Cognitive Impairment in People Living with HIV and the Impact of Mood: Results from a Cross-Sectional Study.

Background: Human Immunodeficiency Virus (HIV) infection represents a significant public health concern and, consequently, the incidence of HIV-Associated Neurocognitive Disorder (HAND) has grown over the years. The present study aims to assess HAND with the Montreal Cognitive Assessment (MoCA) in People Living With HIV/AIDS (PLWHA) to find significant associations with cognitive impairment. Methods: The study included 210 PLWHA, aged from 30 to 81 years, of whom, 137 (65.2%) were males. They were assessed at the Immunology Service of the University Hospital of Monserrato, Cagliari, Italy, between November 2022 and April 2023. Results: The sample showed an overall optimal response to antiretroviral therapy, as shown by the excellent levels of CD4+ lymphocytes and HIV RNA copies. A sum of 115 subjects (54.8%) were considered cognitively impaired and the multivariate analysis demonstrated that it was independently associated with duration of infection (OR: 0.96), age (OR: 1.12), alanine aminotransferase (ALT) (OR: 1.02), and depression (OR: 1.33). By dichotomizing the variables, the significance of the association was confirmed for age (65-year threshold) (χ2: 5.142, p = 0.0233) and depression (χ2: 7.834, p = 0.0051). Conclusions: Our study demonstrates that it is hard to find both statistically and clinically significantly associated variables with cognitive impairment in PLWHA, and that the strongest independent association is with depressed mood.

HCV treatment in Sardinian HIV-HCV coinfected patients: a real-life perspective study on safety, efficacy, and immune reconstitution.

BACKGROUND: HIV-HCV co-infected patients have long been considered difficult-to-treat. The introduction of direct-acting antivirals (DAAs) changed this paradigm.We evaluated the efficacy and safety of DAA-based regimens and the impact of DAAs-induced HCV clearance on the immunological status in HIV-HCV co-infected patients. RESEARCH DESIGN AND METHODS: HIV patients starting HCV treatment with DAAs were included. Sustained virological response at 12 weeks after DAAs treatment (SVR12) was assessed. CD4+ and CD8+ blood cell count and CD4+/CD8+ ratio were recorded at baseline and six months post DAA treatment. We enrolled 201 patients, 76.1% males, median age 54 years, the most common genotypes 3 (29.8%) and 1a (29.4%), 40.3% with cirrhosis, 32.3% with prior interferon-based treatment. All patients were on antiretroviral treatment, 24.4% on methadone maintenance therapy and 22.6% on psychotropic drugs. RESULTS: SVR12 was 98.4%, the most common side effects were pruritus (8.4%), headache (7.4%) and fatigue (5.9%). An increase in CD4+ and CD8+ cell count was observed six months after completion of DAAs treatment, in particular in patients with low CD4+ cell count at baseline. CONCLUSIONS: DAAs treatment resulted in high SVR12 rates, was well tolerated and Increased CD4+ and CD8+, especially in patients with low CD4+ cell count at baseline.

The Repeatable Battery for the Assessment of Neuropsychological Status as a screening strategy for HIV-Associated Neurocognitive Disorders.

HIV-infected people are at risk for neurocognitive impairment (HIV-Associated Neurocognitive Disorders - HAND). To evaluate whether the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), a widely used neurocognitive screening tool, could be a valid instrument for HAND identification, we evaluated 166 HIV-infected subjects. Our results showed that 96 (57.8%) HIV-infected scored RBANS Total Index Score <85 (at least one SD below the normal), 12 (7.2%) of them scored RBANS Total Index Score <70 (at least 2 SD below the normal, indicating a possible HIV-Associated Dementia). The more compromised areas were Immediate and Delayed Memory, and Attention. In the group with RBANS Total Index Score <85, there were significantly lower scores of Mini Mental State Examination (P = 0.0008), Clock Drawing Test (P = 0.0015) and higher score of Geriatric Depression Scale (P = 0.02) compared to the RBANS Total Index Score ≥85 group. Using a stepwise logistic regression, considering RBANS Total Index Score as dependent variable, we found a positive interaction with tenofovir/emtricitabine assumption (P = 0.027), Clock Drawing Test (P = 0.0125) and educational level (P = 0.0054). Being the viro-immunological markers not capable of predicting cognitive decline in HIV-infected individuals, our data suggest that RBANS may be a valid tool for the early identification of HIV-related cognitive impairment.

Resting-state functional connectivity MRI analysis in Human Immunodeficiency Virus and Hepatitis C Virus co-infected subjects. A pilot study.

