The role of autophagy in the progression of HIV infected cardiomyopathy.

Although highly active antiretroviral therapy (HAART) has changed infection with human immunodeficiency virus (HIV) from a diagnosis with imminent mortality to a chronic illness, HIV positive patients who do not develop acquired immunodeficiency syndrome (AIDs) still suffer from a high rate of cardiac dysfunction and fibrosis. Regardless of viral load and CD count, HIV-associated cardiomyopathy (HIVAC) still causes a high rate of mortality and morbidity amongst HIV patients. While this is a well characterized clinical phenomena, the molecular mechanism of HIVAC is not well understood. In this review, we consolidate, analyze, and discuss current research on the intersection between autophagy and HIVAC. Multiple studies have linked dysregulation in various regulators and functional components of autophagy to HIV infection regardless of mode of viral entry, i.e., coronary, cardiac chamber, or pericardial space. HIV proteins, including negative regulatory factor (Nef), glycoprotein 120 (gp120), and transactivator (Tat), have been shown to interact with type II microtubule-associated protein-1 ß light chain (LC3-II), Rubiquitin, SQSTM1/p62, Rab7, autophagy-specific gene 7 (ATG7), and lysosomal-associated membrane protein 1 (LAMP1), all molecules critical to normal autophagy. HIV infection can also induce dysregulation of mitochondrial bioenergetics by altering production and equilibrium of adenosine triphosphate (ATP), mitochondrial reactive oxygen species (ROS), and calcium. These changes alter mitochondrial mass and morphology, which normally trigger autophagy to clear away dysfunctional organelles. However, with HIV infection also triggering autophagy dysfunction, these abnormal mitochondria accumulate and contribute to myocardial dysfunction. Likewise, use of HAART, azidothymidine and Abacavir, have been shown to induce cardiac dysfunction and fibrosis by inducing abnormal autophagy during antiretroviral therapy. Conversely, studies have shown that increasing autophagy can reduce the accumulation of dysfunctional mitochondria and restore cardiomyocyte function. Interestingly, Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, has also been shown to reduce HIV-induced cytotoxicity by regulating autophagy-related proteins, making it a non-antiviral agent with the potential to treat HIVAC. In this review, we synthesize these findings to provide a better understanding of the role autophagy plays in HIVAC and discuss the potential pharmacologic targets unveiled by this research.

A systematic review assessing the association of inflammatory markers with kidney dysfunction in people living with HIV on highly active antiretroviral therapy.

Monitoring chronic diseases, particularly kidney disorders, in people living with HIV (PLWH) is of paramount importance. Here, a systematic search was conducted across electronic search engine and databases like PubMed, Scopus, and Google Scholar, from date of inception until December 2023, to identify pertinent studies reporting on any association between inflammation and kidney function in PLWH. Only six clinical studies in peer-reviewed journals met the inclusion criteria, involving 1467 participants aged 37 to 51, with approximately 17% being females. The report emphasizes the potential impact of highly active antiretroviral therapy (HAART) on kidney function in PLWH, highlighting the significance of monitoring inflammation markers as indicators of kidney function, even when HAART is effective. Acknowledging study limitations, particularly the scarcity of relevant research, the findings highlight a need for more research to inform on clinical guidance to optimize HIV management, particularly regarding kidney health and HAART regimens. Although very limited studies were evaluated, the study lays an important foundation for future research to uncover the complex relationship between HAART, inflammation markers, and kidney health in PLWH.

A multidisciplinary approach for people with HIV failing antiretroviral therapy in South Africa.

