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 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.

The Complex Dysregulations of CD4 T Cell Subtypes in HIV Infection.

Human immunodeficiency virus (HIV) infection remains an important global public health problem. About 40 million people are infected with HIV, and this infection caused about 630,000 deaths in 2022. The hallmark of HIV infection is the depletion of CD4+ T helper lymphocytes (Th cells). There are at least seven different Th subtypes, and not all are the main targets of HIV. Moreover, the effect of the virus in a specific subtype can be completely different from that of the others. Although the most compromised Th subtype in HIV infection is Th17, HIV can induce important dysregulations in other subtypes, such as follicular Th (Tfh) cells and regulatory Th cells (Treg cells or Tregs). Several studies have shown that HIV can induce an increase in the immunosuppressive activity of Tregs without causing a significant reduction in their numbers, at least in the early phase of infection. The increased activity of this Th subtype seems to play an important role in determining the immunodeficiency status of HIV-infected patients, and Tregs may represent a new target for innovative anti-HIV therapies, including the so-called "Kick and Kill" therapeutic method whose goal is the complete elimination of the virus and the healing of HIV infection. In this review, we report the most important findings on the effects of HIV on different CD4+ T cell subtypes, the molecular mechanisms by which the virus impairs the functions of these cells, and the implications for new anti-HIV therapeutic strategies.

Periodontal health in a large cohort of Ugandansliving with HIV: A cross-sectional study.

Background: The impact of periodontitis on large populations of people living with HIV (PLHIV) in resource-constrained settings remains largely un-investigated. This study aims to address this knowledge gap by providing a comprehensive description of the periodontal health status among a sizable cohort of Ugandans living with HIV. Methods: This was a cross-sectional study with 4,449 participants who were over 18-years old and captured their reported age, gender, tobacco use, length of time on HAART and alcohol use. Periodontal health was assessed using the WHO periodontal probe and the modified CPI data entry form. Descriptive statistics were reported using frequencies for the affected number of sextants in the surveyed participants. This was followed by additional regression analysis using the R statistical computing environment, with the periodontal health outcomes (bleeding on probing, pocket depth and clinical attachment loss) individually as the dependant, recoded as binary outcomes. A multilevel model was run with clinical attachment loss as the dependant variable controlling for all the other factors. The 95% confidence intervals were used to report the level of significance for each test. Results: There were 3,103/4,449 (69.7%) female participants. The mean age was 44.3 years (SD 10.1 years) with a range of 18 to 89 years. About 66% of the participants had bleeding on probing at one or more of the examined sites/tooth surfaces. The odds for bleeding on probing were significantly higher for female participants (adjusted Odds ratio: 1.49, 95% CI 1.19 to 1.86), and higher in individuals who reported tobacco use (adjusted odds ratio 1.62, 95% CI 1.09 to 2.41). Slightly under half of our participants (48.2%) had moderate to severe clinical attachment loss. Conclusions: This study found that among Ugandans living with HIV, periodontal disease is a significant public health concern. The majority (66%) had bleeding on probing, with a sizeable number (48.2%) of participants recording moderate to severe clinical attachment loss, worsened by age and time on HAART. This highlight the need for comprehensive oral health care and targeted interventions for this population.

Changes in the Lipid Asset of HIV/HCV Patients after a Successful Course of Direct-Acting Antivirals.

