Side Effects of didanosine: A Synthesis of Findings from 24 Studies

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Original Abstract of the Article

Major Research Findings

Didanosine (ddI) is a nucleoside reverse transcriptase inhibitor (NRTI) used to treat HIV infection. While it has shown effectiveness in certain studies, ddI has also been linked to potential serious side effects.

The study 21 found that HIV-infected patients receiving combination therapy with ddI and tenofovir (TDF) experienced a decline in CD4+T cells and an increased risk of pancreatitis and hyperglycemia.

The study 24 found that ddI is used as a treatment for chronic hepatitis B, but the balance of efficacy and side effects needs to be considered.

The study 11 found that combination therapy with ddI, stavudine (d4T), and efavirenz (EFV) was less effective and had lower tolerability in treating HIV infection. It also found that 12.5% of patients taking this combination required treatment discontinuation due to peripheral neuropathy.

The study 20 found that in combination therapy with ddI and hydroxyurea, reducing the dose of hydroxyurea could reduce toxicity and increase anti-HIV efficacy.

The study 13 found that NRTIs, such as ddI, can prevent atherosclerosis induced by HIV protease inhibitors.

The study 18 found that ddI is one of the drugs that can cause drug-induced pancreatitis.

The study 12 found that combination therapy with ddI, d4T, and NVP was effective in treating HIV infection and was well tolerated.

The study 3 found that ddI is one of the drugs that can cause retinopathy.

The study found that ddI can cause metabolic side effects.

The study 22 found that ddI can cause exocrine pancreatic insufficiency.

The study 17 found that NRTIs, such as ddI, can affect mitochondrial DNA.

The study 5 found that ddI has many side effects and is expensive, so it should be eliminated from HIV treatment.

The study 14 found that combination therapy with ddI, lamivudine, and EFV was effective and well tolerated in treating HIV infection.

The study 4 found that ddI is one of the drugs that can cause retinopathy.

The study 16 found that combination therapy with ddI, tenofovir, and EFV was effective and well tolerated in treating HIV infection.

The study 9 found that ddI can affect mitochondria in the kidneys.

The study 7 found that encapsulating ddI in nanoparticles may enhance the therapeutic effect of treating HIV infection.

The study 6 found that ddI can increase the risk of acute pancreatitis in HIV-infected patients.

The study 19 found that in combination therapy with ddI and hydroxyurea, reducing the dose of hydroxyurea could increase anti-HIV efficacy.

The study 8 found that antiretroviral drugs, such as ddI, can affect intestinal tissues and functions.

Reasons for Side Effects

ddI may affect mitochondria in cells. 17 . Mitochondria play a crucial role in cellular energy production. ddI’s impact on mitochondria could hinder cellular energy production, leading to various side effects.

Common Side Effects

Neuropathy

ddI can cause peripheral neuropathy. 11 . Peripheral neuropathy manifests as symptoms such as numbness and pain in the hands and feet.

Pancreatitis

ddI can cause pancreatitis. 18 , 21 . Pancreatitis is an inflammation of the pancreas. Symptoms include abdominal pain, nausea, and vomiting.

Metabolic Side Effects

ddI can cause metabolic side effects. . Metabolic side effects include hyperglycemia, dyslipidemia, and lactic acidosis.

Kidney Damage

ddI can cause kidney damage. 9 . Kidney damage can manifest as changes in urine volume, swelling, and elevated blood pressure.

Retinopathy

ddI can cause retinopathy. 3 , 4 . Retinopathy is a disease where abnormalities occur in the retina of the eye. Symptoms include vision loss and narrowing of the visual field.

Side Effect Countermeasures

Neuropathy

If neuropathy symptoms develop, ddI administration should be discontinued. 11 . Additionally, taking supplements like vitamin B complex can help alleviate neuropathy symptoms.

Pancreatitis

If pancreatitis symptoms develop, ddI administration should be stopped, and appropriate treatment should be sought. 18 . Pancreatitis can be life-threatening if it worsens, so early treatment initiation is crucial.

Metabolic Side Effects

If metabolic side effects develop, ddI administration may need to be stopped or the dosage reduced. . Lifestyle changes, such as dietary modification and exercise, are also important.

Kidney Damage

If kidney damage symptoms develop, ddI administration should be stopped, and appropriate treatment should be sought. 9 . In severe cases of kidney damage, dialysis may be required.

Retinopathy

If retinopathy symptoms develop, ddI administration should be stopped, and an ophthalmologist should be consulted. 3 . Early treatment initiation can help prevent vision loss.

