Role Of Human Immunodeficiency Virus Research Articles

The role of community health workers in non-communicable diseases in Cape Town, South Africa: descriptive exploratory qualitative study

BackgroundCommunity health workers (CHW) are an integral part of primary health care re-engineering in South Africa. Cape Town is developing community-orientated primary care, with a central role for CHWs. Their role in human immunodeficiency virus, tuberculosis, maternal and child health has been articulated, but is less clear for non-communicable diseases (NCDs). Non-communicable diseases are now a major contributor to the burden of disease. The aim was to explore the current role of CHWs regarding NCDs in the Eastern sub-district of Cape Town, South Africa.MethodsAn exploratory descriptive qualitative study made use of non-participant observation and qualitative interviews with CHWs, their managers, and nurse coordinators. Data from nine semi-structured interviews and ten observations were analysed with the framework method and Atlas-ti.ResultsThe CHWs were embedded in their communities and provided services via support groups, household visits and delivery of medication. They linked people to care with assistance of nurse coordinators. They could also provide physical care in the home. They lacked the ability to counsel people on the risk factors for NCDs and their role in rehabilitation and palliative care was unclear. More nurse coordinators were needed to provide supportive supervision. Inter-sectoral collaboration was weak and hindered CHWs from addressing social issues. More standardised and comprehensive training should equip CHWs for health promotion and disease prevention during household visits. Data collected in the community needed to be analysed, reported on and integrated with data from the primary care facility. This should also contribute to a community diagnosis. Their relationship with facility-based members of the primary health care team needed to be improved. Attention needed to be given to the requirements for and conditions of employment, as well as working hours and remuneration. Some equipment was absent and hindered their services for NCDs.ConclusionsCHWs have the potential to provide a comprehensive approach to NCDs, but community-orientated primary care needs to be strengthened in many of the key areas to support their activities. In relation to NCDs, they need training in basic and brief behaviour change counselling and risk factors as well as in the areas of rehabilitation and palliative care.

Hypertension in sub-Saharan Africa: the current profile, recent advances, gaps, and priorities.

Recent global and regional reports consistently confirm the high and increasing prevalence of hypertension in sub-Saharan Africa (SSA), with poor detection, treatment, and control rates. This narrative review summarises the burden of hypertension in SSA and recent findings from community-based hypertension management strategies. We further outline prominent risk factors according to recent data and associated underlying mechanisms for hypertension development. An extensive review of literature showed that most countries have reported on the prevalence of hypertension during 2017-2023, despite limitations linked to the lack of nationally representative studies, heterogeneity of sampling and data collection methods. Task-shifting approaches that assign roles to model patients and community health workers reported improved linkage to healthcare services and adherence to medication, with inconsistent findings on blood pressure (BP)-lowering effects over time. The regularly reported risk factors include unhealthy diet, sedentary lifestyle, increased adiposity and underweight, ageing, level of education, and/or income as well as psychosocial factors. Newer data on the pathophysiological mechanisms leading to hypertension and potential areas of intervention are reported from children and adults and include, among others, salt-handling and volume overload, endothelial function, BP dipping patterns and the role of human immunodeficiency virus. To conclude, significant strides have been made in data reporting from SSA on the burden of hypertension in the region as well as biomarker research to improve understanding and identification of areas of intervention. However, gaps remain on linkage between knowledge generation, translation, and implementation research. Coordinated studies addressing both discovery science and public health are crucial to curb hypertension development and improve management in SSA.

CB-0821, a novel CC chemokine receptor 5 (CCR5) inhibitor with improved binding efficacy proposed as anti-HIV candidate: Computational and in vitro approach.

