Effects of didanosine: A Synthesis of Findings from 21 Studies

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Original Abstract of the Article

Main Research Findings

Didanosine is a nucleoside reverse transcriptase inhibitor (NRTI) used to treat HIV infection. Several studies have shown that didanosine can suppress HIV replication and improve patients' immune function. 20 Additionally, didanosine, when combined with other NRTIs, has been shown to have a greater antiviral effect. 9 On the other hand, some studies have reported that didanosine can cause several side effects. For example, didanosine has been linked to pancreatitis, peripheral neuropathy, lactic acidosis, and liver abnormalities. 11 10 16 Moreover, didanosine, when administered to pregnant women, may affect fetal neurodevelopment. Therefore, caution should be exercised when using didanosine during pregnancy. 13

Didanosine has also been suggested to affect mitochondria within cells, potentially causing a decrease in mitochondrial DNA. 7 Such mitochondrial dysfunction may lead to various diseases, including retinopathy, cardiomyopathy, and diabetes. 12 2 21

Didanosine may also interact with other drugs. For example, didanosine, when used with tenofovir, has been reported to increase the risk of pancreatitis. 11 Therefore, it is important to consult your doctor about possible interactions with other medications before taking didanosine.

Benefits and Risks

Benefits Summary

Didanosine is an effective medication for treating HIV infection. It can suppress HIV replication and improve patients' immune function. Additionally, it can achieve a greater antiviral effect when combined with other NRTIs.

Risks Summary

Didanosine can cause side effects such as pancreatitis, peripheral neuropathy, lactic acidosis, and liver abnormalities. It can also affect fetal neurodevelopment when administered to pregnant women. Didanosine may interact with other medications. It is crucial to consult your doctor about possible interactions with other medications before taking didanosine.

Comparison between Studies

Commonalities in Studies

Multiple studies have shown that didanosine is an effective treatment for HIV infection. They have also found that didanosine, when combined with other NRTIs, can achieve a greater antiviral effect.

Differences in Studies

Research on the side effects of didanosine has yielded varying results. For instance, the risk of pancreatitis, when using didanosine and tenofovir together, has been reported in some studies, but not in others. 11

Consistency and Contradictions in Results

While didanosine is an effective treatment for HIV infection, it does carry the risk of side effects. The findings on the risk of these side effects have varied between studies, necessitating further research.

Practical Application and Considerations

Didanosine should be taken only under the guidance of a doctor. Before taking didanosine, discuss your health condition and any potential interactions with other medications with your doctor. If you experience any abnormalities while taking didanosine, immediately consult your doctor.

Limitations of Current Research

Research on the side effects of didanosine is still insufficient. More research is also needed on the long-term effects of didanosine.

Future Research Directions

Further research on the side effects of didanosine is essential. Research focusing on the long-term effects of didanosine is particularly crucial. Additionally, research on methods to mitigate the side effects of didanosine is necessary.

Conclusion

Didanosine is an effective treatment for HIV infection, but it does come with the risk of side effects. It's crucial to take didanosine under the guidance of a doctor and be aware of potential side effects. Further research on the side effects of didanosine is essential.

Literature analysis of 21 papers
Positive Content
14
Neutral Content
2
Negative Content
5
Article Type
3
0
0
2
21
1.

New-Onset Diabetes and Antiretroviral Treatments in HIV-Infected Adults in Thailand.

Author: RiyatenPrakit, SalvadoriNicolas, TraisathitPatrinee, Ngo-Giang-HuongNicole, CresseyTim R, LeenasirimakulPrattana, TechapornroongMalee, BowonwatanuwongChureeratana, KantipongPacharee, NilmanatAmpaipith, YutthakasemsuntNaruepon, ChutanuntaApichat, ThongpaenSuchart, KlinbuayaemVirat, DeckerLuc, Le CœurSophie, LallemantMarc, CapeauJacqueline, MaryJean-Yves, JourdainGonzague

Lower risk of diabetes
Higher risk of diabetes

The incidence of diabetes in a large cohort of HIV-infected adults in Thailand was relatively low, but those exposed to stavudine + didanosine or cumulative exposure ≥ 1 year to zidovudine had a significantly higher risk of diabetes. Cumulative exposure ≥ 1 year to tenofovir and emtricitabine was associated with a lower risk of diabetes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

2.

