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.

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.

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.

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.

Investigating the Role of Anti-TPO Antibodies in HIV-Associated Thrombocytopenia before and after Initiation of HAART: A Case-Control Longitudinal Study.

This longitudinal, case-control study aimed to investigate the role of thrombopoietin (TPO) and anti-TPO antibodies in HIV-associated thrombocytopenia, focusing on the changes seen before and after the initiation of highly active antiretroviral therapy (HAART). Patients were assessed before and at least six months after the initiation of HAART. In total, 75 PLWHIV (age/sex-matched and randomized at 2:1, according to thrombocytopenia status) were included in this study. The baseline assessment revealed significantly higher TPO levels in thrombocytopenic patients (140.45 vs. 106.8 mg/mL, p = 0.008). Furthermore, anti-TPO-positive patients displayed lower platelet counts (109,000 vs. 139,000/L, p = 0.002) and TPO levels (114.7 vs. 142.7 mg/mL, p = 0.047). Longitudinally, HAART initiation reduced the frequency of thrombocytopenia from 75.47% to 33.96% (p < 0.001) and elevated the median platelet counts from 131,000 to 199,000 (p < 0.001). No significant difference in median platelet counts was found post-HAART among the anti-TPO subgroups (p = 0.338), a result contrasting with pre-HAART findings (p = 0.043). Changes in anti-TPO status corresponded with significant platelet count alterations (p = 0.036). Notably, patients who became anti-TPO negative showed a median increase of 95,000 platelets (IQR: 43,750-199,500). These marked differences between subgroups underscore the potential role of anti-TPO antibodies in modulating the hematological response to HAART. Further research is needed to elucidate the complex interplay between HIV infection, HAART, and thrombocytopenia.

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.

Background: 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. Aim: This study assessed the prevalence of LV systolic dysfunction in children on highly active antiretroviral therapy (HAART) with established clinical stage 1 HIV-disease. Materials and Methods: 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. Results: 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). Conclusion: 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.

Pulmonary Arterial Hypertension Associated with Portal Hypertension and HIV Infection: Comparative Characteristics and Prognostic Predictors.

BACKGROUND: Pulmonary arterial hypertension (PAH) may complicate both portal hypertension (Po-PAH) and HIV infection (HIV-PAH). These two conditions, however, frequently coexist in the same patient (HIV/Po-PAH). We evaluated clinical, functional, hemodynamic characteristics and prognostic parameters of these three groups of patients. METHODS: We included patients with Po-PAH, HIV-PAH and HIV/Po-PAH referred to a single center. We compared clinical, functional and hemodynamic parameters, severity of liver disease [Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease-Na (MELD-Na) scores], CD4 count and highly active antiretroviral therapy (HAART) administration. Prognostic variables were identified through Cox-regression analysis. RESULTS: Patients with Po-PAH (n = 128) were the oldest, patients with HIV-PAH (n = 41) had the worst hemodynamic profile and patients with HIV/Po-PAH (n = 35) had the best exercise capacity. Independent predictors of mortality were age and CTP score for Po-PAH, HAART administration for HIV-PAH, MELD-Na score and hepatic venous-portal gradient for HIV/Po-PAH. CONCLUSIONS: Patients with HIV/Po-PAH are younger and have a better exercise capacity than patients with Po-PAH, have a better exercise capacity and hemodynamic profile compared to patients with HIV-PAH, and their prognosis seems to be related to the hepatic disease rather than to HIV infection. The prognosis of patients with Po-PAH and HIV-PAH seems to be related to the underlying disease.

Spirulina platensis Ameliorates Oxidative Stress Associated with Antiretroviral Drugs in HepG2 Cells.

