The COVID-19, tuberculosis and HIV/AIDS: Ménage à Trois.

In December 2019, a novel pneumonic condition, Coronavirus disease 2019 (COVID- 19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), broke out in China and spread globally. The presentation of COVID-19 is more severe in persons with underlying medical conditions such as Tuberculosis (TB), Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) and other pneumonic conditions. All three diseases are of global concern and can significantly affect the lungs with characteristic cytokine storm, immunosuppression, and respiratory failure. Co-infections of SARS-CoV-2 with HIV and Mycobacterium tuberculosis (Mtb) have been reported, which may influence their pathogenesis and disease progression. Pulmonary TB and HIV/AIDS patients could be more susceptible to SARS-CoV-2 infection leading to lethal synergy and disease severity. Therefore, the biological and epidemiological interactions of COVID-19, HIV/AIDS, and TB need to be understood holistically. While data is needed to predict the impact of the COVID-19 pandemic on these existing diseases, it is necessary to review the implications of the evolving COVID-19 management on HIV/AIDS and TB control, including therapy and funding. Also, the impact of long COVID on patients, who may have this co-infection. Thus, this review highlights the implications of COVID-19, HIV/AIDS, and TB co-infection compares disease mechanisms, addresses growing concerns, and suggests a direction for improved diagnosis and general management.

Experiences of peer navigators implementing a bilingual multilevel intervention to address sexually transmitted infection and HIV disparities and social determinants of health.

INTRODUCTION: Sexually transmitted infections (STIs) and human immunodeficiency virus (HIV) disproportionately affect young gay, bisexual and other men who have sex with men (GBMSM) and transgender women of colour. We explored the experiences of community-based peer navigators ('Community Navigators') who participated in Impact Triad, a bilingual multilevel intervention developed by our community-based participatory research partnership to reduce STIs and HIV and address social determinants of health (e.g., employment, education, social support and discrimination) among young GBMSM and transgender women of colour. METHODS: Individual in-depth interviews were conducted with 15 Community Navigators who participated in Impact Triad. Themes were identified through constant comparison. RESULTS: Community Navigators' mean age was 31.4 years. Seven were self-identified as African American/Black, 5 as Latine, 2 as multiracial/multiethnic, 1 as Asian American, 10 as cisgender men, 4 as transgender women and 1 as gender nonbinary. Thirteen themes emerged in three domains: (1) key aspects of the Community Navigator role (e.g., desire to serve as a community resource, the importance of being part of the communities in which one was working, the value of having an official role, being connected to other Community Navigators to problem-solving and sustaining intervention aspects long-term); (2) experiences implementing Impact Triad (e.g., engaging community members, meeting prioritized needs, building trust, using social media, increasing awareness and knowledge and challenges related to COVID-19) and (3) lessons learned for future interventions (e.g., facilitating access to broader resources, building additional skills and increasing interactions among Community Navigators). CONCLUSION: Interviews identified important learnings about serving as Community Navigators and implementing Impact Triad that can guide future efforts to address STI/HIV disparities and social determinants of health through community-based peer navigation. PATIENT OR PUBLIC CONTRIBUTION: Throughout this intervention trial, our partnership worked collaboratively with a study-specific community advisory board (CAB) comprised primarily of young GBMSM and transgender women of colour. Members of this CAB participated in all aspects of the trial including trial design, intervention development, recruitment and retention strategies, data collection and analysis, interpretation of findings and dissemination.

On the Evolutionary Trajectory of SARS-CoV-2: Host Immunity as a Driver of Adaptation in RNA Viruses.

Host immunity can exert a complex array of selective pressures on a pathogen, which can drive highly mutable RNA viruses towards viral escape. The plasticity of a virus depends on its rate of mutation, as well as the balance of fitness cost and benefit of mutations, including viral adaptations to the host's immune response. Since its emergence, SARS-CoV-2 has diversified into genetically distinct variants, which are characterised often by clusters of mutations that bolster its capacity to escape human innate and adaptive immunity. Such viral escape is well documented in the context of other pandemic RNA viruses such as the human immunodeficiency virus (HIV) and influenza virus. This review describes the selection pressures the host's antiviral immunity exerts on SARS-CoV-2 and other RNA viruses, resulting in divergence of viral strains into more adapted forms. As RNA viruses obscure themselves from host immunity, they uncover weak points in their own armoury that can inform more comprehensive, long-lasting, and potentially cross-protective vaccine coverage.