Background: Highly Active Antiretroviral Therapy (HAART) for HIV infection and Direct-Acting Antivirals (DAA) for HCV infection currently represent the main treatment options for HIV/HCV co-infected patients. However, HAART has been associated with increased lipids. This study aimed to evaluate lipid profile changes after the DAA cycle in HIV/HCV co-infected patients undergoing HAART/DAA therapy. Methods: A prospective, longitudinal, observational study among HIV/HCV co-infected patients undergoing HAART/DAA treatment was conducted at the Infectious Diseases Unit of the University Hospital of Salerno. Inclusion criteria were age > 18 years, written informed consent, completion of the DAA cycle, and virologic suppression on HAART. Changes in the lipid profile were analyzed from baseline during and after DAA therapy at 12, 24, and 48 weeks after the sustained virologic response (SVR). A t-test was used to compare continuous variables. An analysis of variance was performed for each antiretroviral drug and genotype. Results: Fifty-four HIV/HCV patients (men/women n. 34/20 [68/32%], median age 56 years), all naïve to HCV therapy, were enrolled. HCV infection was caused by genotype 1 in 55% of cases and by genotype 3 in 29%. An increase in total cholesterol was recorded after the DAA treatment (from 165.03 ± 46.5 to 184.7 ± 44.9 mg/dL, p < 0.0001), after 12, 24, and 48 weeks, and in LDL-C at 24 weeks follow-up (at baseline 86.7 ± 34 mg/dL to 103.4 ± 41.38 mg/dL, p < 0.0001). Conclusions: Changes in the lipid profile after combined DAA/HAART treatment represent an important prognostic index. Further evaluation of cardiovascular-associated risk is necessary to implement appropriate prevention strategies.

Distinct profile of antiviral drugs effects in aortic and pulmonary endothelial cells revealed by high-content microscopy and cell painting assays.

Antiretroviral therapy have significantly improved the treatment of viral infections and reduced the associated mortality and morbidity rates. However, highly effective antiretroviral therapy (HAART) may lead to an increased risk of cardiovascular diseases, which could be related to endothelial toxicity. Here, seven antiviral drugs (remdesivir, PF-00835231, ritonavir, lopinavir, efavirenz, zidovudine and abacavir) were characterized against aortic (HAEC) and pulmonary (hLMVEC) endothelial cells, using high-content microscopy. The colourimetric study (MTS test) revealed similar toxicity profiles of all antiviral drugs tested in the concentration range of 1 nM-50 µM in aortic and pulmonary endothelial cells. Conversely, the drugs' effects on morphological parameters were more pronounced in HAECs as compared with hLMVECs. Based on the antiviral drugs' effects on the cytoplasmic and nuclei architecture (analyzed by multiple pre-defined parameters including SER texture and STAR morphology), the studied compounds were classified into five distinct morphological subgroups, each linked to a specific cellular response profile. In relation to morphological subgroup classification, antiviral drugs induced a loss of mitochondrial membrane potential, elevated ROS, changed lipid droplets/lysosomal content, decreased von Willebrand factor expression and micronuclei formation or dysregulated cellular autophagy. In conclusion, based on specific changes in endothelial cytoplasm, nuclei and subcellular morphology, the distinct endothelial response was identified for remdesivir, ritonavir, lopinavir, efavirenz, zidovudine and abacavir treatments. The effects detected in aortic endothelial cells were not detected in pulmonary endothelial cells. Taken together, high-content microscopy has proven to be a robust and informative method for endothelial drug profiling that may prove useful in predicting the organ-specific endothelial toxicity of various drugs.

Diffuse gingival hypertrophied Kaposi sarcoma as an initial presentation of HIV Infection.

Kaposi sarcoma is an indolent angio-proliferative spindle- cell tumor derived from endothelial and immune cells infected with Human herpes virus type 8(HHV-8). In the era of highly active antiretroviral (HAART), Kaposi sarcoma is a rare form of initial presentation of HIV infection [1]. The author presents a case of diffuse gingival hypertrophied Kaposi sarcoma in 18-year-old male newly diagnosed RVI patient. After confirming the diagnosis patient started on HAART and mouth care. Surgical excision is the first line of treatment with HAART, since this patient has low CD4 count of 30 cells/mm3 which will complicate the surgery. So, we are waiting for CD4 count to increase above 200 cells/mm3 to undergo surgical excision. The case is representative of HIV complexity and aimed to bring awareness of unusual presentation of HIV.This case also reminds us how important early initiation of HAART is.

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.

Changing Paradigm of Yeast Isolates in HIV-Seropositive Patients with Oropharyngeal Candidiasis (OPC).

