Virologic and Immunologic Activity of Continued Lamivudine (3TC) vs Delavirdine (DLV) in Combination With Indinavir (IDV) and Zidovudine (ZDV) or Stavudine (d4T) in 3TC-Experienced Subjects

Completed · Phase 2

Conditions studied: HIV Infections

In brief

To compare the proportion of patients in the 2 zidovudine (ZDV)-containing arms who have a plasma HIV RNA concentration below the limit of detection (defined as 500 copies/ml or less) at Weeks 20 and 24 \[AS PER AMENDMENT 8/24/98: HIV RNA concentration below the limit of detection is now defined as 200 copies/ml or less\]. To compare the safety and tolerability of the different treatment regimens. To compare the decrease in plasma HIV-1 RNA and the change in CD4 count from baseline to the average of Weeks 20 and 24 \[AS PER AMENDMENT 12/19/97: and to the average of Weeks 44 and 48; AS PER AMENDMENT 8/24/98: and the average of Weeks 88 and 96\] in the 2 ZDV-containing arms. To study the emergence of resistance to ZDV, lamivudine (3TC), stavudine (d4T), delavirdine (DLV), and indinavir (IDV) in treated patients. To correlate the antiviral and immunologic activity and emergence of drug resistance with pharmacologic parameters of study drugs. To delineate the pharmacokinetic interactions of IDV and DLV. \[AS PER AMENDMENT 12/19/97: To delineate the possible development of cellular resistance to nucleoside analogs and the consequences of switching nucleoside study drugs on intracellular phosphorylation.\] To document rates and patterns of adherence over the course of the study, from day of randomization through 48 weeks. \[AS PER AMENDMENT 8/24/98: To define long-term durability of the virologic activity of the different treatment regimens, as defined by the proportion of patients with plasma HIV-1 RNA levels that remains below the limit of detection. To define long-term tolerability of the different treatment regimens.\] Although a change in reverse transcriptase (RT) inhibitors is recommended when adding or changing protease inhibitors in a treatment regimen, the choice of available RT inhibitors is often limited by prior exposure, toxicity, or pharmacologic interaction with the protease inhibitors. This study addresses the question of whether to continue 3TC or substitute the nonnucleoside reverse transcriptase inhibitor (NNRTI) DLV when adding IDV to therapy for patients previously treated with ddI or d4T plus 3TC who have greater than 500 copies/ml of plasma HIV-1 RNA. Although the activity of DLV as monotherapy or in combination with nucleoside reverse transcriptase inhibitors is of limited duration due to rapid emergence of resistance, it is possible that DLV will contribute significantly to the activity of 3-drug regimens that include a new RT inhibitor plus a protease inhibitor.

Key facts

Study ID

NCT00000882

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

300

Last updated by the study team

2013-07-29

Who can join

Age: 12 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Concurrent Medication:
• Required:
• Patients completing ACTG 306 who remain on blinded therapy through the extension period or
• Patients on stable (6 months or greater) ddI/3TC or d4T/3TC combination therapy who have plasma HIV-1 levels higher than 500 copies/ml by the Amplicor HIV-1 Monitor Assay.
• Allowed following contact with Protocol Pharmacologist:
• Diltiazem, nifedipine, phenytoin, and warfarin.
• Patients must have:
• Absolute CD4 count of 200 cells/mm3 or greater.
• HIV-1 RNA levels greater than 500 copies/ml by the Amplicor HIV-1 Monitor assay. NOTE:
• This is a requirement for those receiving study medication. [AS PER AMENDMENT 12/19/97:
• HIV-1 infection must be documented by any licensed ELISA test kit and confirmed by either Western blot, HIV culture, HIV antigen, plasma HIV RNA, or a second antibody test by a method other than ELISA at any time prior to entry.]
• Signed, informed consent from a parent or legal guardian for patients under 18 years of age.
• Life expectancy of at least 24 weeks.

You may not qualify if…

• Co-existing Condition:
• Patients with the following symptoms or conditions are excluded:
• Unexplained temperature of 38.5 C or higher for 7 consecutive days, or chronic diarrhea defined as more than 3 liquid stools per day persisting for 15 days, within 30 days prior to study entry.
• Proven or suspected acute hepatitis within 30 days prior to study entry.
• Malignancy that requires systemic chemotherapy. NOTE:Patients with minimal Kaposi's sarcoma (KS) fewer than 5 cutaneous lesions and no visceral disease or tumor-associated edema) are allowed to enroll provided that they do not require systemic therapy.
• Concurrent Medication:
• Excluded:
• Concurrent ZDV (for patients other than those rolling over from ACTG 306).
• Any experimental antiretroviral agents or other experimental therapies.
• Acute therapy for an infection or other medical illnesses within 14 days prior to study entry.
• Recombinant erythropoietin (rEPO), G-CSF, or GM-CSF within 30 days prior to study entry.
• Interferons, interleukins, or HIV vaccines within 30 days prior to study entry.
• Rifampin, rifabutin, cisapride, triazolam, midazolam, terfenadine, astemizole, or loratadine, within 14 days prior to study entry.
• Patients with the following prior conditions are excluded:
• History of acute or chronic pancreatitis.
• History of Grade 2 or higher bilateral peripheral neuropathy. [AS PER AMENDMENT 12/19/97: Patients with Grade 2 or 3 peripheral neuropathy due to current use of ddI/3TC or d4T/3TC and who have a screening viral load above 500 copies/ml are eligible as they will be randomized to a regimen that does not contain an agent associated with peripheral neuropathy toxicity.]
• Prior Medication:
• Excluded:
• Prior NNRTI or protease inhibitor therapy.
• Prior ZDV (for patients other than those rolling over from ACTG 306).
• Previous induction or maintenance therapy with foscarnet.

Where it is running

• Univ of Alabama at Birmingham — Birmingham, Alabama, United States
• Univ of California / San Diego Treatment Ctr — San Diego, California, United States
• Stanford at Kaiser / Kaiser Permanente Med Ctr — San Francisco, California, United States
• Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium — San Jose, California, United States
• San Mateo AIDS Program / Stanford Univ — Stanford, California, United States
• Stanford Univ Med Ctr — Stanford, California, United States
• Univ of Colorado Health Sciences Ctr — Denver, Colorado, United States
• Univ of Miami School of Medicine — Miami, Florida, United States
• Queens Med Ctr — Honolulu, Hawaii, United States
• Univ of Hawaii — Honolulu, Hawaii, United States
• Northwestern Univ Med School — Chicago, Illinois, United States
• Cook County Hosp — Chicago, Illinois, United States
• Rush Presbyterian - Saint Luke's Med Ctr — Chicago, Illinois, United States
• Louis A Weiss Memorial Hosp — Chicago, Illinois, United States
• Indiana Univ Hosp — Indianapolis, Indiana, United States
• State of MD Div of Corrections / Johns Hopkins Univ Hosp — Baltimore, Maryland, United States
• Johns Hopkins Hosp — Baltimore, Maryland, United States
• Beth Israel Deaconess - West Campus — Boston, Massachusetts, United States
• St Louis Regional Hosp / St Louis Regional Med Ctr — St Louis, Missouri, United States
• SUNY / Erie County Med Ctr at Buffalo — Buffalo, New York, United States
• Beth Israel Med Ctr — New York, New York, United States
• Univ of Rochester Medical Center — Rochester, New York, United States
• Univ of North Carolina — Chapel Hill, North Carolina, United States
• Carolinas Med Ctr — Charlotte, North Carolina, United States
• Moses H Cone Memorial Hosp — Greensboro, North Carolina, United States

Full record on ClinicalTrials.gov

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