scholarly journals Soluble immune checkpoints are dysregulated in COVID-19 and heavy alcohol users with HIV infection

2021 ◽  
Author(s):  
Wei Li ◽  
Fahim Syed ◽  
Richard X Yu ◽  
Jing Yang ◽  
Ying Xia ◽  
...  
Keyword(s):  
Alcohol Abuse ◽  
Hiv Infection ◽  
Biological Significance ◽  
Cancer Therapeutics ◽  
Immune Defense ◽  
Immune Checkpoints ◽  
People Living With Hiv ◽  
Heavy Alcohol ◽  
Alternative Mrna Splicing ◽  
Health And Disease

Immune checkpoints (ICPs) consist of paired receptor-ligand molecules that exert inhibitory or stimulatory effects on immune defense, surveillance, regulation, and self-tolerance. ICPs exist in both membrane and soluble forms in vivo and in vitro. Imbalances between inhibitory and stimulatory membrane-bound ICPs (mICPs) in malignant cells and immune cells in the tumor immune microenvironment (TIME) have been well documented. Blockades of inhibitory mICPs have emerged as an immense breakthrough in cancer therapeutics. However, the origin, structure, production regulation, and biological significance of soluble ICPs (sICPs) in health and disease largely remains elusive. Soluble ICPs can be generated through either alternative mRNA splicing and secretion or protease-mediated shedding from mICPs. Since sICPs are found in the bloodstream, they likely form a circulating immune regulatory system. In fact, there is increasing evidence that sICPs exhibit biological functions including (1) regulation of antibacterial immunity, (2) interaction with their mICP compartments to positively or negatively regulate immune responses, and (3) competition with their mICP compartments for binding to the ICP blocking antibodies, thereby reducing the efficacy of ICP blockade therapies. Here, we summarize current data of sICPs in cancer and infectious diseases. We particularly focus on sICPs in COVID-19 and HIV infection as they are the two ongoing global pandemics and have created the world's most serious public health challenges. A storm of sICPs occurs in the peripheral circulation of COVID-19 patients and is associated with the severity of COVID-19. Similarly, sICPs are highly dysregulated in people living with HIV (PLHIV) and some sICPs remain dysregulated in PLHIV on antiretroviral therapy (ART), indicating these sICPs may serve as biomarkers of incomplete immune reconstitution in PLHIV on ART. We reveal that HIV infection in the setting of alcohol abuse exacerbates sICP dysregulation as PLHIV with heavy alcohol consumption have significantly elevated plasma levels of many sICPs. Thus, both stimulatory and inhibitory sICPs are present in the bloodstream of healthy people and their balance can be disrupted under pathophysiological conditions such as cancer, COVID-19, HIV infection, and alcohol abuse. There is an urgent need to study the role of sICPs in immune regulation in health and disease.

scholarly journals Predominance of PVL-negative community-associated methicillin-resistant Staphylococcus aureus sequence type 8 in newly diagnosed HIV-infected adults, Tanzania

2021 ◽  
Author(s):  
Joel Manyahi ◽  
Sabrina J. Moyo ◽  
Said Aboud ◽  
Nina Langeland ◽  
Bjørn Blomberg
Keyword(s):  
Staphylococcus Aureus ◽  
Hiv Infection ◽  
Diffusion Method ◽  
Molecular Characteristics ◽  
People Living With Hiv ◽  
Newly Diagnosed ◽  
Beta Lactam ◽  
Disk Diffusion Method ◽  
Methicillin Resistant ◽  
Inducible Clindamycin Resistance

AbstractDifficult-to-treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are of concern in people living with HIV infection as they are more vulnerable to infection. We aimed to identify molecular characteristics of MRSA colonizing newly diagnosed HIV-infected adults in Tanzania. Individuals newly diagnosed with HIV infection were recruited in Dar es Salaam, Tanzania, from April 2017 to May 2018, as part of the randomized clinical trial CoTrimResist (ClinicalTrials.gov identifier: NCT03087890). Nasal/nasopharyngeal isolates of Staphylococcus aureus were susceptibility tested by disk diffusion method, and cefoxitin-resistant isolates were characterized by short-reads whole genome sequencing. Four percent (22/537) of patients carried MRSA in the nose/nasopharynx. MRSA isolates were frequently resistant towards gentamicin (95%), ciprofloxacin (91%), and erythromycin (82%) but less often towards trimethoprim-sulfamethoxazole (9%). Seventy-three percent had inducible clindamycin resistance. Erythromycin-resistant isolates harbored ermC (15/18) and LmrS (3/18) resistance genes. Ciprofloxacin resistance was mediated by mutations of the quinolone resistance-determining region (QRDR) sequence in the gyrA (S84L) and parC (S80Y) genes. All isolates belonged to the CC8 and ST8-SCCmecIV MRSA clone. Ninety-five percent of the MRSA isolates were spa-type t1476, and one exhibited spa-type t064. All isolates were negative for Panton-Valentine leucocidin (PVL) and arginine catabolic mobile element (ACME) type 1. All ST8-SCCmecIV-spa-t1476 MRSA clones from Tanzania were unrelated to the globally successful USA300 clone. Carriage of ST8 MRSA (non-USA300) was common among newly diagnosed HIV-infected adults in Tanzania. Frequent co-resistance to non-beta lactam antibiotics limits therapeutic options when infection occurs.

