A Pilot Study of Nevirapine, Indinavir, and Lamivudine among Patients with Advanced Human Immunodeficiency Virus Disease Who Have Had Failure of Combination Nucleoside Therapy

Abstract

The effects of nevirapine, indinavir, and lamivudine in combination were studied among 22 human immunodeficiency virus (HIV)-infected patients with CD4 cell counts < or =50/mm3, whose options for antiretroviral therapy were limited by clinical or laboratory failure or toxicity with previous regimens. Median plasma HIV RNA was 5.16 log10 copies/mL at baseline, decreasing by a median of 3.12 log10 copies/mL at 24 weeks. Median baseline CD4 cell count was 30/mm3, increasing by a median of 95/mm3 at week 24. Adverse reactions led to drug discontinuation in 4 cases. Steady-state pharmacokinetic analysis in 17 patients was consistent with an interaction between nevirapine and indinavir. Nevirapine plasma levels were within the expected range, while indinavir levels were lower than expected. Despite this interaction, the combination of nevirapine, indinavir, and lamivudine was safe and well-tolerated and had substantial antiviral and immunologic effects lasting for the 24-week study.

Pharmacologic Characteristics of Indinavir, Didanosine, and Stavudine in Human Immunodeficiency Virus-Infected Children Receiving Combination Therapy

“…The observation of a relationship between indinavir trough concentration and antiviral effect has been reported by other investigators (1,6,14). For example, in 23 protease inhibitornaïve adults that received an indinavir-containing antiretroviral regimen, those that had suppression of plasma HIV RNA to undetectable levels had higher trough indinavir concentrations than did those with plasma HIV RNA that remained detectable (1).…”

Indinavir, Efavirenz, and Abacavir Pharmacokinetics in Human Immunodeficiency Virus-Infected Subjects

“…The selection of indinavir q12h and q8h dosing regimens to achieve similar AUC 24 s precludes us from drawing conclusions concerning the relationship between the indinavir AUC 24 and the fractional change in the viral load. The indinavir AUC 24 had a very small negative relationship with the fractional change in the viral load, which conflicts with the findings of previous trials, which showed that exposure parameters such as AUC and C min are significant predictors of antiviral activity (8,10,13,21,22; Burger et al, 12th World AIDS Conf., abstr. 42275, 1998).…”

Pharmacokinetics of the Protease Inhibitor Indinavir in Human Immunodeficiency Virus Type 1-Infected Children

“…In adults there are a number of observations showing that the concentration of indinavir in plasma is related to the antiviral response (2,6,15). Therefore, instead of using a fixed dose regimen for each child, it seems logical to monitor the levels of indinavir in plasma shortly after the start of an indinavir-containing regimen and adjust the indinavir dose if necessary.…”