Highly Active Antiretroviral Therapy Research Articles

Plasma IL-33 levels and immune activation in HIV-TB coinfection: a cross-sectional study in Yaoundé, Cameroon.

HIV-1 and Mtb are characterized by immune activation and unbalances production of cytokines, but the expression of IL33 in HIV/TB coinfection remain understudied. This study aimed to evaluate the level of IL-33 in plasma of HIV and M. tuberculosis (HIV/TB) coinfected patients compared to patients with respective mono infections in Yaoundé. a cross-sectional study was conducted among patients attending the pneumology service and HIV treatment center of the Yaoundé Jamot Hospital. Plasma samples of 157 HIV/TB coinfected patients (n =26, 50% males and 50% females, mean age 39), HIV-1 monoinfected patients (n = 41, 41% males and 59% females, mean age 35), TB monoinfected patients (n = 48, 56% males and 44% females, mean age 37) and healthy controls (n = 42, 29% males and 71% females, mean age 32) were examined by enzyme-linked immunoassay (ELISA) to detect the levels of IL-33 cytokine. plasma level of IL-33 were higher in HIV/TB coinfected (33.1±30.9 pg/ml) and TB monoinfected individuals (15.1±2.9 pg/ml) compared to healthy controls (14.0±3.4 pg/ml) and could not be detected in most of the HIV-1 monoinfected individuals (12.6±8.7 pg/ml). Interestingly, the increased plasma level of IL-33 in HIV/TB coinfected patients showed a statistically significant difference between healthy controls (33.1±30.9 pg/ml vs 14.0±3.4 pg/ml, P<0.0001) and HIV-1 monoinfected patients (33.1±30.9 pg/ml vs 12.6±8.7 pg/ml, P=0.0002). We further found that IL-33 was higher in patients with high viral load group (40.6±59.7 pg/ml vs 12.6±1.8 pg/ml), P= 0.47) whereas patients under highly active antiretroviral therapy (HAART) showed decreased level of IL-33 concentration as the number of years under ART increased. Our data showed a positive association between plasma IL-33 and viral load in the context of HIV/TB coinfection in our study population with a positive Pearson coefficient of r=0.21. this study indicates that plasma level of IL-33 differs among HIV/TB coinfected patients and respective monoinfections patients. The increased level of plasma IL-33 reveals that IL-33 measurement in HIV-1 monoinfected patients may represent an early predictor of development of tuberculosis.

Other specific types of diabetes and exocrine pancreatic insufficiency (update2023)

The heterogenous category "specific types of diabetes due to other causes" encompasses disturbances in glucose metabolism due to other endocrine disorders such as acromegaly or hypercortisolism, drug-induced diabetes (e.g. antipsychotic medications, glucocorticoids, immunosuppressive agents, highly active antiretroviral therapy (HAART), checkpoint inhibitors), genetic forms of diabetes (e.g. Maturity Onset Diabetes of the Young (MODY), neonatal diabetes, Down‑, Klinefelter- and Turner Syndrome), pancreatogenic diabetes (e.g. postoperatively, pancreatitis, pancreatic cancer, haemochromatosis, cystic fibrosis), and some rare autoimmune or infectious forms of diabetes. Diagnosis of specific diabetes types might influence therapeutic considerations. Exocrine pancreatic insufficiency is not only found in patients with pancreatogenic diabetes but is also frequently seen in type1 and long-standing type2 diabetes.

Bartonella henselae Infective Endocarditis: A Rare Cause of Pauci-Immune Necrotizing Glomerulonephritis—A Case Report

