Advanced Acquired Immune Deficiency Syndrome Research Articles

Interaction between antiretroviral therapy regimens and body mass index on triglyceride levels in people living with HIV: a cross-sectional and longitudinal study

ObjectiveTo investigate how antiretroviral therapy (ART) regimens and body mass index (BMI) interact to affect triglyceride (TG) levels in people living with HIV (PLWH).MethodsThis research involved 451 men living with HIV for cross-sectional analysis, and 132 underwent follow-up assessments in 2021 and 2023. Multivariate logistic regression identified key factors, while covariance regression models assessed interactions between ART regimens and BMI on TG levels.ResultsThe result of this cross-sectional study indicated that advanced AIDS (acquired immune deficiency syndrome) stage (OR = 2.756, P = 0.003), higher BMI (OR = 1.131, P = 0.003), and waist-hip ratio (WHR, OR = 44.684, P = 0.019) are closely associated with high triglyceride levels. Additionally, regimens containing zidovudine (AZT) (OR = 3.927, P < 0.001) or protease inhibitors/integrase strand transfer inhibitors (PI/INSTI) (OR = 5.167, P < 0.001) were significantly linked to hypertriglyceridemia. Cross-sectional and longitudinal analyses from 2021 to 2023 emphasized that changes in BMI interact with antiretroviral treatment regimens to affect TG levels in PLWH (Pinteraction < 0.05). Especially in the AZT-based drug regimen, the correlation between BMI and TG is more prominent.ConclusionThe interaction between ART regimens and BMI influences TG levels in PLWH, indicating that weight management is crucial for reducing the risk of hypertriglyceridemia in this population.

Central Pontine Myelinolysis with Minimal Hyponatremia in the Setting of AIDS.

Central pontine myelinolysis (CPM) is classically attributed to overly rapid correction of profound hyponatremia. However, there are case reports of this disease in the setting of normal serum sodium or minimal hyponatremia. These cases have been hypothesized to be secondary to other metabolic disturbances such as hyperglycemia or hypophosphatemia. Eunatremic CPM has also been described in patients with advanced acquired immune deficiency syndrome (AIDS). The mortality risk in this special population is significantly higher than those with hyponatremia-associated CPM, but the mechanisms are unclear. We discuss a case of a man with AIDS who developed CPM with minimal hyponatremia and no other metabolic disturbances. Common variables within this population, such as hypoalbuminemia and lymphoma, are discussed as potential factors contributing to the pathophysiology. Reporting these atypical cases is crucial to our understanding of how to prevent future cases.

Perineal reconstruction with local flaps: technique and results

Wide excision of perineal lesions, often including the entire anal canal, may be necessary for benign and malignant conditions. Closure of these large defects is challenging, especially when continence is a goal. The aim of this study was to assess our experience with local flap closure of large perineal defects. From 1994 to 2009, 20 patients underwent wide perineal and/or anal canal excisions and reconstruction using local flaps. Mean age was 45 years (range 20-65 years), 13 were male, and 8 (40 %) were immunocompromised. Primary indications included anal or perineal squamous cell carcinoma-(n = 12), Buschke-Lowenstein tumor (n = 3), and anal intraepithelial neoplasia (n = 3), hidradenitis, stenosis, ectropion, and traumatic cloaca repair (n = 1 each). Primary procedures included wide local excision of large neoplastic lesions-(n = 15) (mean size 10 cm, range 5-18 cm), abdominoperineal resection (APR) (n = 2), perineoplasty with sphincteroplasty-(n = 1), and others-(n = 2). All were reconstructed with bilateral local flaps (V-Y 18, S 2). Thirteen had complete excision of the anal canal to the anorectal ring preserving the sphincters. Six (30 %) had ostomies; 2 with APR and 4 temporary. There were no perioperative deaths. Mean hospital stay was 4.2 days. Follow-up averaged 35 months (range 3-87 months) in survivors. Five patients died during follow-up; 2 of complications of acquired immune deficiency syndrome (AIDS) and 3 of cancer (2 treated palliatively). Wound dehiscence occurred in 6 (30 %) patients: in 3 cases, this was minor dehiscence and healed quickly; in 3 cases, it was major dehiscence and occurred in the 2 radiation/APR patients and in one patient with advanced AIDS. Radiation was the only significant risk factor (P < .05). Twelve of 14 eligible patients with long-term follow-up and an intact anal canal are fully continent, and 2 are partially continent (1 traumatic cloaca; 1 the same as before surgery). Local flap reconstruction of the perineum and anal canal is an excellent method of managing large perineal defects. Most heal primarily, even in immunocompromised patients, and continence may be preserved. Local flaps should be avoided in irradiated patients.