Pericardial Adipose Tissue Volume Is Independently Associated With Human Immunodeficiency Virus Status and Prior Use of Stavudine, Didanosine, or Indinavir.

Author: KnudsenAndreas D, Krebs-DemmerLisanne, BjørgeNatascha I D, ElmingMarie B, GelpiMarco, SigvardsenPer E, LebechAnne-Mette, FuchsAndreas, KühlJørgen T, KøberLars, LundgrenJens, NordestgaardBørge G, KofoedKlaus F, NielsenSusanne D

Cardiovascular risk

HIV status was independently associated with larger pericardial adipose tissue volume, which is a risk factor for cardiovascular disease. Severe immunodeficiency, stavudine, didanosine, and indinavir were also associated with larger pericardial adipose tissue volume.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Association between antiretrovirals and thyroid diseases: a cross-sectional study.

Author: SilvaGuilherme Almeida Rosa da, AndradeMayra Christina Teixeira, SuguiDaniel de Alvarenga Salém, NunesRafael Fernandes, PintoJorge Francisco da Cunha, Eyer SilvaWalter de Araujo, FerryFernando Raphael de Almeida, AzevedoMarcelo Costa Velho Mendes de, MottaRogerio Neves

Immune reconstitution
Stavudine use

The prevalence of thyroid disease in HIV-infected patients was higher than previously reported. There was an association between historical stavudine use and subclinical hypothyroidism. Immune reconstitution had a trend towards protection against thyroid diseases.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

4.

Cytochrome 2B6 polymorphism and efavirenz-induced central nervous system symptoms : a substudy of the ANRS ALIZE trial.

Author: GallienS, JournotV, LoriotM-A, SauvageonH, MorlatP, ReynesJ, ReliquetV, ChêneG, MolinaJ-M,

CNS symptoms

Genetic variations in the cytochrome P450 (CYP) 2B6 gene have been linked to significant differences in efavirenz pharmacokinetics. However, clinical data on the relationship between CYP2B6 polymorphisms and efavirenz-induced central nervous system (CNS) symptoms is limited.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

5.

Polymer-Based Nanoparticles as Drug Delivery Systems for Purines of Established Importance in Medicine.

Author: SzykPiotr, Czarczynska-GoslinskaBeata, MlynarczykDariusz T, ŚlusarskaBarbara, KockiTomasz, Ziegler-BorowskaMarta, GoslinskiTomasz

Increased efficacy
Purine drug delivery
Reduced toxicity

Purine derivatives are crucial in treating autoimmune diseases, cancers, and viral infections, but their use is limited by unfavorable properties. This review examines the potential of polymer-based nanoparticles as drug delivery systems for purines, highlighting their ability to enhance drug effects, improve retention, and reduce toxicities.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

6.

Exposure to previous cART is associated with significant liver fibrosis and cirrhosis in human immunodeficiency virus-infected patients.

Author: AnadolEvrim, LustKristina, BoeseckeChristoph, Schwarze-ZanderCarolynne, MohrRaphael, WasmuthJan-Christian, RockstrohJürgen Kurt, TrebickaJonel

Liver fibrosis

Modern combined antiretroviral therapy (cART) seems to decrease liver fibrosis in HIV-infected patients, although earlier antiretrovirals may impair liver function.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Observational StudyResearch that observes and collects data on participants' behavior and outcomes in their natural state, without intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

Depletion of Mitochondrial DNA in Differentiated Retinal Pigment Epithelial Cells.

Author: HuXinqian, CaltonMelissa A, TangShibo, VollrathDouglas

Retinopathy treatment
Mitochondrial DNA depletion

This study investigated the effects of treating differentiated retinal pigment epithelial (RPE) cells with didanosine (ddI), finding that ddI-mediated mitochondrial DNA depletion promotes a glycolytic shift in RPE cells and enhances resistance to oxidative damage.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

Anti-retroviral treatment with zidovudine alters pyrimidine metabolism, reduces translation, and extends healthy longevity via ATF-4.

