9 research outputs found
A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less
Background: The efficacy and safety of adding a protease inhibitor to two nucleoside analogues to
treat human immunodeficiency virus type 1 (HIV-1)
infection are not clear. We compared treatment with
the protease inhibitor indinavir in addition to zidovudine
and lamivudine with treatment with the two nucleosides
alone in HIV-infected adults previously treated
with zidovudine.
Methods: A total of 1156 patients not previously
treated with lamivudine or protease inhibitors were
stratified according to CD4 cell count (50 or fewer vs.
51 to 200 cells per cubic millimeter) and randomly
assigned to one of two daily regimens: 600 mg of zidovudine
and 300 mg of lamivudine, or that regimen
with 2400 mg of indinavir. Stavudine could be substituted
for zidovudine. The primary end point was
the time to the development of the acquired immunodeficiency
syndrome (AIDS) or death.
Results: The proportion of patients whose disease
progressed to AIDS or death was lower with indinavir,
zidovudine (or stavudine), and lamivudine (6 percent)
than with zidovudine (or stavudine) and lamivudine
alone (11 percent; estimated hazard ratio,
0.50; 95 percent confidence interval, 0.33 to 0.76;
P�0.001). Mortality in the two groups was 1.4 percent
and 3.1 percent, respectively (estimated hazard
ratio, 0.43; 95 percent confidence interval, 0.19 to
0.99; P=0.04). The effects of treatment were similar
in both CD4 cell strata. The responses of CD4 cells
and plasma HIV-1 RNA paralleled the clinical results.
Conclusions: Treatment with indinavir, zidovudine,
and lamivudine as compared with zidovudine and
lamivudine alone significantly slows the progression
of HIV-1 disease in patients with 200 CD4 cells or
fewer per cubic millimeter and prior exposure to zidovudine.
(N Engl J Med 1997;337:725-33.
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Effect of Rifampin, a Potent Inducer of Drug-Metabolizing Enzymes, on the Pharmacokinetics of Raltegravir▿
Raltegravir is a human immunodeficiency virus type 1 integrase strand transfer inhibitor that is metabolized by glucuronidation via UGT1A1 and may be affected by inducers of UGT1A1, such as rifampin (rifampicin). Two pharmacokinetic studies were performed in healthy subjects: study 1 examined the effect of administration of 600-mg rifampin once daily on the pharmacokinetics of a single dose of 400-mg raltegravir, and study 2 examined the effect of 600-mg rifampin once daily on the pharmacokinetics of 800-mg raltegravir twice daily compared to 400-mg raltegravir twice daily without rifampin. Raltegravir coadministered with rifampin resulted in lower plasma raltegravir concentrations: in study 1, the geometric mean ratios (GMRs) and 90% confidence intervals (90% CIs) for the plasma raltegravir concentration determined 12 h postdose (C12), area under the concentration-time curve from 0 h to ∞ (AUC0-∞), and maximum concentration of drug in plasma (Cmax) (400-mg raltegravir plus rifampin/400-mg raltegravir) were 0.39 (0.30, 0.51), 0.60 (0.39, 0.91), and 0.62 (0.37, 1.04), respectively. In study 2, the GMRs and 90% CIs for raltegravir C12, AUC0-12, and Cmax (800-mg raltegravir plus rifampin/400-mg raltegravir) were 0.47 (0.36, 0.61), 1.27 (0.94, 1.71), and 1.62 (1.12, 2.33), respectively. Doubling the raltegravir dose to 800 mg when coadministered with rifampin therefore compensates for the effect of rifampin on raltegravir exposure (AUC0-12) but does not overcome the effect of rifampin on raltegravir trough concentrations (C12). Coadministration of rifampin and raltegravir is not contraindicated; however, caution should be used, since raltegravir trough concentrations in the presence of rifampin are likely to be at the lower limit of clinical experience
A Controlled Trial of Two Nucleoside Analogues plus Indinavir in Persons with Human Immunodeficiency Virus Infection and CD4 Cell Counts of 200 per Cubic Millimeter or Less
Progress in the field of antiretroviral therapy for human immunodeficiency virus type 1 (HIV-1) infection has brought the end of the zidovudine-monotherapy era,
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an improved understanding of the pathogenesis of HIV-1 disease,
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demonstrations of the prognostic importance of plasma HIV-1 RNA quantification,
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and the availability of increasingly potent therapeutic agents. Much of this progress is linked to the introduction of the HIV-protease inhibitors, drugs that inhibit the processing of Gag and Gag–Pol polyprotein precursors and thus prevent the maturation of virions.
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Trials of HIV-protease inhibitors have shown beneficial effects on CD4 cell counts and plasma HIV-1 . .