Assessment of coronary inflammation in antiretroviral treated people living with HIV infection and active HIV/HCV co-infection

AIDS ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Jean Jeudy ◽  
Pratik Patel ◽  
Nivya George ◽  
Shana Burrowes ◽  
Jennifer Husson ◽  
...  
Keyword(s):  
Hiv Infection ◽  
People Living With Hiv ◽  
Living With Hiv

scholarly journals Heavy alcohol consumption in individuals with HIV infection: Effects on neuropsychological performance

2005 ◽  
Vol 11 (1) ◽  
pp. 70-83 ◽  
Author(s):  
JOHANNES C. ROTHLIND ◽  
TANYA M. GREENFIELD ◽  
ANNE V. BRUCE ◽  
DIETER J. MEYERHOFF ◽  
DEREK L. FLENNIKEN ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Executive Functioning ◽  
Hiv Infection ◽  
Synergistic Effects ◽  
Heavy Drinking ◽  
Heavy Alcohol ◽  
Heavy Drinkers ◽  
Heavy Alcohol Use ◽  
Active Alcohol

Higher rates of alcohol use have been reported in HIV+ individuals compared to the general population. Both heavy alcohol use and HIV infection are associated with increased risk of neuropsychological (NP) impairment. We examined effects of heavy active alcohol use and HIV on NP functioning in a large sample of community-residing HIV+ individuals and HIV− controls. The four main study groups included 72 HIV− light/non-drinkers, 70 HIV− heavy drinkers (>100 drinks per month), 70 HIV+ light/non-drinkers, and 56 HIV+ heavy drinkers. The heavy drinking group was further subdivided to assess effects of the heaviest levels of active alcohol use (>6 drinks per day) on NP functioning. A comprehensive NP battery was administered. Multivariate analysis of covariance was employed to examine the effect of HIV and alcohol on NP functioning after adjusting for group differences in age and estimated premorbid verbal intellectual functioning. The analyses identified main effects of heavy drinking and HIV on NP function, with greatest effects involving the contrast of HIV+ heavy drinkers and the HIV− light drinkers. Synergistic effects of heaviest current drinking and HIV infection were identified in analyses of motor and visuomotor speed. Supplementary analyses also revealed better NP function in the HIV+ group with antiretroviral treatment (ART) and lower level of viral burden, a finding that was consistent across levels of alcohol consumption. Finally, heavy alcohol use and executive functioning difficulties were associated with lower levels of self-reported medication adherence in the HIV+ group. The findings suggest that active heavy alcohol use and HIV infection have additive adverse effects on NP function, that they may show synergistic effects in circumstances of very heavy active alcohol use, and that heavy drinking and executive functioning may mediate health-related behaviors in HIV disease. (JINS, 2005, 11, 70–83.)

Health-related quality of life of people living with HIV infection in Spain: a gender perspective

AIDS Care ◽  
2019 ◽  
Vol 31 (12) ◽  
pp. 1509-1517 ◽  
Author(s):  
Carmina R. Fumaz ◽  
Maider Larrañaga-Eguilegor ◽  
Sonia Mayordomo-López ◽  
Sandra Gómez-Martínez ◽  
Marian González-García ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Hiv Infection ◽  
People Living With Hiv ◽  
Health Related Quality ◽  
Gender Perspective ◽  
Related Quality ◽  
Health Related ◽  
Living With Hiv

scholarly journals HIV status alters disease severity and immune cell responses in beta variant SARS-CoV-2 infection wave

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Farina Karim ◽  
Inbal Gazy ◽  
Sandile Cele ◽  
Yenzekile Zungu ◽  
Robert Krause ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Disease Severity ◽  
Immune Cell ◽  
Supplemental Oxygen ◽  
People Living With Hiv ◽  
Cell Counts ◽  
Cell Changes ◽  
Living With Hiv ◽  
Second Wave ◽  
Hiv Negative

There are conflicting reports on the effects of HIV on COVID-19. Here we analyzed disease severity and immune cell changes during and after SARS-CoV-2 infection in 236 participants from South Africa, of which 39% were people living with HIV (PLWH), during the first and second (beta dominated) infection waves. The second wave had more PLWH requiring supplemental oxygen relative to HIV negative participants. Higher disease severity was associated with low CD4 T cell counts and higher neutrophil to lymphocyte ratios (NLR). Yet, CD4 counts recovered and NLR stabilized after SARS-CoV-2 clearance in wave 2 infected PLWH, arguing for an interaction between SARS-CoV-2 and HIV infection leading to low CD4 and high NLR. The first infection wave, where severity in HIV negative and PLWH was similar, still showed some HIV modulation of SARS-CoV-2 immune responses. Therefore, HIV infection can synergize with the SARS-CoV-2 variant to change COVID-19 outcomes.

