scholarly journals Deciphering DNA Methylation in HIV Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Thilona Arumugam ◽  
Upasana Ramphal ◽  
Theolan Adimulam ◽  
Romona Chinniah ◽  
Veron Ramsuran

With approximately 38 million people living with HIV/AIDS globally, and a further 1.5 million new global infections per year, it is imperative that we advance our understanding of all factors contributing to HIV infection. While most studies have focused on the influence of host genetic factors on HIV pathogenesis, epigenetic factors are gaining attention. Epigenetics involves alterations in gene expression without altering the DNA sequence. DNA methylation is a critical epigenetic mechanism that influences both viral and host factors. This review has five focal points, which examines (i) fluctuations in the expression of methylation modifying factors upon HIV infection (ii) the effect of DNA methylation on HIV viral genes and (iii) host genome (iv) inferences from other infectious and non-communicable diseases, we provide a list of HIV-associated host genes that are regulated by methylation in other disease models (v) the potential of DNA methylation as an epi-therapeutic strategy and biomarker. DNA methylation has also been shown to serve as a robust therapeutic strategy and precision medicine biomarker against diseases such as cancer and autoimmune conditions. Despite new drugs being discovered for HIV, drug resistance is a problem in high disease burden settings such as Sub-Saharan Africa. Furthermore, genetic therapies that are under investigation are irreversible and may have off target effects. Alternative therapies that are nongenetic are essential. In this review, we discuss the potential role of DNA methylation as a novel therapeutic intervention against HIV.

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Patience Adzordor ◽  
Clement Avoka ◽  
Vitalis Bawontuo ◽  
Silas Agbesi ◽  
Desmond Kuupiel

Abstract Background Sub-Saharan Africa (SSA) homes most of the people living with HIV/AIDS in the world. Adolescents/young people are a vulnerable population and at high risk of HIV infection. Identifying and bridging the research gaps on the disclosure of HIV-positive status among adolescents, particularly to their sexual partners, is essential to inform appropriate policy planning and implementation towards preventing HIV transmission. This study will aim to explore literature and describe the evidence on HIV-positive status disclosure among adolescents in SSA. Methods The framework provided by Arksey and O’Malley’s framework and improved by Levac and colleagues will be used to conduct a scoping review. A keyword search for relevant literature presenting evidence on HIV-positive status disclosure among adolescents in SSA will be conducted in CINAHL, PubMed, Science Direct, Google Scholar, and SCOPUS. Date limitations will be removed, but Boolean terms “AND” and “OR” as well as Medical Subject Headings terms will be included where possible and syntax modified to suit the database during the search. Additional relevant articles will be sought from the reference lists of all included studies using a snowballing method. Two reviewers will independently screen the articles at the abstract and full-text screening phases in order to reduce bias and improve the reliability of this study’s findings. A tabular form will be developed using Microsoft Word and piloted for data extraction. Thematic content analysis will be conducted, and a narrative summary of all relevant outcomes reported. Quality appraisal of the included studies for this proposed study will be performed utilizing the recent mixed methods appraisal tool. Discussion The evidence produced by this review may help inform policy and strategies to reduce the incidence of HIV infection among adolescents and improve social support for adolescents living with HIV/AIDS in SSA. It may also reveal literature gaps to guide future researches to further inform HIV policies for adolescents in SSA. Platforms such as peer review journals, policy briefs, and conferences will be used to disseminate this study’s findings.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nandu Goswami ◽  
Per Morten Fredriksen ◽  
Knut E. A. Lundin ◽  
Chidozie Agu ◽  
Simiat Olanike Elias ◽  
...  