The CC chemokine receptor 5 (CCR5) serves a pivotal role in human immunodeficiency virus 1 (HIV-1) infection by acting as a co-receptor and facilitating the binding of the viral envelope glycoprotein (env). Maraviroc (MVC), a Food and Drug Administration-approved monocarboxylic acid amide, is one of the CCR5 inhibitors employed in HIV treatment. Despite the existence of approved drugs, the emergence of drug resistance underscores the necessity for novel compounds to combat resistance and enhance therapeutic efficacy. In this study, CB-0821, identified from the ChemBridge library, emerged as a promising CCR5 inhibitor. Molecular dynamics simulations indicate comparable dynamic properties for CB-0821 and MVC. In silico comparisons with other CCR5 inhibitors emphasize CB-0821's superior binding affinity, positioning it as a potential lead compound. Evaluations of the dissociation constant (Ki) and absorption, distribution, metabolism, and excretion predictions suggest CB-0821 as a well-tolerated drug. Furthermore, the dose-dependent inhibition of CCR5 by CB-0821 in Peripheral blood mononuclear cells (PBMCs) (ranging from 10 to 200nM) demonstrates efficacy, coupled with nontoxicity to Vero cells at concentrations up to 500nM. These results underscore the potential of CB-0821 in HIV antiviral therapy, calling for additional preclinical validations before advancing to clinical considerations.

IRF5-TNOP3 polymorphisms are associated with elite control of HIV infection: A retrospective study.

IRF5-TNPO3polymorphisms have previously been related to immune response, and TNPO3 plays a role inhuman immunodeficiency virus(HIV)-1infection after nuclear import. Therefore, we analyzed the genetic association between IRF5-TNPO3 polymorphisms and the HIV elite control in long-term nonprogressors (LTNPs). We performed a retrospective cohort study on 183 LTNPs, who were antiretroviral therapy-naïvewith CD4+ ≥ 500 cells/mm3 , viral load ≤10 000 copies/mL, and asymptomatic over 10 years after HIV seroconversion. The primary outcome variable was HIV elite control (undetectable viral load in at least 90% of the measurements for at least 1year). Seven IRF5-TNPO3polymorphisms were genotyped using Agena Bioscience's MassARRAY platform. We found a significant association between specific IRF5-TNPO3genotypes and HIV elite control: rs2004640 TT (aOR = 2.05;p = 0.041), rs10954213 AA (aOR = 1.95;p = 0.035), rs2280714 TT (aOR = 2.02;p = 0.031), and rs10279821 CC (aOR = 2.12;p = 0.017). We also found a significant association between IRF5-TNPO3haplotype TATC composed of the favorable significant polymorphisms (rs2004640, rs10954213, rs2280714, and rs10279821) and the HIV elite control (aOR = 1.59;p = 0.048).IRF5-TNPO3rs2004640, rs10954213, rs2280714, and rs10279821 polymorphisms were related to HIV elite control in LTNPs. Our data provide new knowledge about the impact of IRF5-TNPO3polymorphisms on HIV pathogenesis to understand the phenomenon of natural HIV control.

HIV infection and cardiovascular pathology

According to modern literature data, the role of human immunodeficiency virus (HIV) infection has been proven as an independent risk factor (RF) for atherosclerosis and cardiovascular diseases (CVDs), including coronary artery disease, heart failure, and sudden cardiac death. The role of antiretroviral therapy (ART) in the occurrence of CVD remains debatable. On the one hand, ART is a mandatory component in CVD prevention, since there are numerous confirmations of the association of high viral load and noncompensated immune status with an increased risk of CVD. On the other hand, the use of certain classes of ART agents is associated with the development of dyslipidemia, insulin resistance, and type 2 diabetes, which are risk factors for CVD. In this regard, the current HIV treatment protocols require an assessment of CVD risk factors to select the optimal ART regimen. It must be remembered that when using generally accepted algorithms and scales for assessing the risk of CVD, the real risk may remain underestimated in HIV-infected patients. This literature review presents a patient data management algorithm developed by the American Heart Association and describes statin therapy in patients with HIV infection.

A Systematic Review Exploring the Range of Renal Complications of Human Immunodeficiency Virus.

Human immunodeficiency virus (HIV) is a viral infection which progressively leads to acquired immunodeficiency syndrome (AIDS) in the absence oftreatment. This happens through the destruction of crucial cells in the immune system, such as the helper T cells, dendritic cells, and macrophages. Since the first case was isolated in the 20th century, the disease has spread rapidly among humans, with significant renal, cardiovascular, respiratory, and neurological complications. It is predominantly sexually transmitted but non-sexual transmission.A relationship between HIV and renal diseases has been suggested for a long time, but only a few systematic studies have centered on this association. This systematic review aims to analyze the possible association between HIV and renal diseases as well as the range and pathogenesis of these renal diseases. HIV remains a critical infectious disease globally, inciting substantial morbidity and mortality. Studies have shown that people living with HIV (PLWH) are at increased risk of acute and chronic kidney disease. This review is based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Google Scholar, and Cochrane databases were searched exhaustively using the inclusion criteria of free full-text English papers that have exclusively studied humans in the last 20 years. Sixteen articles were selected including a systematic review, observational studies, and comprehensive narrative reviews on the role of HIV in the etiology of renal diseases, and were systemically reviewed and analyzed to elicit the wide range of possible renal complications resulting from HIV infection.