Background: South Africa (SA) has the largest antiretroviral therapy (ART) programme worldwide. Multiple factors contribute to virological failure (VF), including poor adherence and viral resistance mutations. A multidisciplinary team (MDT) clinic dedicated to those with VF may be of benefit; however, very little data from SA exist. Objectives: To assess whether an MDT approach achieved virological suppression (VS) in patients failing second-line-ART (2LART); assess the number of MDT sessions required to achieve VS; assess local resistance mutation patterns and whether the MDT reduced the number of genotypic resistance testing (GRT) required. Method: An observational, retrospective, cross-sectional chart review study was conducted between January 2018 and December 2019 at a Target High Viral Load (VL) MDT clinic in KwaZulu-Natal, SA. Results: Ninety-seven medical records were eligible. Women accounted for 63% of patients, with a mean age of 37 years. A significant reduction in the first VL measurement following the MDT was seen (median reduction 2374 c/mL; P < 0.001). This was maintained at the second VL measurement post-MDT (median reduction 2957 c/mL; P < 0.001). Patients attended a mean of 2.71 MDT sessions and 73.2% achieved VS, resulting in 61.86% fewer GRTs required. Of the GRTs performed, nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitor-related mutations were noted most frequently. Conclusion: The MDT approach resulted in a significant reduction in VL, with most participants achieving VS. The MDT was successful in reducing the need for GRT. Resistance mutations were similar to those found in other studies conducted across SA.

Tenofovir-Associated Kidney Dysfunction and Bone Fracture: A Case Report and Literature Review.

Tenofovir is an integral part of antiretroviral therapy used to treat HIV. Long-term use of tenofovir has been associated with decreased glomerular filtration rate, leading to chronic kidney disease, as well as acidosis, electrolyte imbalances, and tubular dysfunction. Tenofovir can also disrupt bone health by decreasing renal phosphate absorption, contributing to osteomalacia. This leads to disruption in mineral metabolism, elevated parathyroid hormone levels, and ultimately, low bone mineral density. Replacing tenofovir with alternative antiretroviral therapy can improve kidney function if done early in the course of the disease. Here, we discuss a case of a 65-year-old woman with HIV who presented with advanced renal failure and hypophosphatemia-induced bone fracture attributed to long-term use of tenofovir. We conclude monitoring kidney function and considering alternative antiretroviral therapy is important to prevent and manage these side effects in patients on long-term tenofovir therapy.

Making new drugs the hard way.

A new drug can have its origin in either pharma, biotech or academia. In general, discovery scientists working in pharma and biotech are advantaged over their academic counterparts and the relative advantages and disadvantages associated are discussed in depth. Against all odds, an increasing number of important drugs have had their origins in academia. This article reports three case studies from the Liotta Research Group (LRG), which explores the special circumstances that allowed these drug development campaigns to be successful. The first involves the antiretroviral agent, emtricitabine. In this case efficient synthetic methodology, developed in the LRG, coupled with some key university and commercial sector partnerships, enabled a group of academic collaborators to discover and develop a highly effective HIV reverse transcriptase inhibitor. The second case study involves the discovery and development of the breakthrough hepatitis C drug, sofosbuvir. Based on key input from Professors Schinazi and Liotta at Emory University, scientists at the Emory startup, Pharmasset, identified the nucleoside core of the drug that would become sofosbuvir. Subsequent analysis of its phosphorylation profile by Pharmasset scientists suggested that converting it to its corresponding monophosphate prodrug would circumvent a kinase block and enable it to be an effective hepatitis C polymerase inhibitor. The third case study describes the formation of DRIVE (Drug Innovation Ventures at Emory)/EIDD (Emory Institute for Drug Development), which were created to circumvent unintended impediments for carrying out academic drug discovery and development. Although DRIVE/EIDD is a wholly-owned, not-for-profit subsidiary of Emory University, it contains many attributes that enables it to operate much more nimbly than a typical academic laboratory. With an experienced drug development team and no shareholders to distract them, DRIVE/EIDD was able to focus its attention of the development of drugs to address viral diseases of global concern. In particular, their strategy to identify and develop an antiviral agent active against multiple single-stranded RNA viruses led to molnupiravir, a broadly active, oral drug that received Emergency Use Authorization for the treatment of SARS-CoV-2 infections (i.e., COVID-19).

Association between CD4 lymphocyte count and the incidence of comorbidities in Human immunodeficiency virus positive patients with virological suppression after antiretroviral treatment.