Abstract Background COVID-19 has affected almost every country in the world, especially in terms of health system capacity and economic burden. People from sub-Saharan Africa (SSA) often face interaction between human immunodeficiency virus (HIV) infection and non-communicable diseases such as cardiovascular disease. Role of HIV infection and anti-retroviral treatment (ART) in altered cardiovascular risk is questionable and there is still need to further carry out research in this field. However, thus far it is unclear, what impact the COVID-19 co-infection in people living with HIV (PLHIV), with or without therapy will have. The ENDOCOVID project aims to investigate whether and how HIV-infection in COVID-19 patients modulates the time course of the disease, alters cardiovascular risk, and changes vascular endothelial function and coagulation parameters/ thrombosis risk. Methods A total of 1026 patients will be included into this study. Cardiovascular research PLHIV with (n = 114 in each of the three recruiting centers) - or without - ART (n = 114 in each of the three recruiting centers) with COVID-19 and HIV-negative with COVID-19 (n = 114 in each of the three recruiting centers) will be carried out via clinical and biochemical measurements for cardiovascular risk factors and biomarkers of cardiovascular disease (CVD). Vascular and endothelial function will be measured by brachial artery flow-mediated dilatation (FMD), carotid intima-media thickness (IMT) assessments, and retinal blood vessel analyses, along with vascular endothelial biomarkers and cogualation markers. The correlation between HIV-infection in COVID-19 PLHIV with or without ART and its role in enhancement of cardiovascular risk and endothelial dysfunction will be assessed at admission, weekly, at discharge and, 4 weeks post-discharge (if possible). Impact of project The ENDOCOVID project aims to evaluate in the long-term the cardiovascular risk and vascular endothelial function in PLHIV thus revealing an important transitional cardiovascular phenotype in COVID-19. The study was registered under clinicaltrials.gov (NCT04709302).


Author(s):  
Mark J. Siedner ◽  
Prossy Bibangambah ◽  
June‐Ho Kim ◽  
Alexander Lankowski ◽  
Jonathan L. Chang ◽  
...  

Background Although ≈70% of the world's population of people living with HIV reside in sub‐Saharan Africa, there are minimal prospective data on the contributions of HIV infection to atherosclerosis in the region. Methods and Results We conducted a prospective observational cohort study of people living with HIV on antiretroviral therapy >40 years of age in rural Uganda, along with population‐based comparators not infected with HIV. We collected data on cardiovascular disease risk factors and carotid ultrasound measurements annually. We fitted linear mixed effects models, adjusted for cardiovascular disease risk factors, to estimate the association between HIV serostatus and progression of carotid intima media thickness (cIMT). We enrolled 155 people living with HIV and 154 individuals not infected with HIV and collected cIMT images at 1045 visits during a median of 4 annual visits per participant (interquartile range 3–4, range 1–5). Age (median 50.9 years) and sex (49% female) were similar by HIV serostatus. At enrollment, there was no difference in mean cIMT by HIV serostatus (0.665 versus 0.680 mm, P =0.15). In multivariable models, increasing age, blood pressure, and non–high‐density lipoprotein cholesterol were associated with greater cIMT ( P <0.05), however change in cIMT per year was also no different by HIV serostatus (0.004 mm/year for HIV negative [95% CI, 0.001–0.007 mm], 0.006 mm/year for people living with HIV [95% CI, 0.003–0.008 mm], HIV×time interaction P =0.25). Conclusions In rural Uganda, treated HIV infection was not associated with faster cIMT progression. These results do not support classification of treated HIV infection as a risk factor for subclinical atherosclerosis progression in rural sub‐Saharan Africa. Registration URL: https://www.ClinicalTrials.gov ; Unique identifier: NCT02445079.


2021 ◽  
Vol 18 (2) ◽  
pp. 87-97
Author(s):  
Hubaida Fuseini ◽  
Ben A. Gyan ◽  
George B. Kyei ◽  
Douglas C. Heimburger ◽  
John R. Koethe

Author(s):  
Massimo Leone ◽  
Fausto Ciccacci ◽  
Stefano Orlando ◽  
Sandro Petrolati ◽  
Giovanni Guidotti ◽  
...  

Eighty percent of people with stroke live in low- to middle-income nations, particularly in sub-Saharan Africa (SSA) where stroke has increased by more than 100% in the last decades. More than one-third of all epilepsy−related deaths occur in SSA. HIV infection is a risk factor for neurological disorders, including stroke and epilepsy. The vast majority of the 38 million people living with HIV/AIDS are in SSA, and the burden of neurological disorders in SSA parallels that of HIV/AIDS. Local healthcare systems are weak. Many standalone HIV health centres have become a platform with combined treatment for both HIV and noncommunicable diseases (NCDs), as advised by the United Nations. The COVID-19 pandemic is overwhelming the fragile health systems in SSA, and it is feared it will provoke an upsurge of excess deaths due to the disruption of care for chronic diseases such as HIV, TB, hypertension, diabetes, and cerebrovascular disorders. Disease Relief through Excellent and Advanced Means (DREAM) is a health programme active since 2002 to prevent and treat HIV/AIDS and related disorders in 10 SSA countries. DREAM is scaling up management of NCDs, including neurologic disorders such as stroke and epilepsy. We described challenges and solutions to address disruption and excess deaths from these diseases during the ongoing COVID-19 pandemic.


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