stavudine / Generic mfg. - LARVOL DELTA

Peripheral Neuropathy: A Review. (PubMed, JAMA) - "Other causes of neuropathy include hereditary causes, such as Charcot-Marie-Tooth disease, toxic neuropathy from medications (chemotherapies [eg, cisplatin, paclitaxel, vincristine], amiodarone, or HIV nucleotide reverse transcriptase inhibitors [eg, stavudine, zalcitabine]); alcohol; vitamin deficiencies such as vitamin B12; and monoclonal gammopathies...First-line medications for neuropathic pain are the α2-δ calcium channel subunit ligands, such as gabapentin and pregabalin; serotonin norepinephrine reuptake inhibitors, such as duloxetine and venlafaxine; and tricyclic antidepressants, such as amitryptyline and nortriptyline...Diabetes is the most common cause of peripheral neuropathy in Western countries. First-line therapies for neuropathic pain include gabapentin, pregabalin, duloxetine, and amitriptyline."

Journal • Addiction (Opioid and Alcohol) • Diabetes • Diabetic Neuropathy • Genetic Disorders • Human Immunodeficiency Virus • Hypotension • Infectious Disease • Metabolic Disorders • Monoclonal Gammopathy • Neuralgia • Pain • Peripheral Neuropathic Pain

The Vortex-Slurry Implementation: A Cheap, Easy, and Ultrafast Mechanochemical Tool to Synthesize/Screen Pharmaceutical Salts and Cocrystals. (PubMed, ACS Omega) - "The improvements achieved by this new implementation were validated by resynthesizing already reported salts and cocrystals and by presenting a new solid form for the antiviral drug Stavudine (DT4), which is an orally administered second-line drug in HIV treatment. Theoretical studies revealed that this implementation enhances the activation energy of the system due to the ball bearings' helical movements. It is expected that this implementation can spread to the scientific community, allowing manufacturability of new drug candidates and generating improvements in the quality of life of patients."

Journal • Human Immunodeficiency Virus • Infectious Disease

Dolutegravir-associated hyperglycemia: a narrative review. (PubMed, AIDS Res Ther) - "Potential mechanisms include mitochondrial dysfunction from previous exposure to NRTIs like stavudine and zidovudine, which causes mitochondrial toxicity and predisposes patients to hyperglycemia upon switching to dolutegravir; magnesium chelation, which is borrowed from dolutegravir's mode of action (dolutegravir inhibits the action of integrase by chelation of magnesium required as a cofactor by the HIV enzyme); and chronic inflammation, with elevated pro-inflammatory markers like IL-6, CRP, and TNF-α contributing to insulin resistance. The narrative review highlights variability in hyperglycemia among patients, influenced by genetics, lifestyle, and prior antiretroviral therapy. The exact nature of dolutegravir-associated hyperglycemia, whether due to insulin resistance or reduced insulin release, remains unclear, although insulin resistance is significant."

Journal • Review • Diabetes • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Metabolic Disorders • Type 2 Diabetes Mellitus • IL6 • TNFA

HIV resistance to dolutegravir varies with co-administered agents. (PubMed, Clin Infect Dis) - "Multivariable analysis of 183 viremic (≥200c/mL) participants from four cohorts (N=660 participants) found dolutegravir-resistance in 21 (11.5%). Dolutegravir-resistance was greater with dolutegravir+lamivudine+zidovudine/(one on stavudine) (OR=19.4, 95%CI 5.1-74.3) or dolutegravir+lamivudine+abacavir (OR=5.4, 95%CI 1.1-25.8), compared to dolutegravir+lamivudine+tenofovir."

Journal • Human Immunodeficiency Virus • Infectious Disease

Untargeted Metabolite Profile Associations with Body Mass Index, Waist-Hip Ratio, and Antiretroviral Therapy in >1300 People with HIV: the Swiss HIV Cohort Study. (PubMed, J Infect Dis) - "In PWH from Switzerland, untargeted metabolite profiling revealed multiple unreported associations with different ART agents, and previously reported associations with BMI."

Journal • Genetic Disorders • Human Immunodeficiency Virus • Infectious Disease • Obesity

Lipodystrophy in HIV: Evolving Challenges and Unresolved Questions. (PubMed, Int J Mol Sci) - "Following the replacement of certain antiretroviral drugs, particularly the thymidine-analog reverse transcriptase inhibitors stavudine and zidovudine, with less toxic alternatives, the incidences of lipoatrophy and lipomatosis significantly declined...Although the widespread use of modern antiretroviral drugs-especially integrase strand transfer inhibitors and non-lipoatrophic reverse transcriptase inhibitors such as tenofovir alafenamide-has reduced the incidences of severe forms of lipodystrophy, these regimens are not entirely free of adipose tissue-related effects...While these morphological changes may not be as pronounced as those seen in classic HIV-associated lipodystrophy, they can still pose significant health risks. The continued optimization of treatment regimens and the vigilant monitoring of adipose tissue alterations and metabolic status remain essential strategies to improve the health of PLWH."