COVID-19 in people living with HIV: a single-center descriptive study.

INTRODUCTION: People living with human immunodeficiency virus (PLHIV) may suffer more severe symptoms of coronavirus disease 2019 (COVID-19) due to their immunocompromised status, even if they are undetectable. Human immunodeficiency virus (HIV) infection has been reported as an independent factor associated with higher mortality in patients with COVID-19. The present study aims to describe the clinical characteristics of PLHIV and COVID-19 in one center in Mexico. METHODOLOGY: We conducted an observational retrospective monocentric cohort study of PLHIV diagnosed with COVID-19 between 1 March 2020 and 30 April 2021. SARS-CoV-2 was detected by polymerase chain reaction (PCR) of a nasopharyngeal swab sample, clinical features, and epidemiological characteristics. RESULTS: We identified 55 PLHIV with COVID-19. The median age was 36 years (IQR 25-41.5 years), and 54 patients were men. The median duration of HIV-1 infection was 4.3 years (Interquartile range, IQR 2.6-7.2 years), and 100% were on antiretroviral therapy (ART). The last HIV-1 RNA viral load analysis of the patients was 52/55 (94.5%) indicating that they were in virological suppression. The median CD4+ T-cell count was 734/mm3 (IQR 541.5-921/mm3). The most frequent pre-existing comorbidities found were obesity (21.8%), hypertension (7.2%), and diabetes (5.4%). Only one death was reported (1.8%). CONCLUSIONS: It has been reported that COVID-19/HIV/AIDS co-infection has a higher risk of mortality, admission to intensive care, and complications. However, our study found that people living with HIV-1 with adequate virological control did not present a severe course of COVID -19.

Changes of human immunodeficiency virus (HIV) burden globally and in China over three decades: a secondary analysis of global HIV statistics.

BACKGROUND: A more comprehensive understanding of the trends of incidence, prevalence, and mortality in human immunodeficiency virus (HIV), and their complex interrelationships, may provide important evidence for decision-making related to HIV prevention and control. The variances in these indices between different population groups, genders, and ages are critical to decipher evolving patterns of the HIV epidemic in specific populations. METHODS: A secondary analysis of relevant data was conducted using data extracted from the Global Burden of Disease study of 2019. HIV/acquired immune deficiency syndrome (AIDS) incidence, prevalence, AIDS-related mortality, and mortality-to-prevalence ratio (MPR) for annual percentage change, average annual percentage change (AAPC), and corresponding 95% confidence intervals (CIs) were calculated using joinpoint regression statistical analysis. RESULTS: The AAPC of HIV/AIDS incidence, prevalence, AIDS-related mortality rate, and MPR were -1.4 (95% CI: -1.6, -1.2), 4.1 (95% CI: 4.0, 4.3), 2.0 (95% CI: 1.7, 2.3), and -2.1 (95% CI: -2.3, -1.8) between 1990 and 2019 globally, and were 3.5 (95% CI: 2.2, 4.8), 6.9 (95% CI: 6.8, 7.0), 8.1 (95% CI: 7.1, 9.1), and 1.2 (95% CI: 0.1, 2.3) in China during the same period. In terms of differences in the preceding indicators by gender, we observed a similar pattern of trends for male and female genders both globally and in China during the entire study period. Each specific age group exhibits a distinct pattern in terms of incidence, prevalence, mortality rate, and MPR both globally and in China. CONCLUSIONS: Prevalence and mortality rates of HIV/AIDS have increased between 1990 and 2019 globally and in China. While the incidence rate and MPR have declined globally over the past three decades, these two indicators are observed to present an increasing trend in China. There is a high HIV burden among young and middle-aged adults globally; however, the elderly have a high HIV burden in China. HIV screening at older age should be scaled up, and patients with advanced HIV disease should be provided early with additional care and health resources.