BACKGROUND: The incidence of comorbidities is higher in HIV-positive patients than in the general population due to factors, such as HIV-related chronic inflammation. There is no consensus on whether a low CD4 lymphocyte count after virological suppression at long-term follow-up increases the risk of comorbidities. This study evaluates the association between CD4 lymphocyte count and the incidence of comorbidities during the first 5 years of virological suppression after highly active antiretroviral treatment. METHODS: We conducted a cohort study of HIV-positive adults who achieved virological suppression in an HIV program between 2002 and 2016 in Colombia. A generalized equation estimation model was used to estimate the association between CD4 lymphocyte count and the incidence of comorbidities. RESULTS: A follow-up period of at least 1 year was completed in 921 HIV-positive patients with virological suppression. We found 71 comorbidities during a maximum of 5 years of follow-up; 41 (59%) were AIDS-defining comorbidities and 19 (46%) of them occurred during the first semester. Thirty cases of non-AIDS- defining comorbidities were diagnosed.We did not find any association between CD4 lymphocyte count and the incidence of comorbidities (OR 0.92, CI 95% 0.45 -1.91 for CD4 201-499 cells/µL vs CD4 ≤200 cells/µL, and OR 0.55, 95% CI 0.21-1.44 for CD4 ≥500 cells/µL vs CD4 ≤200 cells/µL). CONCLUSION: No association was found between CD4 lymphocyte count and the incidence of AIDS-defining or non-AIDS-defining comorbidities in patients with virological suppression. Further studies are needed to assess the risk of comorbidities in this population to design interventions aimed at improving their prognosis.

Impact of serious adverse drug reactions on the quality of life of patients on highly active antiretroviral therapy in Maiduguri, northeast Nigeria: a four-year retrospective study.

ABSTRACTSerious adverse drug reactions (sADRs) have a serious impact on the progress being made in providing antiretroviral therapy. The presence of HIV/AIDS and its complications associated with sADRs, has a negative effect on the quality of life (QoL) of people living with HIV/AIDS (PLWHA). This was a descriptive retrospective cohort study of 400 adult HIV patients in which the QoL of PLWHA with sADRs was compared to patients that did not experience ADR who had been on antiretroviral therapy (ART) was followed up for 48 months using the WHOQOL-HIV BREF to measure QoL. Out of 400 patients, 373 (93.25%) respondents completed the study with an overall mean age was 40.8 years (SD ± 8.64). One hundred and ninety-nine patients (53.4%) reported to have experiencing sADR. The response consistently showed significantly higher mean scores in the QoL of patients who had no ADRs in the psychological, social and environments state of health domains compared to those who had ADRs with mean scores (P = 0.000, 0.037 and 0.028), respectively. This study revealed significantly higher scores in patients who had no ADRs compared to those who had ADRs. Low QoL due to serious ADR may add additional burden to HIV disease and complications, and the related discrimination often faced by PLWHA. This study would help clinicians pay serious attention to identifying and promptly managing ADR.

Point prevalence of metabolic syndrome in HIV positive patients.

Introduction: Human immunodeficiency virus (HIV)-related morbidity and mortality have declined over time, but this increased longevity may lead to the development of other diseases, which may further manifest as the metabolic syndrome (MS). Method: To find out the point prevalence of MS in HIV positive patients, a cross-sectional prospective observational study was conducted on 200 patients who approached ART plus Centre of Government Medical College and Hospital Jammu, including 50 symptomatic patients HIV negative as controls. Results: The mean age group in MS was 37.85 ± 6.61. Males consisted of 55% (110) and females consisted of 45% (90). The overall prevalence of MS was 13.5%, with prevalence in males being 16.3% and in females 10%. Patients receiving first line highly active antiretroviral therapy (HAART) showed a 24% prevalence, while that of second line HAART showed a 14% prevalence. Central obesity (47.3%) was the most common component of MS followed by hyperglycemia (43.3%), hypertriglyceridemia (38.6%), and low high density cholesterol (HDL-C) level (38.6%). Out of 84 males with MS, 94% (79) males were having hypertriglyceridemia, 88% (74) were hypertensive, and 72% (60) were having FBS >=100. Out of 66 females with MS, 100% (66) females had central obesity and 88% (58) had hypertriglyceridemia and low HDL-C levels. Conclusion: The metabolic complications as a result of treatment with HAART leave HIV patients at a risk of developing cardiovascular disease and diabetes in spite of improvements in morbidity and mortality. Risk factors like central obesity, hypertension, hyperglycemia, and hypertriglyceridemia should be taken into consideration well before to prevent the add-on effect of developing MS.

