Drug Combinations and Effect Parameters of Zidovudine, Stavudine, and Nevirapine in Standardized Drug-Sensitive and Resistant HIV Type 1 Strains*

Zhu, Qing-Yu; Scarborough, Alex; Polsky, Bruce; Chou, Ting‐Chao

doi:10.1089/aid.1996.12.507

Cited by 26 publications

(17 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Second, we have determined that our results are in agreement with those that have been published previously. For example, with the combination of efavirenz and AZT-TP, we have obtained results similar to those obtained by Carroll et al (3) (Table 2); and we found that the combination of AZT and d4T acted additively in the HIV-1 RT enzyme assay and antagonistically in the virus replication assay (data not shown), in agreement with the results of Hoggard et al (13) and Zhu et al (28). Finally, we tested efavirenz in combination with itself and found that it acted, as expected, additively to inhibit both HIV-1 RT function in the enzyme assay and HIV-1 replication in the yield reduction assay (data not shown).…”

Section: Discussionsupporting

confidence: 92%

“…The best example is the combination of AZT and d4T. Although there is some disagreement in the literature whether this combination acts additively or antagonistically in an in vitro cell-based system to inhibit HIV-1 replication (13,20,28), this combination has been shown to interact antagonistically with the cellular thymidine kinase (13). The different results seen in the two HIV-1 replication systems are believed to be due more to differences in the concentrations and the ratios of the compounds tested than to a difference in the cell types or virus strains used (12; Merrill et al, reply).…”

Section: Discussionmentioning

confidence: 99%

“…For example, data from in vitro enzyme-and cell-based systems have led to the prediction that the combination of AZT and stavudine (d4T) may be less efficacious than either compound alone due to the antagonistic effect that the combination has on the cellular thymidine kinase (13,20,28). Recently, this was found to be true in the clinical setting, in which HIV-1-infected patients responded better to monotherapy with d4T than to combination therapy with d4T and AZT (11).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Potency of Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) Used in Combination with Other Human Immunodeficiency Virus NNRTIs, NRTIs, or Protease Inhibitors

King

Klabe

Reid

et al. 2002

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Potency of Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) Used in Combination with Other Human Immunodeficiency Virus NNRTIs, NRTIs, or Protease Inhibitors

King

Klabe

Reid

et al. 2002

Antimicrob Agents Chemother

View full text Add to dashboard Cite

“…The d4T-AZT-RBV combination was tested as an antagonism control, since previous reports have shown RBV-d4T to be strongly antagonistic (25,26), RBV-AZT to be strongly antagonistic (25), and d4T-AZT to be additive to antagonistic (27,28). The triple combination d4T-AZT-RBV showed strong antagonism, with a mean CI value of Ͼ5.9.…”

Section: Resultsmentioning

confidence: 99%

The Combined Anti-HIV-1 Activities of Emtricitabine and Tenofovir plus the Integrase Inhibitor Elvitegravir or Raltegravir Show High Levels of SynergyIn Vitro

Kulkarni

Hluhanich

McColl

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Highly active antiretroviral therapy (HAART) is the current standard of care for HIV infection and involves treatment with a combination of three or more antiretroviral agents. Generally, these are combinations of two or more drug classes which target different steps of the HIV-1 replication cycle. The most extensively studied anti-HIV-1 drug combinations are those of nucleoside/nucleotide reverse transcriptase (RT) inhibitors (NRTIs) and nonnucleoside RT inhibitors (NNRTIs). NRTIs are competitive inhibitors of HIV-1 RT that cause chain termination of viral DNA polymerization and form the two-drug backbone of most regimens. The third agents are chosen from the different drug classes, consisting of NNRTIs (noncompetitive inhibitors of HIV-1 RT), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs). The first single-tablet regimen containing an INSTI was recently approved and consists of the two NRTIs emtricitabine (FTC) and tenofovir (TFV) disoproxil fumarate (TDF), an oral prodrug of TFV; the INSTI elvitegravir (EVG); and the pharmacoenhancer cobicistat (COBI), which increases EVG concentrations (1).Combinations of antiviral inhibitors can directly affect the antiviral potency of their counterparts in an additive, antagonistic, or synergistic manner. Determination of the in vitro antiviral interactions between inhibitors used together in patients is an important component of the drug development process. Combinations that show antagonism should be avoided, and combinations that show synergy may have added benefit in vivo. There have been a number of studies showing that combinations of NRTIs plus NNRTIs inhibit HIV-1 infection more efficiently than the additive effect expected for the individual drugs studied alone, thus demonstrating synergy in vitro (2-9). For example, combinations of efavirenz (EFV)-TFV, EFV-FTC, rilpivirine (RPV)-TFV, and RPV-FTC have shown moderate to strong antiviral synergy against HIV-1 in cell culture (3,10). Studies have also shown that some combinations within a drug class, such as two or more NRTIs, can act synergistically in vitro (11)(12)(13)(14)(15)(16)(17). In-depth studies have been performed on the combination of FTC and TFV, and these two drugs show synergy (by median-effect analysis, combination index range of 0.52 to 0.56) to strong synergy (by MacSynergy analysis, synergy volumes of 153 to 181 nM 2 %) against HIV-1 in cell culture (3, 10). This has been partially explained by a positive metabolic interaction between FTC and TFV that leads to higher levels of phosphorylation to the active metabolites when dosed in combination and more efficient trapping of TFV in a dead-end chainterminated complex (3, 10, 17). Combinations of NRTIs or NNRTIs with INSTIs have also shown additive to synergistic effects in vitro (18,19). As combination therapies are the standard of care in HIV treatment, it is important to understand how newer inhibitors in different classes work in combination with existing therapies. This study evaluates the in vitro anti-HIV activity ...

show abstract

“…They have synergistic activity with nucleoside reverse transcriptase inhibitors (NRTIs) (7,9,35), high potency that is comparable to that of protease inhibitors (PIs) (27,29,30), proven durability (K. Tashima, S. Staszewski, M. Nelson, A. Rachlis, D. Skiest, R. Stryker, L. Bessen, V. Wirtz, S. Overfield, and D. Sahner, Abstr. XV Int.…”

mentioning

confidence: 99%

TMC125 Displays a High Genetic Barrier to the Development of Resistance: Evidence from In Vitro Selection Experiments

Vingerhoets¹,

Azijn²,

Fransen³

et al. 2005

J Virol

229

181

View full text Add to dashboard Cite

show abstract

Drug Combinations and Effect Parameters of Zidovudine, Stavudine, and Nevirapine in Standardized Drug-Sensitive and Resistant HIV Type 1 Strains*

Cited by 26 publications

References 38 publications

Potency of Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) Used in Combination with Other Human Immunodeficiency Virus NNRTIs, NRTIs, or Protease Inhibitors

Potency of Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) Used in Combination with Other Human Immunodeficiency Virus NNRTIs, NRTIs, or Protease Inhibitors

The Combined Anti-HIV-1 Activities of Emtricitabine and Tenofovir plus the Integrase Inhibitor Elvitegravir or Raltegravir Show High Levels of SynergyIn Vitro

TMC125 Displays a High Genetic Barrier to the Development of Resistance: Evidence from In Vitro Selection Experiments

Contact Info

Product

Resources

About