Lately, Spirulina platensis (SP), as an antioxidant, has exhibited high potency in the treatment of oxidative stress, diabetes, immune disorder, inflammatory stress, and bacterial and viral-related diseases. This study investigated the possible protective role of Spirulina platensis against ARV-induced oxidative stress in HepG2 cells. Human liver (HepG2) cells were treated with ARVs ((Lamivudine (3TC): 1.51 µg/mL, tenofovir disoproxil fumarate (TDF): 0.3 µg/mL and Emtricitabine (FTC): 1.8 µg/mL)) for 96 h and thereafter treated with 1.5 µg/mL Spirulina platensis for 24 h. After the treatments, the gene and protein expressions of the antioxidant response pathway were determined using a quantitative polymerase chain reaction (qPCR) and Western blots. The results show that Spirulina platensis decreased the gene expressions of Akt (p < 0.0001) and eNOS (↓p < 0.0001) while, on the contrary, it increased the transcript levels of NRF-2 (↑p = 0.0021), Keap1 (↑p = 0.0002), CAT (↑p < 0.0001), and NQO-1 (↑p = 0.1432) in the HepG2 cells. Furthermore, the results show that Spirulina platensis also decreased the protein expressions of NRF-2 (↓p = 0.1226) and pNRF-2 (↓p = 0.0203). Interestingly, HAART-SP induced an NRF-2 pathway response through upregulating NRF-2 (except for FTC-SP) (↑p < 0.0001), CAT (↑p < 0.0001), and NQO-1 (except for FTC-SP) (↑p < 0.0001) mRNA expression. In addition, NRF-2 (↑p = 0.0085) and pNRF-2 (↑p < 0.0001) protein expression was upregulated in the HepG2 cells post-exposure to HAART-SP. The results, therefore, allude to the fact that Spirulina platensis has the potential to mitigate HAART-adverse drug reactions (HAART toxicity) through the activation of antioxidant response in HepG2 cells. We hereby recommend further studies on Spirulina platensis and HAART synergy.

Sociodemographic predictors associated with the spectrum of non-opportunist neuroretinal disease of non-infectious etiology in patients with HIV/AIDS: A scoping review.

BACKGROUND: Non-infectious retinal disease, even in the HAART era, continues to be one of the most common diagnoses in patients with HIV, with prevalences of up to 27% of cases. This study aims to characterize the association between demographic variables and their role. As a risk factor for the development of non-opportunistic non-infectious retinal disease in patients with HIV/AIDS. METHODS: An integrative review of the literature was carried out according to Arksey O'Malley's approach, based on the PICO methodology and following the PRISMA recommendations; An exhaustive search was carried out in databases of articles that were filtered using established criteria, with their extraction and analysis carried out qualitatively. RESULTS: Ocular manifestations from any cause develop from 35 years of age in patients with HIV/AIDS, with the highest risk for age-related macular degeneration over the fourth decade of life and for the development of neuroretinal disorder on the fifth decade of life; some studies report a slight tendency to diagnose macular degeneration in women and those who acquired AIDS through sexual contact; data contrasted with increased risk for diagnosing neuroretinal disorder in homosexual men who also use intravenous drugs, possibly due to oversampling in studies; non-Hispanic whites and African Americans were the races most commonly affected by neuroretinal disease; the means between the 11.3-14.5 years elapsed since the HIV diagnosis were more frequently associated with cognitive impairment and both in those with high or low CD4 counts, and in patients with high or low viral loads, neuroretinal disease without Statistically significant differences. Adherence and early initiation of HAART had a modest impact on the development of neuroretinal disease. DISCUSSION: Even in the HAART era, non-infectious neuroretinal disease and cytomegalovirus retinitis remain the most frequent ocular diagnoses, however, different studies argue an increase in age-related non-infectious retinal diseases in patients with HIV, theories that are may explain by the increase in life expectancy, the metabolic effects of HAART itself or the generalized pro-inflammatory state in this group of patients, it is essential to recognize this new diagnostic challenge in order to direct preventive efforts through the use of cost-effective sociodemographic risk predictors towards that technological tools for diagnosis and treatment can be targeted. CONCLUSIONS: HIV/AIDS patients who present at the ophthalmological consultation with the suggested sociodemographic predictors have a high risk of visual impairment due to non-infectious retinopathy, therefore prevention, diagnosis and treatment efforts directed at these diseases should be increased.

Cytomegalovirus retinitis in the highly active anti-retroviral therapy era.

