Effects of stavudine: A Synthesis of Findings from 22 Studies

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Original Abstract of the Article

Major Research Findings

Stavudine, a nucleoside reverse transcriptase inhibitor used to treat HIV, has been shown to have several adverse effects, primarily related to its mitochondrial toxicity. Multiple studies indicate that stavudine can lead to a decrease in mitochondrial DNA (mtDNA) copy number, potentially affecting cellular energy production and contributing to metabolic complications. 5 , 14 , 3 This can result in various problems such as lipodystrophy (abnormal fat distribution), insulin resistance, and bone loss. 5 , 14 , 19 , 3 , 4 In addition to affecting metabolic function, stavudine has also been linked to peripheral neuropathy, a condition affecting nerves that can cause pain, numbness, and weakness. 6 Moreover, studies in animals have demonstrated potential harmful effects of stavudine during pregnancy, impacting the development of liver, pancreas, and kidneys in both the mother and the fetus. 15 , 7 Therefore, these findings highlight the importance of considering the potential risks associated with stavudine use, particularly its long-term consequences, and carefully monitoring patients for any adverse effects.

Benefits and Risks

Benefits Summary

Stavudine, when used as part of a combination antiretroviral therapy, can effectively suppress HIV replication and improve the immune system in HIV-infected individuals. 17 This, in turn, reduces the risk of developing opportunistic infections, which are serious illnesses that often affect people with weakened immune systems. 17

Risks Summary

Stavudine carries several risks associated with its use. Its most significant adverse effect is mitochondrial toxicity, which can lead to various metabolic problems, including lipodystrophy, insulin resistance, and bone loss. 5 , 14 , 3 , 4 Additionally, stavudine can cause peripheral neuropathy, a painful condition affecting nerves in the limbs. 6 The drug can also pose potential risks during pregnancy, potentially affecting the developing fetus. 15 , 7 Therefore, it is crucial to weigh the potential benefits of stavudine treatment against these risks and monitor patients closely for any adverse effects.

Comparison Between Studies

Commonalities Between Studies

Several studies consistently demonstrate that stavudine can have a negative impact on mitochondrial function, leading to a decrease in mtDNA copy number, and potentially resulting in metabolic complications such as lipodystrophy and insulin resistance. 5 , 14 , 3 , 4 Moreover, these studies highlight the effectiveness of stavudine in suppressing HIV replication when used as part of combination therapy and its role in reducing the incidence of opportunistic infections. 17

Differences Between Studies

The extent and frequency of stavudine's side effects can vary depending on the study. For instance, the incidence of peripheral neuropathy associated with stavudine use may differ across studies. 6 Additionally, the interactions between stavudine and other HIV medications can also vary based on the study's specific design and the combination of drugs used. 2

Consistency and Contradictions of Results

The evidence consistently suggests that stavudine can have detrimental effects on mitochondrial function. However, the extent and frequency of side effects can vary across different studies. This variation is likely due to factors such as the study population, dosage of stavudine, and the combination of other antiretroviral medications used in the study.

Implications for Daily Life

Stavudine is an effective treatment option for HIV infection, but it is crucial to understand the potential risks associated with its use. Closely monitoring patients for any side effects and ensuring regular check-ups with healthcare professionals are vital. If patients experience symptoms like abnormal fat distribution, insulin resistance, or bone loss, they should immediately consult with their doctor to discuss potential alternative treatment options.

Limitations of Current Research

Current research on stavudine has limitations. Long-term effects of stavudine are not fully understood, and individual variations in susceptibility to its side effects require further investigation.

Future Research Directions

Future research should focus on understanding the long-term impact of stavudine, investigating individual variations in response to the drug, and exploring potential interactions with other HIV medications. Moreover, the development of alternative HIV treatment options with improved safety profiles and fewer adverse effects is highly desirable.

Conclusion

Stavudine is an effective antiretroviral medication for HIV infection, but it is essential to be aware of its potential risks, primarily related to its mitochondrial toxicity. Close monitoring for adverse effects, regular follow-ups with healthcare providers, and open communication about potential concerns are crucial when using stavudine.

Literature analysis of 22 papers
Positive Content
14
Neutral Content
1
Negative Content
7
Article Type
5
0
0
1
22
1.

A placebo-controlled trial of didanosine plus stavudine, with and without hydroxyurea, for HIV infection. The Swiss HIV Cohort Study.

Author: RutschmannO T, OpravilM, ItenA, MalinverniR, VernazzaP L, BucherH C, BernasconiE, SudreP, LeducD, YerlyS, PerrinL H, HirschelB

Reduced HIV-1 RNA
Lymphopenia

Hydroxyurea improves the antiviral activity of didanosine (ddl) and stavudine (d4T) in HIV-positive patients. However, it also induces lymphopenia, which may limit its overall benefit in increasing CD4 cell counts.

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

2.

A multiple drug interaction study of stavudine with agents for opportunistic infections in human immunodeficiency virus-infected patients.