Enhanced levels of CCL19 in patients with advanced acquired immune deficiency syndrome (AIDS)

Based on the ability to recruit lymphocytes and dendritic cells to lymphoid tissue and to promote inflammation, we hypothesized a role for dysregulated CCL19 and CCL21 levels in human immunodeficiency virus (HIV)-infected patients with advanced immunodeficiency, and in particular in those with accompanying Mycobacterium avium complex (MAC) infection. The hypothesis was explored by studies in HIV-infected patients with and without MAC infection, as well as in vitro, examining the ability of proteins from MAC to promote CCL19 and CCL21 responses in peripheral blood mononuclear cells (PBMC) during highly active anti-retroviral therapy (HAART). Our main findings were: (i) raised serum levels of CCL19 in HIV-infected patients with CD4(+) T cell count <50 cells/µl compared with HIV-infected patients with CD4(+) T cell count >500 cells/µl and healthy controls, with particularly high levels in those with MAC infection; (ii) elevated plasma levels of CCL19 predicted a higher mortality in acquired immune deficiency syndrome (AIDS)-patients, independent of ongoing MAC infection; and (iii) marked production of CCL19 in MAC-stimulated peripheral blood mononuclear cells (PBMC) and pronounced disturbances in MAC-induced CCL19 production in PBMC from HIV patients that was partly reversed during HAART. Our findings suggest the involvement of CCL19 in AIDS patients with advanced immunodeficiency, potentially mediating both adaptive and maladaptive responses.

Disseminated tuberculosis in human immunodeficiency virus infection: ineffective immunity, polyclonal disease and high mortality.

Disseminated tuberculosis (TB) is a major cause of death in patients with the acquired immune-deficiency syndrome (AIDS), but its pathogenesis and clinical features have not been defined prospectively. Human immunodeficiency virus (HIV) infected adults with a CD4 count ≥ 200 cells/μl and bacille Calmette-Guérin scar underwent immunologic evaluation and subsequent follow-up. Among 20 subjects who developed disseminated TB, baseline tuberculin skin tests were ≥15 mm in 14 (70%) and lymphocyte proliferative responses to Mycobacterium tuberculosis were positive in 14 (70%). At the time of diagnosis, fever ≥2 weeks plus ≥5 kg weight loss was reported in 16 (80%) patients, abnormal chest X-rays in 7/17 (41%), and positive sputum cultures in 10 (50%); median CD4 count was 30 cells/μl (range 1-122). By insertion sequence (IS) 6110 analysis, 14 (70%) blood isolates were clustered and 3/8 (37%) concurrent sputum isolates represented a different strain (polyclonal disease). Empiric TB treatment was given to eight (40%) patients; 11 (55%) died within a month. Disseminated TB in HIV occurs with cellular immune responses indicating prior mycobacterial infection, and IS6110 analysis suggests an often lethal combination of reactivation and newly acquired infection. Control will require effective prevention of both remotely and recently acquired infection, and wider use of empiric therapy in patients with advanced AIDS and prolonged fever.