Do correlates of white matter features differ between older men and women living with human immunodeficiency virus?

Given estrogen's role in human immunodeficiency virus (HIV) disease progression and the higher rates of neurocognitive decline in affected women, the purpose of this study was to assess whether the relationship of white matter features and reproductive hormone levels differed between men versus women (sex as a moderator), controlling for selected cardiometabolic risk factors, HIV-related health indicators, and demographics in an aging population of persons living with HIV (PLWH). Older PLWH (50 y and older; 44 women and 35 men; mean ± SD age, 59.8 ± 0.6 y; 55.7% women; 72.2% non-Hispanic Black) participated in a cross-sectional study involving a fasting blood draw and a demographic survey (visit 1) and a magnetic resonance imaging scan (visit 2) to determine white matter volume and white matter hyperintensity (WMH) volume. Associations between reproductive hormones (follicle-stimulating hormone [FSH], estradiol, testosterone, dehydroepiandrosterone sulfate [DHEA-S]) and white matter features were assessed in linear regression models. Covariates were age, body mass index, hypertension, diabetes, dyslipidemia, current smoking status, CD4 count, and cranial size. For white matter volume, a sexually dimorphic interaction was seen for DHEA-S (B = 21.23; P = 0.012) and observed for FSH (B = -22.97, P = 0.08) with a trend for significance after controlling for risk factors. In women, higher white matter volume was associated with higher DHEA-S (B = 13.89, P = 0.017) and lower FSH (B = 23.58, P = 0.01). No hormone associations were shown in men for white matter volume. For WMH volume, no significant interaction effects between sex and reproductive hormones were identified. For WMH, sex did not predict associations with reproductive hormones after controlling for risk factors. Although sexually dimorphic interactions of reproductive hormones and total white matter volume were demonstrated, our study findings do not support a role for sex-based differences in reproductive hormones as predictive correlates of WMH in a small sample of older PLWH.

Etiology of meningitis among adults in three quaternary hospitals in Mozambique, 2016-2017: The role of HIV.

BackgroundMeningitis remains an important cause of morbi-mortality in adults in sub-Saharan Africa. Data on the etiological investigation of meningitis in adults in Mozambique is limited and most studies were conducted in southern Mozambique. Identification of the etiology of meningitis in adults are crucial to guide prevention and treatments strategies. In this study, we determine the burden of fungal and bacterial meningitis among adults at the three largest hospitals in Mozambique.MethodWe performed analysis of data from the routine sentinel surveillance system for meningitis in Mozambique from January 2016 to December 2017. Cerebrospinal fluid (CSF) samples were collected from eligible adults (≥18 years old) who met World Health Organization (WHO) case definition criteria for Meningitis. All samples were tested by cryptococcal antigen (CrAg) lateral flow assay (LFA), culture and triplex real-time polymerase chain reaction (qPCR) assay and all patients were tested for human immunodeficiency virus (HIV) using the national algorithm for HIV testing.ResultsRetrospective analysis of 1501 CSF samples from adults clinically suspected of meningitis revealed that 10.5% (158/1501) were positive for bacterial and fungal meningitis. Of these 158 confirmed cases, the proportion of Cryptococcal meningitis and pneumococcal meningitis was38.6% (95% CI: 31.0% to 46.7%) and 36.7% (95% CI: 29.2% to 44.7%), respectively. The other bacterial agents of meningitis identified include Neisseria meningitidis (8.9%; 14/158), Escherichia coli (6.3%; 10/158), Haemophilus influenzae (5.1%; 8/158) and S. aureus (4.4%; 7/158), which represent (24.7%; 39/158) of the total confirmed cases.ConclusionAltogether, our findings show a high burden of Cryptococcal meningitis among adults in Mozambique, especially in people living with HIV, followed by pneumococcal meningitis. Our findings suggest that rollout of CrAg Lateral Flow Assay in the health system in Mozambique for early detection of cryptococcus neoformans is necessary to improve overall patient care.