Cytomegalovirus (CMV) retinitis is an opportunistic infection that has traditionally affected those who have HIV/AIDS or immunosuppressed individuals. CMV retinitis previously infected one-third of AIDS patients in the pre-highly active antiretroviral therapy (HAART) era, but since HAART, Western countries have seen an 80% decrease in the incidence of the disease. More recently, CMV retinitis has been reported in patients who are immunosuppressed, often due to chemotherapy or immunomodulatory medications. The diagnosis of CMV retinitis is often suspected based on clinical findings, with polymerase chain reaction for confirmation of CMV, especially in atypical cases. Highly active antiretroviral therapy and anti-CMV medications (systemic or local) remain the mainstay of treatment. However, for those who are not responsive to HAART, CMV retinitis remains a challenge, and can still lead to significant vision loss. Moreover, a regimen of anti-CMV medications can sometimes lead to viral resistance or organ toxicity. Complications such as immune recovery retinitis and rhegmatogenous retinal detachments continue to threaten the vision of patients who develop CMV retinitis. These complications can arise following initiation of treatment or if patients show disease progression. Proper vision screening for CMV retinitis in immunosuppressed patients at-risk is necessary for early detection and treatment.

Predictores sociodemográficos asociados al espectro de enfermedad neurorretiniana no oportunista de etiología no infecciosa en pacientes con VIH/SIDA: revisión integrativa / Sociodemographic predictors associated with the spectrum of non-opportunist neuroretinal disease of non-infectious etiology in patients with HIV/AIDS: a scoping review

Antecedentes La enfermedad retiniana no infecciosa, aun en la era del tratamiento antirretroviral de gran actividad (TARGA), continúa siendo uno de los diagnósticos más comunes en pacientes con el virus de la inmunodeficiencia humana (VIH), con prevalencias hasta del 27% de los casos. Este estudio se propone caracterizar la asociación entre unas variables demográficas y su papel como factor de riesgo para el desarrollo de la enfermedad retiniana no infecciosa no oportunista en pacientes con VIH/SIDA. Método Se realizó una revisión integrativa de la literatura, según el planteamiento de O’Malley, partiendo de la metodología PICO y siguiendo las recomendaciones elementos de informes preferidos para revisiones sistemáticas y metanálisis (PRISMA); se realizó una búsqueda exhaustiva en bases de datos de artículos que se filtraron mediante criterios establecidos, con la extracción y análisis de los mismos efectuada de forma cualitativa. Resultados Las manifestaciones oculares por cualquier causa se desarrollan desde los 35 años de edad en los pacientes con VIH/SIDA, con el mayor riesgo para la degeneración macular relacionada con la edad sobre la cuarta década de vida y para el desarrollo de trastorno neurorretiniano sobre la quinta; algunos estudios reportan una ligera tendencia para diagnosticar la degeneración macular en mujeres y en aquellas personas que adquirieron SIDA por contacto sexual; estos datos contrastan con un mayor riesgo para diagnosticar el trastorno neurorretiniano en los hombres homosexuales que también usan drogas intravenosas, posiblemente debido un sobremuestreo en los estudios; los blancos no hispánicos y los afroamericanos fueron las razas más comúnmente afectadas por la enfermedad neurorretiniana; las medias entre los 11,3 a 14,5 años transcurridos desde el diagnóstico de VIH se asociaron más frecuentemente con un trastorno cognitivo y tanto en aquellos con recuentos CD4 altos o bajos como en pacientes con cargas (AU)

Background Non-infectious retinal disease, even in the HAART era, continues to be one of the most common diagnoses in patients with HIV, with prevalences of up to 27% of cases. This study aims to characterize the association between demographic variables and their role. as a risk factor for the development of non-opportunistic non-infectious retinal disease in patients with HIV/AIDS Methods An integrative review of the literature was carried out according to Arksey O’Malley's approach, based on the PICO methodology and following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) recommendations; An exhaustive search was carried out in databases of articles that were filtered using established criteria, with their extraction and analysis carried out qualitatively. Results Ocular manifestations from any cause develop from 35 years of age in patients with HIV/AIDS, with the highest risk for age-related macular degeneration over the fourth decade of life and for the development of neuroretinal disorder on the fifth decade of life; some studies report a slight tendency to diagnose macular degeneration in women and those who acquired AIDS through sexual contact; data contrasted with increased risk for diagnosing neuroretinal disorder in homosexual men who also use intravenous drugs, possibly due to oversampling in studies; non-Hispanic whites and African Americans were the races most commonly affected by neuroretinal disease; the means between the 11.3 to 14.5 years elapsed since the HIV diagnosis were more frequently associated with cognitive impairment and both in those with high or low CD4 counts, and in patients with high or low viral loads, neuroretinal disease without Statistically significant differences. Adherence and early initiation of HAART had a modest impact on the development (AU)

Modelling trends of CD4 counts for patients on antiretroviral therapy (ART): a comprehensive health care clinic in Nairobi, Kenya.