Background Oropharyngeal candidiasis (OPC) is a common fungal infection in HIV-seropositive patients. Understanding the spectrum of yeast isolates and their antifungal susceptibility patterns is crucial for effective management. This study aimed to determine the yeast isolates, antifungal susceptibility patterns, and associated factors in HIV-seropositive patients with OPC. Material and methods A prospective observational study was conducted on 350 HIV-seropositive patients attending an Integrated Counselling and Testing Centre (ICTC) at the Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar. Yeast isolates from oropharyngeal lesions were identified, and their antifungal susceptibility was determined by automated method VITEK 2. Demographic characteristics, highly active antiretroviral therapy (HAART) status, and CD4+ cell count categories were analyzed for associations. Results This study of 350 HIV-seropositive patients revealed that 100 tested positive for Candida, with distinct differences between HAART (n=67) and non-HAART (n=33) groups. HAART patients had a younger age distribution and higher median CD4+ cell counts (350 vs. 250 cells/mm³, U = 175, p < 0.05) compared to non-HAART patients. Candida albicans was the most common species in both groups, but significant variations in species distribution (χ² = 9.23, p < 0.05) and antifungal susceptibility were noted. Specifically, susceptibility differences were significant for flucytosine (χ² = 7.21, p = 0.027) and voriconazole (χ² = 8.64, p = 0.013), emphasizing the influence of HAART on managing immune function and antifungal resistance in HIV patients. Conclusion This study provides insights into the spectrum of yeast isolates and their antifungal susceptibility patterns in HIV-seropositive patients with OPC. The findings emphasize the importance of considering multiple factors, such as Candida species, HAART status, and individual patient characteristics, in treatment decisions. The results will aid in the development of evidence-based management protocols for this vulnerable population. Further research is warranted to explore additional factors influencing antifungal susceptibility and optimize treatment strategies for this patient population.

Comparison of Switching Between Antiretroviral Agents Versus Introducing Lipid-lowering Agents for HAART-induced Dyslipidemia.

PURPOSE: Highly active antiretroviral therapy (HAART) has brought a significant reduction in HIV/AIDS-related morbidity and mortality. However, metabolic abnormalities (eg, dyslipidemias) have continued to pose significant challenges, warranting a switch between antiretroviral agents and/or the introduction of a statin. Hence, the purposes of this study was to compare the efficacy of switching between antiretroviral agents versus introducing a statin in the long-term management of HAART-induced dyslipidemia in people living with HIV, and to identify the most potent agent in switching therapies. METHODS: A comprehensive literature search of PubMed and Medline identified articles published from the years 2000 to 2020 in the English language, resulting in 84 articles, 30 of which were selected based on inclusion and exclusion criteria. Information on primary and secondary outcomes was extracted. Statistical analysis was done on the variables, and the differences between groups were considered significant at P < 0.05. FINDINGS: Statin use was associated with significant reductions in triglycerides and total cholesterol (TC) at 6 weeks (both, P < 0.01). A switch of antiretroviral agents was associated with gradual reductions in TC and triglycerides for up to 48 weeks (both, P < 0.01). Statin use was associated with a reduced CD4 count at 24 weeks (P < 0.01). A switch of antiretroviral agents was associated with an increased CD4 count at 48 weeks (P < 0.01). IMPLICATIONS: Statins were as effective as switching antiretroviral therapies in the short-term management of TC and triglycerides in patients with HAART-induced dyslipidemia.

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.

Effect of Combined HAART Plus ATT in Patients of Extrapulmonary Tuberculosis in HIV Patients and Effect on Quality of Life.

HIV is a disease which reduces human resistant to fight. When our immunity becomes so weak that we are not able to fight even the common commensals of our body, this leads to what is called as an opportunistic infection. Tuberculosis is one of those most common type of opportunistic infection and in this pulmonary tuberculosis is more common. Extrapulmonary tuberculosis with HIV is the area of lesser research. In this study we tried to prove the Prevalence of extrapulmonary tuberculosis in AIDS patients and also the effect of combined HAART and ATT on prevalence of extrapulmonary tuberculosis and also its effect on Quality of life of the patient. This is a retrospective study conducted in a tertiary centre in the Department of Otorhinolaryngology & head and neck surgery from January 2020 to December 2020. A total of 80 patients were studied for 1 year. Confirmed cases of AIDS with extra pulmonary tuberculosis in head and neck region were studied, keeping all ethical issues in mind and after complete treatment of ATT along with HAART. After treatment, a significant number of patients got resolved with EPTB and gave positive response on their quality of life. Not only pulmonary tuberculosis, extrapulmonary tuberculosis with HIV is on the rise nowadays. Combined treatment of both can help in decreasing prevalence of extrapulmonary tuberculosis and improves quality of life.

