Human immunodeficiency virus-associated neurocognitive disorders (HAND) occurs globally and across different genetic clades of the virus. However, few studies have examined HAND in South Africa, despite the prevalence of HIV in this region of the world, and the predominance of clade C. The present study examined the relationship between a number of demographic and clinical variables in a sample of 536 patients attending HIV clinics in South Africa. HAND was present in 23.5% of the sample and was associated with older age, a low educational level among those with post-traumatic stress disorder (PTSD) and alcohol abuse among those with many months since diagnosis. These results suggest that HAND is common among patients in South Africa, and is associated with clinical variables such as PTSD and alcohol abuse. This underlines the impact of HIV on the nervous system and the importance of screening for co morbid mental health conditions.

Clinical Correlates of HIV-Associated Neurocognitive Disorders in South Africa

There are a number of reasons that the accomplishments of clinical trials related to HIV-related neurodegenerative disease (HRND) and the AIDS dementia complex (ADC) have had such limited impact on clinical practice. These include: rapid evolution and progress in the treatment of systemic HIV infection that has quickly outpaced neurological efforts and has markedly reduced disease incidence; ethical constraints that (rightly) demand neurologically compromised patients receive the best available treatment before experimental therapeutics; complicated backgrounds and comorbidities of patients now most susceptible to HRND; and reluctance of general AIDS clinicians and drug companies to look beyond systemic or pivotal outcomes. However, the field has also been slow to adopt methods that better exploit advances in understanding of the pathogenesis of central nervous system (CNS) infection and brain injury, and that might circumvent some of these constraints. Using a simple model of pathogenesis, we propose an approach to characterizing patients, selecting treatment targets, and evaluating outcomes that emphasize a combination of cerebrospinal fluid (CSF) markers. This model begins by using three markers related to cardinal components of HRND: CNS HIV infection (measurement of CSF HIV RNA), intrathecal immunoactivation (CSF neopterin), and brain injury [CSF light chain neurofilament (NFL)]. Careful analysis of this and other marker combinations promises more rational trial design and more rapid progress in managing CNS HIV infection and HRND using both antiviral and adjuvant treatment approaches.

Defining and evaluating HIV-related neurodegenerative disease and its treatment targets: a combinatorial approach to use of cerebrospinal fluid molecular biomarkers.

The advent of combined antiretroviral therapy (cART) has dramatically improved HIV management and patient care of HIV-infected individuals. The cART regimen resulted in a significant reduction of HIV/AIDS-related mortality and greatly improved life expectancies of those patients with access to cART. However, among many HIV-related complications, neurocognitive dysfunction, known as HIV-associated neurocognitive disorder (HAND), has now been a major issue.  While the cART regimen has been effective in reduction of HAND in many patients, the prevalence of HAND is increasing as HIV/AIDS patients live longer.  HIV infection and its subsequent manifestation of HAND is complex.   It is evident that the brain can serve as a sanctuary for HIV replication and HAND can remain in patients even with cART treatment due to poor blood-brain barrier permeability of the majority of current antiretroviral agents. Conceivably, cART needs to have improved central nervous system (CNS) penetration properties for effective treatment and possible prevention of HAND.  Therefore, design and development of new antiretroviral agents that can penetrate into the CNS effectively, could block HIV replication and significantly reduce the viral load in the CNS. This may prevent HAND and related symptoms. HIV protease inhibitors (PIs) are a critical component of cART.  Over the years, we have designed and synthesized a range of highly potent and novel PIs including the FDA approved drug, darunavir, which has been used as a first-line treatment.   In an effort to improve CNS penetration, we have been involved in the design and development of potent PIs with improved in vitro brain penetration properties. Herein we provide a brief review that covers insights and discussion of HAND and our work on PI development to ameliorate HIV-associated neurocognitive disorders.

HIV-Associated Neurocognitive Disorder (HAND) and the Prospect of Brain-Penetrating Protease Inhibitors for Antiretroviral Treatment.

Training Needs and Evaluation of a Neuro-HIV Training Module for Non-Physician Healthcare Workers in Western Kenya

In July of 2006, the National Institute of Mental Health (NIMH) Center for Mental Health Research on AIDS (CMHRA) sponsored the second conference on the Assessment of NeuroAIDS in Africa, which was held in Arusha, Tanzania. The conference mission was to address the regional variations in epidemiology of HIV-related neurological disorders as well as the assessment and diagnosis of these disorders. Participants discussed and presented data regarding the relevance and translation of neuroAIDS assessment measures developed in resource intensive settings and the challenges of neuro-assessment in Africa, including the applicability of current tools, higher prevalence of confounding diseases, and the complexity of diverse cultural settings. The conference presentations summarized here highlight the need for further research on neuroAIDS in Africa and methods for assessing HIV-related neurological disorders.

/pdf/second-assessment-of-neuroaids-in-africa-31fiufhvle.pdf

Second assessment of NeuroAIDS in Africa

Kevin Robertson, Kathy Kopnisky, Jens Mielke, Kuku Appiah, Colin Hall, Richard Price, Johnstone Kumwenda, Cecelia Kanyama, Farida Amod, Christina Marra, Terrie Taylor, Umesh Lalloo, Jennifer Jelsma, Penny Holding, Michael Boivin, Gretchen Birbeck, Noelene Nakasujja, Ian Sanne, Thomas D. Parsons, Amanda Parente, and Karen Tucker, on behalf of the Assessment of NeuroAIDS in Africa Conference Participants

https://ict.usc.edu/pubs/Assessment%20of%20neuroAIDS%20in%20Africa.pdf

Assessment of neuroAIDS in Africa.

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Assessment of neuroAIDS in Africa.