Author: PiscitelliS C, KellyG, WalkerR E, KovacsJ, FalloonJ, DaveyR T, RajeS, MasurH, PolisM A

Combination regimen
Treat opportunistic infections
Minor side effects

Stavudine exposure was not significantly altered when combined with multiple opportunistic infection medications. The drug is well tolerated and has minimal drug interactions.

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.

Language : English

3.

A Direct Comparison of the Effects of the Antiretroviral Drugs Stavudine, Tenofovir and the Combination Lopinavir/Ritonavir on Bone Metabolism in a Rat Model.

Author: ConradieM M, van de VyverM, AndragE, ConradieM, FerrisW F

Bone loss
Bone marrow adiposity
Metabolic complications

This study compared the effects of Stavudine, Tenofovir, and Lopinavir/ritonavir on bone metabolism and lipodystrophy in rats. Stavudine was found to decrease bone mineral density and strength, while Tenofovir and Lopinavir/ritonavir had less impact. Both Stavudine and Tenofovir caused bone marrow adiposity.

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

4.

Effects of switching from stavudine to raltegravir on subcutaneous adipose tissue in HIV-infected patients with HIV/HAART-associated lipodystrophy syndrome (HALS). A clinical and molecular study.

Author: DomingoPere, GutierrezMaría del Mar, Gallego-EscuredoJosé Miguel, TorresFerran, MateoGracia María, VillarroyaJoan, de los SantosIgnacio, DomingoJoan Carles, VillarroyaFrancesc, Del RioLuis, EstradaVicente, GiraltMarta

HALS treatment
RAL efficacy
Mitochondrial dysfunction

This study assessed the effects of switching from stavudine (d4T) to raltegravir (RAL) on metabolic and fat molecular parameters in patients with HIV-1/HAART-associated lipodystrophy syndrome (HALS). Switching to RAL was associated with an increase in limb fat mass and improvement in markers of adipocyte differentiation and mitochondrial function.

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

5.

The early effects of stavudine compared with tenofovir on adipocyte gene expression, mitochondrial DNA copy number and metabolic parameters in South African HIV-infected patients: a randomized trial.

Author: MenezesC N, DuarteR, DickensC, Dix-PeekT, Van AmsterdamD, JohnM-A, IveP, MaskewM, MacphailP, FoxM P, RaalF, SanneI, CrowtherN J

Mitochondrial toxicity

This study compared the effects of standard- and low-dose stavudine with tenofovir (TDF) on adipocyte mtDNA copy number, gene expression, and metabolic parameters in Black South African HIV-infected 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

6.

Effects of a reduced dose of stavudine on the incidence and severity of peripheral neuropathy in HIV-infected adults in South Africa.

Author: PahujaMeera, GroblerAnneke, GlesbyMarshall J, KarimFarina, ParkerGary, GumedeSizwe, NaidooKogieleum

Peripheral neuropathy

This study compared the incidence and severity of peripheral neuropathy in a retrospective cohort of patients receiving stavudine (d4T), an antiretroviral therapy, at different doses. The study aimed to assess the impact of a WHO-recommended dose reduction from 40 mg to 30 mg on d4T-associated toxicities.

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

7.

[Effects of daily administration of a stavudine/nelfinavir association on the fetuses and placentas of female albino rats].

Author: de CarvalhoGisela Maria Vieira Rodrigues, NakamuraMary Uchiyama, SimõesRicardo Santos, AntonioEliana Maria Restum, WagngnerAdriana, FontesTereza Maria Pereira, Kulay JúniorLuiz

No deleterious effects on concepts
Maternal mortality

A combination of stavudine and nelfinavir was found to have no deleterious effects on pregnant rats. While there was one case of maternal mortality in each experimental group, the treatment did not affect concept weights, implantation, or fetal development.

English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : Portuguese

8.

The genetic toxicity effects of lamivudine and stavudine antiretroviral agents.

Author: GuimarãesNilza Nascimento, de AndradeHeloísa Helena Rodrigues, LehmannMaurício, DihlRafael Rodrigues, CunhaKênya Silva

HIV treatment
Genomic instability
Loss of heterozygosity

Nucleoside reverse transcriptase inhibitors (NRTIs), used to treat HIV infections, may cause genomic instability and loss of heterozygosity.

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

9.

Thymidine analogue resistance suppression by V75I of HIV-1 reverse transcriptase: effects of substituting valine 75 on stavudine excision and discrimination.

Author: MatamorosTania, NevotMaría, MartínezMiguel Angel, Menéndez-AriasLuis

HIV treatment

Val(75) mutations in HIV-1 reverse transcriptase affect drug resistance patterns. V75I antagonizes thymidine analogue resistance mutations, increasing susceptibility to AZT and d4T.

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

10.

Mutagenic and recombinagenic effects of lamivudine and stavudine antiretrovirals in somatic cells of Drosophila melanogaster.