Comparison between Studies

Commonalities in Studies

Many studies have shown that ddI is effective in treating HIV infection. However, many studies have also shown that ddI can cause various side effects.

Differences in Studies

Each study has shown different rates and severities of ddI side effects. This could vary depending on factors such as the age, gender, stage of HIV infection, concomitant medications, and dosage of the study participants.

Points to Note for Real-Life Application

ddI is an effective drug for treating HIV infection, but it carries the risk of various side effects. Therefore, when taking ddI, it is important to follow your doctor’s instructions and understand the risks of side effects. Regular monitoring, such as blood tests, is also crucial to allow for early detection and treatment of side effects.

Limitations of Current Research

Research on the side effects of ddI is still not extensive enough. In particular, there are many unknowns regarding long-term side effects and rare side effects. Furthermore, there are no established effective preventative measures or treatments for ddI side effects.

Future Research Directions

Further research on the long-term side effects and rare side effects of ddI is needed. The development of effective preventative measures and treatments for ddI side effects is also crucial.

Conclusion

ddI is an effective drug for treating HIV infection, but it carries the risk of various side effects. When taking ddI, it is important to follow your doctor’s instructions and understand the risks of side effects. Regular monitoring, such as blood tests, is also crucial to allow for early detection and treatment of side effects. Research on the side effects of ddI is still not extensive enough. Further research on the side effects of ddI is needed, and the development of effective preventative measures and treatments for ddI side effects is crucial.

Literature analysis of 24 papers
Positive Content
19
Neutral Content
2
Negative Content
3
Article Type
5
0
1
5
24
1.

A double-blind randomised controlled trial of paracetamol, diclofenac or the combination for pain relief after caesarean section.

Author: MunishankarB, FettesP, MooreC, McLeodG A

Pain relief

A combination of diclofenac and paracetamol was found to be more effective in reducing morphine use after elective caesarean section than paracetamol alone.

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

2.

Effects of Pipemidic Acid, Phenazopyridine HCL and Sodium Diclofenac on Pain Perception Following Endoscopic Urological Surgery: Double-blinded Randomized-Controlled Trial.

Author: YuriPrahara, AliZulfikar, RasyidNur, BirowoPonco

Pain relief
Endoscopic urological surgery

Oral analgesics, including pipemidic acid, phenazopyridine, and sodium diclofenac, were effective in reducing pain after endoscopic urological surgery in 80 patients. Pipemidic acid demonstrated a superior analgesic effect compared to the other two drugs.

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

3.

[Toxic retinopathies].

Author: KellnerUlrich, KellnerSimone, WeinitzSilke, FarmandGhazaleh

Retinopathy

This study discusses the toxic effects of various medications on the retina, the light-sensitive layer at the back of the eye. It highlights the importance of recognizing these side effects, which can mimic other eye diseases.

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

Language : German

4.

MULTIMODAL IMAGING IN DIDANOSINE RETINOPATHY.

Author: ShiferaAmde Selassie, SinghMandeep

Retinopathy

Multimodal retinal imaging findings in a patient with didanosine retinopathy were highlighted, demonstrating the absence of progression during a 1.5-year follow-up.

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 : English

5.

A farewell to didanosine: harm reduction and cost savings by eliminating use of didanosine.

Author: DziubanEric J, RaizesElliot, KoumansEmilia H

HIV treatment
Toxicities

Didanosine, an HIV drug, has been linked to adverse events and is now rarely used in resource-rich settings. Despite this, 20 countries still purchase it, costing 3.2-10.3 times more than a similar drug, lamivudine. Given its toxicities, monitoring needs, drug interactions, inconvenience, and cost, national ART programs should consider discontinuing didanosine.

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.

Language : English

6.

Antiretroviral drugs and acute pancreatitis in HIV/AIDS patients: is there any association? A literature review.

Author: OliveiraNatalia Mejias, FerreiraFelipe Augusto Yamauti, YonamineRaquel Yumi, ChehterEthel Zimberg

HIV/AIDS treatment
Acute pancreatitis
Myelotoxicity

This review examines the association between antiretroviral drugs and acute pancreatitis in HIV-seropositive patients. Zidovudine, efavirenz, protease inhibitors, didanosine, zalcitabine, and stavudine have been reported to cause acute pancreatitis. The review highlights the importance of considering antiretroviral drug-induced pancreatitis in patients with abdominal pain and elevated pancreatic enzymes.

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.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

7.

Submicron-size biodegradable polymer-based didanosine particles for treating HIV at early stage: an in vitro study.