Bartonella sp. are the most common causes of culture-negative infective endocarditis (IE) cases in the United States. Although, infection-related glomerulonephritis can frequently mimic primary vasculitis due to pauci-immune pattern, majority of previously reported cases of Bartonella henselae-associated glomerulonephritis have immune-complex deposits on immunofluorescence. We present a rare case of B henselae IE-related pauci-immune necrotizing glomerulonephritis. Timely recognition of this atypical presentation led to appropriately directed medical therapy. A 33-year-old Caucasian male with a history of human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART), alcohol abuse, previous subarachnoid hemorrhage (SAH), and recent wisdom tooth extraction (on amoxicillin) was transferred from an outside hospital for further evaluation of severe headache. He was diagnosed with an SAH and right anterior cerebral artery mycotic aneurysm. The serum creatinine at the outside hospital was 292 umol/L (3.3 mg/dL) with a previously normal baseline around 2 years ago. The serum creatinine at our institution was 256 umol/L (3.0 mg/dL). The urinalysis demonstrated +100 protein, +3 blood and 29 red blood cells/high power field. The urine protein creatinine ratio (UPC) was 1.7 g/g. Serologic evaluation was positive for a low C4 10.2 mg/dL, elevated rheumatoid factor 40 IU/mL and an elevated proteinase 3 (PR-3) antineutrophilic cytoplasmic antibodies (ANCA Ab) 4.0 U/mL. A transesophageal echocardiogram (TEE) showed echo densities on both mitral and aortic valve. Blood cultures were negative. Further serologic evaluation was positive for B henselae IgG titer of 1:2560 (normal <1:320) with a negative IgM titer. A percutaneous kidney biopsy revealed pauci-immune necrotizing glomerulonephritis, with 14/16 glomeruli globally sclerotic, and 2 glomeruli with active segmental necrotizing lesions. There was no evidence of immune-complex deposition on immunofluorescence or electron microscopy. Clinical findings were consistent with B henselae IE associated mycotic aneurysm and necrotizing glomerulonephritis. Empiric treatment for an active glomerulonephritis with immunosuppressive agents was deferred on admission, given concern for an underlying infectious process and mycotic aneurysms in an HIV-positive patient. He received antibiotic treatment with doxycycline and ceftriaxone with gentamicin for synergy. Despite this, the mitral and aortic valve regurgitation worsened, and he developed congestive heart failure requiring aortic valve replacement and mitral valve repair. The explanted aortic valve was positive for B henselae by polymerase chain reaction (PCR) confirming the diagnosis of B henselae IE. Immunosuppression was deferred due to timely identification of an atypical presentation of B henselae-associated ANCA antibodies-positive, pauci-immune necrotizing glomerulonephritis. A course of antibiotic treatment resulted in improved renal functions along with undetectable B henselae and PR3 Ab titers. The serum creatinine decreased to 176 umol/L (2 mg/dL) and remained stable 12 months after discharge. B henselae IE should be suspected in patients with pauci-immune necrotizing glomerulonephritis and culture-negative IE. This is imperative for optimal decision making in the management of such patients. Having high clinical suspicion can avoid unnecessary and potentially deleterious use of immunosuppressive agents.

Correlate of Left Ventricular Systolic Function in Children with Human Immunodeficiency Virus Infection on Combined Highly Active Antiretroviral Medications in Aminu Kano Teaching Hospital, Kano State.

Human immunodeficiency virus (HIV) affects many organ systems in the body including the cardiovascular system, often manifesting as a subclinical left ventricular (LV) systolic dysfunction that may progress to heart failure. This study assessed the prevalence of LV systolic dysfunction in children on highly active antiretroviral therapy (HAART) with established clinical stage 1 HIV-disease. The study was a cross-sectional comparative study conducted in Aminu Kano Teaching Hospital from April to August 2019 on 200. It involved study participants comprising 100 WHO clinical stage 1 HIV-infected children and 100 control subjects, aged between 1 and 18 years selected using systematic sampling method. Echocardiography was carried out on the study participants who had already completed a pretested questionnaire. Out of 100 HIV-infected children studied, 49 were males and 51 females (Male: Female ratio; 0.96:1.0). The mean age at diagnosis of HIV infection was 2.6 (±2.6 years) and the median viral load was 35 copies/ml. The mean ejection and shortening fractions in HIV-infected children were 59.0% and 31.0%, respectively, compared to 64.4% and 34.0% in control subjects, respectively, and were statistically significant (P = 0.000). The prevalence of LV systolic dysfunction was 8.0% (8 out of 100) in HIV-infected children while the control groups had zero prevalence (P = 0.002). The age at diagnosis correlated negatively with LV systolic dysfunction (r = 0.23, P = 0.02). This study found a subclinical LV systolic dysfunction in an HAART-established clinical stage 1 HIV-infected children. The age at diagnosis was negatively correlated with the LV systolic function. This study, therefore, support the inclusion of routine echocardiography into the evaluation of HIV-infected children.

To explore patients’ perceptions about motivators and barriers of adherence to highly active antiretroviral therapy among people living with HIV: A qualitative study

ABSTRACT Objective: For people living with HIV (PLHIV), strict adherence to highly active antiretroviral therapy (HAART) is the key to effective treatment and retention in human immunodeficiency virus (HIV) care. There are many factors which promote or halt the antiretroviral therapy (ART) adherence practices. Therefore, the present study aimed to examine the HAART adherence levels and to explore patients’ views about barriers and facilitators to HIV treatment adherence. Methods: Semi-structured interviews were conducted among 15 PLHIV at the ART clinic of Dr. Ram Manohar Lohia Hospital, New Delhi. Interviews were audio-recorded in the local Hindi language, and bilingual experts (English and Hindi) transcribed verbatim. Qualitative data were coded for themes and subthemes and analyzed using a phenomenological approach as per thematic content analysis. Results: Feeling of hopelessness, delayed ART initiation, difficult initial phase of ART, forget to take ART on time, fear of disclosure of HIV diagnosis, lack of privacy and negative social support, and impact of lockdown due to COVID-19 were revealed as significant barriers to ART adherence. At the same time, commitment to raise and educate children, ART to increase life span, maintain oneself to be physically fit and healthy, only a single pill per day, very supportive counselors and health-care professionals, and hope to give birth to a healthy child were identified as facilitators of HIV retention. Conclusion: Understanding patient’s perception about ART adherence, its motivational and barrier factors which are directly affecting ART adherence and retention of PLHIV in HIV treatment and follow-ups are of utmost importance to improve ART adherence during HIV patient care services.