Exploring salivary metabolome alterations in people with HIV: towards early diagnostic markers.

Background: The human immunodeficiency virus (HIV) remains a critical global health issue, with a pressing need for effective diagnostic and monitoring tools. Methodology: This study explored distinctions in salivary metabolome among healthy individuals, individuals with HIV, and those receiving highly active antiretroviral therapy (HAART). Utilizing LC-MS/MS for exhaustive metabolomics profiling, we analyzed 90 oral saliva samples from individuals with HIV, categorized by CD4 count levels in the peripheral blood. Results: Orthogonal partial least squares-discriminant analysis (OPLS-DA) and other analyses underscored significant metabolic alterations in individuals with HIV, especially in energy metabolism pathways. Notably, post-HAART metabolic profiles indicated a substantial presence of exogenous metabolites and changes in amino acid pathways like arginine, proline, and lysine degradation. Key metabolites such as citric acid, L-glutamic acid, and L-histidine were identified as potential indicators of disease progression or recovery. Differential metabolite selection and functional enrichment analysis, combined with receiver operating characteristic (ROC) and random forest analyses, pinpointed potential biomarkers for different stages of HIV infection. Additionally, our research examined the interplay between oral metabolites and microorganisms such as herpes simplex virus type 1 (HSV1), bacteria, and fungi in individuals with HIV, revealing crucial interactions. Conclusion: This investigation seeks to contribute understanding into the metabolic shifts occurring in HIV infection and following the initiation of HAART, while tentatively proposing novel avenues for diagnostic and treatment monitoring through salivary metabolomics.

Estimated Pulse Wave Velocity as a Novel Non-Invasive Biomarker for Metabolic Syndrome Among People Living with HIV.

Purpose: This study aims to investigate the relationship between estimated pulse wave velocity (ePWV) and metabolic syndrome (MetS) in people living with HIV (PLWH), proposing a novel and convenient predictor for early detection of MetS in PLWH. Patients and Methods: A total of 485 PLWH were enrolled. These participants were categorized into two groups based on the estimated pulse wave velocity (ePWV) level. Demographic and clinical data were collected to investigate the correlation between ePWV and MetS. Results: The cohort of 485 PLWH was categorized into high-ePWV and low-ePWV groups based on ePWV cutoff value of 10 m/s. We observed significant differences in components of MetS including triglycerides (TG, P < 0.05), HDL cholesterol (HDL-C, P < 0.01), systolic blood pressure (SBP, P < 0.001), diastolic blood pressure (DBP, P < 0.05), and fasting plasma glucose (FPG, P < 0.001) between the two groups. Furthermore, we employed receiver operating characteristic (ROC) curves to demonstrate the effectiveness of ePWV as a predictive indicator for MetS in PLWH (AUC = 0.739, P < 0.001). According to the ROC curve, the optimal cut-off value of ePWV was 7.4 m/s, and its sensitivity and specificity in diagnosing MetS in PLWH were 79.03% and 64.07%, respectively. Although the 7.4 m/s cutoff increased the false positive rate compared to the traditional cutoff, it significantly reduced the rate of missed diagnoses, effectively identifying 79.03% of PLWH with MetS. Conclusion: ePWV is a non-invasive and convenient novel biomarker with predictive capabilities for MetS in PLWH.

Hepatitis C virus eradication in people living with human immunodeficiency virus: Where are we now?

Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV, according to World Health Organization. People living with HIV (PLWH) are six times greater affected by HCV, compared to HIV negative ones; the greater prevalence is encountered among people who inject drugs and men who have sex with men: the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection. These patients experience a high rate of chronic hepatitis, which if left untreated progresses to end-stage liver disease and hepatocellular carcinoma (HCC) HIV infection increases the risk of mother to child vertical transmission of HCV. No vaccination against both infections is still available. There is an interplay between HIV and HCV infections. Treatment of HCV is nowadays based on direct acting antivirals (DAAs), HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono- and coinfected individuals, especially when used at an early stage of fibrosis, reducing liver disease mortality and morbidity. Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication, the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV. HCV eradication can determine dyslipidemia, since HCV promotes changes in serum lipid profiles and may influence lipid metabolism. In addition to these apparent detrimental effects on the lipid profile, the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function. The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.

