NLRP3 and IL-1ß Gene Expression Is Elevated in Monocytes From HIV-Treated Patients With Neurocognitive Disorders.

BACKGROUND: Systemic immune activation and inflammation in chronic HIV infection are driving factors of non-AIDS-related events, including neurocognitive impairment. The role of inflammasome in monocytes from patients with HIV infection has been extensively studied, but its association with the extent of neurocognitive dysfunction has been poorly investigated. METHODS: We enrolled 79 HIV-positive patients; 44 with varying levels of HIV-associated neurocognitive disorder (HAND) and 35 without and 8 healthy donors. HAND subtypes included asymptomatic neurocognitive impairment (asymptomatic neurocognitive impairment; n = 19), mild neurocognitive disorder (MND; n = 17), and HIV-associated dementia (n = 8). We quantified plasmatic concentrations of proinflammatory cytokines (TNF-α, IL-6, IL-17A, IL-1ß, and IFN-γ) for all HIV patients, and the mRNA expression of genes involved in the inflammasome activity (NLRP3, PYCARD, NAIP, AIM2, IL-1ß, and IL-18) in monocytes of a subgroup of 28 HIV patients and 8 healthy donors. RESULTS: HIV patients' plasma concentrations of IFN-γ, IL-1ß, and IL-17A were undetectable. Levels of TNF-α and IL-6 were similar among the HIV patient groups. A trend toward an increased expression of inflammasome genes according to neurocognitive disorder severity was observed. Of note, the NLRP3 mRNA relative expression was higher in MND compared with other groups, and IL-1ß was lower in MND than HIV-associated dementia patients. CONCLUSIONS: Changes in inflammasome components in circulating monocytes according to different HAND severity suggest that NLRP3 may be a possible biomarker or target to better understand and treat the link between systemic inflammation and neurocognitive impairment in HIV infection.

HIV in Iran: onset, responses, and future directions.

Iran, a country in the Middle East and North Africa (MENA) region, has been actively involved in the fight against HIV/AIDS over the past three decades. The unique features of the HIV epidemic in Iran are reflected by the modes of transmission and its recent changes to improve management and prevention programs. In this review, we recount the initial onset and subsequent spread of HIV infection in Iran, beginning with the first case diagnosed to the ongoing responses and most recent achievements in controlling this epidemic. Although in the MENA region, Iran is one of the pioneers in implementing pertinent policies including harm reduction services to decrease HIV incidence, drug injection still continues to be the major risk of infection. In line with other nations, the programs in Iran aim at the UNAIDS 90-90-90 targets (UNAIDS 90-90-90 global targets to end the AIDS epidemic by 2020: by 2020, 90% of all people living with HIV will know their HIV status; 90% of all people with diagnosed HIV infection will receive sustained antiretroviral therapy; and 90% of all people receiving antiretroviral therapy will have viral suppression) and to eliminate mother-to-child HIV transmission. In this article, we discuss the strengths and shortcomings of the current HIV programs and offer suggestions to provide a better perspective to track and respond to the HIV epidemic. More generally, our account of the national religious and cultural circumstances as well as obstacles to the approaches chosen can provide insights for decision-makers in other countries and institutions with comparable settings and infrastructures.

HIV Prevalence and Correlations in Prisons in Different Regions of the World: A Review Article.

The prevalence of HIV is substantially higher among prisoners than the general population, while the incidence varies considerably in different regions around the world. If we consider Sub-Saharan Africa as one region with the highest prevalence of HIV, data on African prisoners would be limited. Despite the low prevalence of HIV in the Middle East and North Africa, its incidence is rising in these regions with a few exceptions; there are insufficient data on HIV prevalence in prisons. A similar situation is present in both Pacific and Central Asia as well as in Eastern Europe. A high rate of infection is mainly observed among prisoners in Western and Central parts of Europe, since the data from these are more available than other parts. Nowadays, the sexual transmission mode and tattooing are important ways in HIV risks among prisoners after injecting drug use as the most common route of HIV transmission in all regions. However, it is difficult to compare and analyze the prevalence of HIV among prisoners in different regions regarding the limited data and different methods which they used in collecting data. Eventually, it can certainly be said that prisons are one of the high-risk places for HIV transmission; on the other hand, can be a suitable place for implementing HIV case-finding, linkage to treatment and harm reduction programs.

