stavudine / Generic mfg. - LARVOL DELTA

On the Verge of the 3000th Publication: Reflections on Deceptions, Successes and Perspectives. (PubMed, Molecules) - "A lifelong career devoted to the development of specific antiviral agents eventually yielded, besides (almost) 3000 publications, about ten antiviral compounds that were approved and marketed as antiviral drugs, i.e., DHPA (Duviragel®), BVDU (Zostex®, Mevir®, Brivir®…), VACV (Zelitrex®, Valtrex®), d4T (Stavudine®), emivirine (Coactinon®), rilpivirine (Edurant®), HPMPC (Vistide®), PMEA (Hepsera®), tenofovir (Viread®) and AMD-3100 (Mozobil®), with the latter as a hematopoietic stem cell mobilizer. The targeted viruses for these compounds were herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), human immunodeficiency virus (HIV), and hepatitis B virus (HBV). For other viruses, such as filo-, rhabdo-, arena-, myxo-, polyoma- and papillomaviruses, strategies have been elaborated that should facilitate future developments of antiviral drugs."

Journal • Review • Cytomegalovirus Infection • Hepatitis B • Herpes Simplex • Herpes Zoster • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Oncology • Varicella Zoster

National cross-sectional survey on acquired HIV drug resistance in Haiti in 2023: warnings resistance to dolutegravir (AIDS 2026) - "3.77% of HIVs were resistant to dolutegravir and bictegravir, 4.4% to cabotegravir, 4.72% to raltegravir, and 5.03% to elvitegravir. Additionally, 15.19% of the viral strains were resistant to abacavir, 13.92% to lamivudine and emtricitabine, 6.65% to zidovudine, 8.23% to stavudine and didanosine, and 4.13% to tenofovir...Furthermore, some HIVs strains developed resistance against efavirenz (49.37%), nevirapine (50%), Rilpivirine (20.25%), Etravirine (12.66%), and doravirine (3.61%). Finally, HIV genome resistance was 0.63% against atazanavir/ritonavir and indinavir/ritonavir, 0.95% against lopinavir/ritonavir and 0.32% against darunavir/ritonavir. HIV acquired pharmacoresistance is moderate in Haiti and requires innovating adapted strategy for preventing its development, its transmission, and for protecting PLHIV health, while emphasizing on children and male individuals."

Human Immunodeficiency Virus • Infectious Disease • Respiratory Diseases

Prevalence and associated factors of malnutrition among adults living with HIV on ART: a pilot study. (PubMed, Metabol Open) - "K-means clustering identified two distinct phenotypic groups; younger participants with lower BMI, and lower PAL showed increased risk of malnutrition according to MUST (p = 0.003) and MNA (p = 0.006). Although malnutrition prevalence was low, it was associated with greater depressive symptoms, lower PAL and BMI, and younger age, underscoring the need for comprehensive, multidimensional assessment and integrated care approaches addressing nutritional, psychological, and lifestyle factors."

Journal • Anorexia • CNS Disorders • Depression • Genetic Disorders • Human Immunodeficiency Virus • Infectious Disease • Lipodystrophy • Metabolic Disorders • Psychiatry

Mechanistic insights into plasmid transfer inhibition in Enterobacterales by nucleoside analogues. (PubMed, NPJ Antimicrob Resist) - "Alongside the known inhibitor azidothymidine (AZT), didanosine, stavudine, and trifluridine reduced plasmid conjugation in both species without affecting growth. Conversely, famciclovir and zalcitabine promoted pCTgfp conjugation in E. coli, while aciclovir and valaciclovir enhanced pKpQILgfp conjugation in K. pneumoniae...The exogenous addition of zinc acetate to inhibit RecA or the end product of methionine metabolism, S-adenosyl-methionine, restored pKpQILgfp conjugation in K. pneumoniae. Overall, our results indicated that existing NAs, including AZT, represent structural scaffolds for the development of potent conjugation inhibitors and highlight motility, DNA repair, and methionine metabolism as potential key factors in plasmid conjugation."

Journal • Infectious Disease • Pneumonia

Chronic HIV infection complicated by pancreatitis, pancreatic tail pseudocyst and atraumatic splenic rupture: a case report. (PubMed, AIDS Res Ther) - "This case illustrates a plausible "pancreas-spleen axis" in which chronic pancreatitis with a pancreatic tail pseudocyst leads to local vascular and parenchymal fragility, predisposing to ASR in a patient with chronic HIV infection and incomplete immune reconstitution. It emphasizes the need to consider ASR in PLWH presenting with acute abdomen, particularly when imaging shows pancreatic tail pathology. Early CT, prompt surgical decision-making, and multidisciplinary management between infectious disease specialists and surgeons are critical for favorable outcomes."

Journal • Dyslipidemia • Gastroenterology • Hematological Disorders • Human Immunodeficiency Virus • Hypertriglyceridemia • Hypotension • Infectious Disease • Oncology • Pain • Pancreatitis • Thrombocytosis

Coumarin-stavudine (d4T) novel hybrid ProTides with dual-functionality and enhanced anti-HIV activity. (PubMed, Eur J Med Chem) - "Surprisingly, two phosphorodiamidate derivatives were isolated, revealing a new class of phosphorodiamidating reagents enabling efficient synthesis of diamidate prodrugs. This multifunctional ProTide platform combined enhanced potency, reduced toxicity, and built-in fluorescence, offering promising avenues for next generation nucleoside and non-nucleoside ProTide and diamidate based therapeutics."

Journal • Human Immunodeficiency Virus • Infectious Disease

A systematic review assessing body mass index and waist circumference as predictors for the development of type 2 diabetes mellitus among people living with HIV on antiretroviral therapy. (PubMed, BMC Infect Dis) - "Body Mass Index is a consistent and potential predictor of T2DM among PLWH on ART, while the role of WC appears variable and context dependent. These findings support the inclusion of BMI monitoring in HIV care, though further research is needed to clarify the predictive utility of WC and refine screening thresholds for this population."

Journal • Review • Diabetes • Genetic Disorders • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

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