Learning from community-based HIV prevention to inform control and mitigation of the COVID-19 pandemic.

The current COVID-19 pandemic and the likelihood of future viral pandemics demonstrate a need for strategic prevention campaigns that integrate biomedical, structural, and behavioral interventions within larger scale comprehensive public health initiatives. In Human Immunodeficiency Virus (HIV) prevention, community-based efforts have resulted in reductions in transmission rates, increases in testing, increases in biomedical prevention uptake, and increased engagement in secondary and tertiary prevention efforts. In this paper, we review three community-based strategies (health communication, accessible screening, and accessible prevention resources) that have demonstrated effectiveness in HIV prevention and offer recommendations for utilizing these strategies in the COVID-19 pandemic. For example, health communication strategies have positively influenced HIV testing behavior, sex communication, and condom use among HIV negative individuals and treatment initiation, treatment adherence, and retention in care among people living with HIV. In addition, studies have shown that improving accessibility of HIV screening and prevention resources in community venues such as schools, pharmacies, mobile-testing sites, churches, hair salons, and bars is useful for increasing the uptake of HIV testing, especially among disproportionately affected populations and those deemed hard to reach. Despite differences in modes of transmission, it is plausible that a synergistic multilevel response with emphasis on community-based efforts could lead to similar outcomes for the current COVID-19 pandemic and future viral pandemics. Community-based prevention strategies offer an opportunity to integrate, and bolster disconnected and siloed initiatives that achieve limited impacts independently.

Infectious Diseases/Human Immunodeficiency Virus Physician Ambassadors: Advancing Policy to Improve Health.

Infectious diseases/human immunodeficiency virus (ID/HIV) physicians and other healthcare professionals advocate within the healthcare system to ensure adults and children receive effective treatment. These advocacy skills can be used to inform domestic and global infectious diseases policies to improve healthcare systems and public health. ID/HIV physicians have a unique frontline perspective to share with federal policymakers regarding how programs and policies benefit patients and public health. Providing this input is critical to the enactment of legislation that will maximize the response to infectious diseases. This article discusses the advocacy of ID/HIV physicians and other healthcare professionals in federal health policy. Key issues include funding for ID/HIV programs; the protection of public health and access to healthcare; improving research opportunities; and advancing the field of ID/HIV, including supporting the next generation of ID/HIV clinicians. The article also describes best practices for advocacy and provides case studies illustrating the impact of ID/HIV physician advocacy.

Associations of the COVID-19 pandemic with quality of life: A cross-sectional study of older-age people with and without HIV in rural Uganda.

Background: COVID-19-related lockdowns and other public health measures may have differentially affected the quality of life (QOL) of older people with and without human immunodeficiency virus (HIV) in rural Uganda. Methods: The Quality of Life and Aging with HIV in Rural Uganda study enrolled people with and without HIV aged over 49 from October 2020 to October 2021. We collected data on COVID-19-related stressors (behavior changes, concerns, interruptions in health care, income, and food) and the participants' QOL. We used linear regression to estimate the associations between COVID-19-related stressors and QOL, adjusting for demographic characteristics, mental and physical health, and time before vs after the lockdown during the second COVID-19 wave in Uganda. Interaction between HIV and COVID-19-related stressors evaluated effect modification. Results: We analyzed complete data from 562 participants. Mean age was 58 (standard deviation (SD) = 7); 265 (47%) participants were female, 386 (69%) were married, 279 (50%) had HIV, and 400 (71%) were farmers. Those making ≥5 COVID-19-related behavior changes compared to those making ≤2 had worse general QOL (estimated linear regression coefficient (b) = - 4.77; 95% confidence interval (CI) = -6.61, -2.94) and health-related QOL (b = -4.60; 95% CI = -8.69, -0.51). Having access to sufficient food after the start of the COVID-19 pandemic (b = 3.10, 95% CI = 1.54, 4.66) and being interviewed after the start of the second lockdown (b = 2.79, 95% CI = 1.30, 4.28) were associated with better general QOL. Having HIV was associated with better health-related QOL (b = 5.67, 95% CI = 2.91,8.42). HIV was not associated with, nor did it modify the association of COVID-19-related stressors with general QOL. Conclusions: In the context of the COVID-19 pandemic in an HIV-endemic, low-resource setting, there was reduced QOL among older Ugandans making multiple COVID-19 related behavioral changes. Nonetheless, good QOL during the second COVID-19 wave may suggest resilience among older Ugandans.