BACKGROUND AND PURPOSE: Hepatitis C virus (HCV) co-infection's role on cognitive impairment of human immunodeficiency virus (HIV) positive patients is still debated and functional neuroimaging evaluation on this matter is lacking. To provide further insight about HCV's neuro-effects on HIV associated neurocognitive disorder (HAND), we performed a pilot resting state (RS) functional connectivity magnetic resonance imaging (fcMRI) study to find eventual functional connectivity alteration that could reflect HCV related cognitive performance degradation. METHODS: Eighteen patients (8 HIV, 10 HIV + HCV), either impaired or not impaired, were assessed with RS fcMRI. A statistic model including cognitive testing results was elaborated during data processing to evaluate brain networks alteration related to actual cognitive status in patients. RESULTS: Statistically significant different patterns of connectivity were found: HCV co-infection modified 17 ROIs' connectivity with 45 supra-threshold connections (p-FDR min 0.0022, max 0.0497). ROIs most involved were right pallidum, brainstem, vermian lobules 1-2 and right cerebellar lobule 10. Graph theory analysis did not demonstrate significant difference between networks, but HCV related modifications at ROI's local level were found, with particular involvement of ROIs of frontal lobe, basal ganglia and cerebellum. Increased fronto-striatal dysfunctions have been already reported as consequences of HCV infection and could reflect an additive effect. Cerebellar alterations are associated with HIV and HAND, but not with HCV infection, suggesting a synergic effect of HCV. CONCLUSION: Our study demonstrates RS fcMRI can help to understand the interactions between HIV and HCV co-infection, and our preliminary results suggest synergic effects of HCV in HIV-related brain functional modification.

HLA-dependent hypersensitivity to nevirapine in Sardinian HIV patients.

BACKGROUND: Hypersensitivity reaction to nevirapine, which in some cases can be fatal, shows a higher prevalence in Sardinia in comparison with other Italian regions. OBJECTIVE: This study demonstrates that hypersensitive reaction to nevirapine in Sardinian HIV-infected patients is associated with the HLA Cw8-B14 haplotype. These two HLA class I antigens are in strong linkage disequilibrium in the Sardinian population. METHODS: Forty-nine Sardinian HIV-positive patients treated with nevirapine were studied. Thirteen (26%), developed a hypersensitive reaction thus requiring the drug to be discontinued. HLA class I and II molecular typing was performed in both nevirapine-hypersensitive and nevirapine-tolerant patients. To avoid biased representation of the allele frequencies in the two groups of treated patients, molecular typing was also performed in 82 HIV-positive patients who had not been treated with nevirapine. RESULTS: Considerable overlap was observed for the clinical, immunological and demographic characteristics of the 13 hypersensitive patients and 36 tolerant patients. Clinical parameters included viral load, status of HIV infection, CD4 and CD8 cell counts, hepatitis C virus/hepatitis B virus co-infections. Forty-six percent (6/13) of the nevirapine-hypersensitive subjects had the HLA-Cw8 and HLA-B14(65) antigens compared with 5% (2/36) of the nevirapine-tolerant group (P = 0.004; Pc = 0.05). CONCLUSION: In agreement with other recent reports, the utility of HLA typing in HIV patients to identify genetic factors that may confer susceptibility to drug-induced hypersensitive reaction was confirmed. A careful choice of antiretroviral therapy in susceptible individuals should significantly reduce the risk of severe hypersensitive reaction.

Virologic correlates of adherence to antiretroviral medications and therapeutic failure.

Adherence to antiretroviral therapy affects the pharmacokinetics of antiviral drugs and activates a cascade of events ultimately leading to therapeutic success or failure. An optimal adherence usually affords minimal rounds of virus replication and rare spontaneous mutations, which are unable to be fixed in the genome because of the competition of wild-type (more fit) strains. Therefore, adherence-based therapeutic success is mostly accompanied by the prevalence of wild-type strains. In case of poor adherence, virus replication is substantial, and mutations randomly occurring tend to be fixed within the genome. Under these conditions, mutated-resistant strains will outgrow wild-type virus (sensitive to antivirals and thereby unable to compete enough with resistant strains for cellular targets): thus, therapeutic failure occurs, and mutated resistant strains are predominant. In the case of very low or absent adherence, virologic failure occurs, although wild-type virus (whose replication is not significantly affected by antivirals) is not outgrown by mutated strains randomly produced but unable to be fixed within the genome. Taken together, these events and their consequences strongly support the relevance of a tight and continuous monitoring of adherence to antiretroviral drugs to prevent the risk of development of mutated strains often cross-resistant to the majority of antiretroviral drugs currently available.