Document Detail


Combination therapy with indinavir, ritonavir, and delavirdine and nucleoside reverse transcriptase inhibitors in patients with HIV/AIDS who have failed multiple antiretroviral combinations.
MedLine Citation:
PMID:  11590527     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Ritonavir (RTV) and delavirdine (DLV) are inhibitors of cytochrome P450 (CYP) 3A4, the specific CYP that metabolizes indinavir (IDV). We hypothesized that patients who have failed multiple therapies containing protease inhibitors would still respond to IDV if high plasma concentrations were achieved. We retrospectively examined the antiviral efficacy of the combination of RTV, DLV, and IDV in heavily antiretroviral-experienced patients.
METHOD: A chart review of patients treated with IDV/RTV/DLV and two nucleoside reverse transcriptase inhibitor (NRTI) drugs was performed. Only patients who failed at least three highly active antiretroviral therapy (HAART) regimens and remained on IDV/RTV/DLV therapy for at least 2 months were included. Plasma concentrations for IDV and RTV were obtained if patients were still on therapy.
RESULTS: Ten participants were identified who qualified for this study. The median plasma HIV RNA prior to initiating IDV/RTV/DLV was 359,300 copies/mL. Nine of the 10 patients had failed nonnucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens in the past. Eight out of 10 patients had at reduction in HIV RNA. Four of eight patients maintained the 1 log(10) reduction in HIV RNA past 6 months. Mean CD4 cell count increased from 142+/-99 to 273+/-126 cells/mm(3). Genotypic data available on six patients showed multiple protease gene mutations. Plasma concentration of IDV in three patients (two troughs and one 7 hours postdose) were >1,000 ng/mL.
CONCLUSION: Our data suggests that in heavily antiretroviral drug-treated patients, partial antiretroviral response to RTV/IDV/DLV can still be achieved. The use of IDV/RTV/DLV and two NRTIs as salvage therapy has merit in patients who have no viable treatment options. A prospective trial utilizing this drug combination is warranted.
Authors:
M Grodesky; E P Acosta; N Fujita; S Mason; J G Gerber
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  HIV clinical trials     Volume:  2     ISSN:  1528-4336     ISO Abbreviation:  HIV Clin Trials     Publication Date:    2001 May-Jun
Date Detail:
Created Date:  2001-10-08     Completed Date:  2002-01-09     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  100936377     Medline TA:  HIV Clin Trials     Country:  United States    
Other Details:
Languages:  eng     Pagination:  193-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Anti-HIV Agents / pharmacokinetics,  therapeutic use*
CD4 Lymphocyte Count
Delavirdine / therapeutic use*
Drug Resistance, Viral / genetics
Drug Therapy, Combination
HIV Infections / drug therapy*
HIV Protease / genetics
HIV-1 / isolation & purification,  physiology
Humans
Indinavir / pharmacokinetics,  therapeutic use*
Male
Middle Aged
RNA, Viral / blood
Reverse Transcriptase Inhibitors / pharmacokinetics,  therapeutic use*
Ritonavir / pharmacokinetics,  therapeutic use*
Salvage Therapy
Treatment Failure
Viral Load
Grant Support
ID/Acronym/Agency:
P30-AI 27767/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/RNA, Viral; 0/Reverse Transcriptase Inhibitors; 5W6YA9PKKH/Indinavir; DOL5F9JD3E/Delavirdine; EC 3.4.23.-/HIV Protease; O3J8G9O825/Ritonavir

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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