Bifactor SEM and MIRT Structure of a 12-Item Human Immunodeficiency Virus Stigma Scale in Peruvian Adults.

The stigma associated with human immunodeficiency virus (HIV) can lead to prejudice and discrimination against people who have been infected by this virus, consequently, it is important to have a validated tool to measure this phenomenon. However, there is only 1 national precedent that has validated the scores of this instrument in its 21-item version. Therefore, this study examined the bifactor structural equation method (SEM) and multidimensional item response theory (MIRT) structure of a 12-item human immunodeficiency virus stigma scale in Peruvian adults. We evaluated 342 patients (57.6% female and 42.45% male) diagnosed with HIV receiving highly active antiretroviral therapy (HAART) from a hospital located in East Lima, aged 18 to 45 years (M = 31.4, SD = 9.79). A SEM was used to test 2 measurement models, a 4-factor correlated oblique model and a bifactor model due to high interfactor relationships. Acceptable fit indices were identified for the oblique model (χ2/df = 1.26, SRMR = 0.044, RMSEA [90% CI] = 0.028 [0.000-0.047], CFI = 0.996, TLI = 0.994). In the same way, similar results were evident for the bifactor model (χ2/df = 1.14, SRMR = 0.039, RMSEA [90% CI] = 0.020 [0.000-0.044], CFI = 0.998, TLI = 0.997), however, in the latter it showed a greater explanation for the unidimensional model (H = 0.87, PUC = 0.82, LCA = 0.70), which was also evidenced by the bifactor MIRT analysis. It is concluded that the 12-item HIV Stigma Scale meets the psychometric properties of internal structure and unifactorial reliability.

Hippocampus and Prefrontal Cortex Following the Use of Anti-Retroviral Therapy in Adult Wistar Rats: Therapeutic Role of Epigallocatechin Gallate.

The contribution of prefrontal-hippocampal interactions to brain function of people infected with HIV may be aggravated by toxicities due to long-term use of antiretroviral agents. This study was designed to investigate the curative potential of Epigallotatechin gallate (EGCG) in the treatment of neurodegenerative disorders as a possible consequence of antiretroviral toxicity. Twenty-four adult male Wistar rats, weighing 80~100g, were divided into four groups and treated as follows: control A (distilled water), B (HAART), C (EGCG 2.5mg/kg), D (EGCG 2.5mg/kg) + HAART) Brain histology, immunohistochemistry, and oxidative stress markers such as superoxide dismutase (SOD), glutathione (GSH),catalase (CAT) and malondialdehyde (MDA) were examined. The use of highly active antiretroviral therapy (HAART) showed extensive architectural deformation with pyknotic neuronal cells and obliterated neurons in the hippocampus and prefrontal cortex. Expression of inflammasome cells was also evident in this group. MDA levels increased significantly with a significant reduction in the levels of GSH, as well as antioxidant enzyme (SOD and CAT) activities compared to other treatment groups. Treatment with EGCG resulted in partial neuronal restoration of histopathological alterations, and modulation of NLRP3 inflammasome in the hippocampus and prefrontal cortex. EGCG also showed significant improvements in terms of increased antioxidant levels of SOD, GSH, CAT and a reduced MDA level and well-preserved brain architecture. Epigallocatechin gallate improves brain morphology and function with a reversal of HAART-induced alterations.

Spirulina platensis Mitigates the Inhibition of Selected miRNAs that Promote Inflammation in HAART-Treated HepG2 Cells.

The introduction of highly active antiretroviral therapy (HAART) in the treatment of HIV/AIDS has recently gained popularity. In addition, the significant role of microRNA expression in HIV pathogenesis cannot be overlooked; hence the need to explore the mechanisms of microRNA expression in the presence of HAART and Spirulina platensis (SP) in HepG2 cells. This study investigates the biochemical mechanisms of microRNA expression in HepG2 cells in the presence of HAART, SP, and the potential synergistic effect of HAART−SP. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine cell viability following SP treatment. The cellular redox status was assessed using the quantification of intracellular reactive oxygen species (ROS), lipid peroxidation, and a lactate dehydrogenase (LDH) assay. The fluorometric JC-1 assay was used to determine mitochondrial polarisation. The quantitative polymerase chain reaction (qPCR) was also employed for micro-RNA and gene expressions. The results show that MiR-146a (p < 0.0001) and miR-155 (p < 0.0001) levels increased in SP-treated cells. However, only miR-146a (p < 0.0001) in HAART−SP indicated an increase, while miR-155 (p < 0.0001) in HAART−SP treatment indicated a significant decreased expression. Further inflammation analysis revealed that Cox-1 mRNA expression was reduced in SP-treated cells (p = 0.4129). However, Cox-1 expression was significantly increased in HAART−SP-treated cells (p < 0.0001). The investigation revealed that HepG2 cells exposed to HAART−SP treatment showed a significant decrease in Cox-2 (p < 0.0001) expression. mRNA expression also decreased in SP-treated cells (p < 0.0001); therefore, SP potentially controls inflammation by regulating microRNA expressions. Moreover, the positive synergistic effect is indicated by normalised intracellular ROS levels (p < 0.0001) in the HAART−SP treatment. We hereby recommend further investigation on the synergistic roles of SP and HAART in the expression of microRNA with more focus on inflammatory and oxidative pathways.

