Effects of delavirdine: A Synthesis of Findings from 30 Studies

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Original Abstract of the Article

Major Research Findings

Delavirdine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that has been shown to be effective in treating HIV-1 infection. 1 , 24 , 17 , 30 , 26 , 9 , 25 , 8 , 23 , , 27 , 16 , 11 , 22 , 4 , 15 , 3 . These studies have shown that delavirdine can suppress the replication of HIV-1. Delavirdine has also been shown to be effective in combination therapy with other anti-HIV drugs. 29 , 24 . Furthermore, delavirdine inhibits the replication of HIV-1 by binding to the active site of HIV-1 reverse transcriptase and blocking its function. 19 , 28 . However, it is known that delavirdine can cause the emergence of resistant viruses. 18 , 28 . Additionally, delavirdine may cause gastrointestinal side effects. 1 . Furthermore, delavirdine can interact with other drugs. 26 , 12 , 5 .

Benefits and Risks

Benefit Summary

Delavirdine is effective in suppressing the replication of HIV-1, and is also effective in combination therapy with other anti-HIV drugs. Additionally, delavirdine inhibits the replication of HIV-1 by binding to the active site of HIV-1 reverse transcriptase and blocking its function. These effects can help improve the condition of HIV-1 infected patients and extend their lifespan.

Risk Summary

Delavirdine can cause the emergence of resistant viruses. Additionally, delavirdine may cause gastrointestinal side effects and can interact with other drugs.

Comparison Between Studies

Commonalities Between Studies

Many studies have shown that delavirdine is effective in suppressing the replication of HIV-1. Delavirdine has also been shown to be effective in combination therapy with other anti-HIV drugs.

Differences Between Studies

There are different results reported by different studies regarding the effectiveness and safety of delavirdine. For example, 1 reported gastrointestinal side effects with delavirdine, but this was not reported in other studies. This may be due to differences in the study population and research methods. Additionally, different studies have reported different rates of resistant virus emergence with delavirdine. This may be due to differences in the duration of delavirdine administration, dosage, and patient background. Furthermore, different studies have reported different results regarding the interaction of delavirdine with other drugs. This may be due to differences in the combination of delavirdine with other drugs and patient background.

Consistency and Contradictions of Results

There are different results reported by different studies regarding the effectiveness and safety of delavirdine. This may be due to differences in the study population and research methods. However, many studies have shown that delavirdine is effective in suppressing the replication of HIV-1. Delavirdine has also been shown to be effective in combination therapy with other anti-HIV drugs. These results suggest that delavirdine may play an important role in the treatment of HIV-1 infection.

Noteworthy Points for Real-World Applications

Delavirdine may play an important role in the treatment of HIV-1 infection, but caution should be taken regarding the emergence of resistant viruses, the risk of side effects, and the possibility of interactions with other drugs. Therefore, it is important to follow the doctor's instructions and undergo regular checkups when using delavirdine.

Limitations of Current Research

The effectiveness and safety of delavirdine have not yet been fully elucidated. Therefore, further research is needed. In particular, more detailed research is needed on the long-term effects and safety of delavirdine.

Future Research Directions

More detailed research is needed on the long-term effects and safety of delavirdine. Additionally, further research is needed on the interaction of delavirdine with other drugs. Furthermore, research is needed on ways to prevent the emergence of delavirdine-resistant viruses.

Conclusion

Delavirdine may play an important role in the treatment of HIV-1 infection. However, caution should be taken regarding the emergence of resistant viruses, the risk of side effects, and the possibility of interactions with other drugs. Therefore, it is important to follow the doctor's instructions and undergo regular checkups when using delavirdine. Further research is expected to clarify the effectiveness and safety of delavirdine.

Literature analysis of 30 papers
Positive Content
27
Neutral Content
3
Negative Content
0
Article Type
1
0
0
7
30
1.

Efficacy and safety of delavirdine mesylate with zidovudine and didanosine compared with two-drug combinations of these agents in persons with HIV disease with CD4 counts of 100 to 500 cells/mm3 (ACTG 261). ACTG 261 Team.

Author: FriedlandG H, PollardR, GriffithB, HughesM, MorseG, BassettR, FreimuthW, DemeterL, ConnickE, NevinT, HirschM, FischlM

HIV-1 treatment
Gastrointestinal side effects
Rash

Delavirdine + zidovudine + didanosine was safe and showed modest antiviral activity and CD4 cell count benefit compared with two-drug regimens in patients with HIV-1 infection. Gastrointestinal side effects and rash were reported.

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.
Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number 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.
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

2.

Overall benefit of antiretroviral treatment on the risk of fracture in HIV: nested case-control analysis in a health-insured population.

Author: MundyLinda M, YoukAda O, McComseyGrace A, BowlinSteve J

Fracture reduction

Antiretroviral therapy is associated with a reduced risk of fracture in persons with HIV infection. However, specific drug-specific exposure-response relationships for fracture require 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

3.

Current insights and molecular docking studies of HIV-1 reverse transcriptase inhibitors.

