A synthetic peptidemimetic substrate of the human immunodeficiency virus 1 (HIV-1) protease with a nonhydrolyzable pseudodipeptidyl insert at the protease cleavage site was prepared. The peptide U-81749 inhibited recombinant HIV-1 protease in vitro (inhibition constant Ki of 70 nanomolar) and HIV-1 replication in human peripheral blood lymphocytes (inhibitory concentration IC50 of 0.1 to 1 micromolar). Moreover, 10 micromolar concentrations of U-81749 significantly inhibited proteolysis of the HIV-1 gag polyprotein (p55) to the mature viral structural proteins p24 and p17 in cells infected with a recombinant vaccinia virus expressing the HIV-1 gag-pol genes. The HIV-1 like particles released from inhibitor-treated cells contained almost exclusively p55 and other gag precursors, but not p24. Incubation of HIV-like particles recovered from drug-treated cultures in drug-free medium indicated that inhibition of p55 proteolysis was at least partially reversible, suggesting that U-81749 was present within the particles.

To assess the relationship between mean efavirenz (EFV) plasma concentration and clinical effect during the first 48 weeks of combination antiretroviral therapy (cART), the baseline CD4 cell count was recorded and plasma EFV concentration and CD4 cell count were measured every 12 weeks. HIV-RNA viral load was determined in the 48th week of cART. In total, 42 subjects were recruited and grouped according to their mean concentration of EFV during the study period: groups A, B and C with EFV concentrations (mean) <2 mg/L (1.8 mg/L), 2-4 mg/L (2.9 mg/L) and >4 mg/L (5.5 mg/L), respectively. The CD4 cell counts in group C increased more quickly than in groups B and A, although this was not statistically significant (211 ± 176/μL versus 151 ± 145/μL and 172 ± 105/μL, respectively; P = 0.799). Groups B and C had higher rates of HIV viral load suppression than group A (P = 0.017). For treatment-naïve Chinese HIV-infected patients, EFV plasma concentrations above 2 mg/L appear to suppress HIV replication more effectively than concentrations below 2 mg/L.