Human immunodeficiency virus early phase

Kootstra NA, Zwart BM, Schuitemaker H. 2000. Diminished human immunodeficiency virus type 1 reverse transcription and nuclear transport in primary macrophages arrested in early G phase of the cell cycle.J. Virol. 74 1712-17... 

Ritonavir (Norvir Abbott) is a drug for treating patients infected with human immunodeficiency virus-1 (HIV-1). In solid state the compound consists exclusively of one kind of monoclinic crystals. As this form, now called form I, was not sufficiently bioavailable by the oral route, a liquid formulation containing dissolved ritonavir in a hydroalcoholic solution was developed. It gave satisfactory results during the development and early manufacturing phases. However, in 1998, 2 years after the launch, a second form (form II) precipitated during shelf life. The new form is thermodynamically more stable and about 50% less water-soluble than form I. Within weeks-days, this new form was produced in all the production lines and Abbott had to stop the production of ritonavir. Finally, after considerable effort and expense, a new formulation of ritonavir was developed. 

Tat is a protein of 86 to 101 amino acids confrolling fhe early phase of the human immunodeficiency virus fype 1 (HlV-1) replicafion cycle [68,69]. Yamamoto et al. [70,71] were the first to develop an aptamer that yielded an efficient binding specificity against Tat, but not for other cellular factors. This novel aptamer RNA demonstrated a 133 limes higher binding affinity than the natural RNA fragment binding to Tat (trans-activation response element... 

---