Author: SinghAnkit Kumar, KumarAdarsh, AroraSahil, KumarRaj, VermaAmita, KhalilullahHabibullah, JaremkoMariusz, EmwasAbdul-Hamid, KumarPradeep

HIV drug targets
NRTI and NNRTI efficacy
HIV drug resistance
HIV drug side effects

This review provides an overview of HIV-1 structure, replication cycle, and drug targets. It focuses on nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), including their binding sites, mechanisms of action, FDA-approved drugs, drugs in clinical trials, resistance, adverse effects, molecular docking studies, and highly active antiretroviral therapy (HAART).

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

4.

Challenges and approaches in the discovery of human immunodeficiency virus type-1 non-nucleoside reverse transcriptase inhibitors.

Author: BattiniLeandro, BolliniMariela

HIV-1 treatment

This review covers the development of different classes of NNRTIs over the last two decades, providing an overview of traditional medicinal chemistry strategies for structural modification.

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.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

5.

Pharmacokinetic drug interactions with non-nucleoside reverse transcriptase inhibitors.

Author: MaQing, OkusanyaOlanrewaju O, SmithPatrick F, DicenzoRobert, SlishJudianne C, CatanzaroLinda M, ForrestAlan, MorseGene D

HIV treatment
Drug interactions

This review provides an updated summary of pharmacokinetic interactions with non-nucleoside reverse transcriptase inhibitors (NNRTIs) used in HIV Type 1 treatment. NNRTIs are metabolized by the cytochrome P450 (CYP) system, making them prone to significant drug interactions with other antiretrovirals and concurrent medications.

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.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

8.

A novel molecular mechanism of dual resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors.

Author: NikolenkoGalina N, Delviks-FrankenberryKrista A, PathakVinay K

HIV suppression
Drug resistance
HIV

Mutations in the connection subdomain (CN) and RNase H domain of HIV-1 reverse transcriptase (RT) can confer dual resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs). This study found that these mutations reduce RNase H cleavage, which may allow more time for NNRTIs to dissociate from RT, resulting in resistance.

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

10.

Effect of buprenorphine and antiretroviral agents on the QT interval in opioid-dependent patients.

Author: BakerJennifer R, BestAl M, PadePatricia A, McCance-KatzElinore F

No QT prolongation
Cardiac arrhythmias
QT prolongation

While methadone and levacetylmethadol have been linked to cardiac arrhythmias, buprenorphine, a new drug for opioid dependence treatment, has not been reported to cause QT interval prolongation.

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.

Language : English

11.

Differential activation of human constitutive androstane receptor and its SV23 and SV24 splice variants by rilpivirine and etravirine.

Author: SharmaDevinder, LauAik Jiang, ShermanMatthew A, ChangThomas K H

This study investigated the effects of second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) on the activity of the constitutive androstane receptor (CAR). Rilpivirine and etravirine were found to be less potent inhibitors of CAR activity than first-generation NNRTIs (efavirenz, nevirapine, and delavirdine).

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

14.

Phenotypic susceptibility to nonnucleoside inhibitors of virion-associated reverse transcriptase from different HIV types and groups.

Author: TuaillonEdouard, GueudinMarie, LeméeVéronique, GueitIsabelle, RoquesPierre, CorriganGary E, PlantierJean-Christophe, SimonFrançois, BraunJoséphine

Assess HIV susceptibility

The goal of this study was to evaluate a new assay to assess the susceptibility of HIV to nonnucleoside RT inhibitors (NNRTIs). The study compared the new assay with a standard assay, and also examined the susceptibility of HIV-2 to NNRTIs.

Evaluation StudyResearch that systematically evaluates the effectiveness of a particular program or policy. It measures its outcomes and provides important information for future decision-making.
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.

Therapeutic Potential of Indole Derivatives as Anti-HIV Agents: A Mini-review.

Author: ChenQingtai, WuChongchong, ZhuJinjin, LiEnzhong, XuZhi

Indole anti-HIV drugs
Anti-HIV drug side effects
HIV drug resistance

This review focuses on the recent advancement in indole derivatives with anti-HIV potential. The review covers articles published between 2010 and 2020, discussing the chemical structures, structure-activity relationship, and mechanisms of action of indole derivatives as inhibitors of HIV 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.

Language : English

16.

Design, synthesis and anti-HIV evaluation of novel diarylnicotinamide derivatives (DANAs) targeting the entrance channel of the NNRTI binding pocket through structure-guided molecular hybridization.

Author: LiuZhaoqiang, ChenWenmin, ZhanPeng, De ClercqErik, PannecouqueChristophe, LiuXinyong

HIV-1 inhibition

This study designed and tested a new series of diarylnicotinamide derivatives (DANAs) as potential inhibitors of HIV-1 reverse transcriptase (RT). Several DANAs showed potent activity against wild-type HIV-1 and some were also effective against resistant strains.

Evaluation StudyResearch that systematically evaluates the effectiveness of a particular program or policy. It measures its outcomes and provides important information for future decision-making.
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.

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

19.

Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 Gag-Pol.