HIV-1 Nef Protein Affects Cytokine and Extracellular Vesicles Production in the GEN2.2 Plasmacytoid Dendritic Cell Line.

Plasmacytoid dendritic cells (pDCs) are a unique dendritic cell subset specialized in type I interferon production, whose role in Human Immunodeficiency Virus (HIV) infection and pathogenesis is complex and not yet well defined. Considering the crucial role of the accessory protein Nef in HIV pathogenicity, possible alterations in intracellular signalling and extracellular vesicle (EV) release induced by exogenous Nef on uninfected pDCs have been investigated. As an experimental model system, a human plasmacytoid dendritic cell line, GEN2.2, stimulated with a myristoylated recombinant NefSF2 protein was employed. In GEN2.2 cells, Nef treatment induced the tyrosine phosphorylation of STAT-1 and STAT-2 and the production of a set of cytokines, chemokines and growth factors including IP-10, MIP-1β, MCP-1, IL-8, TNF-α and G-CSF. The released factors differed both in type and amount from those released by macrophages treated with the same viral protein. Moreover, Nef treatment slightly reduces the production of small EVs, and the protein was found associated with the small (size < 200 nm) but not the medium/large vesicles (size > 200 nm) collected from GEN2.2 cells. These results add new information on the interactions between this virulence factor and uninfected pDCs, and may provide the basis for further studies on the interactions of Nef protein with primary pDCs.

Mutations in the HIV-1 3′-Polypurine Tract Can Confer Dolutegravir Resistance

With interest we read the Letter to the Editor of Wei and Sluis-Cremer about the role of human immunodeficiency virus 1 (HIV-1) 3’polypurine tract (3’PPT) mutations in dolutegravir (DTG) resistance 1.…

Advanced Glycation End Products Associated With Cardiometabolic Biomarkers in Treated Human Immunodeficiency Virus Infection.

BackgroundDespite advances in antiretroviral therapy (ART), people living with human immunodeficiency virus (HIV) continue to be at increased risk of cardiometabolic complications compared to HIV-uninfected individuals. Advanced glycation end products (AGEs) are implicated in the development and progression of cardiometabolic complications in the general population. Their role in HIV remains unclear.MethodsACTG A5260s is a prospective open-label randomized trial in which ART-naive people living with HIV were randomized to tenofovir disoproxil fumarate /emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir over 96 weeks. Changes in circulating AGEs with ART initiation were assessed, and linear regression was used to examine the associations between serum AGEs with carotid intima-media thickness (cIMT), visceral and subcutaneous adipose tissue, total fat, lean mass, body mass index, insulin resistance, leptin, and adiponectin.ResultsOverall, 214 participants were included. Ninety percent were male, 48% were White, the median age was 36 years, median HIV-1 RNA was 4.58 log10 copies/mL, and median CD4 count was 338 cells/µL. Most AGEs remained relatively unchanged following 96 weeks of ART initiation, except for methylglyoxal-derived hydroimidazolone 1 (MG-H1), which increased following 96 weeks of ART (mean fold change, 1.15 [95% confidence interval, 1.02–1.30]). No differences were detected across ART regimens. Increases in AGE levels over time were associated with worsening body fat composition measures, insulin resistance, and cIMT, even after adjusting for clinically relevant factors.ConclusionsAGE levels did not decrease following ART initiation. Most AGE levels remained stable, except for MG-H1, which increased. In people with HIV on ART, the accumulation of circulating AGEs over time appears to be independently associated with worsening cardiometabolic biomarkers.Summary: Antiretroviral therapy (ART) does not appear to be effective in reducing advanced glycation end product (AGE) levels. On the contrary, AGE levels seem to increase following ART initiation. Accumulation of AGEs was found to be independently associated with cardiometabolic complications in treated people living with HIV.

