Safety and Effectiveness of Combining Hydroxyurea (HU) With Didanosine (ddI) and Stavudine (d4T) for Treatment of HIV-Infected Adults
Summary
The purpose of this study is to compare the safety and effectiveness of 9 doses of HU in order to find the best dose of HU to use with ddI and d4T in fighting HIV infection.
HU plus ddI plus d4T appears to be a suitable anti-HIV drug combination for long-term control of HIV. This combination can sharply decrease viral load (level of HIV in the body) with few side effects, making it easy to take.
Description
The combination of HU plus ddI plus d4T appears to be suitable for long-term control of HIV in that it: (1) has a novel resistance/rebound profile demonstrating virus suppression even in the presence of ddI-resistant mutants; (2) can produce a pronounced fall in viral load; and (3) is well tolerated (over 200 patients have been treated for up to 3 years with minimal side effects).
Patients are stratified by antiretroviral experience: naive (no more than 2 weeks of therapy) versus experienced (more than 2 weeks). Patients must discontinue all antiretroviral therapy for at least 28 days prior to randomization to 1 of 9 HU treatment arms. Treatment arms are divided into 3 HU dose categories: very low, low, and medium. Within each category HU is administered daily on 3 different dosing schedules. Depending on viral load, patients on the very low and low dose arms may have the opportunity to intensify their HU dose at any time beyond Week 12, provided no Grade 3 or 4 HU-related toxicity is present (these patients are monitored for an additional 8 weeks following intensification). All patients receive ddI and d4T at the same doses every day. When 50% of patients have completed 24 weeks of treatment, an analysis is made to determine whether or not to continue the 52-week study without modifications. Patients are monitored periodically for changes in plasma HIV RNA, CD4 cell counts, weight, and symptoms.
Study Design
Endpoint Classification: Safety Study, Intervention Model: Factorial Assignment, Primary Purpose: Treatment
Conditions
HIV Infections
Intervention
Hydroxyurea, Stavudine, Didanosine
Location
AIDS Healthcare Foundation
Los Angeles
California
United States
90027
Status
Completed
Source
NIH AIDS Clinical Trials Information Service
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00002427
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-08-27T03:59:09-0400
Clinical Trials
To determine the virologic benefits associated with the addition of hydroxyurea (HU) to combination drug therapy with didanosine (ddI), stavudine (d4T), and efavirenz (DMP) in HIV-infected...
A Study of MKC-442 in Combination With Other Anti-HIV Drugs
The purpose of this study is to see if it is safe and effective to give MKC-442 plus stavudine (d4T) plus didanosine (ddI) plus hydroxyurea.
The purpose of this study is to see if it is safe and effective to give MKC-442, didanosine (ddI), stavudine (d4T), and delavirdine (DLV) to HIV-positive patients.
The purpose of this study is to see if it is safe and effective to give a new anti-HIV drug combination to HIV-infected patients who have never taken nonnucleoside reverse transcriptase in...
The purpose of this study is to compare the effectiveness of taking didanosine (ddI) once a day plus stavudine (d4T) twice a day with taking ddI twice a day plus d4T twice a day. This stud...
PubMed Articles
Abacavir has replaced stavudine in antiretroviral therapy (ART) regimens because it has largely been phased out as a result of toxicity concerns; this loss has reduced further the already-limited drug...
Combined antiretroviral therapy (cART) has improved survival in HIV-patients. While the first antiretrovirals, which became available in particular D-drugs (especially didanosine and stavudine) and un...
The haematological and clinical response to hydroxyurea was estimated in HbE-beta, beta thalassaemia and sickle cell anaemia patients of Eastern India, with variable clinical severity and transfusion ...
We conducted the first nation-wide cohort study of sickle cell disease (SCD) in Italy, a Southern European country exposed to intense recent flux migration from endemic areas for SCD. We evaluate the ...
Following widespread use of stavudine, a thymidine analogue, in antiretroviral therapy (ART) over the past three decades, up to a third of children developed lipoatrophy (LA) and/or lipohypertrophy (L...
Medical and Biotech [MESH] Definitions
Didanosine
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite.
Stavudine
A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV.
Hydroxyurea
An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
Encephalitis, Viral
Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of TOGAVIRIDAE INFECTIONS; HERPESVIRIDAE INFECTIONS; ADENOVIRIDAE INFECTIONS; FLAVIVIRIDAE INFECTIONS; BUNYAVIRIDAE INFECTIONS; PICORNAVIRIDAE INFECTIONS; PARAMYXOVIRIDAE INFECTIONS; ORTHOMYXOVIRIDAE INFECTIONS; RETROVIRIDAE INFECTIONS; and ARENAVIRIDAE INFECTIONS.
Meningitis, Viral
Viral infections of the leptomeninges and subarachnoid space. TOGAVIRIDAE INFECTIONS; FLAVIVIRIDAE INFECTIONS; RUBELLA; BUNYAVIRIDAE INFECTIONS; ORBIVIRUS infections; PICORNAVIRIDAE INFECTIONS; ORTHOMYXOVIRIDAE INFECTIONS; RHABDOVIRIDAE INFECTIONS; ARENAVIRIDAE INFECTIONS; HERPESVIRIDAE INFECTIONS; ADENOVIRIDAE INFECTIONS; JC VIRUS infections; and RETROVIRIDAE INFECTIONS may cause this form of meningitis. Clinical manifestations include fever, headache, neck pain, vomiting, PHOTOPHOBIA, and signs of meningeal irritation. (From Joynt, Clinical Neurology, 1996, Ch26, pp1-3)