Prevalence and incidence of anal high-grade squamous intraepithelial lesions in a cohort of cisgender men and transgender women who have sex with men diagnosed and treated during acute HIV acquisition in Bangkok, Thailand.

INTRODUCTION: Men who have sex with men (MSM), especially those living with HIV, are at an increased risk of anal cancer. The prevalence and incidence of its precursor, anal high-grade squamous intraepithelial lesions (HSILs), among MSM who started antiretroviral therapy during acute HIV acquisition are yet to be explored. METHODS: Participants in an acute HIV acquisition cohort in Bangkok, Thailand, who agreed to take part in this study, were enrolled. All participants were diagnosed and started antiretroviral therapy during acute HIV acquisition. Human papillomavirus (HPV) genotyping and high-resolution anoscopy, followed by anal biopsy as indicated, were done at baseline and 6-monthly visits. RESULTS: A total of 89 MSM and four transgender women were included in the analyses. Median age at enrolment was 26 years. Baseline prevalence of histologic anal HSIL was 11.8%. With a total of 147.0 person-years of follow-up, the incidence of initial histologic anal HSIL was 19.7 per 100 person-years. Factors associated with incident anal HSIL were anal HPV 16 (adjusted hazards ratio [aHR] 4.33, 95% CI 1.03-18.18), anal HPV 18/45 (aHR 6.82, 95% CI 1.57-29.51), other anal high-risk HPV (aHR 4.23, 95% CI 1.27-14.14), syphilis infection (aHR 4.67, 95% CI 1.10-19.90) and CD4 count <350 cells/mm3 (aHR 3.09, 95% CI 1.28-7.48). CONCLUSIONS: With antiretroviral therapy initiation during acute HIV acquisition, we found the prevalence of anal HSIL among cisgender men and transgender women who have sex with men to be similar to those without HIV. Subsequent anal HSIL incidence, although lower than that of those with chronic HIV acquisition, was still higher than that of those without HIV. Screening for and management of anal HSIL should be a crucial part of long-term HIV care for all MSM.

Cryptosporidium-induced acute kidney injury in a patient with acquired immunodeficiency syndrome.

Cryptosporidium is a pathogen that can cause infectious enteritis especially in immunocompromised patients. Acute kidney injury, electrolyte imbalance, and acid-base disorders may occur as a result of high volumes of intestinal fluid loss, which has not been previously reported to be a common manifestation of cryptosporidiosis. Numerous antigen detection methods can be used to ensure early diagnosis of Cryptosporidium infection, which is crucial to prevent morbidities. We report a unique case of cryptosporidiosis in a 33-year-old male patient with acute kidney injury and profound hypokalemia, hyponatremia, hypocalcemia, hypophosphatemia, hypomagnesemia, and metabolic acidosis. Following the initiation of antiretroviral therapy to human immunodeficiency virus, the patient's symptoms improved and he recovered fully from kidney injury and electrolyte imbalance, highlighting the importance of early antiretroviral therapy.

Biological Depiction of Lipodystrophy and Its Associated Challenges Among HIV AIDS Patients: Literature Review.