Association of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection With Maternal Mortality and Neonatal Birth Outcomes in Botswana by Human Immunodeficiency Virus Status.

OBJECTIVE: To evaluate the combined association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human immunodeficiency virus (HIV) infection on adverse birth outcomes in an HIV-endemic region. METHODS: The Tsepamo Study abstracts data from antenatal and obstetric records in government maternity wards across Botswana. We assessed maternal mortality and adverse birth outcomes for all singleton pregnancies from September 2020 to mid-November 2021 at 13 Tsepamo sites among individuals with documented SARS-CoV-2 screening tests and known HIV status. RESULTS: Of 20,410 individuals who gave birth, 11,483 (56.3%) were screened for SARS-CoV-2 infection; 4.7% tested positive. People living with HIV were more likely to test positive (144/2,421, 5.9%) than those without HIV (392/9,030, 4.3%) (P=.001). Maternal deaths occurred in 3.7% of those who had a positive SARS-CoV-2 test result compared with 0.1% of those who tested negative (adjusted relative risk [aRR] 31.6, 95% CI 15.4-64.7). Maternal mortality did not differ by HIV status. The offspring of individuals with SARS-CoV-2 infection experienced more overall adverse birth outcomes (34.5% vs 26.6%; aRR 1.2, 95% CI 1.1-1.4), severe adverse birth outcomes (13.6% vs 9.8%; aRR 1.2, 95% CI 1.0-1.5), preterm delivery (21.4% vs 13.4%; aRR 1.4, 95% CI 1.2-1.7), and stillbirth (5.6% vs 2.7%; aRR 1.7 95% CI 1.2-2.5). Neonates exposed to SARS-CoV-2 and HIV infection had the highest prevalence of adverse birth outcomes (43.1% vs 22.6%; aRR 1.7, 95% CI 1.4-2.0). CONCLUSION: Infection with SARS-CoV-2 at the time of delivery was associated with 3.7% maternal mortality and 5.6% stillbirth in Botswana. Most adverse birth outcomes were worse among neonates exposed to both SARS-CoV-2 and HIV infection.

Aptamer-Linked Photonic Crystal Assay for High-Throughput Screening of HIV and SARS-CoV-2.

We present a microplate assay for the detection of HIV and SARS-CoV-2 which involves the preadsorption of carboxy-modified polystyrene microspheres to the microplate wells and their self-assembly leading to the formation of a photonic crystal colloidal array (PCCA). PCCA is then cross-linked with amino-modified aptamers selected for viral cell surface glycoproteins, i.e., S1-protein of SARS-CoV-2 and gp120 of the human immunodeficiency virus (HIV), to develop an aptamer-linked photonic crystal assay (ALPA). ALPA is then utilized as a proof-of-concept method for the detection of S1-protein, gp120, and two whole viruses, i.e., SARS-CoV-2 and HIV, as well. The aptamers are stable at room temperature and can bind with the viruses' proteins via hydrogen bonding. This binding leads to color generation from PCCA, and the signal can easily be measured and quantified by a UV/vis spectrometer. The assay carries the advantage of a two-step detection process by the addition of the virus sample directly to a 96-well microplate and incubation of 5 min followed by convenient detection through a UV/vis-spectrometer. The assay does not require any additional reagents and can be customized for similar viruses utilizing specific aptamers targeting their cell surface receptors.

Recent Developments in Electrochemical-Impedimetric Biosensors for Virus Detection.

