Lamivudine induced pure red cell aplasia and HIV-1 drug resistance-associated mutations: a case report

Kakubu, Mireille A Mpalang; Bikinesi, Tarisai; Katoto, Patrick DMC

doi:10.1093/omcr/omad022

Cited by 4 publications

(2 citation statements)

References 12 publications

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“…Serial laboratory studies did not reveal signs of liver toxicity (e.g. elevated liver enzymes, bilirubin, hypoglycemia, anemia) or cytopenia, which are previously-reported 3TC-related adverse events [32][33][34] . Given that weight loss has been reported in previous studies of 3TC-containing antiretroviral regimens 35 , we compared standing weights at baseline and after 24 weeks of treatment.…”

Section: Safety and Treatment-emergent Adverse Eventsmentioning

confidence: 70%

A pilot study to investigate the safety and feasibility of antiretroviral therapy for Alzheimer’s disease (ART-AD)

Sullivan,

Zuniga,

Ramirez

et al. 2024

Preprint

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Retrotransposons are viral-like DNA sequences that constitute approximately 41% of the human genome. Studies in Drosophila, mice, cultured cells, and human brain indicate that retrotransposons are activated in settings of tauopathy, including Alzheimer disease, and causally drive neurodegeneration. The antiretroviral medication 3TC (lamivudine), a nucleoside analog reverse transcriptase inhibitor, limits retrotransposon activation and suppresses neurodegeneration in tau transgenic Drosophila, two mouse models of tauopathy, and in brain assembloids derived from patients with sporadic Alzheimer disease. We performed a 24-week phase 2a open-label clinical trial of 300 mg daily oral 3TC (NCT04552795) in 12 participants aged 52-83 years with a diagnosis of mild cognitive impairment due to suspected Alzheimer disease. Primary outcomes included feasibility, blood brain barrier penetration, effects of 3TC on reverse transcriptase activity in the periphery, and safety. Secondary outcomes included changes in cognition and fluid-based biomarkers of neurodegeneration and neuroinflammation. All participants completed the six-month trial; one event of gastrointestinal bleeding due to a peptic ulcer was reported. 3TC was detected in blood and cerebrospinal fluid (CSF) of all participants, suggestive of adherence to study drug and effective brain penetration. Cognitive measures remained stable throughout the study. Glial fibrillary acidic protein (GFAP) (P=0.03) and Flt1 (P=0.05) were significantly reduced in CSF over the treatment period; Ab42/40 (P=0.009) and IL-15 (P=0.006) were significantly elevated in plasma. While this is an open label study of small sample size, the significant decrease of some neurodegeneration- and neuroinflammation-related biomarkers in CSF, significantly elevated levels of plasma Ab42/40, and a trending decrease of CSF NfL after six months of 3TC exposure suggest a beneficial effect on subjects with mild cognitive impairment due to suspected Alzheimer disease. Feasibility, safety, tolerability, and central nervous system (CNS) penetration assessments further support clinical evaluation of 3TC in a larger placebo-controlled, multi-dose clinical trial.

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Section: Safety and Treatment-emergent Adverse Eventsmentioning

confidence: 70%

A pilot study to investigate the safety and feasibility of antiretroviral therapy for Alzheimer’s disease (ART-AD)

Sullivan,

Zuniga,

Ramirez

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…Zidovudine (AZT) and other antiretroviral drugs may provoke bone marrow toxicity and lead to anaemia in individuals with HIV. Lamivudine (3TC) was identi ed as the responsible agent of pure red cell aplasia anaemia kind [39]. Recently, cases of DTG-induced acquired sideroblastic anaemia and eryptosis have been documented, potentially increasing the risk of anaemia [47].…”

Section: Discussionmentioning

confidence: 99%

Unveiling the Prevalence of Anaemia and Its Predictors Among Adults on Highly Active Antiretroviral Therapy in the Dolutegravir Era: a Retrospective Cross-sectional Study

Zewdu,

Zeleke,

Ferede

et al. 2024

Preprint

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Introduction Both HIV/AIDS and anaemia are the most pressing public health issues globally. Moreover, there is a dearth of evidence regarding the frequency, severity, and prevalence of anaemia among HIV/AIDS-positive patients receiving antiretroviral therapy in Ethiopia following the rollout of the dolutegravir-based regimen by 2019 as the preferred first-line regimen. Thus, this study is aimed at assessing the prevalence, severity, and associated factors of anaemia among adult HIV-positive ART-experienced patients in Woreta Primary Hospital (WPH). Methods A health institution-based retrospective cross-sectional study design was conducted to evaluate the prevalence and factors influencing anaemia in HIV/AIDS-positive patients from February 2019 to September 2023. Medical record abstraction tools were used to gather data. Employing initially bivariate and then multivariate logistic regression models, the data were evaluated to uncover factors linked with anaemia. The Hosmer-Lemeshow goodness-of-fit test was applied to investigate the model's validity. Results The total prevalence of anaemia was 31.5% [95% CI: 28.9–33.8]. The prevalence of mild, moderate, and severe anaemia was 20.42%, 10.38%, and 0.70%, respectively. Predictors independently linked with anaemia were: female sex (AOR: 1.08), age ≥40 years (AOR: 1.21), lived with HIV >10 years (AOR: 2.31), CD4 counts <200 cells/μL (AOR: 3.81), nonsuppressed viral load (AOR: 1.28), history of opportunistic infections (AOR: 1.54), WHO clinical stage III & IV (AOR: 1.37, & 2.23, respectively), and history of parasitic infestation (AOR: 2.81). Conclusions A sizeable proportion of subjects were found anaemic. Female sex, older age, longer periods lived with the virus, lower CD4 count, nonsuppressed viral load, history of opportunistic infections, WHO clinical stages III and IV, and history of parasitic infestation were the contributing factors. Therefore, to improve the anaemic status and living circumstances of HIV-positive patients, immediate action on the linked variable is needed.

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Efavirenz/lamivudine/tenofovir-disoproxil-fumarate

2024

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Lamivudine induced pure red cell aplasia and HIV-1 drug resistance-associated mutations: a case report

Cited by 4 publications

References 12 publications

A pilot study to investigate the safety and feasibility of antiretroviral therapy for Alzheimer’s disease (ART-AD)

A pilot study to investigate the safety and feasibility of antiretroviral therapy for Alzheimer’s disease (ART-AD)

Unveiling the Prevalence of Anaemia and Its Predictors Among Adults on Highly Active Antiretroviral Therapy in the Dolutegravir Era: a Retrospective Cross-sectional Study

Efavirenz/lamivudine/tenofovir-disoproxil-fumarate

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