International neurocognitive normative study: neurocognitive comparison data in diverse resource-limited settings: AIDS Clinical Trials Group A5271

Abstract

Summary ACTG A5271 collected neurocognitive normative comparison test data in 2400 at-risk HIV seronegative participants from Brazil, India, Malawi, Peru, South Africa, Thailand and Zimbabwe. The participants were enrolled in strata by site (10 levels), age (2 levels), education (2 levels), and gender (2 levels). These data provide necessary normative data infrastructure for future clinical research and care in these diverse resource limited settings. Infrastructure for conducting neurological research in resource limited settings (RLS) is limited. The lack of neurological and neuropsychological (NP) assessment, and normative data needed for clinical interpretation impede research and clinical care. Here we report on ACTG 5271, which provided neurological training of clinical site personnel, and collected neurocognitive normative comparison data in diverse settings. At 10 sites in seven RLS countries, we provided training for NP assessments. We collected normative comparison data on HIV- participants from Brazil (n=240), India (n=480), Malawi (n=481), Peru (n=239), South Africa (480), Thailand (n=240) and Zimbabwe (n=240). Participants had a negative HIV test within 30 days before standardized NP exams were administered at baseline, and 770 at six-months. Participants were enrolled in 8 strata, gender (female and male), education (<10 years and ≥ 10 years), and age (<35 years and ≥35 years). Of 2400 enrolled, 770 completed the six-month follow up. As expected, significant between-country differences were evident in all the neurocognitive test scores (p<.0001). There was variation between the age, gender and education strata on the neurocognitive tests. Age and education were important variables for all tests; older participants had poorer performance and those with higher education had better performance. Women had better performance on verbal learning/memory and speed of processing tests, while men performed better on motor tests. This study provides the necessary neurocognitive normative data needed to build infrastructure for future neurological and neurocognitive studies in diverse RLS. These normative data are a much-needed resource for both clinicians and researchers.

Analysis of the WHO ICTRP for novel coronavirus clinical trial registrations

“…This can effectively reduce the wastage of research resources, publication bias, the selective bias in reporting the data, as well as promote good communication. [ 11 ] Based on the analysis of the COVID-19 registration trials, the ChiCTR registration guide divides the study types into 7 categories: interventional studies, preventive studies, diagnostic tests, prognostic studies, and observational studies, etc. [ 12 ] However, its registration guidelines are unclear in classifying research according to the nature and purpose of the research.…”

HIV-associated neurocognitive disorder

“…The challenge is even greater when working globally across cultural differences, and potentially with different variants of virus. [11–13] Recent studies have evaluated several short performance tests including mini-medical state examination, International HIV dementia scale (IHDS), Montreal cognitive assessment, Simioni symptom questionnaire and cognitive assessment tool-rapid version (CAT-rapid) all compared with a standard full neuropsychological examination. [14,15] Such combinations as the IHDS and CAT-rapid performed well for detecting dementia, but no short testing was sensitive for the mild HAND that is the major clinical problem.…”

HIV Cerebrospinal Fluid Escape and Neurocognitive Pathology in the Era of Combined Antiretroviral Therapy: What Lies Beneath the Tip of the Iceberg in Sub-Saharan Africa?

“…The lack of neurocognitive normative comparison data for this setting is also a limitation [ 13 ]. These challenges have been partly addressed by various diagnostic accuracy studies and the collection of neurocognitive normative data [ 14 , 15 , 16 , 17 , 18 ]. In the absence of NP testing, several studies in SSA have attempted to determine an approximate prevalence of HAND using screening tools.…”

“…It requires a battery of NP tests, that require a specific skill set to deliver and sometimes specialised equipment. These tests were developed in resource-rich settings [ 13 ] and until recently normative scores did not exist for resource-limited settings (RLS) [ 15 , 18 ]. Studies compiling normative comparative data in RLS have largely used small convenience samples [ 14 , 17 , 18 , 22 , 89 ].…”

“…Studies compiling normative comparative data in RLS have largely used small convenience samples [ 14 , 17 , 18 , 22 , 89 ]. Two studies have collected large-scale, comprehensive normative neurocognitive data in RLS, using broadly representative participants of the local HIV-negative population and found country specific differences in NP performance [ 15 , 90 ]. This highlights the need for further research to firstly evaluate NP tests in SSA to limit cultural bias and inform on the appropriate NP tests to use for each setting.…”