Exposure to 3TC of HIV-1 mutant strains containing non-nucleoside reverse transcriptase inhibitor (NNRTI)-specific mutations in their reverse transcriptase (RT) easily selected for double-mutant viruses that had acquired the characteristic 184-Ile mutation in their RT in addition to the NNRTI-specific mutations. Conversely, exposure of 3TC-resistant 184-Val mutant HIV-1 strains to nine differen...

BACKGROUND The HIV-1 nucleoside RT inhibitor (NRTI)-resistance mutation, K65R confers intermediate to high-level resistance to the NRTIs abacavir, didanosine, emtricitabine, lamivudine, and tenofovir; and low-level resistance to stavudine. Several lines of evidence suggest that K65R is more common in HIV-1 subtype C than subtype B viruses. METHODS AND FINDINGS We performed ultra-deep pyrosequ...

BACKGROUND Hypersusceptibility to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) was described in association with reverse-transcriptase (RT) mutations conferring resistance to nucleoside reverse-transcriptase inhibitors (NRTIs). We evaluated the effect of RT mutations associated with hypersusceptibility to NNRTIs on the response to efavirenz-based therapy. METHODS We analyzed an obs...

HIV type-1 (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs) are key drugs of highly active antiretroviral therapy (HAART) in the clinical management of AIDS/HIV infection. NNRTI-based HAART regimes effectively suppress viral reproduction, are not cytotoxic and show favourable pharmacokinetic properties. First-generation NNRTIs suffer the rapid selection of viral variants, hamper...

Bromodomain-containing protein 4 (BRD4) is an intracellular that regulates expression of various cellular functions. This study investigated whether BRD4 inhibition can alter the immunomodulatory and antitumor effects radiation therapy (RT). A murine breast cancer cell line was implanted into BALB/c mice. The dual-tumor model used to evaluate abscopal RT. total 24 Gy delivered inhibitor injecte...

After zidovudine (ZDV), a 3′-azido analogue of thymidine, was found to be an effective antiretroviral drug against HIV [1,2], other nucleoside analogues inhibiting reverse transcriptase (RT) soon followed: didanosine (ddI), zalcitabine (ddC), lamivudine (3TC), stavudine (D4T), and recently abacavir (1592U89) [3–7]. These drugs have demonstrated efficacy in reduction of morbidity and mortality, ...

Theoretical calculations for some structural and electronic properties of the azide moiety in the nucleoside reverse transcriptase (RT) inhibitor 3′-azido-3′deoxythymidine (AZT) are reported. These properties, which include geometrical properties in three dimensional space, Hirshfeld charges, electrostatic potential (MEP), vibrational frequencies, and core and valence ionization spectra, are em...

The nucleoside transport systems in cultured epididymal epithelium were characterized and found to be similar between the proximal (caput and corpus) and distal (cauda) regions of the epididymis. Functional studies revealed that 70% of the total nucleoside uptake was Na(+) dependent, while 30% was Na(+) independent. The Na(+)-independent nucleoside transport was mediated by both the equilibrati...

Polyclonal antibodies were raised against the nitrobenzylthioinosine (NBMPR)-sensitive nucleoside transporter of human erythrocyte membranes. On Western blots of these membranes they labeled the broad "band 4.5" region (average apparent M(r) 55,000), which contains both the nucleoside and glucose transport proteins. However, they did not recognize the glucose transporter when this was prepared ...