Clinical Trial of Brain-Penetrating HIV Drugs to Prevent Cognitive Impairment in China
Central Nervous System Diseases
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||Clinical Trial of CNS Penetrating ART to Prevent NeuroAIDS in China|
- Decline in neuropsychological performance at 48 weeks [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]Comparison of decline in NP performance between treatment groups.
|Study Start Date:||July 2010|
|Estimated Study Completion Date:||March 2015|
|Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Better-Penetrating Antiretroviral Therapy
BP-ART: zidovudine, lamivudine, nevirapine
48 weeks of zidovudine 300 mg orally twice daily, lamivudine 300 mg orally daily, nevirapine 200 mg orally daily for the first 14 days then 400 mg orally twice daily
Other Name: Retrovir, Epivir, Viramune
Active Comparator: Worse-Penetrating Antiretroviral Therapy
WP-ART: tenofovir, lamivudine, efavirenz
48 weeks of tenofovir disoproxil fumarate 300 mg orally daily, 3TC 300 mg orally daily, EFV 600 mg orally daily
Other Name: Viread, Epivir, Sustiva
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.
Please refer to this study by its ClinicalTrials.gov identifier: 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|