Various structural factors influenced early antiretroviral therapy initiation amongst HIV infected prisoners: a qualitative exploration in South Ethiopia

BackgroundEarly initiation of antiretroviral therapy (ART) reduces the development of acquired immunodeficiency syndrome (AIDS), non-AIDS related comorbidities and mortality, and prevents transmission. However, the prevalence of delayed ART initiation amongst prisoners in sub-Saharan African countries is high and the contributing factors to this are relatively unknown.MethodsQualitative interviewing was employed to understand the prisoners’ lived world with regard to initiating ART and associated barriers and facilitators in the South Ethiopian prison system. We interviewed seven (five male and two female) inmates living with HIV (ILWH) and eleven stakeholders who had a role in human immunodeficiency virus (HIV) care provision for incarcerated people. A phenomenological approach was used to analyse the interview data in which meaning attributed to the lived experiences of the participants was abstracted.ResultsIn this study, participants discussed both barriers to, and facilitators of, early ART initiation during incarceration. The barriers included a lack of access to voluntary counselling and testing (VCT) services, poor linkage to care due to insufficient health staff training, uncooperative prison security systems and loss of privacy regarding disclosure of HIV status. Insufficient health staff training and uncooperative prison security systems both contributed to a loss of patient privacy, ultimately resulting in treatment refusal. Although most participants described the importance of peer education and support for enhancing HIV testing and treatment programs amongst prisoners, there had been a decline in such interventions in the correctional facilities. Service providers suggested opportunities that a prison environment offers for identification and treatment of HIV infected individuals and implementation of peer education programs.ConclusionsOur study identified crucial barriers to and facilitators of early ART initiation amongst prisoners, a key HIV priority population group. Interventions that address the barriers while strengthening the facilitators may enhance a greater utilisation of ART.

Physiologically Relevant Concentrations of Dolutegravir, Emtricitabine, and Efavirenz Induce Distinct Metabolic Alterations in HeLa Epithelial and BV2 Microglial Cells.

Microglia, the resident brain phagocytes, likely play a key role in human immunodeficiency virus (HIV) infection of the central nervous system (CNS) and subsequent neuropathogenesis; however, the nature of the infection-induced changes that yield damaging CNS effects and the stimuli that provoke microglial activation remains elusive, especially in the current era of using antiretroviral (ARV) drugs for ARV therapy (ART). Altered microglial metabolism can modulate cellular functionality and pathogenicity in neurological disease. While HIV infection itself alters brain energy metabolism, the effect of ARV drugs, particularly those currently used in treatment, on metabolism is understudied. Dolutegravir (DTG) and emtricitabine (FTC) combination, together with tenofovir (TAF or TDF), is one of the recommended first line treatments for HIV. Despite the relatively good tolerability and safety profile of FTC, a nucleoside reverse transcriptase inhibitor, and DTG, an integrase inhibitor, adverse side effects have been reported and highlight a need to understand off-target effects of these medications. We hypothesized that similar to previous ART regimen drugs, DTG and FTC side effects involve mitochondrial dysfunction. To increase detection of ARV-induced mitochondrial effects, highly glycolytic HeLa epithelial cells were forced to rely on oxidative phosphorylation by substituting galactose for glucose in the growth media. We assessed ATP levels, resazurin oxidation-reduction (REDOX), and mitochondrial membrane potential following 24-hour exposure (to approximate effects of one dose equivalent) to DTG, FTC, and efavirenz (EFV, a known mitotoxic ARV drug). Further, since microglia support productive HIV infection, act as latent HIV cellular reservoirs, and when dysfunctional likely contribute to HIV-associated neurocognitive disorders, the experiments were repeated using BV2 microglial cells. In HeLa cells, FTC decreased mitochondrial REDOX activity, while DTG, similar to EFV, impaired both mitochondrial ATP generation and REDOX activity. In contrast to HeLa cells, DTG increased cellular ATP generation and mitochondrial REDOX activity in BV2 cells. Bioenergetic analysis revealed that DTG, FTC, and EFV elevated BV2 cell mitochondrial respiration. DTG and FTC exposure induced distinct mitochondrial functional changes in HeLa and BV2 cells. These findings suggest cell type-specific metabolic changes may contribute to the toxic side effects of these ARV drugs.

Plasma Extracellular Vesicle Subtypes May be Useful as Potential Biomarkers of Immune Activation in People With HIV

Background:Extracellular vesicles (EVs) are intercellular messengers with epigenetic potential since they can shuttle microRNA (miRNA). EVs and miRNA play a role in human immunodeficiency virus (HIV) infection immunopathogenesis. Chronic immune activation and systemic inflammation during HIV infection despite effective antiretroviral therapy (ART) are associated with non-acquired immunodeficiency syndrome (AIDS) comorbidities in people living with HIV (PLWH). Analysis of plasma EVs and their miRNA content may be useful as immune activation or inflammatory biomarkers in PLWH receiving ART. In this study, we hypothesized that the number, size, and miRNA of large and small EVs could reflect immune activation associated with an elevated CD8 T-cell count or a low CD4/CD8 ratio in PLWH.Methods:Plasma EVs subtype purified from PLWH and uninfected controls were sized using dynamic light scattering and quantified using flow cytometry and acetylcholine esterase (AChE) activity. Expression of mature miRNAs miR-92, miR-155, miR-223 was measured by quantitative reverse-transcriptase polymerase chain reaction in EVs and leucocytes.Results:HIV infection induces increased production of small EVs in plasma. EV subtypes were differentially enriched in miR-92, miR-155, and miR-223. Positive correlations between CD8 T-cell count and large EVs abundance and small EVs AChE activity were observed. CD4/CD8 ratio was negatively correlated with small EV AChE activity, and miRNA-155 level per small EV was negatively correlated with CD8 T-cell count.Conclusions:These findings suggest that quantifying large or small EVs and profiling miRNA content per EV might provide new functional biomarkers of immune activation and inflammation.

Enhancement of HIV-1 Env-Specific CD8 T Cell Responses Using Interferon-Stimulated Gene 15 as an Immune Adjuvant.

Induction of the endogenous innate immune system by interferon (IFN) triggers the expression of many proteins that serve like alarm bells in the body, activating an immune response. After a viral infection, one of the genes activated by IFN induction is the IFN-stimulated gene 15 (ISG15), which encodes a ubiquitin-like protein that undergoes a reversible posttranslational modification (ISGylation). ISG15 protein can also act unconjugated, intracellularly and secreted, acting as a cytokine. Although ISG15 has an essential role in host defense responses to microbial infection, its role as an immunomodulator in the vaccine field remains to be defined. In this investigation, we showed that ISG15 exerts an immunomodulatory role in human immunodeficiency virus (HIV) vaccines. In mice, after priming with a DNA-ISG15 vector mixed with a DNA expressing HIV-1 gp120 (DNA-gp120), followed by a booster with a modified vaccinia virus Ankara (MVA) vector expressing HIV-1 antigens, both wild-type ISG15-conjugated (ISG15-wt) and mutant unconjugated (ISG15-mut) proteins act as immune adjuvants by increasing the magnitude and quality of HIV-1-specific CD8 T cells, with ISG15-wt providing better immunostimulatory activity than ISG15-mut. The HIV-1 Env-specific CD8 T cell responses showed a predominant T effector memory (TEM) phenotype in all groups. Moreover, the amount of DNA-gp120 used to immunize mice could be reduced 5-fold after mixing with DNA-ISG15 without affecting the potency and the quality of the HIV-1 Env-specific immune responses. Our study clearly highlights the potential use of the IFN-induced ISG15 protein as immune adjuvant to enhance immune responses to HIV antigens, suggesting that this molecule might be exploitable for prophylactic and therapeutic vaccine approaches against pathogens.IMPORTANCE Our study described the potential role of ISG15 as an immunomodulatory molecule in the optimization of HIV/AIDS vaccine candidates. Using a DNA prime-MVA boost immunization protocol, our results indicated an increase in the potency and the quality of the HIV-1 Env-specific CD8 T cell response. These results highlight the adjuvant potency of ISG15 to elicit improved viral antigen presentation to the immune system, resulting in an enhanced HIV-1 vaccine immune response. The DNA-ISG15 vector could find applicability in the vaccine field in combination with other nucleic acid-based vector vaccines.

Alzheimer's disease-like perturbations in HIV-mediated neuronal dysfunctions: understanding mechanisms and developing therapeutic strategies.

