Lopinavir/ritonavir: a protease inhibitor for HIV-1 treatment

Generation of Infectious Feline Immunodeficiency Virus (FIV) Encoding FIV/Human Immunodeficiency Virus Chimeric Protease

“…The chimeric FIV/HIV system demonstrated that HIV-1 PR inhibitors with broad-spectrum properties, such as LPV, DRV, and TL-3, can be distinguished using comparative studies of WT and chimeric FIVs, both in vitro and ex vivo. DRV and LPV are new FDA-approved HIV-1 PR inhibitors that are effective against WT HIV-1 and many drug-resistant HIV-1 mutants, and they have high genetic barriers (i.e., they require many mutations for drug resistance to develop) (3,33,53). Conversely, RTV, an older HIV-1 PR inhibitor, was not very potent against the 6s-98S/H PRs; it also displays a lower genetic barrier and is not as effective against many of the common drug-resistant mutants found in HIV-1 PR.…”

Basis of selection of first and second line highly active antiretroviral therapy for hiv/aids on genetic barrier to resistance: a literature review.

“…The decision to use low or high genetic antiretroviral regimens as initial cART in treatment naïve patients is not definitive and is largely governed by availability especially in resource-limited settings. Booster PI-based regimens generally have a high genetic barrier to resistance (1,13,15,16,(18)(19)(20) and are recommended for use but gastrointestinal adverse drug effects precludes their use as first line therapy and is mainly reserved for second line therapy21. Selection of low genetic barrier combinations on the contrary, may result into broad class resistance hence reducing treatment options10, 11.…”

Antiretroviral drug toxicity in relation to pharmacokinetics, metabolic profile and pharmacogenetics

“…Moderate to severe diarrhea, nausea and vomiting as well as severe (grade 3 --4) laboratory abnormalities, such as elevated cholesterol, triglycerides and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are reported in > 2% of patients treated with LPV/RTV [81,82,85,86]. LPV exposure has been suggested to be directly correlated to drug tolerability and therapeutic efficacy: a target trough concentration of 1 mg/l [68] is required to achieve viral suppression and a threshold of 4 mg/l is required when five or fewer LPV baseline resistance mutations are present [87].…”