Gastric Burkitt Lymphoma: A Rare Cause of Upper Gastrointestinal Bleeding in a Child With HIV/AIDS

Gastric Burkitt Lymphoma: A Rare Cause of Upper Gastrointestinal Bleeding in a Child With HIV/AIDS

Quality of Life of Patients with Advanced Cancer and Acquired Immune Deficiency Syndrome and their Family Caregivers

Although definitions of palliative care include quality of life as a central concern, little research has been published about both the quality of life of patients with advanced illness and their family members, and particularly the changes in their quality of life over time. The aims of this prospective longitudinal pilot study were to: (1) establish the reliability of multidimensional quality of life instruments based on patients with acquired immune deficiency syndrome (AIDS) and patients with cancer and caregivers; (2) identify differences in quality of life between patients with advanced AIDS and cancer, and their family caregivers with consideration of mortality, attrition, and compliance rates; and (3) examine differences in demographic variables and their potential confounding effect when measuring quality of life. The sample included 101 patients with advanced illness (63 patients with advanced AIDS and 38 with advanced cancer) and 81 family caregivers (43 caregivers for patients with AIDS and 38 caregivers for patients with cancer). Data collection involved the monthly completion of the McGill Quality of Life Questionnaire (MQOL) for patients, and the Quality of Life Scale (QLS) for family caregivers. Reliability of the MQOL and QLS were established for patients with AIDS and patients with cancer and caregivers. Based on the MQOL, patients with advanced AIDS reported a lower total quality of life, and lower psychological quality of life, and a higher physical quality of life compared to patients with advanced cancer. There were no significant differences between patient groups on the one-item physical well-being subscale, or the existential well-being, and support subscales. Based on the QLS, AIDS caregivers reported greater overall quality of life, greater psychological well-being, and greater spiritual well-be- ing than cancer caregivers. There were no significant differences between AIDS and cancer caregivers with respect to physical or social well-being. From baseline entry into the study to third month of participation, there were no significant changes in total quality of life scores for patient or caregiver groups, although trends indicated a moderately high total quality of life over time for all patient and caregiver groups. Fourteen of 63 (22%) patients with AIDS patients died, while 19 of 38 (50%) patients with advanced cancer died after enrollment. Forty-six of 63 (73%) patients with advanced AIDS withdrew for various reasons other than death at some point during the 12 month time frame of the study, while 15 of 38 (39%) patients with advanced cancer withdrew. There were significant differences on all demographic variables for patients with advanced cancer and AIDS. Only religious affiliation was significantly related to quality of life for patients with AIDS, while gender was the only variable associated with quality of life for patients with cancer. There were significant differences on all demographic variables between caregivers with the exception of gender and living arrangements. Only the relationship between patients and caregivers and marital status were significantly associated with quality of life for cancer caregivers. In palliative care research, the challenge is to design studies that will capture changes in the domains of quality of life over time, yet will minimize participant burden and subsequent attrition rates. By measuring quality of life as an outcome variable in palliative care, health professionals can identify changes in the domains of quality of life over time for various patient populations and their family caregivers, and respond with appropriate interventions, which promote or maintain their quality of life even as death approaches.

Mucocutaneous Manifestation of Cryptococcal Infection: Report of a Case and Review of the Literature

Cryptococcus neoformans is a fungal organism that commonly affects patients that are seropositive for the human immunodeficiency virus (HIV), most notably patients with advanced acquired immune deficiency syndrome (AIDS) and CD4 lymphocyte cell count of less than 100 copies/mL.1-3 The incidence of cryptococcosis in patients with AIDS in the era before highly active antiretroviral therapy (HAART) had been reported in large studies to range from 6% to 12%.4-7 In a recent study, cryptococcal infection was the AIDS-defining illness in 3% and the cause of death in 5% of HIV-infected patients.