BACKGROUND: In resource-limited settings, changes in CD4 counts constitute an important component in patient monitoring and evaluation of treatment response as these patients do not have access to routine viral load testing. In this study, we quantified trends on CD4 counts in patients on highly active antiretroviral therapy (HAART) in a comprehensive health care clinic in Kenya between 2011 and 2017. We evaluated the rate of change in CD4 cell count in response to antiretroviral treatment. We further assessed factors that influenced time to treatment change focusing on baseline characteristics of the patients and different initial drug regimens used. This was a retrospective study involving 432 naïve HIV patients that had at least two CD4 count measurements for the period. The relationship between CD4 cell count and time was modeled using a semi parametric mixed effects model while the Cox proportional hazards model was used to assess factors associated with the first regimen change. RESULTS: Majority of the patients were females and the average CD4 count at start of treatment was 362.1 [Formula: see text]. The CD4 count measurements increased nonlinearly over time and these trends were similar regardless of the treatment regimen administered to the patients. The change of logarithm CD4 cell count rises fast for in the first 450 days of antiretroviral initiation. The average time to first regimen change was 2142 days. Tenoforvir (TDF) based regimens had a lower drug substitution(aHR 0.2682, 95% CI:0.08263- 0.8706) compared to Zidovudine(AZT). CONCLUSION: The backbone used was found to be associated with regimen changes among the patients with fewer switches being observed, with the use of TDF when compared to AZT. There was however no significant difference between TDF and AZT in terms of the rate of change in logarithm CD4 count over time.

Joint Replacement Surgeries Can Be Safely Performed in HIV Patients.

Whether joint replacement surgery can be performed safely on HIV patients is still a matter of debate. This study aimed to report the surgical efficacy and complications of joint replacement surgery in HIV patients. A total of 21 HIV patients and 27 non-HIV patients who underwent arthroplasties in our hospital were retrospectively reviewed. The 21 HIV patients received 29 joint replacement surgeries including 27 cases of total hip arthroplasty (THA) and 2 cases of total knee arthroplasty (TKA). The non-HIV patients received 16 THA, 10 TKA, and 3 unicompartmental arthroplasty (UKA). The length of hospital stay of HIV patients was significantly lower than that of non-HIV patients. At the last follow-up, there were no significant complications both in the HIV group and the non-HIV groups. No medical staff had any occupational exposure. We concluded that joint replacement surgery in HIV patients is safe and effective. Optimization of patients is key to treatment success. Strictly following the standardized protection protocol can prevent the risk of occupational exposure.

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.

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

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Multicenter Study of Controlling Nutritional Status (CONUT) Score as a Prognostic Factor in Patients With HIV-Related Renal Cell Carcinoma.

Objective: In recent years, the controlled nutritional status (CONUT) score has been widely recognized as a new indicator for assessing survival in patients with urological neoplasms, including renal, ureteral, and bladder cancer. However, the CONUT score has not been analyzed in patients with HIV-related urological neoplasms. Therefore, we aimed to evaluate the prognostic significance of the CONUT score in patients with HIV-related renal cell carcinoma (RCC). Methods: A total of 106 patients with HIV-related RCC were recruited from four hospitals between 2012 and 2021, and all included patients received radical nephrectomy or partial nephrectomy. The CONUT score was calculated by serum albumin, total lymphocyte counts, and total cholesterol concentrations. Patients with RCC were divided into two groups according to the optimal cutoff value of the CONUT score. Survival analysis of different CONUT groups was performed by the Kaplan-Meier method and a log rank test. A Cox proportional risk model was used to test for correlations between clinical variables and cancer-specific survival (CSS), overall survival (OS), and disease-free survival (DFS). Clinical variables included age, sex, hypertension, diabetes, tumor grade, Fuhrman grade, histology, surgery, and CD4+ T lymphocyte count. Result: The median age was 51 years, with 93 males and 13 females. At a median follow-up of 41 months, 25 patients (23.6%) had died or had tumor recurrence and metastasis. The optimal cutoff value for the CONUT score was 3, and a lower CONUT score was associated with the Fuhrman grade (P=0.024). Patients with lower CONUT scores had better CSS (HR 0.197, 95% CI 0.077-0.502, P=0.001), OS (HR 0.177, 95% CI 0.070-0.446, P<0.001) and DFS (HR 0.176, 95% CI 0.070-0.444, P<0.001). Multivariate Cox regression analysis indicated that a low CONUT score was an independent predictor of CSS, OS and DFS (CSS: HR=0.225, 95% CI 0.067-0.749, P=0.015; OS: HR=0.201, 95% CI 0.061-0.661, P=0.008; DFS: HR=0.227, 95% CI 0.078-0.664, P=0.007). In addition, a low Fuhrman grade was an independent predictor of CSS (HR 0.192, 95% CI 0.045-0.810, P=0.025), OS (HR 0.203, 95% CI 0.049-0.842, P=0.028), and DFS (HR 0.180, 95% CI 0.048-0.669, P=0.010), while other factors, such as age, sex, hypertension, diabetes, tumor grade, histology, surgery, and CD4+ T lymphocyte count, were not associated with survival outcome. Conclusion: The CONUT score, an easily measurable immune-nutritional biomarker, may provide useful prognostic information in HIV-related RCC.