scholarly journals Sexually transmitted infections among HIV positive patients: a five year retrospective study

2019 ◽  
Vol 5 (1) ◽  
pp. 23
Author(s):  
N. Saravanan ◽  
Murugan Swamiappan ◽  
Rajkumar Kannan ◽  
G. Arul Raja
Keyword(s):  
Hiv Infection ◽  
Sexually Transmitted Infections ◽  
Tamil Nadu ◽  
Clinical Manifestations ◽  
Hiv And Aids ◽  
People Living With Hiv ◽  
Hiv Patients ◽  
Sexually Transmitted ◽  
Number Of Patients ◽  
Clinical Records

<p class="abstract"><strong>Background:</strong> Sexually transmitted infections (STIs) are the most well established risk factors for the spread of HIV infection. STIs act as cofactors and facilitators for HIV transmission. The effects of HIV infection on immunity can increase susceptibility to other STIs. The aims and objectives of the study were to determine the prevalence of co-infection of sexually transmitted infections among people living with HIV and AIDS.</p><p class="abstract"><strong>Methods:</strong> A retrospective chart review of the data collected from the clinical records of all HIV patients who had attended the STI clinic of Chengalpattu Medical College, Chengalpattu, Tamil Nadu during the five years period, from January 2013 to December 2017, was carried out. Demographic data, clinical manifestations, co-infection of STIs among HIV patients, laboratory investigations and treatment were collected. The data collected were computed and analyzed statistically.<strong></strong></p><p class="abstract"><strong>Results:</strong> During the study period of 5 years from 2013 to 2017 the total number of patients attended the STI clinic were 10825, among that males were 4534 (41.88%) and females were 6291 (58.12%). STIs/RTIs were seen in 2560 (23.65%) cases among the total number of patients attended. HIV was found to be positive in 294 cases, in that 168 (57.15%) were males and 126 (42.85%) were females. In male HIV patients, 51 (30.36%) had co-infection with other STIs/RTIs. In female HIV patients, 57 (45.24) % had co-infection with other STIs/RTIs. Viral STIs was the common co-infection seen in males and vaginal cervical discharge was common in females.</p><p class="abstract"><strong>Conclusions:</strong> STI/RTI co-infection, both symptomatic and asymptomatic are common among PLHIV. Hence they should be regularly counselled regarding the significance of periodic screening for STI/RTIs avoidance of high risk sexual behaviour.</p>

scholarly journals Deciphering DNA Methylation in HIV Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Thilona Arumugam ◽  
Upasana Ramphal ◽  
Theolan Adimulam ◽  
Romona Chinniah ◽  
Veron Ramsuran
Keyword(s):  
Dna Methylation ◽  
Hiv Infection ◽  
Therapeutic Strategy ◽  
New Drugs ◽  
Sub Saharan Africa ◽  
Epigenetic Mechanism ◽  
People Living With Hiv ◽  
Modifying Factors ◽  
Autoimmune Conditions ◽  
Sub Saharan

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.

scholarly journals Long-acting antiretrovirals: a new era for the management and prevention of HIV infection

2021 ◽  
Author(s):  
Paul Thoueille ◽  
Eva Choong ◽  
Matthias Cavassini ◽  
Thierry Buclin ◽  
Laurent A Decosterd
Keyword(s):  
Hiv Infection ◽  
Drug Exposure ◽  
Real Life ◽  
Effective Vaccine ◽  
Therapeutic Drug ◽  
People Living With Hiv ◽  
Medical Procedure ◽  
Clinical Pharmacokinetics ◽  
Long Acting ◽  
Prevention Of Hiv

Abstract The long-acting antiretroviral cabotegravir and rilpivirine combination has just received FDA, EMA and Health Canada approval. This novel drug delivery approach is about to revolutionize the therapy of people living with HIV, decreasing the 365 daily pill burden to only six intramuscular injections per year. In addition, islatravir, a first-in-class nucleoside reverse transcriptase translocation inhibitor, is intended to be formulated as an implant with a dosing interval of 1 year or more. At present, long-acting antiretroviral therapies (LA-ARTs) are given at fixed standard doses, irrespectively of the patient’s weight and BMI, and without consideration for host genetic and non-genetic factors likely influencing their systemic disposition. Despite a few remaining challenges related to administration (e.g. pain, dedicated medical procedure), the development and implementation of LA-ARTs can overcome long-term adherence issues by improving patients’ privacy and reducing social stigma associated with the daily oral intake of anti-HIV treatments. Yet, the current ‘one-size-fits-all’ approach does not account for the recognized significant inter-individual variability in LA-ART pharmacokinetics. Therapeutic drug monitoring (TDM), an important tool for precision medicine, may provide physicians with valuable information on actual drug exposure in patients, contributing to improve their management in real life. The present review aims to update the current state of knowledge on these novel promising LA-ARTs and discusses their implications, particularly from a clinical pharmacokinetics perspective, for the future management and prevention of HIV infection, issues of ongoing importance in the absence of curative treatment or an effective vaccine.

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