Molecular mechanisms underpinning the protection against antiretroviral drug-induced sperm-endocrine aberrations and testicular toxicity: A review.

The introduction of highly active antiretroviral therapy (HAART) has revolutionized the treatment of HIV/AIDS worldwide. The HAART approach is the combination of two or more antiretroviral drugs of different classes and are responsible for patient's survival and declining death rates from HIV/AIDS and AIDS-related events. However, the severe and persistent reproductive side effect toxicity of HAART regimens is of great concern to patients within the reproductive age. Till date, the underlying pathophysiology of the HAART-induced reproductive toxicity remains unraveled. Nevertheless, preclinical studies show that oxidative stress and inflammation may be involved in HAART-induced sperm-endocrine deficit and reproductive aberrations. Studies are emerging demonstrating the efficacy of plant-based and non-plant products against the molecular alterations and testicular toxicity of HAART. The testicular mechanisms of mitigation by these products are associated with enhancement of testicular steroidogenesis, spermatogenesis, inhibition of oxidative stress and inflammation. This review presents the toxic effects of HAART on spermatogenesis, reproductive hormones and testis integrity. It also provides insights on the molecular mechanisms underlying the mitigation of HAART testicular toxicity by plant-based and non-plant agents. However, effect of repurposing clinical drugs to combat HAART toxicity is unknown, and more mechanistic studies are evidently needed. Altogether, plant-based and non-plant products are potential agents for prevention of rampant endocrine dysfunction and testicular toxicity of HAART.

Determinants of hemoglobin level and time to default from Highly Active Antiretroviral Therapy (HAART) for adult clients living with HIV under treatment; a retrospective cohort study design.

HIV/AIDS is one of the most devastating infectious diseases affecting humankind all over the world and its impact goes beyond public health problems. This study was conducted to investigate the joint predictors of hemoglobin level and time to default from treatment for adult clients living with HIV/AIDS under HAART at the University of Gondar Comprehensive and Specialized Hospital, North-west Ethiopia. The study was conducted using a retrospective cohort design from the medical records of 403 randomly selected adult clients living with HIV whose follow-ups were from September 2015 to March 2022. Hemoglobin level was projected using Sahli's acid-hematin method. Hence, the hemoglobin tube was filled with N/10 hydrochloric acid up to 2 g % marking and the graduated tube was placed in Sahli's hemoglobin meter. The blood samples were collected using the finger-pick method, considering 22 G disposable needles. The health staff did this. From a total of 403 adult patients living with HIV/AIDS included in the current study, about 44.2% defaulted from therapy. The overall mean and median estimated survival time of adult clients under study were 44.3 and 42 months respectively. The patient's lymphocyte count (AHR = 0.7498, 95% CI: (0.7411: 0.7587), p-value < 0.01), The weight of adult patients living with HIV/AIDS (AHR = 0.9741, 95% CI: (0.9736: 0.9747), p-value = 0.012), sex of adult clients (AHR = 0.6019, 95% CI: (0.5979, 0.6059), p-value < 0.01), WHO stages III compared to Stage I (AHR = 1.4073, 95% CI: (1.3262, 1.5078), p-value < 0.01), poor adherence level (AHR = 0.2796, 95% CI: (0.2082, 0.3705) and p-value < 0.01), bedridden patients (AHR = 1.5346, 95% CI: (1.4199, 1.6495), p-value = 0.008), and opportunistic infections (AHR = 0.2237, 95% CI: (0.0248, 0.4740), p-value = 0.004) had significant effect on both hemoglobin level and time to default from treatment. Similarly, other co-morbidity conditions, disclosure status of the HIV disease, and tobacco and alcohol addiction had a significant effect on the variables of interest. The estimate of the association parameter in the slope value of Hgb level and time default was negative, indicating that the Hgb level increased as the hazard of defaulting from treatment decreased. A patient with abnormal BMI like underweight, overweight, or obese was negatively associated with the risk of anemia (lower hemoglobin level). As a recommendation, more attention should be given to those patients with abnormal BMI, patients with other co-morbidity conditions, patients with opportunistic infections, and low lymphocytes, and bedridden and ambulatory patients. Health-related education should be given to adult clients living with HIV/AIDS to be good adherents for medical treatment.