BIOCHEMICAL EVALUATION OF THE HEPATIC AND KIDNEY FUNCTIONS IN PATIENTS UNDERGOING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY AT THE BAFOUSSAM REGIONAL HOSPITAL, CAMEROON

Background: Nowadays, one of the main ways to manage HIV infection is the use of highly active antiretroviral therapy (HAART). Despite the benefit associated with the use of antiretrovirals, these could have side effects on certain vital body functions such as the liver and kidneys.&#x0D; Aim of the Study: The main objective of this study was to assess the liver and kidney functions of people living with HIV (PLWHIV) and undergoing highly active antiretroviral therapy at the Bafoussam Regional Hospital (BRH).&#x0D; Methodology: A cross-sectional study was conducted for three months on 100 HIV-positive patients undergoing HAART at the Regional Hospital of Bafoussam. Sociodemographic, clinical and biological data were recorded for each subject and then analyzed using standard procedures. Liver function was explored by the following biochemical parameters: alanine aminotransferase, aspartate aminotransferase, albumin, total and direct bilirubin. The renal function was explored by measuring the creatinine and the serum uric acid levels. Results: Among the 100 patients who participated in the study, 83 were women (83 %) and 17 patients were men (17 %). The most represented age group was between 41 and 50 years old (37 %). The mean age was 47.66 ± 10.2 years. For the liver function assessment, 6 % had elevated alanine aminotransferase activity (greater than 42 IU/L), 8 % had an increase in the aspartate aminotransferase activity (greater than 38 IU/L) and 17% of patients had hypoalbuminemia (below 35 g/L). In addition, 14% of the patients had a high total bilirubin level (greater than 1 mg/dL) and 62% of the patients had a high direct bilirubin level (greater than 0.3 mg/dL). Patients presenting simultaneously an abnormal level of direct and total bilirubin were following the Zidovudine-Lamivudine-Atazan avir-Ritonavir (ZLAR) second line regimen. For the evaluation of renal function, 18% had a high creatinine level (greater than 14 mg/L) and 24% of patients had an abnormal level of uric acid (greater than 60 mg/L), this variation was not associated with antiretroviral treatment (p &gt; 0.05).&#x0D; Conclusion: No significant association was found between the regimen and the variations of certain biochemical parameters. However, compared to ZLAR, Tenofovir-Lamivudine-Dolutegravir (TLD) was the regimen that recorded the largest number of patients with abnormal variations of biochemical parameters involved in this study.

Clinical and behavioral factors associated with undernutrition among highly active antiretroviral therapy users in Southwest Ethiopia.

Globally, about 1.9 billion adults are overweight or obese, while 462 million are underweight. These are primarily found in countries with low and middle incomes, such as Ethiopia. Undernutrition is a frequent health problem among people living with HIV/AIDS; however, no large-scale research, including several health facilities, has been conducted in Ethiopia. Thus, this study aimed to assess the nutritional status and nutrition-related factors among highly active antiretroviral therapy (HAART) users in public hospitals in Southwest Ethiopia. A cross-sectional facility study design was conducted in all public hospitals in Southwest Ethiopia from January to March 2021. A systematic sampling technique was used to select the study participants. The collected data were entered into EpiData 3.1 and then exported to SPSS version 24 for statistical analysis. Binary logistic regression analysis was done to identify the factors associated with the outcome variable. The level of significance was declared at a P-value of <0.05, with their corresponding 95% confidence level. A total of 402 HAART users have participated with a 100% response rate. The proportion of undernutrition (BMI <18.5 kg/m2) and patients with overweight or obesity (BMI ≥25 kg/m2) were 29.3% [95% CI: (24.6-33.5)] and 10% [95% CI: (6.6-12.9)], respectively. Out of undernutrition patients, severe undernutrition (BMI <16 kg/m2) accounted for 5.6%. Factors, such as food insecurity [AOR: 3.21, 95% CI: (1.76-5.91)], history of diarrhea [AOR: 2.86, 95% CI: (1.96-6.78)], CD4 cell count ≤ [AOR: 4.72, 95% CI: (2.14-12.13)], and substance user [AOR: 4.12, 95% CI: (2.31-7.30)], were the independent factors of undernutrition. This study found that the prevalence of undernutrition was high compared with other settings. The government should also pay due attention to improving the treatment of HIV/AIDS by offering nutritional support services in hospitals. Moreover, policymakers and healthcare professionals consider the effects of these factors on nutrition while providing ART services.

LL-37 antimicrobial peptide and heterologous prime-boost vaccination regimen significantly induce HIV-1 Nef-Vpr antigen- and virion-specific immune responses in mice.