Author: McIntyreRebecca L, MolenaarsMarte, SchomakersBauke V, GaoArwen W, KambleRashmi, JongejanAldo, van WeeghelMichel, van KuilenburgAndré B P, PossematoRichard, HoutkooperRiekelt H, JanssensGeorges E

Healthspan extension
Lifespan extension

The study explores the geroprotective effects of zidovudine, an anti-retroviral nucleoside reverse transcriptase inhibitor, in C. elegans. The findings suggest that zidovudine extends lifespan and health span by modifying pyrimidine metabolism and regulating proteostasis, ultimately activating transcription factor 4 (ATF-4).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Safety and antiretroviral effects of combined didanosine and stavudine therapy in HIV-infected individuals with CD4 counts of 200 to 500 cells/mm3.

Author: PollardR B, PetersonD, HardyD, PottageJ, MurphyR L, GatheJ, BeallG, RutkieviczV, ReynoldsL, CrossA P, DunkleL M

Antiretroviral effects
Well tolerated
Peripheral neuropathy

Didanosine and stavudine in combination were generally well tolerated and showed antiretroviral effects in HIV-infected patients. Higher doses of both agents were associated with greater viral load reduction and CD4 count increase.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

[Non-cirrhotic portal hypertension due to didanosina. A rare case].

Author: GameroMaría T, GallardoMaría Susana, AguilarVíctor, BravoEduar, GuevaraJulissa, MejiaFernando

Ascites
Gastrointestinal bleeding
Non-cirrhotic portal hypertension

This case report describes a HIV-infected patient who developed non-cirrhotic portal hypertension (NCPH) after long-term didanosine (DDI) treatment. NCPH is a potentially serious liver disorder that can occur in HIV-infected patients.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : Spanish

11.

Pancreatic toxic effects associated with co-administration of didanosine and tenofovir in HIV-infected adults.

Author: MartínezEsteban, MilinkovicAna, de LazzariElisa, RavasiGiovanni, BlancoJosé L, LarrousseMaria, MallolasJosep, GarcíaFelipe, MiróJosé M, GatellJosé M

Increased pancreatitis risk

This study investigates the risk of pancreatitis when using two anti-HIV drugs, didanosine and tenofovir, together. It found a significantly higher risk of pancreatitis when both drugs were given together compared to each drug individually, suggesting caution is needed when using this combination.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

Prior exposure to thymidine analogs and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors.

Author: GelpiMarco, AfzalShoaib, FuchsAndreas, LundgrenJens, KnudsenAndreas D, DrivsholmNinna, MocroftAmanda, LebechAnne-Mette, LindegaardBirgitte, KühlJørgen T, SigvardsenPer E, KøberLars, NordestgaardBørge G, KofoedKlaus F, NielsenSusanne D

HIV-1 treatment
Cardiovascular disease

Thymidine analogs and didanosine (ddI) have been associated with redistribution of body fat from subcutaneous adipose tissue (SAT) to visceral adipose tissue (VAT), which, in turn, is a risk factor for cardiovascular disease. This study explored differences in adipose tissue distribution between people living with HIV (PLWH) with prior exposure to thymidine analogs and/or ddI, without exposure, and uninfected controls and the association with cardiovascular disease risk factors.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

Risk of cancer in children exposed to antiretroviral nucleoside analogues in utero: The french experience.

Author: HleyhelMira, GoujonStéphanie, SibiudeJeanne, TubianaRoland, DollfusCatherine, FayeAlbert, MandelbrotLaurent, ClavelJacqueline, WarszawskiJosiane, BlancheStéphane,

HIV infection treatment
Cancer risk

This study investigated the oncogenic risk of nucleoside analogues for treating HIV infection in uninfected children exposed in utero. While overall cancer incidence was not significantly different from that expected in the general population, didanosine exposure was associated with a significantly higher risk of cancer, particularly during the first trimester. This highlights the need for comprehensive evaluation of the transplacental genotoxicity of this antiretroviral class.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.