Author: FigueiredoAnna, MooreKatie L, MakJohnson, Sluis-CremerNicolas, de BethuneMarie-Pierre, TachedjianGilda

Gag-Pol multimerization target
HIV-1 replication inhibition

Potent NNRTIs like efavirenz, TMC120, and TMC125 inhibit late stages of HIV-1 replication by enhancing Gag-Pol multimerization and premature protease activation. This suggests that regulating Gag-Pol/Gag-Pol interactions is a new target for HIV-1 production inhibition.

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

20.

Modest decreases in NNRTI susceptibility do not influence virological outcome in patients receiving initial NNRTI-containing triple therapy.

Author: HarriganP Richard, HertogsKurt, VerbiestWerner, LarderBrendan, YipBenita, BrummeZabrina L, AlexanderChristopher, TilleyJessica, O'ShaughnessyMichael V, MontanerJulio S G

NNRTI resistance

This study investigated the prevalence of decreased susceptibility to non-nucleoside reverse transcriptase inhibitors (NNRTIs) in individuals starting antiretroviral therapy for the first time. The study found that while 30% of participants had a four- to ten-fold decrease in susceptibility to NNRTIs, this was not associated with virological outcome. However, a baseline plasma viral load greater than 400 copies per mL was strongly associated with poor virological response to NNRTI-based therapy.

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.

Language : English

21.

The Journey of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) from Lab to Clinic.

Author: NamasivayamVigneshwaran, VanangamudiMurugesan, KramerVictor G, KurupSonali, ZhanPeng, LiuXinyong, KongstedJacob, ByrareddySiddappa N

HIV treatment
Drug resistance

This paper reviews the six NNRTIs approved for HIV-1 treatment, highlighting the lessons learned from their development to clinical studies.

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

23.

Synthesis and biological evaluation of novel 5-alkyl-2-arylthio-6-((3,4-dihydroquinolin-1(2H)-yl)methyl)pyrimidin-4(3H)-ones as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.

Author: ZhangJing, ZhanPeng, WuJingde, LiZhenyu, JiangYan, GeWeiying, PannecouqueChristophe, De ClercqErik, LiuXinyong

Treat HIV-1

This study synthesized and evaluated a series of novel S-DABO analogues as inhibitors of human immunodeficiency virus type-1 (HIV-1). Compounds 6c1, 6c6, and 6b1 showed potent HIV-1 inhibitory activity, similar to or better than nevirapine and delavirdine. These compounds were not active against HIV-2 replication.

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

26.

Modulation of human BCRP (ABCG2) activity by anti-HIV drugs.

Author: WeissJohanna, RoseJohanna, StorchCaroline Henrike, Ketabi-KiyanvashNahal, SauerAlexandra, HaefeliWalter Emil, EfferthThomas

Antiretroviral efficacy
HAART effectiveness
Drug interactions
Viral resistance

This study investigated the influence of anti-HIV drugs on BCRP activity in vitro.

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

Language : English

27.

Fused heterocyclic compounds bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 1: design, synthesis and biological evaluation of novel 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives.

Author: TianYe, DuDeping, RaiDiwakar, WangLiu, LiuHuiqing, ZhanPeng, De ClercqErik, PannecouqueChristophe, LiuXinyong

Anti-HIV activity
High selectivity index

A novel class of 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives displayed excellent anti-HIV activity. Compound 5a was the most promising with an EC50 of 0.07μM against wild-type HIV-1 and a high selectivity index.

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

28.

[Establishment of pharmacological evaluation system for non-nucleoside reverse-transcriptase inhibitors resistant HIV-1].

Author: CaoYing-li, LiShao-xiong, ChenHong, GuoYing

This study established a series of cell-based models that can be used to evaluate the efficacy of non-nucleoside reverse-transcriptase inhibitors (NNRTIs) against HIV-1 strains resistant to commonly used NNRTIs. The models are safe to use in a BSL-2 laboratory and can be used for screening new NNRTIs.

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 : Chinese

29.

In vitro antiviral activity of the novel, tyrosyl-based human immunodeficiency virus (HIV) type 1 protease inhibitor brecanavir (GW640385) in combination with other antiretrovirals and against a panel of protease inhibitor-resistant HIV.

Author: HazenRichard, HarveyRobert, FerrisRobert, CraigCharles, YatesPhillip, GriffinPhilip, MillerJohn, KaldorIstvan, RayJohn, SamanoVincente, FurfineEric, SpaltensteinAndrew, HaleMichael, TungRoger, St ClairMarty, HanlonMary, BooneLawrence

Anti-HIV activity

Brecanavir is a novel HIV-1 protease inhibitor that has been shown to be highly effective in vitro. It is more potent and broadly active than other PIs tested in vitro.

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

Language : English

30.

Emerging anti-HIV drugs.

Author: De ClercqErik

HIV treatment

This article provides an overview of anti-HIV drugs currently licensed for clinical use and those under development. It highlights the different categories of drugs, their mechanisms of action, and the challenges in developing effective combination therapies.

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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