The Catastrophic HPV/HIV Dual Viral Oncogenomics in Concert with Dysregulated Alternative Splicing in Cervical Cancer.

Cervical cancer is a public health problem and has devastating effects in low-to-middle-income countries (LTMICs) such as the sub-Saharan African (SSA) countries. Infection by the human papillomavirus (HPV) is the main cause of cervical cancer. HIV positive women have higher HPV prevalence and cervical cancer incidence than their HIV negative counterparts do. Concurrent HPV/HIV infection is catastrophic, particularly to African women due to the high prevalence of HIV infections. Although various studies show a relationship between HPV, HIV and cervical cancer, there is still a gap in the knowledge concerning the precise nature of this tripartite association. Firstly, most studies show the relationship between HPV and cervical cancer at genomic and epigenetic levels, while the transcriptomic landscape of this relationship remains to be elucidated. Even though many studies have shown HPV/HIV dual viral pathogenesis, the dual molecular oncoviral effects on the development of cervical cancer remains largely uncertain. Furthermore, the effect of highly active antiretroviral therapy (HAART) on the cellular splicing machinery is unclear. Emerging evidence indicates the vital role played by host splicing events in both HPV and HIV infection in the development and progression to cervical cancer. Therefore, decoding the transcriptome landscape of this tripartite relationship holds promising therapeutic potential. This review will focus on the link between cellular splicing machinery, HPV, HIV infection and the aberrant alternative splicing events that take place in HIV/HPV-associated cervical cancer. Finally, we will investigate how these aberrant splicing events can be targeted for the development of new therapeutic strategies against HPV/HIV-associated cervical cancer.

Sociodemographic predictors associated with the spectrum of non-opportunist neuroretinal disease of non-infectious etiology in patients with HIV/AIDS: a scoping review. / Predictores sociodemográficos asociados al espectro de enfermedad neurorretiniana no oportunista de etiología no infecciosa en pacientes con VIH/SIDA: revisión integrativa.

BACKGROUND: Non-infectious retinal disease, even in the HAART era, continues to be one of the most common diagnoses in patients with HIV, with prevalences of up to 27% of cases. This study aims to characterize the association between demographic variables and their role. as a risk factor for the development of non-opportunistic non-infectious retinal disease in patients with HIV/AIDS METHODS: An integrative review of the literature was carried out according to Arksey O'Malley's approach, based on the PICO methodology and following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) recommendations; An exhaustive search was carried out in databases of articles that were filtered using established criteria, with their extraction and analysis carried out qualitatively. RESULTS: Ocular manifestations from any cause develop from 35 years of age in patients with HIV/AIDS, with the highest risk for age-related macular degeneration over the fourth decade of life and for the development of neuroretinal disorder on the fifth decade of life; some studies report a slight tendency to diagnose macular degeneration in women and those who acquired AIDS through sexual contact; data contrasted with increased risk for diagnosing neuroretinal disorder in homosexual men who also use intravenous drugs, possibly due to oversampling in studies; non-Hispanic whites and African Americans were the races most commonly affected by neuroretinal disease; the means between the 11.3 to 14.5 years elapsed since the HIV diagnosis were more frequently associated with cognitive impairment and both in those with high or low CD4 counts, and in patients with high or low viral loads, neuroretinal disease without Statistically significant differences. Adherence and early initiation of HAART had a modest impact on the development of neuroretinal disease. DISCUSSION: Even in the HAART era, non-infectious neuroretinal disease and cytomegalovirus retinitis remain the most frequent ocular diagnoses, however, different studies argue an increase in age-related non-infectious retinal diseases in patients with HIV, theories that are may explain by the increase in life expectancy, the metabolic effects of HAART itself or the generalized pro-inflammatory state in this group of patients, it is essential to recognize this new diagnostic challenge in order to direct preventive efforts through the use of cost-effective sociodemographic risk predictors towards that technological tools for diagnosis and treatment can be targeted. CONCLUSIONS: HIV/AIDS patients who present at the ophthalmological consultation with the suggested sociodemographic predictors have a high risk of visual impairment due to non-infectious retinopathy, therefore prevention, diagnosis and treatment efforts directed at these diseases should be increased.

Changes in body mass index among people living with HIV who are new on highly active antiretroviral therapy: a systematic review and meta-analysis.

In the era of highly active antiretroviral therapy (HAART), obesity is increasingly being reported among people living with HIV (PLHIV). In this study, we reviewed published literature on body mass index (BMI) changes among treatment-naïve adult PLHIV who started HAART and remained on treatment for at least six months. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, four databases were searched, and results of included studies were synthesized to describe the BMI trend among PLHIV on treatment. The search generated 4948 studies, of which 30 were included in the qualitative synthesis and 18 were eligible for the meta-analysis. All the studies showed an increase in group BMI. HAART was associated with increase in BMI (pooled effect size [ES] = 1.58 kg/m2; 95% CI: 1.36, 1.81). The heterogeneity among the 18 studies was high (I2 = 85%; p < .01). Subgroup analyses showed pooled ES of 1.54 kg/m2 (95% CI: 1.21, 1.87) and 1.63 kg/m2 (95% CI: 1.34, 1.91) for studies with follow-up ≤1 year and >1 year, respectively. We conclude that the greatest gain in BMI is in the initial 6-12 months on treatment, with minor gains in the second and subsequent years of treatment.

Predictors of Adherence to Highly Active Antiretroviral Therapy among HIV Patients attending Selected Comprehensive Care Centres in Kericho County, Kenya

Highly Active Antiretroviral Therapy (HAART) is undoubtedly the only proven remedy known to improve the health outcomes and reduce AIDS-related mortality. However, just like other chronic diseases, HIV presents significant challenges in achieving and maintaining adherence to medication. The effectiveness of HAART solely depends on adherence. For maximum medication benefits, a nearperfect adherence levels of >95% is required yet data from different studies indicate that few, if any patients have achieved perfect adherence. The main objective of the study was to the determine predictors of adherence to Highly Active Antiretroviral Therapy among HIV patients attending selected comprehensive care centres in Kericho County. MATERIALS AND METHODS A descriptive cross-sectional study was adopted, involving 280 HIV patients (≥ 15 years) on HAART from three selected Comprehensive Care Centres in Kericho County, Kenya. Quantitative and qualitative data were collected using interviewer administered semi-structured questionnaires and key informant interviews, respectively. Purposive sampling was used to select the three health facilities while systematic sampling was used for participant selection. Adherence was measured using viral load. Data was analyzed using SPSS version 25. Logistic regression analysis was used to determine the association between adherence to HAART and various independent variables. Results were considered to be significant at p < 0.05). RESULTS AND CONCLUSION Seventy six percent (76%) of the respondents had optimal adherence while 24% had sub-optimal adherence. More females than males were on treatment. Use of HAART alternatives was a risk factor for sub-optimal adherence (p=0.011). Having someone/tool to remind of when to take medication and disclosure of HIV positive status to spouse were found to significantly promote adherence to HAART with p=0.034) and p=0.048, respectively. African Journal of Health Sciences Volume 34, Issue No.4, July- August 2021 465 RECOMMENDATIONS Several studies have been done on the socio-demographic and socio-economic factors associated with adherence to HAART. Findings from this study indicate that attitudes and practices towards HAART have significant effects on adherence hence more research should be done on attitudes and practice aspects of adherence