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Working Group Releases Guidelines for Improved Care of HIV-associated Cognitive Impairment

All people with HIV should be screened for HIV-associated neurocognitive disorders soon after testing positive, and those with evidence of impairment should be monitored regularly, according to international consensus guidelines developed by the Mind Exchange Working Group published in the November 28, 2012, advance edition of Clinical Infectious Diseases. Beyond antiretroviral therapy (ART), however, there are limited options for managing neurocognitive problems.

Although severe HIV-related dementia has become uncommon in the era of effective antiretroviral treatment, upwards of half of HIV positive people may experience some degree of neurocognitive impairment -- in many cases only detectable using specialized tests. HIV-associated neurocognitive disorders, or "HAND," are a growing concern as people with HIV age, and they may have practical consequences such as reduced adherence to treatment.

The Mind Exchange Working Group brought together more than 60 experts from 30 countries to develop practical answers to key clinical questions about managing HIV-associated neurocognitive disorders.Based on an international survey of HIV clinicians, the working group formulated 14 questions of greatest clinical importance. An expert group then conducted a literature search for relevant data using PubMed and the Cochrane Library, which guided development of consensus recommendations.

The working group looked at issues in 5 areas: screening, diagnosis, monitoring, treatment or interventions, and prevention. The group was able to reach consensus on all answers.

Recommendations

• All patients with HIV should be screened to assess neurocognitive function using standardized tools, ideally during the first 6 months after HIV diagnosis or soon thereafter.
• If possible, screening should take place before initiation of ART, "as this will establish accurate baseline data and allow for subsequent changes to be more accurately assessed."
• Follow-up testing should occur every 6 to 12 months for higher-risk patients (e.g., those with nadir or lowest-ever CD4 T-cell count < 200 cells/mm³), or every 12 to 24 months for lower-risk patients.
• Neurocognitive assessment should also be done "if there is evidence of clinical deterioration" or "at the time of major changes in clinical status."
• A comprehensive neurocognitive or neuropsychiatric (NP) evaluation is the accepted standard for evaluation of HAND.
• Since resources are limited in many settings, "a presumptive clinical diagnosis of HAND could be based on symptom questionnaires, screening tools, functional assessments, and limited NP testing"; people with evidence of functional impairment could then receive more extensive evaluation.
• Comprehensive NP testing should include at least 5 neurocognitive domains including verbal/language, attention/working memory, abstraction/executive function, learning/recall, speed of information processing, and motor skills.
• To identify other conditions that may contribute to neurocognitive impairment, a number of additional assessments should be done; in older people, "it is important to differentiate HAND from neurodegenerative disorders."
• Clinically stable patients can be monitored for neurocognitive problems approximately every 2 years.
• Frequency of monitoring should be increased if patients show progression of HIV disease, have a low CD4 nadir, are not receiving ART, do not achieve virological suppression on ART, or develop new or worsening neurological symptoms.
• There is little available data about progression of asymptomatic neurocognitive impairment to more severe impairment or dementia, or whether successful ART with viral suppression can prevent or reverse progression.
• Combination ART for approximately 1 year "is associated with modest benefits in NP functioning, particularly attention, processing speed, and executive performance," and the degree of improvement correlates with CD4 cell gains.
• Some studies indicate that antiretroviral drugs with greater central nervous system (CNS) penetration are associated with better neurocognitive outcomes, but data are not consistent and the benefits of changing ART to improve CNS penetration for people who already have well-controlled blood viral load are "unproven."
• However, worsening neurocognitive impairment "may trigger consideration of antiretroviral modification" when other causes have been excluded."
• If patients have persistent neurocognitive problems despite effective ART, consider the possibility of antiretroviral side effects or neurotoxicity.
• Several drugs (including minocycline, memantine, selegiline, lithium, valproic acid, lexipafant, CPI 1189, peptide T, nimodipine, and psychostimulants) have been evaluated as potential therapies for HAND.
• While there is evidence of good safety and tolerability in most of these studies, "effectiveness has not been established" and "no therapy other than combination ART is currently recommended for routine treatment of HAND in the clinic."
• Treating or managing coexisting conditions such as hepatitis C, cardiovascular risk factors, metabolic disorders, major depressive disorder, and anxiety disorders may reduce the severity of neurocognitive impairment.

"The clinical importance of HAND is receiving increasing attention as patients are surviving longer and neurocognitive health has become an issue of importance in the HIV and general community," the Mind Exchange Working Group wrote.

"Both HIV and non-HIV forms of neurocognitive impairment are diagnosed much earlier than they were in the past," they continued. "Despite this, some have questioned the benefit of early diagnoses when there is no proven treatment. But in the context of HIV infection, which is likely to be a chronic disease lasting decades in most patients, we have highlighted that there are already better treatment practices and that early diagnosis is a crucial step in identifying patients at risk, as well as patients in need of more frequent monitoring or specific interventions, including medication adherence checks."

"Until now, many practical clinical questions regarding the management of cognitive dysfunction in patients with HIV have remained unanswered," working group chair Scott Letendre from theUniversity of California at San Diego said in a press release. "For the first time, we have been able to put together clear guidance to help clinicians make an accurate diagnosis of cognitive dysfunction in patients with HIV, differentiating it from other common causes of neurocognitive impairment in older patients. We hope the result will be that appropriate treatment will be initiated at the earliest opportunity so that our patients can achieve the best possible outcomes."

12/18/12

Reference

Mind Exchange Working Group. Assessment, Diagnosis and Treatment of Human Immunodeficiency Virus (HIV)-Associated Neurocognitive Disorders (HAND): A Consensus Report of the Mind Exchange Program. Clinical Infectious Diseases. November 28, 2012 (Epub ahead of print).

Other Source

New Practical Guidance for Improved Patient Care in HIV-Associated Neurocognitive Disorder. Press release. November 30, 2012.