional Study ◽

The Body ◽

Categorical Variables ◽

Continuous Variables ◽

Sectional Study ◽

Cross Sectional ◽

Obese Adolescent ◽

School Based ◽

Prevalence Of Obesity ◽

Mexican Adolescents

Background/Aim: Obesity in adolescents is increasing; as such, the aim of this study was to determine the prevalence of obesity in Mexican adolescents and examine its possible association with hours of sleep. Methods: A school-based cross-sectional study was carried out. This study included 863 adolescents aged between 11 and 16 years. The prevalence of obesity was estimated using the body mass index (BMI). The duration of sleep (and other information) was assessed by a self-reported questionnaire. The Cochran–Mantel–Hansel test for categorical variables and a general linear model for continuous variables were used to evaluate the interaction effect of BMI and sex with respect to sleeping and assessed activity conditions. Results: It was found that 47.6% of the adolescents were overweight/obese. Men were more frequently overweight/obese than women (52.6% vs. 41.8%, p = 0.002). Moreover, overweight/obese adolescents were younger and spent fewer daily hours watching television (p < 0.05). Men practiced sports more hours per week than women (p = 0.04). However, women spent more daily time on the internet (p = 0.05), and overweight/obese adolescent women slept fewer hours than overweight/obese men and adolescents with normal weight (p = 0.008). Conclusions: The development of strategies for the prevention of overweight/obesity and the improvement of sleep duration should include a gender perspective to improve health habits in Mexican adolescents.

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Factors Influencing HIV Drug Resistance among Pregnant Women in Luanda, Angola: Findings from a Cross-Sectional Study

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed6010029 ◽

2021 ◽

Vol 6 (1) ◽

pp. 29

Author(s):

Cruz S. Sebastião ◽

Joana Morais ◽

Miguel Brito

Keyword(s):

Drug Resistance ◽

Pregnant Women ◽

Rural Areas ◽

Cross Sectional Study ◽

Drug Resistant ◽

Sectional Study ◽

Cross Sectional ◽

Hiv Drug Resistance ◽

Hiv 1 ◽

High Educational

The increase in HIV infection and drug-resistant strains is an important public health concern, especially in resource-limited settings. However, the identification of factors related to the propagation of infectious diseases represents a crucial target offering an opportunity to reduce health care costs as well as deepening the focus on preventing infection in high-risk groups. In this study, we investigate the factors related to drug resistance among HIV-infected pregnant women in Luanda, the capital city of Angola. This was a part of a cross-sectional study conducted with 42 HIV-positive pregnant women. A blood sample was collected, and HIV-1 genotyping was carried out using an in-house method. Multivariate analyses were performed to determine the interaction between sociodemographic characteristics and drug resistance. HIV drug resistance was detected in 44.1% of the studied population. High probabilities of drug resistance were observed for HIV-infected pregnant women living in rural areas (AOR: 2.73; 95% CI: 0.50–14.9) with high educational level (AOR: 6.27; 95% CI: 0.77–51.2) and comorbidities (AOR: 5.47; 95% CI: 0.28–106) and infected with a HIV-1 non-B subtype other than subtype C (AOR: 1.60; 95% CI: 0.25–10.3). The present study reports high HIV drug resistance. Furthermore, older-age, rural areas, high educational levels, unemployed status, having comorbidities, and HIV-1 subtypes were factors related to drug resistance. These factors impact on drug susceptibility and need to be urgently addressed in order to promote health education campaigns able to prevent the spread of drug-resistant HIV strains in Angola.

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Kidney Biopsy in Type 2 Diabetes: A Multicenter Cross-Sectional Study

American Journal of Nephrology ◽

10.1159/000514259 ◽

2021 ◽

pp. 1-10

Author(s):

Jonathan M. Chemouny ◽

Mickaël Bobot ◽

Aurélie Sannier ◽

Valentin Maisons ◽

Noémie Jourde-Chiche ◽

...

Keyword(s):