Language : English

14.

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) Induce Pathological Pain through Wnt5a-Mediated Neuroinflammation in Aging Mice.

Author: YuanSubo, ShiYuqiang, GuoKaiwen, TangShao-Jun

Chronic pain
Neuroinflammation

This study found that nucleoside reverse transcriptase inhibitors (NRTIs) used in HIV treatment can induce chronic pain in aging patients by activating the Wnt5a signaling pathway, which leads to neuroinflammation in the spinal cord.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

15.

Antiviral Screening of Multiple Compounds against Ebola Virus.

Author: DowallStuart D, BewleyKevin, WatsonRobert J, VasanSeshadri S, GhoshChandradhish, KonaiMohini M, GausdalGro, LorensJames B, LongJason, BarclayWendy, Garcia-DorivalIsabel, HiscoxJulian, BosworthAndrew, TaylorIrene, EasterbrookLinda, PitmanJames, SummersSian, Chan-PensleyJenny, FunnellSimon, VipondJulia, CharltonSue, HaldarJayanta, HewsonRoger, CarrollMiles W

EBOV treatment
None mentioned

This study screened eighteen compounds for antiviral activity against Ebola virus (EBOV). Three promising compounds, 17-DMAG, BGB324, and NCK-8, showed some effect against lethal infection in a guinea pig model of EBOV disease, suggesting their potential for further investigation.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Treatment-limiting renal tubulopathy in patients treated with tenofovir disoproxil fumarate.

Author: HamzahL, JoseS, BoothJ W, HegaziA, RaymentM, BaileyA, WilliamsD I, HendryB M, HayP, JonesR, LevyJ B, ChadwickD R, JohnsonM, SabinC A, PostF A

HIV/HBV treatment
Renal tubulopathy
eGFR decline

This observational cohort study investigated the risk factors for developing severe renal tubulopathy in patients receiving tenofovir disoproxil fumarate (TDF)-containing antiretroviral therapy. The study found that older age, white ethnicity, immunodeficiency, and co-administration of ddI and PI were risk factors for tubulopathy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Observational StudyResearch that observes and collects data on participants' behavior and outcomes in their natural state, without intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Epidemiology and factors associated with peripheral neuropathy among HIV infected patients in Gondar, Ethiopia: A cross-sectional study.

Author: AdemKedir Sany, JanakiramanBalamurugan, GebremeskelBerihu Fisseha, ChalaMulugeta Bayisa, GelawAsmare Yitayeh, AlemuKassahun

HIV associated sensory neuropathy

This study investigated the burden and predictors of HIV-associated sensory neuropathy (HIV-SN) among people living with HIV (PLHIV) in Ethiopia. The study found a significant burden of HIV-SN, with several demographic, health, and clinical characteristics associated with its development.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

20.

Effects of two formats of informed consent on knowledge amongst persons with advanced HIV disease in a clinical trial of didanosine.

Author: TindallB, FordeS, RossM W, GoldsteinD, BarkerS, CooperD A

Improved knowledge
Increased knowledge levels

Most subjects obtain information about HIV-related issues from their healthcare providers. Subjects generally believe their healthcare providers act in their best interests and should be allowed to choose between participating in a clinical trial or receiving medication outside of a trial. Providing information in both written and verbal formats can significantly improve knowledge levels about clinical trials.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

21.

Cardiomyocytes are Protected from Antiretroviral Nucleoside Analog-Induced Mitochondrial Toxicity by Overexpression of PGC-1α.

Author: LiuYongmin, ShimEunwoo, Crespo-MejiasYasmin, NguyenPhuongGiang, GibbonsAlexander, LiuDaniel, ShideEric, PoirierMiriam C

Mitochondrial protection

This study investigated the protective effects of PGC-1α overexpression against nucleoside reverse transcriptase inhibitor (NRTI)-induced mitochondrial toxicity in cardiomyocytes. PGC-1α overexpression was found to protect cardiomyocytes from NRTI-induced growth inhibition, apoptosis, and oxidative stress.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., IntramuralFunding provided by the NIH for research projects within the NIH.

Language : English

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