Clinical Trial of Brain-Penetrating HIV Drugs to Prevent Cognitive Impairment in China
Condition: HIV Infections; Central Nervous System Diseases; Dementia
MeSH terms: Nervous System Diseases; Central Nervous System Diseases
Study type: Interventional
Phase: Phase 4

Summary: 
      This primary aim of the project is to determine the association between antiretroviral
      therapy that better distributes into the central nervous system and prevention of
      HIV-associated neurocognitive impairment.
    

Detailed description: 
      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.
    

Intervention name(s): zidovudine-lamivudine-nevirapine; tenofovir-lamivudine-efavirenz
Intervention type(s): Drug; Drug
Intervention description(s): 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; 96 weeks of tenofovir disoproxil fumarate 300 mg orally daily, lamivudine 300 mg orally daily, efavirenz 600 mg orally daily
Other intervention name(s): Retrovir, Epivir, Viramune; Viread, Epivir, Sustiva
Intervention MeSH terms: Tenofovir; Lamivudine; Zidovudine; Efavirenz; Nevirapine; Lamivudine, zidovudine drug combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Prevention; Anti-Retroviral Agents; Neuropsychological Tests