Type 2 Diabetes ◽

Total Population ◽

Cross Sectional Study ◽

Rapid Progression ◽

Hypertensive Nephropathy ◽

Cross Sectional ◽

Recent Onset ◽

Atypical Features ◽

Retinal Examination

Introduction: Kidney biopsies (KBs) are performed in patients with type 2 diabetes (T2D) to diagnose non-diabetic or hypertensive kidney disease (NDHKD) potentially requiring specific management compared to diabetic and or hypertensive nephropathy (absence of NDHKD). Indications for KB are based on the presence of atypical features compared to the typical course of diabetic nephropathy. In this study, we assessed the association of different patterns of atypical features, or KB indications, with NDHKD. Methods: Native KBs performed in patients with T2D were analyzed. Data were collected from the patients’ records. KB indications were determined according to the presence of different atypical features considered sequentially: (1) presence of any feature suggesting NDHKD which is not among the following ones, (2) recent onset of nephrotic syndrome, (3) low or rapidly declining estimated glomerular filtration rate (eGFR), (4) rapid increase in proteinuria, (5) short duration of diabetes, (6) presence of hematuria, or (7) normal retinal examination. Results: Among the 463 KBs analyzed, NDHKD was diagnosed in 40% of the total population and 54, 40, 24, and 7% of the KBs performed for indications 1–4 respectively. Conversely, no patient who underwent KB for indications 5–7 displayed NDHKD. Logistic regression analyses identified eGFRCKD-EPI >15 mL/min/1.73 m2, urinary protein-to-Cr ratio <0.3 g/mmol, hematuria, HbA1c <7%, and diabetes duration <5 years as predictors of NDHKD, independently from the indication group. Conclusion: NDHKD is frequent in T2D. Despite the association of hematuria with NDHKD, our results suggest that presence of hematuria and absence of DR are insufficient to indicate KB in the absence of concurrent atypical features. Conversely, rapid progression of proteinuria and rapid deterioration of eGFR are major signals of NDHKD.

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Clinical situation of Venezuelan migrants living with HIV in a hospital in Lima, Peru

International Journal of STD & AIDS ◽

10.1177/09564624211024080 ◽

2021 ◽

pp. 095646242110240

Author(s):

Genesis S Huerta-Vera ◽

Manuel A Amarista ◽

Fernando A Mejía ◽

Ana B Graña ◽

Elsa V Gonzalez-Lagos ◽

...

Keyword(s):

Viral Suppression ◽

Clinical Situation ◽

Cross Sectional Study ◽

People Living With Hiv ◽

Sectional Study ◽

Cross Sectional ◽

Epidemiological Trends ◽

Clinical Conditions ◽

Living With Hiv

Due to a huge crisis extensive to health services many Venezuelan people living with HIV (PLWH) had migrated abroad, including Peru where favorable laws were in place until June 2019. We describe the health status and epidemiological trends of PLWH from Venezuela at an HIV program in Lima. We analyzed baseline and follow-up data of all Venezuelan PLWH enrolled in our HIV program from January 2017 to December 2019. A cross-sectional study in a subsample served to describe ARV adherence and context of migration. Between 2017-2019 our HIV Program registered 398 Venezuelan PLWH, representing 20% of the 2018 annual enrollments; numbers decreased since mid-2019. The median age was 30 years (IQR 26;37) and 90.5% were men. Between 2017 and 2019, the proportion with diagnosis in Peru increased from 14.3% to 60.9%; of AIDS stage at entry, from 8.8% to 27.2%. By December 2019, 182/250 (72.8%) were still in care, and 43 (10.8%) had not started ART. Viral suppression evaluated in 195, was achieved in 71.8%. From 2017 to 2019, migrant PLWH arrived in worsened clinical conditions, with increasing diagnosis in Peru; the flow of migrant PLWH entering care diminished with less favorable laws. Viral suppression rates were suboptimal.

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The importance of dysphagia screening and nutritional assessment in hospitalized patients

Einstein (São Paulo) ◽

10.1590/s1679-45082018ao4189 ◽

2018 ◽

Vol 16 (2) ◽

Cited By ~ 5

Author(s):

Patrícia Amaro Andrade ◽

Carolina Araújo dos Santos ◽

Heloísa Helena Firmino ◽

Carla de Oliveira Barbosa Rosa

Keyword(s):

Nutritional Status ◽

Global Assessment ◽

Assessment Tool ◽

Nutritional Assessment ◽

Cross Sectional Study ◽

Hospitalized Patients ◽

The Body ◽

Subjective Global Assessment ◽

Cross Sectional ◽

Knee Height

ABSTRACT Objective: To determine frequency of dysphagia risk and associated factors in hospitalized patients as well as to evaluate nutritional status by using different methods and correlate the status with scores of the Eating Assessment Tool (EAT-10). Methods: This was a cross-sectional study including 909 inpatients of a philanthropic hospital. For the diagnosis of dysphagia we used an adapted and validated Brazilian version of the Eating Assessment Tool (EAT-10). The nutritional status was evaluated through the subjective global assessment, and anthropometric measurements included weight, calf and arm circumference, and knee height. The Mann-Whitney test, associations using the Pearson’s χ2 and Spearman’s correlation were used to verify differences between the groups. Results: The prevalence of dysphagia risk was 10.5%, and aging was the associated factor with this condition. Patients at risk presented lower values of arm and calf circumference, variables that correlated inversely with the Eating Assessment Tool (EAT-10) score. Malnutrition was observed in 13.2% of patients based on the subjective global assessment and in 15.2% based on the Body Mass Index. Conclusion: Screening for dysphagia and malnutrition should be introduced in hospitals routine to avoid or minimize damages caused by dysphagia or malnutrition, especially among older people.

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