Author: PattnaikGurudutta, SinhaBiswadip, MukherjeeBiswajit, GhoshSaikat, BasakSandip, MondalSubhasish, BeraTanmoy

HIV infection control
Reduced toxicity
Sustained drug delivery

This study aimed to develop poly(d,l-lactic-co-glycolic acid)-based nanoparticles containing didanosine and to observe their uptake by macrophages in vitro.

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

8.

Evaluation of HIV protease and nucleoside reverse transcriptase inhibitors on proliferation, necrosis, apoptosis in intestinal epithelial cells and electrolyte and water transport and epithelial barrier function in mice.

Author: Braga NetoManuel B, AguiarCarolina V, MacielJamilly G, OliveiraBruna M C, SevillejaJesus E, OriáReinaldo B, BritoGerly A C, WarrenCirle A, GuerrantRichard L, LimaAldo A M

AIDS treatment
Diarrhea

Protease inhibitors (PIs) and reverse transcriptase drugs are used to treat AIDS. These drugs can cause diarrhea, which can limit their long-term efficacy and treatment compliance. A study is being conducted to investigate the effects of these drugs on intestinal histopathology and function.

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.

Tenofovir renal toxicity targets mitochondria of renal proximal tubules.

Author: KohlerJames J, HosseiniSeyed H, Hoying-BrandtAmy, GreenElgin, JohnsonDavid M, RussRodney, TranDung, RaperC Michael, SantoianniRobert, LewisWilliam

HIV treatment
Renal toxicity

Tenofovir, an HIV reverse transcriptase inhibitor, can cause renal tubular toxicity in HIV transgenic mice. Tenofovir appears to target mitochondrial toxicity in the renal proximal tubules.

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

11.

Poor efficacy and tolerability of stavudine, didanosine, and efavirenz-based regimen in treatment-naive patients in Senegal.

Author: CanestriAnna, SowPapa Salif, VrayMuriel, NgomFatou, M'boupSouleymane, KaneCoumba Toure, DelaporteEric, GueyeMandoumé, PeytavinGilles, GirardPierre Marie, LandmanRoland,

Virologic efficacy
Mortality
Treatment-limiting side effects

The combination therapy of d4T, ddI, and EFV showed a decrease in virologic efficacy due to high mortality rate and treatment modifications caused by adverse events.

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.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

Nucleoside reverse transcriptase inhibitors prevent HIV protease inhibitor-induced atherosclerosis by ubiquitination and degradation of protein kinase C.

Author: BradshawEmily L, LiXiang-An, GuerinTheresa, EversonWilliam V, WilsonMelinda E, Bruce-KellerAnnadora J, GreenbergRichard N, GuoLing, RossStuart A, SmartEric J

Atherosclerosis prevention

Alpha-tocopherol did not prevent ritonavir-induced atherosclerosis in LDLR null mice. However, co-treatment with didanosine or D4T, nucleoside reverse transcriptase inhibitors, did prevent atherosclerosis by inhibiting the upregulation of CD36 and cholesterol accumulation.

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.
Retracted PublicationCases where a publication has been formally withdrawn due to the discovery of serious errors or misconduct.

Language : English

14.

Clinically stable treatment-experienced adults receiving tenofovir and didanosine.

Author: Di BiagioAntonio, BeltrameAndrea, CenderelloGiovanni, FerreaGiuseppe, De MariaAndrea

Immunological success

Tenofovir (TDF) and didanosine (ddI) combination therapy does not have a higher risk of early immunological or virological failure in drug-experienced patients. However, treatment success may depend on the historical CD4+ nadir.

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.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

15.

Simplicity and efficacy of a once-daily antiretroviral regimen with didanosine, lamivudine, and efavirenz in naïve patients: the VESD study.

Author: SantosJ, PalaciosR, LópezM, GálvezM C, LozanoF, de la TorreJ, RíosM J, López-CortésL F, RiveroA, Torres-TortosaM,

Sustained viral suppression
Well-accepted
Adverse side-effects
Lack of treatment response

The once-daily combination of didanosine-lamivudine-efavirenz resulted in sustained viral suppression and was well-accepted by patients. Associated adverse events and virological failures were few.

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.
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

16.

Simplification therapy with once-daily didanosine, tenofovir and efavirenz in HIV-1-infected adults with viral suppression receiving a more complex antiretroviral regimen: final results of the EFADITE trial.