HIV infection still remains a leading cause of morbidity and mortality worldwide. The inability of highly-active antiretroviral therapy in HIV-1 eradication led to development of therapeutic vaccines. Exploiting effective immunogenic constructs and potent delivery systems are important to generate effective therapeutic vaccines, and overcome their poor membrane permeability. Among HIV-1 proteins, the Nef and Vpr proteins can be considered as antigen candidates in vaccine design. In this study, the immunogenicity of Nef-Vpr antigen candidate in different regimens along with antimicrobial peptide LL-37 (as a DNA carrier) and Montanide 720 (as an adjuvant) was studied in mice. Moreover, the secretion of cytokines was assessed in virion-exposed mice lymphocytes in vitro. Our data indicated that groups immunized with the homologous protein + Montanide regimen (group 1), and also the heterologous DNA + LL-37 prime/protein + Montanide boost regimen (group 2) could significantly generate strong immune responses as compared to groups immunized with the DNA constructs (groups 3 & 4). Moreover, immunization of mice with the homologous DNA + LL-37 regimen in low dose of DNA (5µg) could induce higher immune responses than the homologous naked DNA regimen in high dose of DNA (50µg) indicating the role of LL-37 as a cell penetrating peptide. Additionally, the heterologous DNA + LL-37 prime/protein + Montanide boost regimen (group 2) induced significantly IFN-gamma secretion from virion-exposed lymphocytes in vitro. Generally, the use of LL-37 for DNA delivery, Montanide 720 as an adjuvant, and heterologous DNA prime/protein boost strategy could significantly increase IgG2a, IFN-gamma, and Granzyme B, and maintain cytokine secretion after exposure to virions. Indeed, the heterologous DNA + LL-37 prime/protein + Montanide boost regimen can be considered as a potent strategy for development of therapeutic HIV vaccines.

Seroprevalence of hepatitis B and C virus among highly active antiretroviral therapy experienced children in Gondar, Ethiopia

BackgroundGlobally, chronic viral hepatitis is the cause of mortality alongside human immunodeficiency virus/acquired immunodeficiency syndrome and tuberculosis. Published reports on the seroprevalence of hepatitis B and C viruses among HIV-infected children are lacking in sub-Saharan Africa. Hence, this study aimed to determine the seroprevalence of hepatitis B and C viruses among highly active antiretroviral therapy (HAART)-experienced children at the University of Gondar Comprehensive Specialized Hospital.MethodsWe conducted a hospital-based cross-sectional study to determine the seroprevalence of hepatitis B and C viruses among HAART-experienced children from January to May 2020. We collected the socio-demographic characteristics of study participants with pretested questioners and clinical data from medical records. We performed enzyme-linked immunosorbent assay-based laboratory test for serum hepatitis B surface antigens and anti-hepatitis C virus antibodies. Finally, we analyzed the frequency of all variables, determined the association of independent variables with hepatitis B and C viruses by using univariable and then multivariable logistic regression.ResultsA total of 241 HAART-experienced children were enrolled, 49.8% of whom were girls. The median age of participants was 13 years (interquartile range 11–14). The seroprevalence of hepatitis B and C virus infection among HAART-experienced children were 9.5% and 2.9%, respectively. Being underweight was significantly associated with both hepatitis B virus (AOR = 3.87: 95% CI; 1.04–14.46, P = 0.044) and hepatitis C virus infections (AOR = 4.54: 95% CI; 1.21–17.04, P = 0.025).ConclusionsThis study showed that the magnitude of hepatitis B and C viruses was high among HIV-infected children who were under HAART and did not know their hepatitis B and C infection status before. Being underweight was associated with both hepatitis viruses. Therefore, screening for hepatitis B and C viruses should be a routine measure for all HIV-infected children.

Medicinal Chemistry of Anti-HIV-1 Latency Chemotherapeutics: Biotargets, Binding Modes and Structure-Activity Relationship Investigation

The existence of latent viral reservoirs (LVRs), also called latent cells, has long been an acknowledged stubborn hurdle for effective treatment of HIV-1/AIDS. This stable and heterogeneous reservoir, which mainly exists in resting memory CD4+ T cells, is not only resistant to highly active antiretroviral therapy (HAART) but cannot be detected by the immune system, leading to rapid drug resistance and viral rebound once antiviral treatment is interrupted. Accordingly, various functional cure strategies have been proposed to combat this barrier, among which one of the widely accepted and utilized protocols is the so-called 'shock-and-kill' regimen. The protocol begins with latency-reversing agents (LRAs), either alone or in combination, to reactivate the latent HIV-1 proviruses, then eliminates them by viral cytopathic mechanisms (e.g., currently available antiviral drugs) or by the immune killing function of the immune system (e.g., NK and CD8+ T cells). In this review, we focuse on the currently explored small molecular LRAs, with emphasis on their mechanism-directed drug targets, binding modes and structure-relationship activity (SAR) profiles, aiming to provide safer and more effective remedies for treating HIV-1 infection.