Journal • Review • Cardiovascular • Dyslipidemia • Genetic Disorders • Human Immunodeficiency Virus • Infectious Disease • Lipodystrophy • Metabolic Disorders • Obesity

Leukocyte count and new-onset diabetes mellitus in people with HIV: A longitudinal study. (PubMed, HIV Med) - "High leukocyte count is an independent DM risk factor in people with HIV in Switzerland and increases the risk of DM to a degree similar to traditional and HIV-related risk factors, up to 10 years before DM diagnosis."

Journal • Observational data • Diabetes • Dyslipidemia • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Metabolic Disorders • Obesity

Design, synthesis and biological evaluation of anti-HIV-1 Vif inhibitors based on prodrug strategy. (PubMed, Bioorg Med Chem Lett) - "Among them, the two most effective compounds, A1 and A7, were found to inhibit HIV-1IIIB at nanomolar concentrations (EC50 = 8.1 nM, EC50 = 9.4 nM) in C8166 cells, which were 95 and 81 times higher than the parent drug 6 m, respectively, and 2.7 and 2.3 times higher than that of stavudine (d4T). The stability of compound A1 in the medium suggests that it can effectively release the parent drugs 6 m and stavudine with a half-life of 6 h, suggesting that it is a potential dual-target prodrug targeting HIV Vif and reverse transcriptase."

Journal • Human Immunodeficiency Virus • Infectious Disease

Follow-up of phenotype and metabolic changes in adult males living with HIV on combination antiretroviral therapy (CART) for a decade. (PubMed, Sci Rep) - "At end of the study period, Zidovudine-based ART accounted for 54.57% while Stavudine and Tenofovir based ART accounted for 28.37% and 17.05% respectively. Male PLWH on CART for more than a decade featured increased body weight, higher body fat percentage, total body fat mass higher abdominal adiposity and increased fat mass in upper limbs alongside, Furthemore, reduced beta cell function, impaired glucose tolerance, insulin resistance and lower testosterone levels were observed. The proportion of PLWH with diabetes, prediabetes and non-diabetic individuals were (20.6% n = 6), (34.5%; n = 10) and (44.8%: n = 13) respectively."

Journal • Observational data • Dyslipidemia • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • Obesity

Effects of antiretrovirals on major adverse cardiovascular events in the REPRIEVE trial: a longitudinal cohort analysis. (PubMed, Lancet HIV) - P3 | "Previous and current use of abacavir increases the hazard of MACE among people with HIV at low-to-moderate CVD risk, suggesting that abacavir should be avoided and previous exposure considered when assessing the risk of MACE in this population."

Adverse events • Journal • Atherosclerosis • Cardiovascular • Human Immunodeficiency Virus • Infectious Disease • CD4

A Prospective Cohort of Children With HIV Infection (clinicaltrials.gov) - P=N/A | N=500 | Completed | Sponsor: The HIV Netherlands Australia Thailand Research Collaboration | Trial completion date: Jun 2024 ➔ Sep 2024 | Trial primary completion date: Jun 2024 ➔ Sep 2024 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Viremia Does Not Independently Predict Cardiovascular Disease in People With HIV: A RESPOND Cohort Study. (PubMed, Open Forum Infect Dis) - "We first analyzed the associations between 6 measures of viremia (time-updated, before antiretroviral therapy [ART], viremia category, and measures of cumulative viremia) and CVD after adjusting for the variables in the D:A:D CVD score (age, sex/gender, smoking, family history, diabetes, recent abacavir, CD4 count, blood pressure, cholesterol, high-density lipoprotein, cumulative use of stavudine, didanosine, indinavir, lopinavir, and darunavir). In this large international cohort, HIV viremia was not associated with CVD when adjusting for established risk factors. Our results did not show viremia to be predictive of CVD among people with HIV."

Journal • Cardiovascular • Diabetes • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • Myocardial Infarction • CD4

A programmatic assessment of dolutegravir adverse events and discontinuations in Uganda. (PubMed, HIV Med) - "AEs were common in this African cohort, and dolutegravir discontinuation was driven by hyperglycaemia and erectile dysfunction. Previous use of older ART with known mitochondrial toxicity was associated with neuropsychiatric AEs and hyperglycaemia. African countries used these drugs for longer periods, and this may contribute to this risk."