Studying the Changes in Physical Functioning and Oxidative Stress-Related Molecules in People Living with HIV after Switching from Triple to Dual Therapy.

BACKGROUND: Physical activity could increase the production of oxidative stress biomarkers, affecting the metabolism and excretion of antiretroviral drugs and, consequently, the clinical outcome. Nowadays, people living with HIV (PLWH) are mostly switching from triple to dual therapy, but no data are available in terms of physical functioning and oxidative stress. The aim of this study was to evaluate if some antioxidant biomarkers and physical functioning tests could be different according to triple or dual antiretroviral therapy. METHODS: PLWH were evaluated at baseline (BL), while treated with three drugs, and six months after the switch to dual therapy. Physical functioning was quantified using validated tools. Mitochondrial and cytosol antioxidant molecules were evaluated through liquid chromatography. RESULTS: Twenty-five patients were analyzed. A statistically significant difference between triple and dual therapy was found for mitochondrial glutathione, but not for physical tests. Evaluating differences between physically active and inactive individuals, the following statistically significant differences were suggested, considering triple therapy (mitochondrial n-formyl-methionine p = 0.022, triglycerides p = 0.023) and double therapy (mitochondrial glycine p = 0.035, cytosol glutamic acid p = 0.007, cytosol s-adenosylmethionine p = 0.021). CONCLUSIONS: For the first time, this study suggests possible differences in terms of antioxidant molecules and physical functioning in PLWH switching from triple to dual therapy.

Exploring the association between erythema multiforme and HIV infection: some mechanisms and implications.

Erythema multiforme (EM) is an immune-mediated mucocutaneous condition characterized by hypersensitivity reactions to antigenic stimuli from infectious agents and certain drugs. The most commonly implicated infectious agents associated with EM include herpes simplex virus (HSV) and Mycoplasma pneumoniae. Other infectious diseases reported to trigger EM include human immunodeficiency virus (HIV) infection and several opportunistic infections. However, studies focusing on EM and human immunodeficiency virus (HIV) infection are scarce. even though the incidence of EM among HIV-infected individuals have increased, the direct and indirect mechanisms that predispose HIV-infected individuals to EM are not well understood. In turn, this makes diagnosing and managing EM in HIV-infected individuals an overwhelming task. Individuals with HIV infection are prone to acquiring microorganisms known to trigger EM, such as HSV, Mycobacterium tuberculosis, Treponema pallidum, histoplasmosis, and many other infectious organisms. Although HIV is known to infect CD4 + T cells, it can also directly bind to the epithelial cells of the oral and genital mucosa, leading to a dysregulated response by CD8 + T cells against epithelial cells. HIV infection may also trigger EM directly when CD8 + T cells recognize viral particles on epithelial cells due to the hyperactivation of CD8 + T-cells. The hyperactivation of CD8 + T cells was similar to that observed in drug hypersensitivity reactions. Hence, the relationship between antiretroviral drugs and EM has been well established. This includes the administration of other drugs to HIV-infected individuals to manage opportunistic infections. Thus, multiple triggers may be present simultaneously in HIV-infected individuals. This article highlights the potential direct and indirect role that HIV infection may play in the development of EM and the clinical dilemma that arises in the management of HIV-infected patients with this condition. These patients may require additional medications to manage opportunistic infections, many of which can also trigger hypersensitivity reactions leading to EM.

Improved outcomes following gastrointestinal surgery among people living with HIV in the HAART-era: A scoping review.