Author: BarriosAna, NegredoEugenia, DomingoPere, EstradaVicente, LabargaPablo, AsensiVíctor, MoralesDolores, SantosJesús, ClotetBonaventura, SorianoVincent,

Improve lipid profile
Reduce pill burden
CD4+ cell decline

A study compared the effectiveness of switching to a simpler antiretroviral regimen (tenofovir, didanosine, and efavirenz) versus remaining on the same regimen in HIV-1-infected patients. The simpler regimen was as effective as the original regimen in suppressing HIV-1 RNA when low doses of didanosine were used. However, the simpler regimen was associated with lower CD4+ cell counts, particularly when higher doses of didanosine were used.

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.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
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

17.

Nucleoside reverse transcriptase inhibitors, mitochondrial DNA and AIDS therapy.

Author: LewisWilliam

AIDS treatment
Mitochondrial toxicity

Nucleoside analogue reverse transcriptase inhibitors (NRTIs) are important for the treatment of HIV infection but can cause mitochondrial toxicity. Further research is needed to understand the mechanisms of this toxicity.

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, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

18.

Drug-induced pancreatitis: an update.

Author: TrivediChirag D, PitchumoniC S

Drug-induced pancreatitis

Drug-induced pancreatitis (DIP) is a significant and often overlooked adverse drug reaction. A list of medications associated with pancreatitis is provided, with classification based on the strength of evidence.

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.

Language : English

19.

Optimal suppression of HIV replication by low-dose hydroxyurea through the combination of antiviral and cytostatic ('virostatic') mechanisms.

Author: LoriFranco, FoliAndrea, GroffAntonella, LovaLuca, WhitmanLucia, BakareNyasha, PollardRichard B, LisziewiczJulianna

Immune activation limitation
Viral load suppression
Pancreatic toxicity

Hydroxyurea and didanosine are drugs used to treat HIV/AIDS. This study discusses the virostatic effects of these drugs and the potential for pancreatic toxicity.

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

20.

Lowering the dose of hydroxyurea minimizes toxicity and maximizes anti-HIV potency.

Author: LoriFranco, PollardR B, WhitmanL, BakareN, BlickG, ShalitP, FoliA, PetersonD, TennenbergA, SchraderS, RashbaumB, FarthingC, HermanD, NorrisD, GreigerP, FrankI, GroffA, LovaL, AsmuthD, LisziewiczJ

HIV viral load reduction
Improved CD4 count
Toxicity

This study optimized hydroxyurea dosage for HIV-infected patients, minimizing toxicity while maximizing antiviral efficacy. The optimal dose of 600 mg daily was associated with fewer adverse events and better antiviral efficacy compared to higher doses.

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.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

21.

Paradoxical CD4+ T-cell decline in HIV-infected patients with complete virus suppression taking tenofovir and didanosine.

Author: BarriosAna, RendónAna, NegredoEugenia, BarreiroPablo, Garcia-BenayasTeresa, LabargaPablo, SantosJesús, DomingoPere, Sánchez-CondeMatilde, MaidaIvana, Martín-CarboneroLuz, NúñezMarina, BlancoFrancisco, ClotetBonaventura, SambeatMaria Antonia, GilPaloma, Gonzalez-LahozJuan, CooperDavid, SorianoVincent

HIV treatment
Hyperglycemia
Pancreatitis

Tenofovir (TDF) and didanosine (ddI) are potent antiretroviral drugs, but their combination has been questioned due to pharmacokinetic interactions and potential side effects, including pancreatitis and hyperglycemia.

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.
Controlled Clinical TrialA clinical trial that evaluates the effectiveness of a treatment by comparing a group that receives the intervention with a group that receives a placebo or standard treatment.
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.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

23.

Antiretrovirals, Part II: focus on non-protease inhibitor antiretrovirals (NRTIs, NNRTIs, and fusion inhibitors).

Author: ZaporMichael J, CozzaKelly L, WynnGary H, WortmannGlenn W, ArmstrongScott C

Antiretroviral therapy
Drug interactions
Side effects
Toxicities

This review summarizes non-protease inhibitor antiretroviral drugs, including nucleoside and nucleotide analogue reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and cell membrane fusion inhibitors. It explains how these drugs work, their side effects, toxicities, and drug interactions.

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

24.

The treatment of chronic hepatitis B.

Author: VoiosuR

Disease progression prevention
HBeAg seroconversion
Quality of life improvement
Low efficacy
Side effects

Treatment for chronic hepatitis B is recommended in cases with significant biological and histological activity, with interferon and nucleoside analogues being the most commonly used drugs.

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

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