100 ANALYSIS OF PROGNOSTIC PREDICTORS AND DIFFERENCES BETWEEN SUBGROUPS OF PULMONARY ARTERIAL HYPERTENSION ASSOCIATED WITH PORTAL HYPERTENSION AND HIV INFECTION

Abstract Background Pulmonary arterial hypertension (PAH) represents a rare complication of both portal hypertension (Po-PAH) and HIV infection (HIV-PAH). Due to overlapping risk factors, in the latter patients there may frequently be a hepatic involvement that can cause portal hypertension, resulting in an overlap PAH form associated with both portal hypertension and HIV (HIV/Po-PAH). Methods A retrospective analysis was conducted on 204 patients with Po-PAH (128), HIV-PAH (41) and HIV/Po-PAH (35) referred to our centre from 1993 to 2021, with the aim of describing the clinical, functional and haemodynamic characteristics and identifying the prognostic determinants. At baseline, in patients with Po-PAH and HIV/Po-PAH, the severity of liver disease was estimated using the Child-Turcotte-Pugh (CTP) score, MELD score (Model for End-stage Liver Disease); instead, in patients with HIV-PAH and HIV/Po-PAH it was defined whether they received HAART (Highly Active Anti-Retroviral Therapy) and the CD4+ lymphocytes number. Data are expressed as median (interquartile range) and compared with Dunn's test. Prognostic determinants were identified by univariate and multivariate Cox-regression analysis. Survival was assessed using Kaplan Meier method. Patients were treated according to ESC/ERS guidelines. Results HIV-infected patients [40 (37-43) years] and HIV/Po-PAH [44 (39-48) years] are younger than Po-PAH patients [53 (44-60) years]; the exercise capacity assessed by the 6-minute walking test of patients with HIV/Po-PAH [516 (432-571) m] was superior to both patients with Po-PAH [426 (366-504) m] and HIV-PAH [448 (370-510) m], presumably justified by the demographic and haemodynamic differences between these groups. In fact, patients with concomitant portal hypertension (Po-PAH and HIV/Po-PAH) have a better haemodynamic profile than patients with HIV-PAH, specifically, lower pulmonary vascular resistance [6.2 (4.9-8.8) and 7.0 (5.5-11.2) WU vs 8.9 (7.5-12.2) WU] and higher cardiac index [3.1 (2.6-3.8) and 3.0 (2.7-3.7) l/min/m2 vs 2.6 (2.2-2.9) l/min/m2] and mixed venous oxygen saturation [70 (65-75) and 67 (62-71) % vs 61 (55-66)%] values. Despite these differences, the survival of the three groups of patients was not statistically different (5-year survival of patients with Po-PAH was 41%;of patients with HIV/Po-PAH was 46%; and of patients with HIV-PAH was 51%; log-rank test p-value= 0.059) and the prognostic factors that emerge at the multivariate analysis are only parameters associated with the underlying disease. In particular, the parameters independently associated with prognosis are, in patients with Po-PAH, only the CTP score [HR 1.665 (CI 1.153-2.403), p= 0.007]; in patients with HIV-PAH only the treatment with HAART [HR 0.283 (CI 0.119-0.675), p= 0.004]; in patients with HIV/Po-PAH both MELD-Na+ [HR 1.224 (CI 1.064-1.408), p= 0.005] and trans-hepatic venous gradient [HR 1.125 (CI 1.026-1.235), p= 0.013]. Conclusions in patients with Po-PAH, HIV-PAH, and HIV/Po-PAH adequately treated with PAH medications, the prognosis seems to be related to the underlying disease. This may explain why their survival is not statistically different despite significant demographic, exercise and hemodynamic differences.

2311. Long-term prognosis and risk factors for overall mortality in patients with progressive multifocal leukoencephalopathy

Abstract Background Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by reactivation of JC virus, almost in patients with immunosuppressive conditions. PML is a fatal infection with a reported 3-month mortality rate of 30–50% and a 2-month mortality rate of up to 90% in the non-human immunodeficiency virus (HIV) population. Despite high mortality, studies on PML are still lacking due to its low prevalence and incidence. Therefore, this study aimed to figure out long-term prognosis of PML and prognostic factors for mortality through a long observation period. Methods We retrospectively reviewed 68 PML patients with admitted to two tertiary hospitals in South Korea from 1999 to 2021. A total of 47 PML patients were finally enrolled after exclusion. The primary endpoint was long-term overall mortality. For survival analysis, Kaplan-Meier curve and Cox proportional hazards model were used. Each patient was followed up until death or until the end of the study period, whichever came first. Results The median follow-up duration was 20 (interquartile range [IQR], 3–79) months. The median age was 46 years, 27 (57.4%) were diagnosed with HIV, 19 (40.4%) were using immunosuppressive drugs. The median last follow-up modified Rankin Scale (mRS) was higher in non-HIV PML patients group (5 [IQR, 4–6] vs 4 [IQR, 2–5], p=0.020). The median survival duration was 184 (IQR 74–1,566) days in the non-HIV group and 1,564 (IQR 254–3,444) days in the HIV group. The overall mortality rate of PML patients was significantly higher in non-HIV group (80.0% vs 40.7%, p=0.007), also confirmed by the Kaplan-Meier curve and log-rank test (p=0.007). Initial mRS (HR 1.685, 95% CI: 1.028–2.762, p=0.038), HIV patients with highly active antiretroviral therapy (HAART) (HR 0.374, 95% CI: 0.172–0.815, p=0.013) had a significant effect on overall mortality. Conclusion With the widespread adoption of HAART, the survival duration of HIV patients with PML has been extended, but the mortality rate is still high. Also, the prognosis for PML in non-HIV patients is still frustrated. Initial mRS is a significant risk factor for long-term overall mortality in PML patients. Early detection of PML and early initiation of HAART in HIV patients may improve the patient's prognosis. Disclosures All Authors: No reported disclosures.