BACKGROUND: This study aimed to review the varied 1-4 gastrointestinal (GI) system surgical outcomes among people living with Human Immunodeficiency Virus (PLWH) in the HAART-era. METHODS: MEDLINE and EMBASE were searched for primary publications on GI surgery outcomes exclusively in HAART-treated HIV patients. NSQIP-reported complications (NRCs), all-cause complications (ACC) and HIV disease parameters were extracted. RESULTS: 12 studies met study inclusion criteria, examining bowel (4), bariatric (5), cholecystectomy (1), appendectomy (1), and other general abdominal operations (1). The NRC rate was 0%, ≥44.4% and 13.3% in bariatric, bowel and appendix surgeries, respectively. Over half of NRCs were infectious. HAART-treated patients had lower ACC, LOS, and sepsis versus untreated-HIV, and higher ACC, LOS and reoperation rates versus HIV-negative patients. CONCLUSION: HAART use is associated with markedly improved NRC outcomes post GI surgery among PLWH; however, these remained inferior to those documented among HIV uninfected individuals.

Clinical Profile of Patients on Highly Active Antiretroviral Therapy (HAART) Seen in a Tertiary Eye Clinic.

Background: Highly active antiretroviral therapy (HAART) is the medication regimen for the management of human immunodeficiency virus. Over time, it has been dubbed to have revolutionised the clinical course and outcomes of HIV/AIDS. Objective: The objective of this study is to determine the clinical factors associated with the ocular manifestation of HIV/AIDS among patients on HAART. Materials and Methods: This was a descriptive cross-sectional study conducted at the ophthalmology department of the University of Nigeria Teaching Hospital (UNTH) in 2017 among adult patients (≥18 years) attending the hospital's antiretroviral therapy (ART) clinic and selected using systematic random sampling technique. Statistical Package for Social Sciences (SPSS) version 21 was used for data analysis, with variables being summarised using frequencies and proportions. Inferential statistics (t test, Chi-square test, and Fisher's exact test) was used to test associations between variables. A level of significance was set at a P value of less than 0.05 corresponding to a 95% confidence interval. Results: A majority of patients were in WHO stages 1 and 2 of HIV and the mean CD4+ cell count of the whole population was 575.0 ± 512.56 cells/µL, while that of those with ocular manifestations was 315.2 ± 290.76 and 633.7 ± 533.54 cells/µL for those who do not have ocular manifestation. There was a significant association between CD4+ cell count and ocular manifestations such as conjunctival microvasculopathy, anterior uveitis, and cytomegalovirus retinitis. Conclusion: Our results suggest that HAART has some positive effect on the clinical profile of people with HIV/AIDS with CD4+ count being a major determinant of ocular manifestations.

Exploring the impact of therapeutic advances in HIV-related mortality in the United States.

Objectives: Mortality from HIV has significantly declined with the introduction of highly active antiretroviral therapy (HAART). This study sought to examine the longitudinal trends in mortality from HIV-related diseases by race, sex, geographical region, and over time as HAART trends changed. Methods: We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database and performed serial cross-sectional analyses of national death certificate data for all-cause mortality with comorbid HIV from 1999 to 2020. HIV diseases (International Classification of Diseases, Tenth Revision codes B20-B24, O98.7, R75) were listed as the contributing cause of death. We calculated the age-adjusted mortality ratio (AAMR) per 1,000,000 individuals and determined mortality trends using the Joinpoint Regression Program. Subgroup analyses were performed by sex, race, region, and organ system. The study period was further stratified into three groups when specific drug regimens were more prevalent. Results: In the 22-year study period, 251,759 all-cause mortalities with comorbid HIV were identified. The leading cause of death was infectious disease (84.0%, N = 211,438). Men recorded a higher AAMR than women (4.66 vs 1.65, P < 0.01). African American individuals had the highest AAMR (13.46) compared to White, American Indian, and Asian individuals (1.70 vs 1.65 vs 0.47). The South region had the highest AAMR (4.32) and urban areas had a higher AAMR compared to rural areas (1.77 vs 0.88). Conclusions: More than 80% of deaths occurred because of infectious disease over the last 2 decades with a decreasing trend over time when stratified by race, sex, and geographical region. Despite advances in HAART, mortality disparities persist which emphasizes the need for targeted interventions in these populations.