HIV DNA Reservoir Increases Risk for Cognitive Disorders in cART-Nave Patients

Objectives Cognitive impairment remains frequent in HIV, despite combination antiretroviral therapy (cART). Leading theories implicate peripheral monocyte HIV DNA reservoirs as a mechanism for spread of the virus to the brain. These reservoirs remain present despite cART. The objective of this study was to determine if the level of HIV DNA in CD14+ enriched monocytes predicted cognitive impairment and brain injury. Methods We enrolled 61 cART-naïve HIV-infected Thais in a prospective study and measured HIV DNA in CD14+ enriched monocyte samples in a blinded fashion. We determined HAND diagnoses by consensus panel and all participants underwent magnetic resonance spectroscopy (MRS) to measure markers of brain injury. Immune activation was measured via cytokines in cerebrospinal fluid (CSF). Results The mean (SD) age was 35 (6.9) years, CD4 T-lymphocyte count was 236 (139) and log10 plasma HIV RNA was 4.8 (0.73). Twenty-eight of 61 met HAND criteria. The log10 CD14+ HIV DNA was associated with HAND in unadjusted and adjusted models (p = 0.001). There was a 14.5 increased odds ratio for HAND per 1 log-value of HIV DNA (10-fold increase in copy number). Plasma CD14+ HIV DNA was associated with plasma and CSF neopterin (p = 0.023) and with MRS markers of neuronal injury (lower N-acetyl aspartate) and glial dysfunction (higher myoinositol) in multiple brain regions. Interpretation Reservoir burden of HIV DNA in monocyte-enriched (CD14+) peripheral blood cells increases risk for HAND in treatment-naïve HIV+ subjects and is directly associated with CSF immune activation and both brain injury and glial dysfunction by MRS

Liver Fibrosis Linked to Cognitive Performance in HIV and Hepatitis C

Since HIV impairs gut barriers to pathogens, HIV-infected adults may be vulnerable to Minimal Hepatic Encephalopathy (MHE) in the absence of cirrhosis

Pathogenesis of HIV in the Central Nervous System

HIV can infect the brain and impair central nervous system (CNS) function. Combination antiretroviral therapy (cART) has not eradicated CNS complications. HIV-associated neurocognitive disorders (HAND) remain common despite cART, although attenuated in severity. This may result from a combination of factors including inadequate treatment of HIV reservoirs such as circulating monocytes and glia, decreased effectiveness of cART in CNS, concurrent illnesses, stimulant use, and factors associated with prescribed drugs, including antiretrovirals. This review highlights recent investigations of HIV-related CNS injury with emphasis on cART-era neuropathological mechanisms in the context of both US and international settings

Advancements in dementia research, diagnostics and care in Latin America : highlights from the 2023 Alzheimer's association international conference satellite symposium in Mexico City

While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics and care. In 2023, the Alzheimer’s Association hosted its eighth Satellite Symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. A wide range of topics were covered, including epidemiology, social determinants, dementia national plans, risk reduction, genetics, biomarkers, biobanks, and advancements in treatments. Large initiatives in the region including intra-country support showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care and implement affordable biomarkers in the region was highlighted

HIV, aging, and cognition: emerging issues.

The prevalence of HIV-associated neurocognitive disorder has not changed from the pre- to the potent antiretroviral therapy era, remaining at approximately 50%. In research settings, mild neurocognitive disorder (MND) and so-called asymptomatic neurocognitive impairment (ANI) are now more common than HIV-associated dementia. The diagnosis of ANI is misleading because functional deficits, when tested in a laboratory, and degree of neuropsychologic testing abnormalities are often comparable in patients with ANI and those with symptomatic MND. Age-related comorbidities increase the risk of cognitive impairment in HIV infection. In a cohort of patients aged 60 years or older with excellent antiretroviral therapy adherence, correlates to cognitive impairment were apolipoprotein (Apo) E4 genotype and a novel measure of the effectiveness of antiretroviral drugs in monocytes, the monocyte efficacy (ME) score, with trend associations for diabetes and nadir CD4+ cell count. Management of impairment includes ensuring that patients are on and adhere to antiretroviral therapy and addressing comorbidities. Switching from effective and well-tolerated antiretroviral therapy for patients with mild cognitive impairment is not routinely recommended, but this must still be addressed on a case-by-case basis. This article summarizes a presentation by Victor G. Valcour, MD, at the IAS-USA continuing education program held in Atlanta, Georgia, in April 2013

The phrase: "no ifs, ands, or buts" and cognitive testing. Lessons from an Asian-American community.

This study assessed the clinical utility of repeating the phrase "No ifs, ands, or buts" for cognitive testing in Hawaii. 242 subjects were screened; 25 (10%) had cognitive impairment. 68% of all subjects were unable to say the phrase "No ifs, ands, or buts" (83% of cognitively impaired and 67% of cognitively intact, p = 0.122). Specificity for cognitive impairment was poor

Early-Stage Dementia Diagnosis and Care

Dementia caused by Alzheimer\u27s disease and other factors is taking a tremendous toll on elders and their families. According to the author however, if the disease is diagnosed and treated early, many patients can avoid or delay secondary medical and social complications