Author: FranchiLeonardo Pereira, PentiadoNádia Helena Garofo Rodrigues, SilvaRenata do Nascimento, GuimarãesNilza Nascimento, JesuinoRosália Santos Amorim, de AndradeHeloísa Helena Rodrigues, LehmannMaurício, CunhaKênya Silva

HIV treatment
Genomic instability

Lamivudine and stavudine, antiretroviral drugs, have high recombinagenic potential, potentially leading to genomic instability.

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

11.

Effects of zidovudine and stavudine on mitochondrial DNA of differentiating 3T3-F442a cells are not associated with imbalanced deoxynucleotide pools.

Author: LynxMatthew D, LaClairDarcy D, McKeeEdward E

Mitochondrial DNA depletion

This study investigated whether zidovudine (AZT) toxicity is related to deoxynucleotide pool alterations. Results suggest that AZT toxicity may not be related to deoxynucleotide pool alterations.

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

12.

Effects of the change from Stavudine to tenofovir in human immunodeficiency virus-infected children treated with highly active antiretroviral therapy: studies on mitochondrial toxicity and thymic function.

Author: RossoRaffaella, NasiMilena, Di BiagioAntonio, RepettoErnestina, DentoneChiara, PintiMarcello, NemesElisa, FerraresiRoberta, MussiniCristina, EspositoRoberto, ViscoliClaudio, CossarizzaAndrea

Reduced mitochondrial toxicity

This study examines the mitochondrial toxicity of antiviral drugs in HIV-positive children. Switching from drugs with significant mitochondrial toxicity to less toxic compounds may benefit HIV-positive patients receiving highly active antiretroviral therapy.

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

14.

Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults.

Author: FleischmanAmy, JohnsenStine, SystromDavid M, HrovatMirko, FarrarChristian T, FronteraWalter, FitchKathleen, ThomasBijoy J, TorrianiMartin, CôtéHélène C F, GrinspoonSteven K

Insulin sensitivity
Mitochondrial dysfunction
Stavudine use
mtDNA reduction

This study investigated the effects of short-term stavudine administration on insulin sensitivity and mitochondrial function in healthy subjects. Stavudine significantly reduced insulin sensitivity and decreased mtDNA levels in muscle, suggesting potential mitochondrial dysfunction.

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.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
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

15.

Effects of chronic stavudine exposure on liver, pancreas and kidneys of pregnant rats and their fetuses: morphological and biochemical aspects.

Author: BarretoRegina Lúcia Braga, SoaresJosé Maria, SimõesRicardo Santos, MacielGustavo Arantes Rosa, SimõesManuel de Jesus, KulayLuiz

Hepatic toxicity
Pancreatic toxicity

High doses of stavudine produced signs of mild to moderate maternal hepatic and pancreatic toxicity in pregnant rats.

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

Language : English

16.

Effects of discontinuing stavudine or protease inhibitor therapy on human immunodeficiency virus-related fat redistribution evaluated by dual-energy x-ray absorptiometry.

Author: TavassoliNeda, BagheriHaleh, SommetAgnes, DelpierreCyrille, Marion-LatardFabrice, MassipPatrice, AquilinaChristian, BonnetEric, ObadiaMartine, LabauEric, MontastrucJean Louis, BernardJacques

Improved lipoatrophy

Long-term withdrawal of stavudine from the antiretroviral therapy regimen may be associated with significant improvement in lipoatrophy in the lower extremities.

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

Language : English

18.

Mitochondrial effects of a 24-week course of pegylated-interferon plus ribavirin in asymptomatic HCV/HIV co-infected patients on long-term treatment with didanosine, stavudine or both.

Author: BallesterosAngel Luis, MiróOscar, LópezSònia, FusterDaniel, VidelaSebastiá, MartínezEva, GarrabouGlòria, SalasAnna, CôtéHélène, TorJordi, Rey-JolyCelestino, PlanasRamon, ClotetBonaventura, TuralCristina

No mitochondrial impact
None specified

Adding ribavirin (RBV) to didanosine (ddI) or stavudine (d4T) therapy in HCV/HIV co-infected patients does not impact mitochondrial function.

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

19.

Effects of zidovudine, stavudine and beta-aminoisobutyric acid on lipid homeostasis in mice: possible role in human fat wasting.

Author: MaisonneuveCaroline, IgoudjilAnissa, BegricheKarima, LettéronPhilippe, GuimontMarie-Christine, BastinJean, LaigneauJean-Pierre, PessayreDominique, FromentyBernard

Lipoatrophy

Stavudine (d4T) and zidovudine (AZT) may contribute to lipoatrophy by increasing fatty acid oxidation in non-adipose tissue, leading to a catabolic effect on body adiposity.

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.

Stavudine effects on rat pregnancy outcome.

Author: BarretoRegina Lúcia Braga, de Jesus SimõesManuel, AmedAbes Mahmed, Soares JúniorJosé Maria, Oliveira-FilhoRicardo Martins, KulayLuiz

Increased resorptions

This study assessed the effects of stavudine during pregnancy in rats. The study found that stavudine had a negative impact on pregnancy outcome, particularly in terms of intrauterine concept survival.

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

Language : English

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