Adverse events • Journal • Cardiovascular • Diabetes • Erectile Dysfunction • Gastrointestinal Disorder • Human Immunodeficiency Virus • Hypertension • Infectious Disease • Metabolic Disorders • Obesity • Psychiatry

Feline Adenovirus Isolate Shows Silent Nucleotide Alterations, Alternative Receptor/Coreceptor Binding, High Resistance to Disinfectants and Antiviral Drugs, as Well as Immunomodulation. (PubMed, Animals (Basel)) - "The FeAdV isolate was found to be more sensitive to heat, low pH and detergents, but more resistant to alkaline and free chlorine treatments, as well as to ribavirin, stavudine and cidofovir treatments, than other human AdV types. The cohabitation of cats with humans might result in reverse zoonotic infection. Felids appear to be susceptible to persistent and productive adenovirus infection, but further studies are needed to better understand the clinical and epidemiological implications."

Immunomodulating • Journal • Immunology • Infectious Disease • Oncology • IL10 • TGFB1

Developing an HIV-specific falls risk prediction model with a novel clinical index: a systematic review and meta-analysis method. (PubMed, BMC Infect Dis) - "Our meta-analysis identifies predictors of falls in people living with HIV, emphasizing physiological, behavioral, and HIV-specific factors. Integrating these into clinical practice could mitigate falls-related sequelae. We propose a novel approach to falls risk prediction using a novel clinical index, resulting in a HIV-specific falls risk assessment tool."

Clinical • Journal • Retrospective data • Review • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Depression • Human Immunodeficiency Virus • Hypertension • Infectious Disease • Pain • Psychiatry • CD4

Association of cardiovascular disease risk with liver steatosis and fibrosis in people living with hiv in low- and middle-income countries. (PubMed, AIDS) - "Higher CVD risk was associated with steatosis but not with significant fibrosis in PLWH in our LMIC cohort."

Journal • Cardiovascular • Fibrosis • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • CD4

Metabolic engineering of Escherichia coli for thymidine production (PubMed, Sheng Wu Gong Cheng Xue Bao) - "Thymidine, as a crucial precursor of anti-AIDS drugs (e.g., zidovudine and stavudine), has wide application potential in the pharmaceutical industry. The engineered THY6-2 strain produced 11.10 g/L thymidine in a 5 L bioreactor with a yield of 0.04 g/g glucose and productivity of 0.23 g/(L·h). In this study, we constructed a strain that used glucose as the only carbon source for efficient production of thymidine and did not harbor plasmids, which provided a reference for the research on other pyrimidine nucleosides."

Journal • Human Immunodeficiency Virus • Infectious Disease

Weighted gene coexpression network analysis and machine learning for the determination of tfh cell and B cell infiltrating biomarkers in thymoma-associated myasthenia gravis. (PubMed, Heliyon) - "Draggability analysis identified the therapeutic target genes PTGS2 and ALB, along with significant drugs including Firocoxib, Alclofenac, Pyridostigmine, and Stavudine...The interaction between numerous activated B cells and follicular helper T cells is closely associated with THYM-MG pathogenesis from a bioinformatics perspective. Hub genes (including SP6, SCUBE3, B3GNT7, and MAGEL2) may be downregulated in immune cells in THYM-MG and associated with progression."

Biomarker • Journal • Machine learning • CNS Disorders • Myasthenia Gravis • Oncology • Solid Tumor • Thymoma • Thymus Cancer • CD4 • PACERR • PTGS2

Mortality and virologic outcomes of antiretroviral therapy among HIV-positive children and adolescents: a prospective, multicenter, longitudinal, cohort study in China (AIDS 2024) - "This study began in 2008 when the recommended first-line treatment regimen was zidovudine (AZT) or stavudine (D4T) plus lamivudine (3TC) plus nevirapine (NVP) or efavirenz (EFV); second-line treatment regimen was included Lopinavir/ritonavir (LPV/r) -based regimens. The longitudinal cohort study demonstrated the efficacy of China's ART program among HIV-positive children which was beneficial to countries with limited resources."

Clinical • Human Immunodeficiency Virus • Infectious Disease • Pediatrics • CD4

Detailed modelling of viremia exposure does not independently predict cardiovascular disease in people with HIV (AIDS 2024) - "We fitted Cox models including the variables in the D:A:D score (age, gender, smoking, family history, diabetes, current abacavir, CD4 count, blood pressure, cholesterol, high-density lipoprotein, stavudine, didanosine, indinavir, lopinavir, and darunavir; all time-updated). In this large cohort, HIV viremia was not associated with CVD after adjusting for established risk factors. Although we are unable to analyze the impact of viremia before HIV diagnosis, our results provide evidence against a role for viral load in predicting CVD among people with HIV."