Lipodystrophy syndrome is a medical condition characterized by the absence of adipose tissue without any underlying starvation or macromolecule breakdown. In HIV AIDS patients, the use of highly active antiretroviral therapy (HAART) can lead to an acquired form of lipodystrophy, with a prevalence ranging from 10% to 83% among HIV AIDS patients. It was aimed to review the current understanding of biological depiction and challenges related to lipodystrophy in AIDS patients. Relevant articles published in the English language were searched in PubMed, Google Scholar, and Google. Keywords used for the search were: lipodystrophy, lipodystrophy and HIV, ART and lipodystrophy, HIV treatment, metabolic syndrome and HIV. Articles with full abstract information were read for those that met the objective criteria of the review, then full text of the articles was accessed and used. It was revealed by the literature that patients who developed lipodystrophy are characterized by insulin abnormality, obesity, diabetes mellitus, dyslipidemia, fatty liver disease, and ovarian dysfunction. Anthropometric measurements have been known to change significantly with lipodystrophy. HIV patients suffering from hepatitis C virus, hepatitis B virus, who take a protease inhibitor, are changing treatment or duration of treatment, and are women are the common risk factors for lipodystrophy. The metabolic syndrome seen in HIV patients associated with lipodystrophy can further be complicated to different adverse health effects and can result in increased morbidity and mortality rate if not treated. Existing studies have successfully identified several challenges faced by HIV AIDS patients due to lipodystrophy, including low self-esteem, compromised quality of life, and poor treatment adherence. However, it is crucial to acknowledge that there may be numerous other challenges that have yet to be discovered, emphasizing the need for further studies. It is recommended that managing dyslipidemia, treating diabetes mellitus, modifying lifestyle, and improving the anthropometric measurements have crucial roles to halt further complications associated with lipodystrophy.

A systematic review assessing the potential use of cystatin c as a biomarker for kidney disease in people living with HIV on antiretroviral therapy.

The introduction of antiretroviral therapy (ART) has significantly prolonged the lifespan of people living with human immunodeficiency virus (PLWH). However, the sustained use of this drug regimen has also been associated with a cluster of metabolic anomalies, including renal toxicity, which can lead to the development of kidney diseases. In this study, we reviewed studies examining kidney disease in PLWH sourced from electronic databases such as PubMed/MEDLINE, Scopus, and Google Scholar, as well as gray literature. The narrative synthesis of data from these clinical studies demonstrated that the serum levels of cystatin C remained unchanged or were not affected in PLWH on ART, while the creatinine-based glomerular filtration rate (GFR) fluctuated. In fact, some of the included studies showed that the creatinine-based GFR was increased in PLWH taking tenofovir disoproxil fumarate-containing ART, perhaps indicating that the use of both cystatin C- and creatinine-based GFRs is vital to monitor the development of kidney disease in PLWH. Clinical data summarized within this study indicate the potential detrimental effects of tenofovir-based ART regimens in causing renal tubular injury, while highlighting the possible beneficial effects of dolutegravir-based ART on improving the kidney function in PLWH. However, the summarized literature remains limited, while further clinical studies are required to provide insights into the potential use of cystatin C as a biomarker for kidney disease in PLWH.

High-sensitivity C-reactive protein among people living with HIV on highly active antiretroviral therapy: a systemic review and meta-analysis.

The pathological consequences of inflammation persist in people living with the human immunodeficiency virus (PLWH), regardless of the positive outcomes of highly active antiretroviral therapy (HAART). The current systematic review and meta-analysis aims to understand and explore the levels of high-sensitivity C-reactive protein (hs-CRP) and other cardiovascular disease (CVD)-risk factors including lipid profiles among PLWH on HAART. Major electronic databases including PubMed, Scopus, and Web of Science were searched to retrieve relevant global literature reporting on hs-CRP levels in PLWH on HAART. A total of twenty-two studies with an average participant age of 40 years were eligible for this systematic review and meta-analysis. Majority of the included studies were from Africa (n = 11), the United States (n = 6), and Europe (n = 5). Our systemic review showed that most studies reported increased levels of hs-CRP among PLWH on HAART when compared to controls (PLWH not on HAART or those without HIV), especially in studies from Africa. This was supported by a meta-analysis showing significantly elevated levels of hs-CRP in PLWH on HAART when compared to PLWH not on HAART (standardised mean difference [SMD] = 0.56; 95% CI = 0.10­1.01, z = 2.41; p = 0.02) or those without HIV (SMD = 1.19; 95% CI = 0.76­1.63, z = 5.35; p < 0.001). Where lipid profiles, as a major predictor for CVD risk, were also impaired in PLWH on HAART when compared to PLWH not on HAART and HIV-negative participants. In conclusion, elevated levels of hs-CRP and lipid levels are prevalent in PLWH on HAART, this may increase the risk of CVD complications, especially for those people living in Africa. However, more evidence in larger population studies is required to confirm these outcomes and unveil any possible clinical implications of HAART-induced modulation of hs-CRP levels in PLWH.

