Combination Nucleoside/Nucleotide Reverse Transcriptase Inhibitors for Treatment of HIV Infection

Abstract

Introduction The combination of two nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) and a third agent from another antiretroviral class is currently recommended for initial antiretroviral therapy. In general, N(t)RTIs remain relevant in subsequent regimens. There are currently six nucleoside reverse transcriptase inhibitors and one nucleotide reverse transcriptase inhibitor drug entities available, and several formulations that include two or more N(t)RTIs in a fixed dose combination. These entities have heterogeneous pharmacological and clinical properties. Accordingly, toxicity, pill burden, dosing frequency, potential drug-drug interaction, pre-existing antiretroviral drug resistance, and co-morbid conditions should be considered when constructing a regimen. This approach is critical in order to optimize virologic efficacy and clinical outcomes. Areas covered In this article, we review N(t)RTI combinations used in the treatment of HIV-infected adults. The pharmacological properties of each N(t)RTI, and the clinical trials which have influenced treatment guidelines are discussed. Expert Opinion It is likely that N(t)RTIs will continue to dominate the global landscape of HIV treatment and prevention, despite emerging interest in N(t)RTI-free combination therapy. Clinical domains where only few alternatives to N(t)RTIs exist include treatment of HIV/HBV co-infection and HIV-2. There is a need for novel N(t)RTIs with enhanced safety and resistance profiles compared to current N(t)RTIs.

Pengaruh Lama Penggunaan Kombinasi ARV (TDF+3TC+EFV) terhadap Jumlah Sel CD4+ Pasien HIV/AIDS

“…5,6 Obat ARV yang digunakan adalah golongan Nucleoside Reverse Trancriptase Inhibitor (NRTI), Non Nucleoside Reverse Trancriptase Inhibitor (NNRTI), dan Protease Inhibitor (PI). 7 Kombinasi obat yang sering digunakan di RSUD Dr. Iskak yaitu Tenofovir+Lamivudin+ Efavirenz (TDF+3TC+EFV) yang berbentuk tablet Fixed Dose Combination (FDC). Dasar pemberian obat tersebut disesuaikan kondisi infeksi HIV/AIDS masing-masing pasien.…”

Enhanced Antiviral Ability by a Combination of Zidovudine and Short Hairpin RNA Targeting Avian Leukosis Virus

“…The genomic structure of ALV is highly similar to that of the human immunodeficiency virus (HIV), whereas both of them rely on reverse transcriptase (RT) for genome replication ( Hurwitz and Leis, 1972 ; Battula and Loeb, 1976 ; Nasioulas et al, 1995 ; Coffin and Fan, 2016 ). RT inhibitors like lamivudine (LAM) and zidovudine (AZT) were designed to inhibit the replication efficiency of retroviruses, and many of them have been proved to be effective in several viruses, especially the HIV ( Durand-Gasselin et al, 2008 ; Akanbi et al, 2012 ; Clark and Hu, 2015 ; Berruti et al, 2021 ). However, the wide application of RT inhibitors has also led to the emergence of many drug-resistant virus strains, which may even cause a more serious epidemic ( Fanning et al, 2003 ; Kantor et al, 2004 ; Bulteel et al, 2014 ; Mulato et al, 2021 ).…”

2′‐Fluoro‐6′‐methylene carbocyclic adenosine and its phosphoramidate prodrug: A novel anti‐HBV agent, active against drug‐resistant HBV mutants

“…As for the drug discovery of viral infections, nucleosides have played a major role since AIDS became an epidemic throughout the world . In search of treating AIDS, a viral enzyme, reverse transcriptase was targeted.…”