Cervical Cytology and Herpes Simplex Virus Type-2 Serology Among Human Immune Deficiency Virus Infected Women on Highly Active Antiretroviral Therapy in Enugu, Nigeria.

The prevalence of Human Immunodeficiency Virus (HIV) and Herpes Simplex Virus type-2 (HSV-2) infections are high and the programme for Cervical Cancer Screening is weak in Nigeria. Prevalence of Herpes Simplex Virus Type-2 co-infection and cervical cytology among HSV-2 co-infected Human Immunodeficiency Virus Sero-positive (HIV+) women on Highly Active Antiretroviral Therapy (HAART) attending Human Immunodeficiency Virus clinic at University of Nigeria Teaching Hospital (UNTH) Ituku/Ozalla Enugu, Nigeria. A cross-sectional, hospital-based study. Active participants included 105 HIV seropositive women on HAART and104 HIV seronegative (HIV-) women who passed inclusion criteria and signed written informed consent. Each participant was coded with a specific number. A structured questionnaire was used to obtain the socio-demographic and medical history. Serum was obtained for HSV-2 serology test for all participants and HIV screening for HIV-negative participants. Cervical smears were collected for Papanicolaou stains and Immunocytochemistry using anti-P16INKa antibody. Prevalence of HSV-2+ was 50.5% among HIV+ women on HAART and 16.3% among HIV- women, Odds Ratios [95% CI]; p-value was 5.21 [2.74-9.94]; p < 0.0001. HIV+ women on HAART co-infected with HSV-2 significantly had more Cervical Lesions, 11.4% compared to HIVwomen uninfected with HSV-2, 4.8%, OR [95% CI]; p-value 4.8 (1.58-14.54); p = 0.006. The prevalence of HSV-2 was significantly high among HIV+ women on HAART. HSV-2+ co-infection could be an enhancer of Cervical Lesions among HIV+ women on HAART. Hence, anti-herpetic agent introduction and screening for HSV-2 among HIV+ patients are recommended.

Anxiety and Associated Factors Among Clients on Highly Active Antiretroviral Therapy (HAART) in Public Hospitals of Southern Ethiopia: A Multi-Center Cross-Sectional Study.

Anxiety is an unpleasant feeling of fear, apprehension, and nervousness without any apparent stimulus. Anxiety is one of the co-morbidities that are often overlooked in treating patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Anxiety is worse among people with HIV/AIDS than the general population. Few studies have been conducted on prevalence of anxiety in people receiving antiretroviral treatment and limited evidence is available on its associated factors. Therefore, the objective of this study was to investigate the magnitude and associated factors of anxiety among clients on highly active antiretroviral therapy in public hospitals of Southern Ethiopia. An institution-based cross-sectional study was conducted in public hospitals of Southern Ethiopia. Simple random sampling method was used to recruit study participants. Data collection was done by using a structured questionnaire regarding medical data related to HIV/AIDS. Seven items of the Hospital Anxiety and Depression Scale (HADS) were also used to measure the anxiety level. Oslo social support scale and perceived stigma scale were used to measure social support and stigma respectively. Bivariate and multivariate logistic regression analyses were computed with 95% CI to identify different explanatory variables. Significance was declared at p<0.05. Multi-collinearity was checked by variance inflation factors and Hosmer-Lemeshow test was used to check model fitness. Prevalence of anxiety among clients on HAART in selected public hospitals of Southern Ethiopia was found to be 25.6%. Females (AOR=3.24, 95% CI [1.32, 7.97]), being widowed (AOR=5.47, 95% CI [1.08, 29.72], monthly income 1425-2280 Ethiopian birr (AOR=7.29, 95% CI [2.55, 20.88]), comorbid conditions (AOR=5.47, 95% CI [1.92, 15.62]), perceived stigma (AOR=8.34, 95% CI [3.49, 19.91]) were factors associated with anxiety. Approximately one-fourth of participants living with HIV/AIDS had anxiety. Being female, widowed, medium income, comorbid conditions, and perceived stigma were significantly associated with anxiety. This finding highlights the importance of mental health assessment, early detection and treatment of anxiety as an integral component of HIV/AIDS care.