Endothelial dysfunction and cardiovascular diseases in people living with HIV on specific highly active antiretroviral therapy regimen: A systematic review of clinical studies.

Despite the improved efficacy of highly active antiretroviral therapy (HAART) in viral suppression, emerging evidence indicates an increased burden of noncommunicable diseases in people living with HIV (PLWH). Immune activation and persistently elevated levels of inflammation have been associated with endothelial dysfunction in PLWH, likely contributing to the development of cardiovascular diseases (CVDs). Here, electronic search databases including PubMed, Google Scholar, Cochrane Library, and Science Direct were used to retrieve scientific evidence reporting on any association between markers of endothelial function and CVD-related outcomes in PLWH on HAART. Extracted data was subjected to quality assessment using the Downs and Black checklist. Most (60 %) of the results indicated the presence of endothelial dysfunction in PLWH on HAART, and this was mainly through reduced flow mediated dilation and elevated serum makers of adhesion molecules like ICAM-1, VCAM-1, and P-selectin. The summarized evidence indicates an association between persistently elevated markers of endothelial dysfunction and a pro-inflammatory state in PLWH on HAART. Only a few studies reported on improved endothelial function markers in PLWH on HAART, while limited evidence is available to prove that endothelial dysfunction is associated with CVD-risk, which could be attributed to therapeutic effects of HAART. Limited studies with relatively high quality of evidence were included in this systematic review. In conclusion, results from this review lay an important foundation for future research, even a meta-analysis, that will improve the understanding of the contributing factors to the burden of CVDs in PLWH on HAART.

Weight loss and mortality in people living with HIV: a systematic review and meta-analysis.

BACKGROUND: In the first reported cases of human immunodeficiency virus (HIV) infection, people living with HIV (PLHIV) suffered weight loss, which was an independent predictor of mortality. Highly active antiretroviral therapy (HAART) has changed this scenario for ideal weight, overweight, and even obesity. However, some PLHIV, even on HAART, continue to lose weight. Thus, the guiding question of the study was: do PLHIV hospitalized using HAART with weight loss have higher mortality than hospitalized PLHIV using HAART without weight loss? METHOD: A systematic review and meta-analysis of prospective cohort studies published in English, Spanish, or Portuguese, searched in the MedLine, Embase, and LILACS databases from March 2020, until October 2023, reported by MOOSE. We analyzed the methodological quality and risk of bias using the Joanna Briggs Institute Critical Appraisal Tool for Cohort Studies; used the risk ratio (RR) to calculate the probability of hospitalized PLWH who lost weight dying, applied the random effect model and created the funnel plot. We used the inverse variance test estimated by the Mantel-Haenszel method, considering a 95% confidence interval (CI), heterogeneity (I2), total effect size (Z), and significance value of p < 0.05. We performed a sensitivity analysis with meta-regression and meta-analyses on subgroups to diagnose influence and outliers. The quality of evidence and strength of recommendation were analyzed using the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE). RESULTS: We included 10 of the 711 studies identified, totaling 1,637 PLHIV. The studies were from South Africa (1), Canada (1), China (1), Brazil (1), Cameroon (1), Ethiopia (1), Thailand (1), Colombia (1), and Tanzania (2), from 1996 to 2017. The average age of the participants was 33.1 years old, and the male was predominant. The leading causes of hospital admission were related to co-infections, and the average hospitalization time was 20.5 days. The prevalence of death in hospitalized PLHIV using HAART who lost weight was 57.5%, with a 1.5 higher risk of dying (RR: 1.50, 95% CI: 1.03, 2.19, p = 0.04) than hospitalized PLHIV who did not lose weight. CONCLUSION: We concluded, with a very low confidence level, that that weight loss significantly increased the risk of death in hospitalized PLWH using HAART. TRIAL REGISTRATION AND FUNDING: PROSPERO International Prospective Register of Systematic Reviews CRD42020191246 https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020191246 .