Excessive exposure to toxic substances or chemicals in the environment and various pathogens, including viruses and bacteria, is associated with the onset of numerous brain abnormalities. Among them, pathogens, specifically viruses, elicit persistent inflammation that plays a major role in Alzheimer's disease (AD) as well as dementia. AD is the most common brain disorder that affects thought, speech, memory and ability to execute daily routines. It is also manifested by progressive synaptic impairment and neurodegeneration, which eventually leads to dementia following the accumulation of Aβ and hyperphosphorylated Tau. Numerous factors contribute to the pathogenesis of AD, including neuroinflammation associated with pathogens, and specifically viruses. The human immunodeficiency virus (HIV) is often linked with HIV-associated neurocognitive disorders (HAND) following permeation through the blood–brain barrier (BBB) and induction of persistent neuroinflammation. Further, HIV infections also exhibited the ability to modulate numerous AD-associated factors such as BBB regulators, members of stress-related pathways as well as the amyloid and Tau pathways that lead to the formation of amyloid plaques or neurofibrillary tangles accumulation. Studies regarding the role of HIV in HAND and AD are still in infancy, and potential link or mechanism between both is not yet established. Thus, in the present article, we attempt to discuss various molecular mechanisms that contribute to the basic understanding of the role of HIV-associated neuroinflammation in AD and HAND. Further, using numerous growth factors and drugs, we also present possible therapeutic strategies to curb the neuroinflammatory changes and its associated sequels.

Role of HIV and Antiretroviral Therapy on the Expression of Placental Transporters in Women with HIV.

Treatment guidelines recommend continuation of combination antiretroviral therapy (cART) throughout pregnancy for all women living with human immunodeficiency virus (HIV). Many of these drugs are substrates of transporters expressed in the placenta and therefore play a role in fetal exposure. As placental transporters can be impacted by both HIV infection and drug therapy, our objective was to explore the impact of HIV infection and cART on transporter expression. Drug transporter expression was examined in human placental samples collected from women with HIV (n = 25) and from healthy HIV(-) controls (n = 23). The effect of exposure to drugs commonly used in cART during pregnancy was examined in vitro in placental villous explants obtained from healthy women. Gene expression was measured via qRT-PCR. Several ABC (ABCG2, ABCC1,2,4) and SLC (SLC21A9, SLC22A1,3,11) transporters were significantly downregulated in placentas isolated from HIV(+) women as compared with HIV(-) controls (p < 0.05-0.001), while ABCB1 and SLC21A12 were significantly upregulated (p < 0.001). Twenty-four to 48-h exposure of human placental explants to agents used in cART resulted in significant upregulation of ABCB1 and downregulation of SLC22A11. Our findings suggest that transplacental transport may be compromised during HIV infection due to altered expression of clinically important transporters. Furthermore, in vitro results indicate that cART imposes significant alterations in placental transporters but not all changes are consistent with findings in the placenta from HIV(+) women, indicating disease effects. As this may impact in utero-fetal exposure to clinically used medications, further studies are needed to determine the overall impact on maternal-fetal transfer.

Neurocognitive functioning in MDR-TB patients with and without HIV in KwaZulu-Natal, South Africa.

Optimising medication adherence is one of the essential factors in reversing the tide of a TB-HIV syndemic in sub-Saharan Africa, especially South Africa. Impairment in key neurocognitive domains may impair patients' ability to maintain adherence to treatment, but the level of cognition and its relationship to HIV status has not been examined in individuals with drug-resistant TB. We therefore investigated performance on several key neurocognitive domains in relationship to HIV status in a multidrug-resistant tuberculosis patients (MDR-TB) sample. We enrolled microbiologically confirmed MDR-TB inpatients at a TB-specialist referral hospital in KwaZulu-Natal province, South Africa. We collected cross-sectional data on sociodemographic, clinical and neurocognitive function (e.g. attention, memory, executive functioning, language fluency, visual-spatial, eye-hand coordination). For the primary analysis, we excluded participants with major depressive episode/substance use disorder (MDE/SUD). We fitted adjusted Poisson regression models to explore the association between HIV and neurocognitive function. We enrolled 200 people with MDR-TB; 33 had MDE/SUD, and data of 167 were analysed (151 HIV+, 16 HIV-). The mean age of participants was 34.2years; the majority were female (83%), and 53% had not completed secondary school. There was evidence of impaired neurocognitive functioning across all domains in both HIV+/- study participants. Based on the regression analyses, individuals with co-infection (MDR-TB/HIV+), as well as those who had longer duration of hospital stays experienced significantly lower cognitive performance in several domains. Poor cognitive performance was significantly related to older age and lower educational attainment. The presence of major depression or substance use disorders did not influence the significance of the findings. Adults with MDR-TB have significant neurocognitive impairment, especially if HIV positive. An integrated approach is necessary in the management of MDR-TB as cognitive health influences the ability to adhere to chronic treatment, clinical outcomes and functionality.