Serum Interleukin-6 and Weight Loss in Antiretroviral-naïve and Antiretroviral-treated Patients with HIV/AIDS: Relationships and Predictors.

Cachexia is usually associated with elevated serum interleukin-6 (IL.6) as it stimulates the breakdown of muscle proteins and promotes wasting. A case-control study to evaluate the relationship between weight loss, facial fat loss, and IL-6 in antiretroviral-naïve and treated participants living with HIV/AIDS. IL-6 was assayed by High performance liquid chromatography (HPLC) in 97 in consecutive newly diagnosed antiretroviral-naive (ART-naïve) people living with HIV/AIDS (age ≥18 years); and 118 consecutive, age-matched participants currently on Highly Active Antiretroviral Therapy (HAART), using age as a criterion. In the treated group, 78 (66.7%) subjects were on zidovudine, lamivudine with nevirapine (Z+L+N); 27(23.1%) on tenofovir, lamivudine with emtricitabine (T+L+E); 5(4.3%) on zidovudine, lamivudine with emtricitabine (Z+L+E); 4(3.4%) on zidovudine, lamivudine with tenofovir (Z+L+T); 2(1.7%) on lamivudine, tenofovir with nevirapine (L+T+N); 1(0.9%) on tenofovir, zidovudine, emtricitabine (Z+T+E). A total of 215 participants: 97 ART-naive and 118 HAART-treated, age-matched subjects (40.3±9.6 versus 42.7±10.20years, p=0.08). The mean IL-6 was significantly higher in naïve than treated (0.69±0.04 versus 0.66±0.04 pg/ml, p =0.002). In all, 73 subjects experienced weight loss, 56(76.7%) naive, 17(23.3%) treated, p <0.0001, with significantly higher IL-6 in those with weight loss (0.69±0.05 versus 0.67±0.05pg/ml, p= 0.047). Fifty-eight (27.0%) subjects experienced facial fat loss, 49 (84.5%) naïve, and 9 (15.5%) treated, p <0.0001, with significantly higher IL-6 in those with facial fat loss (0.7 ± 0.05 versus 0.67±0.05pg/ml, p= 0.0001). Negative correlation exists between IL-6 and CD4+ count (r=-0.141, p=0.041). In logistic regression, independent predictors of weight loss include: IL-6 (Adjusted Odds Ratio, aOR 1.3, 95%CI 0·1-2·6, p=0.047); HIV duration (aOR 11.6, p <0.0001); AIDS-defining illness (aOR 3.5, p <0.0001); CD4+ count (aOR 3.2, p=0.004); HAART status (aOR 2.7, p<0.0001). HIV infection is associated with elevation of serum interleukin-6, which likely contributes to weight and facial fat loss among the treatment-naïve participants; while HAART is associated with suppressed IL-6 levels, thereby ameliorating weight and facial fat loss. Inverse relationship exists between serum IL-6 and CD4+ count; serum IL-6 could differentiate between mild- to moderate and severe immunosuppressive states.

Relationships Among Trajectories of Sleep Disturbance, Depression, and Antiretroviral Therapy in Persons Newly Diagnosed with HIV: A One-and-a-Half-Year Observational Longitudinal Study.

Sleep disturbance is one of the most prevalent symptoms among persons living with HIV (PLWH). However, the trajectory of sleep patterns in persons newly diagnosed with HIV remains underrecognized. The current study aimed to estimate the trajectory of sleep quality and its associated factors among newly diagnosed PLWH. A prospective study was conducted in the outpatient clinic of a medical center in southern Taiwan from January 2015 to December 2017. Our primary outcome was sleep quality using the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI). Participants completed the questionnaire at baseline and at four follow-up interval visits: at 3-6, 6-9, 9-12 and 12-15 months. A generalized equation estimation (GEE) model was applied to analyze the relationships among poor sleep quality, depression and antiretroviral therapy among persons newly diagnosed with HIV. A total of 217 PLWH were included. The mean age of the sample was 29.3 years, and males (98.6%) were predominant. A total of 56.2% of HIV-infected persons were considered to have poor sleep quality at baseline. After controlling for the confounding effects of demographic characteristics, the following factors increased the risk of poor sleep quality: older age (ß= 0.07, CI: 0.03-0.11, p=0.001), level of depression (ß= 0.32, CI: 0.27-0.37, p<0.001) and detectable viral load (ß= 0.61, CI: 0.04 - 1.18, p= 0.037). However, there was no significant difference in BMI, CD4 counts, HIV viral load, disclosure status, or highly active antiretroviral therapy (HAART) regimen. Our results demonstrate that one in two persons with newly diagnosed HIV had poor sleep quality. Being older, having higher levels of depression, and having detectable HIV viral loads were identified as risk factors for developing poor sleep quality in persons living with HIV.

Vascular disease in Human immunodeficiency virus (HIV) patients on highly active antiretroviral treatment (HAART) in South Africa

Vascular disease in Human immunodeficiency virus (HIV) patients on highly active antiretroviral treatment (HAART) in South Africa