ArticlePLoS clinical trials2007
Factors in AIDS dementia complex trial design: results and lessons from the abacavir trial.
Article in PLoS clinical trials, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Adjunctive therapies for AIDS dementia complex.The Cochrane database of systematic reviews · 2008Pooled it
- Mechanisms underlying HIV-associated cognitive impairment and emerging therapies for its management.Nature reviews. Neurology · 2023Review
- Associations between plasma nucleoside reverse transcriptase inhibitors concentrations and cognitive function in people with HIV.PloS one · 2021Article
- Clinical Trials in Neurovirology: Successes, Challenges, and Pitfalls.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2016Review
- Pharmacokinetics and pharmacodynamics of antiretrovirals in the central nervous system.Clinical pharmacokinetics · 2014Review
- HIV associated neurocognitive disorders in the modern antiviral treatment era: prevalence, characteristics, biomarkers, and effects of treatment.Current HIV/AIDS reports · 2014Review
- Update on HIV dementia and HIV-associated neurocognitive disorders.Current neurology and neuroscience reports · 2014Review
- The recombinant vaccinia virus gene product, B18R, neutralizes interferon alpha and alleviates histopathological complications in an HIV encephalitis mouse model.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2014Article
- Beta2-microglobulin as a diagnostic marker in cerebrospinal fluid: a follow-up study.Disease markers · 2014Article
- Assessment, diagnosis, and treatment of HIV-associated neurocognitive disorder: a consensus report of the mind exchange program.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2013Article
- Review
- Neurocognitive impairment and medication adherence in HIV patients with and without cocaine dependence.Journal of behavioral medicine · 2011Article
- Inflammation in depression: is adiposity a cause?Dialogues in clinical neuroscience · 2011Article
- HIV-associated neurocognitive disorder: pathogenesis and therapeutic opportunities.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2010Review
- Eating ourselves to death (and despair): the contribution of adiposity and inflammation to depression.Progress in neurobiology · 2010Review
- Contributors to neuropsychological impairment in HIV-infected and HIV-uninfected opiate-dependent patients.Journal of clinical and experimental neuropsychology · 2010Article
- Neuropsychological functioning and antiretroviral treatment in HIV/AIDS: a review.Neuropsychology review · 2009Review
- Neurodegeneration and ageing in the HAART era.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2009Review
- Should antiretroviral therapy for HIV infection be tailored for intracerebral penetration?The Netherlands journal of medicine · 2009Review
- The impact of neuropsychological functioning on adherence to HAART in HIV-infected substance abuse patients.AIDS patient care and STDs · 2009Article
Corrections and comments
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Authors and funding
16 authors at 15 institutions in 6 countries.
Funding
Abstract
objectivesTo determine the efficacy of adding abacavir (Ziagen, ABC) to optimal stable background antiretroviral therapy (SBG) to AIDS dementia complex (ADC) patients and address trial design.
designPhase III randomized, double-blind placebo-controlled trial.
settingTertiary outpatient clinics.
participantsADC patients on SBG for > or = 8 wk.
interventionsParticipants were randomized to ABC or matched placebo for 12 wk. OUTCOME MEASURES: The primary outcome measure was the change in the summary neuropsychological Z score (NPZ). Secondary measures were HIV RNA and the immune activation markers beta-2 microglobulin, soluble tumor necrosis factor (TNF) receptor 2, and quinolinic acid.
results105 participants were enrolled. The median change in NPZ at week 12 was +0.76 for the ABC + SBG and +0.63 for the SBG groups (p = 0.735). The lack of efficacy was unlikely related to possible limited antiviral efficacy of ABC: at week 12 more ABC than placebo participants had plasma HIV RNA < or = 400 copies/mL (p = 0.002). There were, however, other factors. Two thirds of patients were subsequently found to have had baseline resistance to ABC. Second, there was an unanticipated beneficial effect of SBG that extended beyond 8 wk to 5 mo, thereby rendering some of the patients at baseline unstable. Third, there was an unexpectedly large variability in neuropsychological performance that underpowered the study. Fourth, there was a relative lack of activity of ADC: 56% of all patients had baseline cerebrospinal fluid (CSF) HIV-1 RNA < 100 copies/mL and 83% had CSF beta-2 microglobulin < 3 nmol/L at baseline.
conclusionsThe addition of ABC to SBG for ADC patients was not efficacious, possibly because of the inefficacy of ABC per se, baseline drug resistance, prolonged benefit from existing therapy, difficulties with sample size calculations, and lack of disease activity. Assessment of these trial design factors is critical in the design of future ADC trials.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.