Viruses, including influenza viruses, MERS-CoV (Middle East respiratory syndrome coronavirus), SARS-CoV (severe acute respiratory syndrome coronavirus), HAV (Hepatitis A virus), HBV (Hepatitis B virus), HCV (Hepatitis C virus), HIV (human immunodeficiency virus), EBOV (Ebola virus), ZIKV (Zika virus), and most recently SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), are responsible for many diseases that result in hundreds of thousands of deaths yearly. The ongoing outbreak of the COVID-19 disease has raised a global concern and intensified research on the detection of viruses and virus-related diseases. Novel methods for the sensitive, rapid, and on-site detection of pathogens, such as the recent SARS-CoV-2, are critical for diagnosing and treating infectious diseases before they spread and affect human health worldwide. In this sense, electrochemical impedimetric biosensors could be applied for virus detection on a large scale. This review focuses on the recent developments in electrochemical-impedimetric biosensors for the detection of viruses.

COVID-19 in the Immunocompromised Host, Including People with Human Immunodeficiency Virus.

This review describes the incidence, epidemiology, and risk factors for mortality of COVID-19 in immunocompromised patients, including persons with human immunodeficiency virus. It describes various preventive measures, including vaccines and their effectiveness and the role of monoclonal antibodies for pre-exposure prophylaxis. It also reviews the different treatment options for immunocompromised individuals, including antivirals, monoclonal antibodies, and immunomodulators. Lastly, it describes the impact of COVID-19 on transplantation and continuity care of this population.

Psychosocial Support Programme Improves Adherence and Health Systems Experiences for Adolescents on Antiretroviral Therapy in Mpumalanga Province, South Africa.

(1) Background: Psychosocial support (PSS) plays a significant role in persistent adherence to and retention in antiretroviral therapy (ART) for adolescents living with the human immunodeficiency virus (ALHIV). This paper qualitatively explores the experiences of ALHIV on ART, who participated in a PSS programme in five public primary healthcare facilities in Mpumalanga Province in South Africa during the COVID-19 pandemic. (2) Methods: Data were collected through 24 focus group discussions with 173 ALHIV on ART and subjected to inductive thematic analysis. Informed consent was obtained before all data collection. (3) Results: The PSS programme facilitated the process of full HIV disclosure to these adolescents with the support of parents/guardians while motivating adherence through peer support groups and health education for improved treatment literacy. Participants reported positive health systems experiences, improved healthcare provider-client relations, and prompt access to health services. (4) Conclusions: The PSS programme successfully kept ALHIV engaged in ART care despite the health service disruptions encountered during the COVID-19 pandemic. We recommend rigorous evaluation of the effects of the PSS intervention on adherence to and retention in ART among ALHIV in HIV-endemic settings.

Vascular Endothelial Growth Factor Receptor 2: Molecular Mechanism and Therapeutic Potential in Preeclampsia Comorbidity with Human Immunodeficiency Virus and Severe Acute Respiratory Syndrome Coronavirus 2 Infections.

This review explored the role of vascular endothelial growth factor receptor-2 (VEGFR-2) in the synergy of preeclampsia (PE), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Downregulation of VEGFR-2 in PE promotes endothelial dysfunction and prevents endothelial cell (EC) migration, proliferation, and differentiation. The HIV-1 accessory protein, tat (trans-activator of transcription), prevents VEGFR-2 signaling via the vascular endothelial growth factor A (VEGF-A) ligand. Combined antiretroviral therapy (cART) may cause immune reconstitution, impaired decidualization, and endothelial injury, thus may be a risk factor for PE development. The VEGF/VEGFR-2 interaction may be associated with SARS-CoV-2-related pulmonary oedema. Endothelial dysfunction and heightened inflammation are both associated with PE, HIV, and SARS-CoV-2 infection; therefore, it is plausible that both characteristics may be exacerbated in the synergy of these events. In addition, this review explored microRNAs (miR) regulating VEGFR-2. An overexpression of miR-126 is evident in PE, HIV, and SARS-CoV-2 infection; thus, modulating the expression of miR-126 may be a therapeutic strategy. However, the involvement of microRNAs in PE, HIV, and SARS-CoV-2 infection needs further investigating. Since these conditions have been evaluated independently, this review attempts to predict their clinical manifestations in their synergy, as well as independently; thereby providing a platform for early diagnosis and therapeutic potential in PE, HIV, and SARS-CoV-2 infection.