Herpes simplex virus-1 entrapped in Candida albicans biofilm displays decreased sensitivity to antivirals and UVA1 laser treatment.

BACKGROUND: Recently, we published data suggesting a mutualistic relationship between HSV-1 and Candida. albicans; in particular: (a) HSV-1 infected macrophages are inhibited in their anti-Candida effector function and (b) Candida biofilm protects HSV-1 from inactivation. The present in vitro study is aimed at testing the effects of Candida biofilm on HSV-1 sensitivity to pharmacological and physical stress, such as antiviral drugs (acyclovir and foscarnet) and laser UVA1 irradiation. We also investigated whether fungus growth pattern, either sessile or planktonic, influences HSV-1 sensitivity to antivirals. METHODS: Mature Candida biofilms were exposed to HSV-1 and then irradiated with laser light (UVA1, 355 λ). In another set of experiments, mature Candida biofilm were co-cultured with HSV-1 infected VERO cells in the presence of different concentrations of acyclovir or foscarnet. In both protocols, controls unexposed to laser or drugs were included. The viral yield of treated and untreated samples was evaluated by end-point titration. To evaluate whether this protective effect might occur in relation with a different growth pattern, HSV-1 infected cells were co-cultured with either sessile or planktonic forms of Candida and then assessed for susceptibility to antiviral drugs. RESULTS: UVA1 irradiation caused a 2 Log reduction of virus yield in the control cultures whereas the reduction was only 1 Log with Candida biofilm, regardless to the laser dose applied to the experimental samples (50 or 100 J/cm2). The presence of biofilm increased the IC90 from 18.4-25.6 J/cm2. Acyclovir caused a 2.3 Log reduction of virus yield in the control cultures whereas with Candida biofilm the reduction was only 0.5 Log; foscarnet determined a reduction of 1.4 Log in the controls and 0.2 Log in biofilm cultures. Consequently, the ICs50 for acyclovir and foscarnet increased by 4- and 12-folds, respectively, compared to controls. When HSV-1 was exposed to either sessile or planktonic fungal cells, the antiviral treatments caused approximately the same weak reduction of virus yield. CONCLUSIONS: These data demonstrate that: (1) HSV-1 encompassed in Candida biofilm is protected from inactivation by physical (laser) and pharmacological (acyclovir or foscarnet) treatments; (2) the drug antiviral activity is reduced at a similar extent for both sessile or planktonic Candida.

Borna disease virus (BDV) infection in psychiatric patients and healthy controls in Iran.

BACKGROUND: Borna disease virus (BDV) is an evolutionary old RNA virus, which infects brain and blood cells of humans, their primate ancestors, and other mammals. Human infection has been correlated to mood disorders and schizophrenia, but the impact of BDV on mental-health still remains controversial due to poor methodological and cross-national comparability. METHOD: This first report from the Middle East aimed to determine BDV infection prevalence in Iranian acute psychiatric disorder patients and healthy controls through circulating immune complexes (CIC), antibodies (Ab) and antigen (pAg) in blood plasma using a standardized triple enzyme immune assay (EIA). Samples of 314 subjects (114 psychiatric cases, 69 blood donors, and 131 healthy controls) were assayed and data analyzed quantitatively and qualitatively. RESULTS: CICs revealed a BDV prevalence of one third (29.5%) in healthy Iranian controls (27.5% controls; 33.3% blood donors). In psychiatric patients CIC prevalence was higher than in controls (40.4%) and significantly correlating with bipolar patients exhibiting overt clinical symptoms (p = 0.005, OR = 1.65). CIC values were significantly elevated in bipolar (p = 0.001) and major depressive disorder (p = 0.029) patients as compared to controls, and in females compared to males (p = 0.031). CONCLUSION: This study supports a similarly high prevalence of subclinical human BDV infections in Iran as reported for central Europe, and provides again an indication for the correlation of BDV infection and mood disorders. Further studies should address the morbidity risk for healthy carriers and those with elevated CIC levels, along with gender disparities.