Recent Advances in HIV-Associated Neurocognitive Disorders

HIV-associated neurocognitive disorders (HAND) are chronic complications of HIV infection in the central nervous system. Clinical presentations include asymptomatic neurocognitive impairment (ANI), mild neurocognitive impairment (MND), and HIV-associated dementia (HAD). In the era of combination antiretroviral therapy (cART), the prevalence of HAD has significantly decreased, but the rates of ANI and MND have increased, impairing patients’ daily functioning, medical adherence, employment, driving abilities, risk of HIV transmission, overall quality of life, and posing challenges to society, economy, families, and public health. This article reviews the latest research findings regarding the pathogenesis, clinical diagnosis and treatment, neuroimaging, and neuropsychological assessment of HAND, aiming to provide insights into the prevention and management of HAND.

HIV-associated neurocognitive disorder(HAND):a review

Objective:According to the World Health Organization,the number of infected people with human immunodeficiency virus(HIV)in 2019 was about 38 million.Using combinational antiretroviral therapy in recent years has increased life expectancy in these people and HIV has been changed from a deadly disease to a chronic one.HIV-associated neurological disorders(HAND)include asymptomatic neurological disorders,Motor neurological disorders,and HIV-associated dementia.Methods:We searched 3 databases(PubMed,Science Direct and Scopus databases)from January 2015 to March 2021 for the keywords;HIV associated with a neurocognitive disorder,HAND and combinational antiretroviral therapy to provide careful consideration of various aspects of these disorders,including;risk factors,their diagnostic methods,their epidemiology,and finally the treatment of HAND.Results:In the initial search,we came across 1351 articles.Three authors did the title-abstract screening,and 270 articles were entered into full-text screening from the previous step.Four authors did the full-text screening,and the screening outcome was 21 articles.We categorized the results of our study into sub-categories,including:risk factors,pathogenicity,clinical manifestations,diagnosis,and epidemiology of HAND.Conclusions:Although the HAND subheading has made great strides,many questions about the disease remain unanswered,and many of the diagnosing established methods are not 100%accurate and as a result of that,this epidemy can’t be fully endured yet.We hope to find and apply further advances and more definitive solutions in the coming decades.

HIV-Associated Nephropathy in an HIV-2-Infected Patient

Background: Human immunodeficiency virus (HIV) type 2 infection is predominantly found in West African nations, and approximately 1 - 2 million people are thought to be infected. HIV-associated nephropathy (HIVAN) occurs in about 7% of patients with HIV-1 infection and is one of the most important causes of end-stage renal disease in this population. The only reported case of HIVAN related to HIV-2 infection was described by Izzedine et al. (2006). Aim: The aim of this paper is to report a case of HIVAN in an HIV-2-infected patient, a rarely described condition. Case presentation: We describe a case of a 40-year-old HIV-2-infected female from Angola hospitalized following a six-month history of fever, fatigue, anorexia and weight loss. Laboratory data revealed anaemia, leukopenia and renal dysfunction with nephrotic range proteinuria. Renal biopsy was performed, revealing findings consistent with HIVAN. Also, a presumed diagnosis of ganglionic tuberculosis was established. Conclusion: The slow progression of HIV-2 disease could explain the low frequency of this condition, however, more studies should be carried out for a better understanding of HIV-2 pathophysiology and its associated complications.

Human immunodeficiency virus-associated dementia complex with positive 14-3-3 protein in cerebrospinal fluid:A case report

BACKGROUND Human immunodeficiency virus(HIV)-associated dementia(HAD)is a subcortical form of dementia characterized by memory deficits and psychomotor slowing.However,HAD often presents with symptoms similar to those of Creutzfeldt-Jakob disease(CJD),particularly in patients with acquired immune deficiency syndrome(AIDS).CASE SUMMARY We report the case of a 54-year-old male who exhibited cognitive dysfunction and secondary behavioral changes following HIV infection and suspected prion exposure.The patient was diagnosed with HIV during hospitalization and his cerebrospinal fluid tested positive for 14-3-3 proteins.His electroencephalogram showed a borderline-abnormal periodic triphasic wave pattern.Contrast-enhanced magnetic resonance imaging revealed moderate encephalatrophy and demyelination.Initially,symptomatic treatment and administration of amantadine were pursued for presumed CJD,but the patient’s condition continued to deteriorate.By contrast,the patient’s condition improved following anti-HIV therapy.This individual is also the only patient with this prognosis to have survived over 4 years.Thus,the diagnosis was revised to HAD.CONCLUSION In the diagnostic process of rapidly progressive dementia,it is crucial to rule out as many potential causes as possible and to consider an autopsy to diminish diagnostic uncertainty.The 14-3-3 protein should not be regarded as the definitive marker for CJD.Comprehensive laboratory screening for infectious diseases is essential to enhance diagnostic precision,especially in AIDS patients with potential CJD.Ultimately,a trial of diagnostic treatment may be considered when additional testing is not feasible.

NLRP3-dependent pyroptosis is required for HIV-1 gp120- induced neuropathology

The human immunodeficiency virus-1(HIV-1)envelope protein gp120 is the major contributor to the pathogenesis of HIVassociated neurocognitive disorder(HAND).Neuroinflammation plays a pivotal role in gp120-induced neuropathology,but how gp120 triggers neuroinflammatory processes and subsequent neuronal death remains unknown.Here,we provide evidence that NLRP3 is required for gp120-induced neuroinflammation and neuropathy.Our results showed that gp120-induced NLRP3-dependent pyroptosis and IL-1βproduction in microglia.Inhibition of microglial NLRP3 inflammasome activation alleviated gp120-mediated neuroinflammatory factor release and neuronal injury.Importantly,we showed that chronic administration of MCC950,a novel selective NLRP3 inhibitor,to gp120 transgenic mice not only attenuated neuroinflammation and neuronal death but also promoted neuronal regeneration and restored the impaired neurocognitive function.In conclusion,our data revealed that the NLRP3 inflammasome is important for gp120-induced neuroinflammation and neuropathology and suggest that NLRP3 is a potential novel target for the treatment of HAND.