Clinical Trial of Brain-Penetrating HIV Drugs to Prevent Cognitive Impairment in China
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|ClinicalTrials.gov Identifier: NCT01340950|
Recruitment Status : Completed
First Posted : April 25, 2011
Last Update Posted : April 4, 2016
|Condition or disease||Intervention/treatment||Phase|
|HIV Infections Central Nervous System Diseases Dementia||Drug: zidovudine-lamivudine-nevirapine Drug: tenofovir-lamivudine-efavirenz||Phase 4|
Advances in treatment have transformed HIV disease to a chronic illness in most individuals in the U.S. The most common central nervous system (CNS) complication of chronic HIV disease is HIV-associated neurocognitive disorder (HAND). In the U.S., HAND prevalence estimates range up to 55% of treated individuals. HAND is also common outside the U.S. For example, our prior project in China identified that more than a third of nearly 150 treated HIV(+) individuals in Anhui and Yunnan provinces had HAND. Data such as these support that the benefits of antiretroviral therapy (ART) can be incomplete, with many patients not returning to normal neurocognitive performance or, worse, developing new neurocognitive impairment while taking ART.
One explanation for this is the limited penetration of some antiretrovirals into the nervous system. Recent reports have identified that worse antiretroviral penetration characteristics are associated with worse control of HIV replication and worse neurocognitive performance. Most reports, however, have focused on treatment - rather than prevention - of HAND. Like many other medical conditions, prevention of HAND may be a more cost-effective public health goal than treating disease that has already occurred.
We are building on our prior work in China by performing a phase 4, randomized, controlled clinical trial of the safety and effectiveness of ART that differs in its penetration characteristics in 250 ART-naive individuals who have normal neurocognitive performance. The primary objective will be to determine the effects of better penetrating (BP) ART (zidovudine-lamivudine-nevirapine) compared with worse penetrating (WP) ART (tenofovir-lamivudine-efavirenz) on the prevention of HAND. We hypothesize that volunteers who are randomized to BP-ART will be less likely to neurocognitively decline over 96 weeks of observation than those who are randomized to WP-ART. The secondary objective will be to assess the influence on study outcomes of two conditions: persistent immune activation and viral hepatitis. In an exploratory aim, the project will also assess the influence on study outcomes of a concise panel of drug disposition-associated genetic polymorphisms.
Demonstrating that HAND can be prevented by using BP-ART should influence HIV treatment guidelines in the U.S., China, and elsewhere and ultimately lead to preservation of normal neurocognitive functioning in people afflicted with HIV/AIDS.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||250 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Clinical Trial of CNS Penetrating ART to Prevent NeuroAIDS in China|
|Study Start Date :||July 2010|
|Actual Primary Completion Date :||July 2014|
|Actual Study Completion Date :||July 2015|
Active Comparator: Better-Penetrating ART
zidovudine 300 mg orally every 12 hours lamivudine 300 mg orally daily nevirapine 200 mg orally every 12 hours
96 weeks of zidovudine 300 mg orally twice daily, lamivudine 300 mg orally daily, nevirapine 200 mg orally daily for the first 14 days then 200 mg orally twice daily
Other Name: Retrovir, Epivir, Viramune
Active Comparator: Worse-Penetrating ART
tenofovir disoproxil fumarate 300 mg orally daily lamivudine 150 mg orally every 12 hours efavirenz 600 mg orally daily
96 weeks of tenofovir disoproxil fumarate 300 mg orally daily, lamivudine 300 mg orally daily, efavirenz 600 mg orally daily
Other Name: Viread, Epivir, Sustiva
- Decline in neuropsychological performance at 96 weeks [ Time Frame: 96 weeks ]Comparison of decline in NP performance between treatment groups.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01340950
|Beijing Ditan Hospital|
|Beijing, Beijing, China|
|Beijing YouAn Hospital|
|Beijing, Beijing, China|
|Principal Investigator:||Scott L Letendre, M.D.||University of California, San Diego|