The Role of Human Immunodeficiency Virus (HIV) Asymptomatic Status When Starting Antiretroviral Therapy on Adherence and Treatment Outcomes and Implications for Test and Treat: The Swiss HIV Cohort Study.

Since the advent of universal test-and-treat , more people living with human immunodeficiency virus (PLHIV) initiating antiretroviral therapy (ART) are asymptomatic with a preserved immune system. We explored the impact of asymptomatic status on adherence and clinical outcomes. PLHIV registered in the Swiss HIV Cohort Study (SHCS) between 2003 and 2018 were included. We defined asymptomatic as Centers for Disease Control and Prevention stage A within 30 days of starting ART, non-adherence as any self-reported missed doses and viral failure as two consecutive viral load>50 copies/mL after >24 weeks on ART. Using logistic regression models, we measured variables associated with asymptomatic status and adherence and Cox proportional hazard models to assess association between symptom status and viral failure. Of 7131 PLHIV, 76% started ART when asymptomatic and 1478 (22%) experienced viral failure after a median of 1.9 years (interquartile range, 1.1-4.2). In multivariable models, asymptomatic PLHIV were more likely to be younger, men who have sex with men, better educated, have unprotected sex, have a HIV-positive partner, have a lower viral load, and have started ART more recently. Asymptomatic status was not associated with nonadherence (odds ratio, 1.03 [95% confidence interval {CI}, .93-1.15]). Asymptomatic PLHIV were at a decreased risk of viral failure (adjusted hazard ratio, 0.87 [95% CI, .76-1.00]) and less likely to develop resistance (14% vs 27%, P < .001) than symptomatic PLHIV. Despite concerns regarding lack of readiness, our study found no evidence of adherence issues or worse clinical outcomes in asymptomatic PLHIV starting ART.

The role of human immunodeficiency virus in the pathogenesis of vernal keratoconjunctivitis-like disease in adults: A demographic and epidemiological study

Purpose:The purpose was to identify and describe patients with new-onset vernal keratoconjunctivitis-like (VKC-like) disease after puberty.Methods:The study consisted of two parts: a prospective observational descriptive study of patients with new-onset VKC-like disease, and a case-control study to determine the relationship of a CD4 count with VKC-like disease in adults, in the setting of human immunodeficiency virus (HIV). Patients were recruited between January 2016 and November 2017 from a Provincial Eye hospital, one of two large referral hospitals in KwaZulu-Natal, South Africa. Patients presenting to the eye clinic were screened and diagnosed at the Primary Eye Care Unit. Inclusion criteria: age 15 years and older with signs and symptoms of new-onset VKC-like disease. Exclusion criteria: a history of childhood atopic diseases, atopic keratoconjunctivitis and patients who declined HIV testing. Data collected included HIV status, CD4 count, antinuclear antibodies and total serum immunoglobulin E.Results:Thirty-three patients were included; females n = 16 and males n = 17. The mean age at presentation was 32.45 ± 9.93 years, 95% CI = 28.94–35.97. Twenty-six patients (78.8%) were HIV positive, 95% CI (62–89). The proportion of HIV positive patients was statistically different from the HIV negative group, Chi-squared = 21.866, P value <0.0001. In the group of HIV positive patients, 72% were classified as immunodeficient according to their CD4 counts. An association was proven between severely immunodeficient patients and the risk of VKC-like disease (Chi-squared = 4.992, P value = 0.0255).Conclusion:In this cohort, a statistically significant association was found between VKC-like disease in adults and an HIV positive status. This association calls for more research on the subject.