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Antimicrobials during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Stavudine is a nucleoside analog reverse transcriptase inhibitor used to treat HIV infection. Among 811 first trimester pregnancies exposed to stavudine, the frequency of birth defects in infants was not increased (Antiretroviral Registry, 2018).
An overview of ProTide technology and its implications to drug discovery
Published in Expert Opinion on Drug Discovery, 2021
Michaela Serpi, Fabrizio Pertusati
The collaboration between McGuigan’s and Balzarini’s laboratories continued along the years and it was of crucial importance for the development of the ProTide technology. The AZT studies were followed by the successful application of the ProTide technology to many more antiviral NAs. Representative examples are 2′,3′-didehydro-2′,3′-dideoxythymidine (d4T, Stavudine) [40–42], 2ʹ,3ʹ-dideoxyadenosine and 2ʹ,3ʹ-didehydro-2ʹ,3ʹ-dideoxyadenosine [43], 2ʹ,3ʹdideoxyadenosine-3ʹ-fluoroadenosine [44], 2ʹ,3ʹ-dideoxydrouridine and 2ʹ,3ʹ-didehydro-2ʹ3’dideoxyuridine [45] and also to the carbocyclic nucleoside Abacavir (ABC, Ziagen) [46], carbocyclic adenosine derivatives [47] and 2ʹ,3ʹ-dideoxy-2ʹ3’-didehydro-7-deazaadenosine [48], to treat different viral infections. A particular case is Stampidine, the stavudine 4-bromophenyloxy L-alanine methyl ester phosphoramidate, developed as anti-HIV agent to overcome the dependence of stavudine from intracellular nucleoside kinase-mediated activation to the nucleoside 5ʹ-monophosphate. Despite the encouraging data from phase I study of Stampidine [49], in development by the Parker Hughes Institute, no further progression of this agent in clinical trials has been reported.
The crosstalk between antiretrovirals pharmacology and HIV drug resistance
Published in Expert Review of Clinical Pharmacology, 2020
Andrea Giacomelli, Laura Pezzati, Stefano Rusconi
The next step of ART development was the dual therapy with NRTIs. Unfortunately, despite an advantage when compared to monotherapy in terms of viral potency (approximately 1.5–2.2 vs 1 log reduction of HIV viremia, respectively) and durability of progression-free survival the benefit was short in time [205,206]. In particular, didanosine plus stavudine demonstrated to be superior after 6 months of treatment in naive patients when compared to ZDV plus 3TC (median −2.23 log copies/mL vs −1.28 log copies/mL, respectively) [207]. Nevertheless, at 12 months the virological efficacy of stavudine plus 3TC was comparable to ZDV plus 3TC [30]. The major drawback of combining two drugs with the same molecular target is the development of cross resistance reducing the efficacy of both components of the regimen [208–210]. This problem was not overcome by the use of a combination of triple NRTIs treatments both in naïve and treatment experienced patients [211,212]. In particular, in a simplification trial conducted by Opravil et al. where ZDV plus 3TC plus ABC was compared to maintain the current PI bases regimen a previous ZDV monotherapy or a dual NRTIs therapy, a proxy of archived drug resistance, resulted significantly associated to a subsequent virological failure [212].
Moving forward with treatment options for HIV-infected children
Published in Expert Opinion on Pharmacotherapy, 2018
Jean-Christophe Beghin, Jean Cyr Yombi, Jean Ruelle, Dimitri Van der Linden
Since 2010, stavudine (d4T) is no longer recommended by the WHO because of its known long-term toxicity (Table 3), and AZT is not recommended in regions with risk of anemia such as malaria-endemic settings [7].