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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 impedes 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 ten 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 6 months. Participants were enrolled in eight strata, gender (female and male), education (<10 and ≥10 years), and age (<35 and ≥35 years). Of 2400 enrolled, 770 completed the 6-month follow-up. As expected, significant between-country differences were evident in all the neurocognitive test scores ( p < 0.0001). 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. [ABSTRACT FROM AUTHOR]

Screening for HIV-associated neurocognitive disorders (HAND) is important to improve clinical outcomes. We compared the diagnostic sensitivity and specificity of the mini-mental state examination, International HIV dementia scale (IHDS), Montreal cognitive assessment, Simioni symptom questionnaire and cognitive assessment tool-rapid version (CAT-rapid) to a gold standard neuropsychological battery. Antiretroviral-experienced participants from Cape Town, South Africa, and Baltimore, USA, were recruited. The sensitivity and specificity of the five tools, as well as those of the combined IHDS and CAT-rapid, were established using 2 × 2 contingency tables and ROC analysis. More than a third (65165) had symptomatic HAND. In detecting HIV-D, the CAT-Rapid had good sensitivity (94 %) and weak specificity (52 %) (cut-point ≤10), while the IHDS showed fair sensitivity (68 %) and good specificity (86 %) (cut-point ≤10). The combined IHDS and CAT-rapid showed excellent sensitivity and specificity for HIV-D at a cut-off score of ≤16 (out of 20; 89 and 82 %). No tool was adequate in screening for any HAND. The combination IHDS and CAT-rapid tool appears to be a good screener for HIV-D but is only fairly sensitive and poorly specific in screening for any HAND. Screening for milder forms of HAND continues to be a clinical challenge. [ABSTRACT FROM AUTHOR]

Despite major advances in the development of antiretroviral therapies, currently available treatments have no effect on the production of HIV-Tat protein once the proviral DNA is formed. Tat is a highly neurotoxic and neuroinflammatory protein, but its effects may be modulated by antibody responses against it. We developed an indirect enzyme-linked immunosorbent assay and measured anti-Tat antibody titers in CSF of a well characterized cohort of 52 HIV-infected and 13 control individuals. We successfully measured anti-Tat antibodies in CSF of HIV-infected individuals with excellent sensitivity and specificity, spanning a broad range of detection from 10,000 to over 100,000 relative light units. We analyzed them for relationship to cognitive function, CD4 cell counts, and HIV viral load. Anti-Tat antibody levels were higher in those without neurocognitive dysfunction than in those with HIV-associated neurocognitive dysfunction (HAND) and in individuals with lower CD4 cell counts and higher viral loads. We provide details of an assay which may have diagnostic, prognostic, or therapeutic implications for patients with HAND. Active viral replication may be needed to drive the immune response against Tat protein, but this robust immune response against the protein may be neuroprotective. [ABSTRACT FROM AUTHOR]

Although human immunodeficiency virus (HIV) clade C virus infects the largest populations worldwide, to date there are no prospective studies reported thus far to determine the incidence or prevalence of HIV dementia in this population. HIV clade C virus is a CCR5-tropic virus and thus predominantly infects macrophages, which are the key cells implicated in the pathogenesis of HIV dementia. However, HIV dementia has only rarely been reported in these populations. The authors thus used a recently developed International HIV Dementia Scale (IHDS) to screen a well-characterized cohort of HIV-infected discordant couples in Pune, India. 48 HIV+ subjects with CD4 cell count 3 and 48 HIV- subjects were studied. The HIV+ subjects had significantly lower IHDS scores compared to the HIV- subjects. 35% of the HIV+ subjects and 15% of the HIV- subjects scored [ABSTRACT FROM AUTHOR]

Sub-Saharan Africa, which has about 12% of the global population, is home to almost 70% of individuals infected with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). A recent survey by the Ugandan Ministry of Health has found the HIV prevalence rate to be approximately 7% in sexually active adults. The predominant HIV subtypes present in Uganda are A and D. Health care resources are well planned but often lack human and fiscal resources. Uganda has adopted the World Health Organization (WHO) “3 by 5” global strategy for the introduction of antiretroviral therapy and has surpassed the target. Neurological complications of the HIV virus are common and often have devastating consequences. A recent study in Kampala found the rate of HIV dementia and peripheral neuropathy at 31% and 47%, respectively. Further studies are urgently required to determine the natural history and treatment outcomes of both these common HIV complications. [ABSTRACT FROM AUTHOR]

Presents papers on HIV dementia, which were presented at the Fourth International Symposium on NeuroVirology and at the Tenth Conference on Neuroscience of HIV Infection. Involvement of dopamine in the pathogenesis of HIV-induced neuro-AIDS; Characterization of SIV long terminal repeat cis-acting sequences; Transcriptional regulation by HIV, Tat and gp120 in astrocytes; Activation of NMDA receptor subtypes by macrophage secretory products; Novel action of minocycline in infection in microglia and macrophages; Induction of the release of matrix metalloproteinases.