Evaluating experiences of HIV-related stigma among people living with HIV diagnosed in different treatment eras in British Columbia, Canada.

There is mixed evidence on whether experiences of HIV-related stigma are mitigated with lived experience. We sought to examine whether people living with HIV (PLWH) with longer living experience reported varying levels of HIV-related stigma. Between January 2016-September 2018, we used purposive sampling to enrol PLWH aged ≥19 across British Columbia, Canada, where participants completed the 10-item Berger HIV Stigma Scale. We conducted bivariate analyzes examining key sociodemographic characteristics and HIV-related stigma scores. Multivariable linear regression modelled the association between year of HIV diagnosis by treatment era and HIV-related stigma scores. We enrolled 644 participants; median age at enrolment was 50 years (Q1-Q3: 42-56), with 37.4% (n = 241) diagnosed before the year 2000. The median HIV-stigma scores of all participants (19.0, Q1-Q3: 13-25, range 0-40) stratified by treatment era were: 17.0 (pre-1996), 20.0 (1996-1999), 20.0 (2000-2009), 19.0 (2010-2018) (p = 0.03). While there was a significant association at the univariate level, year of HIV diagnosis by treatment era was not associated with stigma scores after controlling for age, gender, HIV key populations, ethnicity, relationship status, social support, and ever having a mental health disorder diagnosis. This suggests that PLWH still experience HIV-related stigma today, compared to those diagnosed in earlier time periods.

HIV enteropathy and 'Slim disease': Historical and current perspectives.

OBJECTIVES: Chronic diarrhoea and severe wasting associated with HIV infection were first described in East African patients as slim disease (SD) in 1985. The main histological features are flattening of the villi (villous atrophy) and crypt hyperplasia (elongated crypts), i.e., HIV enteropathy (HIVE). Selective loss of mucosal clusters of differentiation 4 (CD4)+ T helper (Th)17+ lymphocytes is the immunological hallmark of HIVE. This review explores (i) the historical background of HIVE and SD, (ii) the relationship between gut mucosal CD4+ Th17+ and intestinal-resident intra-epithelial gamma delta (IRIE) T lymphocytes in pathogenesis of HIVE, (iii) the role of cytokines in regulation of intestinal epithelial proliferation, and (iv) the role of antiretroviral therapy in HIVE. METHODS: Recent studies have highlighted the role of IRIE T lymphocytes, mostly CD8+, in regulating gut epithelial regeneration. CD4+Th17+ and IRIE T cells are necessary to maintain intestinal barrier integrity and mucosal antimicrobial immune defence. However, the immunological cross-talk between such lymphocyte sub-sets culminating in HIVE is uncertain. We undertook a narrative literature review under the headings 'HIVE', 'SD', and 'Highly active antiretroviral therapy (HAART). Relevant studies were located using the electronic search engines Google Scholar and PubMed from 1984 to 2022. RESULTS: Depletion of Th17+ cells in the lamina propria, attributed to low-level viraemia, is accompanied by concomitant increase in the density of gut mucosal IRIE T lymphocytes in AIDS. The latter express a broad range of cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-17) and chemokines e.g., keratinocyte growth factor, post exposure to HIV-infected cells. Keratinocyte growth factor induces epithelial proliferation mainly in the crypts, leading to functional immaturity of enterocytes, reduced gut absorptive surface area and malabsorption in animal experiments. Of note, the absence of IRIE T cells is associated with a reduction in epithelial cell turnover. Patients with HIVE receiving early HAART show enhanced expression of mucosal repair genes and improvement of gut symptoms. CONCLUSION: Multiple lines of enquiry suggest HIVE is directly related to HIV infection and is a consequence of perturbations in mucosal CD4+Th17+ and IRIE T lymphocytes. The pathological result is enterocyte immaturity and dysfunction. SD whose main features are malabsorption, diarrhoea and weight loss, is a severe clinical expression of HIVE. A better understanding of immuno-pathogenesis of HIVE opens a window of opportunity for the potential use of immunotherapy in HIV disease and other T cell-mediated enteropathies.