Differences in Post-mRNA Vaccination Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Immunoglobulin G (IgG) Concentrations and Surrogate Virus Neutralization Test Response by Human Immunodeficiency Virus (HIV) Status and Type of Vaccine: A Matched Case-Control Observational Study.

Following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination, people living with human immunodeficiency virus (HIV, PLWH) had lower surrogate virus neutralization test response (P = .03) and a trend toward lower immunoglobulin G (IgG) response (P = .08), particularly among those with lower CD4+ T-cell counts and who received the BNT162b2 vaccine. Study of the impact of supplemental vaccine doses among PLWH is needed.

Immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Ad26.CoV2.S Vaccination in People Living With Human Immunodeficiency Virus (HIV).

BACKGROUND: People living with HIV (PLWH) have been reported to have a higher risk of more severe COVID-19 disease and death. We assessed the ability of the Ad26.CoV2.S vaccine to elicit neutralizing activity against the Delta variant in PLWH relative to HIV-negative individuals. We also examined effects of HIV status and suppression on Delta neutralization response in SARS-CoV-2-infected unvaccinated participants. METHODS: We enrolled participants who were vaccinated through the SISONKE South African clinical trial of the Ad26.CoV2.S vaccine in healthcare workers (HCWs). PLWH in this group had well-controlled HIV infection. We also enrolled unvaccinated participants previously infected with SARS-CoV-2. Neutralization capacity was assessed by a live virus neutralization assay of the Delta variant. RESULTS: Most Ad26.CoV2.S vaccinated HCWs were previously infected with SARS-CoV-2. In this group, Delta variant neutralization was 9-fold higher compared with the infected-only group and 26-fold higher relative to the vaccinated-only group. No decrease in Delta variant neutralization was observed in PLWH relative to HIV-negative participants. In contrast, SARS-CoV-2-infected, unvaccinated PLWH showed 7-fold lower neutralization and a higher frequency of nonresponders, with the highest frequency of nonresponders in people with HIV viremia. Vaccinated-only participants showed low neutralization capacity. CONCLUSIONS: The neutralization response of the Delta variant following Ad26.CoV2.S vaccination in PLWH with well-controlled HIV was not inferior to HIV-negative participants, irrespective of past SARS-CoV-2 infection. In SARS-CoV-2-infected and nonvaccinated participants, HIV infection reduced the neutralization response to SARS-CoV-2, with the strongest reduction in HIV viremic individuals.

An Ultrasensitive, One-Pot RNA Detection Method Based on Rationally Engineered Cas9 Nickase-Assisted Isothermal Amplification Reaction.

RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR) have revolutionized molecular diagnostics by offering versatile Cas effectors. We previously developed an isothermal amplification reaction method using Cas9 nickase (Cas9 nAR) to detect genomic DNA. However, slow dissociation of Cas9n from nicked double-stranded DNA (dsDNA) substrates dramatically hampers the cooperation between Cas9n and DNA polymerase, leading to low amplification efficiency. Here, we use structure-guided protein engineering to generate a Cas9n variant with faster kinetics and enhanced targeting specificity, and apply it to develop Cas9 nAR version 2 (Cas9 nAR-v2) by deftly merging reverse transcription with nicking-extension-displacement-based amplification for isothermal, one-pot RNA detection. This assay is validated by detecting Salmonella typhimurium 16S rRNA, Escherichia coli O157:H7 16S rRNA, synthetic SARS-CoV-2 genes, and HIV virus RNA, showing a quantitative analysis over a wide, linear range and a detection limit as low as fewer than ten copies of RNA molecules per reaction (20 µL volume). It also shows an excellent nucleotide-mutation discrimination capability in detecting SARS-CoV-2 variants. Furthermore, Cas9 nAR-v2 is compatible with low-cost point-of-care (POC) tests based on fluorescence and lateral-flow readouts. In summary, this method provides a new paradigm for sensitive, direct RNA detection and would spur the exploration of engineered Cas effectors with improved properties for a wide range of biological applications.