AIDS Presenting with Cutaneous Kaposi's Sarcoma and Bacillary Angiomatosis in the Bone Marrow Mimicking Kaposi's Sarcoma

Kaposi's sarcoma (KS) and bacillary angiomatosis (BA) may be histologically similar. A precise diagnosis is required because of the different management of these diseases. KS or BA involving bone marrow is rare in patients with and without acquired immune deficiency syndrome (AIDS). We report the case of a 40-year-old human immunodeficiency virus (HIV)-positive homosexual male who presented with small KS lesions in the skin and BA in the bone marrow that histologically were similar. Laboratory evaluation revealed anemia and thrombocytopenia; CD4 count was 103/mm3, and the viral load was 750,000 HIV-1 mRNA copies per milliliter in plasma. Bartonella henselae, the etiologic agent of BA, was isolated from a blood culture. DNA sequences of human herpesvirus-8 (HHV-8), the putative etiologic agent of KS, were identified by polymerase chain reaction (PCR) in skin and bone marrow specimens, but antibody anti-HHV-8-encoded protein ORF73, localized signals only in the skin-KS lesion. The patient received clarithromycin and cefotetan for the BA, and antiretroviral therapy for the HIV infection. The skin lesions gradually regressed, the HIV-1 mRNA copy number decreased to less than 400 per milliliter and the CD4 lymphocyte count increased to 665/mm3. In conclusion, vascular lesions of BA and KS may be clinically and histologically similar, both may be associated with advanced AIDS, and an accurate diagnosis is required because of their different management.

Primary Research: Short Communication: Evidence Supporting Rare AIDS-Kaposi's Sarcoma Metastasis In Keeping With Their Vascular Endothelial Evolution

BackgroundIt is postulated that the unusual manifestations of Kaposis's sarcoma cells in nonendothelial brain tissues and on eyeballs in advanced acquired immune deficiency syndrome (AIDS) cases are metastasized AIDS-Kaposi's sarcoma cells arising from vascular endothelial cells.MethodsExperiments were performed to explore the above hypothesis by testing for intercellular adhesion molecule-1 (CD54 antigens) on cutaneous AIDS-Kaposi's sarcoma cells as well as on AIDS-Kaposi's sarcoma cells isolated from eyeballs as studies have illustrated that, unlike localized Kaposi's sarcoma cells of primary lesions, proliferating Kaposi's sarcoma cells in proximity to primary lesions express a negative or diminished phenotype when evaluated for identical surface antigens. Parallel CD54 antigen tests were done on vascular endothelial cells and monocytes/macrophages as endothelial cells are considered evolutionarily related to Kaposi's sarcoma cells and monocytes/macrophages are ideal CD54 antigen positive controls.ResultsOur data showed that only AIDS-Kaposi's sarcoma cells of the eyes did not express CD54 antigens.ConclusionsWe therefore report that our findings support the postulation suggesting AIDS-Kaposi's sarcoma dissemination in advanced AIDS patients in keeping with their vascular endothelial heredity.

Design of some nucleic acid antimetabolites: expectations and reality.

3'-Azido-2'3'-dideoxythymidine (AZT), a thymidine analogue with potent antiretroviral activity against human immunodeficiency virus (HIV) in vitro, has been shown to confer a clinical benefit in patients with advanced acquired immune deficiency syndrome (AIDS). Other 2',3'-dideoxynucleosides, e.g., 2',3'-dideoxy-cytidine and 2',3'-dideoxyadenosine, block the infectivity of HIV against helper/inducer T cells in vitro and protect the cell against the cytopathic effect of the virus. The majority of these antiretroviral agents were synthesized more than twenty years ago as analogues of physiologically important deoxynucleosides in the quest of a more effective cancer chemotherapy. None of the synthetic analogues manifested significant activity when screened against L1210 leukemia in BDF mice despite the fact that the phosphorylation reactions, crucial to the activation of the 2',3'-dideoxynucleosides, are catalyzed by kinases of appropriate target cells. However, the 2',3'-dideoxynucleoside triphosphates, relative to corresponding deoxynucleotides, have a reduced affinity for DNA polymerase alpha, an enzyme that has key DNA synthetic and repair functions in the life of a cell. In contrast, HIV reverse transcriptase, like host cellular DNA polymerase beta (a repair enzyme) and gamma (a mitochondrial enzyme), is much more susceptible to the inhibitory effects of the dideoxynucleotides. This would explain the activity of the fradulent nucleotides at low concentrations against pathogenic retroviruses vis à vis the low cytoxic activity observed with these agents as anti-leukemia drugs.