Cardiovascular • Diabetes • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • Myocardial Infarction • CD4

Severe Acute Liver Injury After Hepatotoxic Medication Initiation in Real-World Data. (PubMed, JAMA Intern Med) - "Incidence rates of severe ALI ranged from 0 events per 10 000 person-years (candesartan, minocycline) to 86.4 events per 10 000 person-years (stavudine). Seven medications (stavudine, erlotinib, lenalidomide or thalidomide, chlorpromazine, metronidazole, prochlorperazine, and isoniazid) exhibited rates of 10.0 or more events per 10 000 person-years, and 10 (moxifloxacin, azathioprine, levofloxacin, clarithromycin, ketoconazole, fluconazole, captopril, amoxicillin-clavulanate, sulfamethoxazole-trimethoprim, and ciprofloxacin) had rates between 5.0 and 9.9 events per 10 000 person-years...In this study, incidence rates of severe ALI using real-world data identified the most potentially hepatotoxic medications and can serve as a tool to investigate hepatotoxicity safety signals obtained from case reports. Case report counts did not accurately reflect the observed rates of severe ALI after medication initiation."

Journal • Real-world • Real-world evidence • Hepatology • Liver Failure

Liver Steatosis is Prevalent in Lean People With HIV and Associated With Exposure to Antiretroviral Treatment-A Cross-sectional Study. (PubMed, Open Forum Infect Dis) - "Furthermore, in lean PLHIV, liver steatosis was associated with CD4 and CD8 counts at enrollment, dual therapy, and history of treatment with raltegravir (aOR: 3.6 [1.53-8.47], P = .003), stavudine (aOR: 3.73 [1.69-8.2], P = .001), and indinavir (aOR: 3.86 [1.59-9.37], P = .003). In addition, (prior) exposure to specific antiretroviral drugs was associated liver steatosis in lean, but not in overweight/obese PHIV. Implementing increased screening protocols could enhance the identification of steatotic liver disease in lean PHIV."

Journal • Observational data • Diabetes • Fibrosis • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus • CD4 • CD8

HIV and adipose tissue: A long history linked to therapeutic classes of antiretrovirals. (PubMed, Ann Endocrinol (Paris)) - "However, among the NRTIs, the thymidine analogues stavudine and zidovudine led to lipoatrophy, either generalized or associated with visceral fat hypertrophy and buffalo hump...More recently, the NRTI tenofovir disoproxyfumarate (TDF) and the NNRTI efavirenz have been associated with inhibition of fat gain but not with clear lipoatrophy...Also, in the NRTI class, TDF has often been replaced by tenofovir alafenamide (TAF) due to bone and renal toxicities, and TAF has been associated with global fat gain...In the global obesogenic worldwide context, PWH are gaining weight as well in relation to poor health life conditions. Taking in charge obesity uses the same strategies as those used in the general population."

Journal • Diabetes • Genetic Disorders • Human Immunodeficiency Virus • Infectious Disease • Lipodystrophy • Metabolic Disorders • Obesity

Portosinusoidal vascular disorder: how to diagnose, how to treat? (EASL-ILC 2024) - "PSVD has been related to prior exposure to immunosuppressive or antineoplastic agents such as azathioprine, oxaliplatin, as well as to numerous other drugs including didanosine and stavudine...The cornerstone of therapy is beta-blockers, either carvedilol and propranolol, and endoscopic variceal ligation...Scarce reported data has demonstrated that survival of PSVD patients after liver transplantation is favourable. Post-transplant (recurrent) PSVD has been reported, although its incidence is unclear."

Addiction (Opioid and Alcohol) • Cardiovascular • CNS Disorders • Fibrosis • Gastrointestinal Disorder • Hematological Disorders • Hepatic Encephalopathy • Hepatology • Immunology • Infectious Disease • Inflammatory Bowel Disease • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Portal Hypertension • Primary Immunodeficiency • Sarcoidosis • Thrombosis • Venous Thromboembolism

Metabolic causes of liver disease among adults living with HIV from low- and middle-income countries: a cross-sectional study. (PubMed, J Int AIDS Soc) - "Metabolic disorders were significant risk factors for liver disease among PLHIV in LMICs. Early recognition of metabolic disorders risk factors might be helpful to guide clinical and lifestyle interventions. Further prospective studies are needed to determine the causative natures of these findings."

Journal • Observational data • Cardiovascular • Diabetes • Dyslipidemia • Fibrosis • Genetic Disorders • Hepatology • Human Immunodeficiency Virus • Hypertension • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus