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Objectives In view of the fact that mucosal damage associated with HIV-1 infection leads to microbial translocation despite successful antiretroviral treatment, we analysed microbial translocation and expression of the gut-homing β7 receptor on peripheral T cells in HIV-1-infected individuals. Methods Fifteen long-term suppressed HIV-1-infected patients, of whom seven had their treatment intensified with maraviroc and eight with raltegravir, were included in the study. Samples at baseline, at week 48 of intensification, and at weeks 12 and 24 after deintensification were analysed for soluble CD14, lipopolysaccharide ( LPS), LPS-binding protein, gut-homing β7 receptor and T-cell subsets. Results The increases in both microbial translocation and expression of the gut-homing β7 receptor on activated CD8 T cells found during maraviroc intensification were reduced after deintensification. Moreover, the correlations between activated β7+ T cells and LPS levels found during intensification with maraviroc ( P = 0.036 and P = 0.010, respectively) were lost during deintensification. In contrast, microbial translocation was stable during raltegravir intensification, with the exception of decreased LPS levels and activated CD4 β7+ T cells, which reverted to baseline values after deintensification. Conclusions Microbial translocation is an important factor in gut immune activation and mucosa inflammation, as evidenced by the association between the dynamics of microbial translocation and activated T cells expressing the gut-homing β7 receptor. The recruitment of activated β7+ T cells to the gut tract when alteration of microbial translocation is maximum may be the major mechanism for recovery of mucosal integrity. [ABSTRACT FROM AUTHOR]

The article presents a study which investigates drug usage among Hispanic men who have sex with men (HMSM) in South Florida. The study used 2 subscales of Behavioral Acculturation Scale, audio-computer assisted self-interview (ACASI) and multivariate analysis. The 566 HMSM respondents were recruited through the internet and community venues. The results show that the respondents have 43% of drug use and 45% unprotected anal sex. It reveals that drug use was linked with HIV seropositiviy, stronger gay community attachment, higher numbers of sex partners and lower homophobia levels. Proyecto Safer Options for Life (SOL), a theoretically grounded intervention that allows respondents to determine how culture and relationships influence HIV risk behaviors, is discussed.

Objective. The goal of this study is to describe the sexual practices, drug use behaviors, psychosocial factors, and predictors of unprotected anal intercourse (UAI) in a sample of Hispanic men who have sex with men (MSM) born in Latin American and Caribbean (LAC) countries who currently reside in Miami-Dade County, Florida. Methods. Hispanic MSM (N = 566) recruited from community and Internet venues completed a computer-assisted self-interview assessing sociodemographic factors, drug use, sexual behaviors, and psychosocial factors. We focused on the 470 men who were born in LAC countries, including Puerto Rico. We first examined separately, by country of origin, the sexual practices, drug use behaviors, and psychosocial factors of the sample. We then collapsed the groups and examined the factors associated with UAI in the previous 6 months for the entire sample of Hispanic MSM from LAC countries. Results. In the previous 6 months, 44% of the sample engaged in UAI, and 41% used club drugs. At the multivariate level, psychological distress, higher number of sexual partners, club drug use, HIV-positive status at the time of immigration, and greater orientation to American culture were significantly associated with UAI in the previous 6 months. Conclusion. Many MSM born in LAC countries engage in HIV-related risk behaviors in the AIDS epicenter of Miami-Dade County, Florida. Culturally appropriate interventions should address these risk behaviors in this underserved population. [ABSTRACT FROM AUTHOR]

Chatbots increase business productivity by handling customer conversations instead of human agents. Similar rationale applies to use chatbots in the healthcare sector, especially for health coaches who converse with clients. Chatbots are nascent in healthcare. Study findings have been mixed in terms of engagement and their impact on outcomes. Questions remain as to chatbot acceptability with coaches and other providers; studies have focused on clients. To clarify perceived benefits of chatbots in HIV interventions we conducted virtual focus groups with 13 research staff, eight community advisory board members, and seven young adults who were HIV intervention trial participants (clients). Our HIV healthcare context is important. Clients represent a promising age demographic for chatbot uptake. They are a marginalized population warranting consideration to avoid technology that limits healthcare access. Focus group participants expressed the value of chatbots for HIV research staff and clients. Staff discussed how chatbot functions, such as automated appointment scheduling and service referrals, could reduce workloads while clients discussed the after-hours convenience of these functions. Participants also emphasized that chatbots should provide relatable conversation, reliable functionality, and would not be appropriate for all clients. Our findings underscore the need to further examine appropriate chatbot functionality in HIV interventions. [ABSTRACT FROM AUTHOR]

There is evidence that risks for HIV and sexually transmitted infections among adolescent females are higher for those with older male sexual partners. Yet, little empirical research has been conducted with male adolescents who engage in sexual activity with older men. In this article, we summarize in a number of ways the range of sexual activity reported by an ethnically diverse sample of 200 gay and bisexual male youth (15-22 years old) in Chicago and Miami. A general pattern of progression from oral sex with men to both receptive and insertive anal sex with men appeared to characterize the sample during their adolescence. Further, there appeared to be a high degree of 'versatile' positioning among the sexually active gay and bisexual young men, in both age-discrepant and age-concordant dyads. Risk analysis revealed having primarily age-concordant partners to be a significant predictor of sexual risk behavior. HIV risk among young gay and bisexual men engaging in sexual activity with older men may occur not only within a distinct biological context from their heterosexual counterparts, but also in a social context that may not as rigidly bound to traditional assumptions about age, gender, and power. The significant associations among participants with partners who were the same age and the risk behavior measures in this analysis have implications for HIV prevention efforts. [ABSTRACT FROM AUTHOR]

Unlabelled: Treatment with highly active antiretroviral therapy (HAART) has been shown to modify viral replication dynamics and lead to a significant recovery of CD4+ T-cells. A retrospective multicentre observational study was performed in a non-study population of 151 HIV-1-infected children, categorized into four groups according to therapy: untreated (NT), on monotherapy (MT) with a nucleoside inhibitor, on combination therapy (CT) with two nucleoside inhibitors, and on HAART, protease inhibitor containing regimens, to assess the "real-life" effectiveness of these different therapies on plasma viral load (VL) and CD4+ T-cells. VL was quantified using a standard molecular assay. CD4+ and CD8+ T-cells subsets were determined by flow cytometry. The HAART group showed the highest relative proportion (RP) of increases in 5, 10, 15 and 20% of CD4+ T-cells over baseline, and the earliest fall-off of VL (0.5, 1, 1.5 and 2 log10 copies ml-1). The RP of the fall-off of 0.5, 1, 1.5 and 2 log10 VL below baseline was 3-fold higher in HAART group than in the MT and CT groups. However, no differences were found among the groups of treated children in reaching undetectable VL.Conclusion: A better evolution of VL and CD4+ T-cells was evident in children on HAART, indicating a positive effect on the immune system and clinical status, inhibiting HIV-1 replication and enabling the recovery of CD4+ T-cell counts. [ABSTRACT FROM AUTHOR]

Abstract: Youth living with HIV (YLH) experience multiple disease‐related stresses along with the same structural and developmental challenges faced by their uninfected peers; alcohol use among YLH represents a risk behavior by virtue of potential effects on youth health and increased likelihood of engaging in unprotected sex while drinking alcohol. Research aimed at better understanding the interplay of individual‐ and neighborhood‐level influences on alcohol use for YLH is needed to inform interventions. This study examined whether socioeconomic disadvantage (SED) and social support influence, independently and through interaction, alcohol use in YLH. Data from the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) consisted of YLH across 538 neighborhoods in the United States who acquired HIV behaviorally. Neighborhood‐specific data were compiled from the 2010 U.S. Census Bureau and matched with individual‐level data from the ATN (N = 1,357) to examine effects that contribute to variation in frequency of alcohol use. Other drug use, being male, being non‐Black, and older age were associated with greater alcohol use. Higher social support was negatively associated with alcohol use frequency. A cross‐level interaction indicated that the association found between decreasing social support and increasing alcohol use frequency was weakened in areas with lower SED. Implications are discussed. [ABSTRACT FROM AUTHOR]

Background: Initiating ART during acute/recent HIV-1 infection reduces viral reservoir formation. It has been proposed that, during this phase, the size of the viral reservoir could be further reduced by the association of immunomodulatory therapy with ART. Contradictory results have emerged, however, from two trials evaluating the impact on immune recovery and the viral reservoir of adding cyclosporine A to ART during primary HIV-1 infection.Patients and methods: Twenty patients with acute/recent HIV-1 infection were randomized to receive ART alone (tenofovir, emtricitabine and lopinavir/ritonavir) or associated with 8 weeks of cyclosporine A (0.3-0.6 mg/kg twice daily). The impact on viral load, immune response and integrated and non-integrated DNA viral reservoir at 0, 8 and 36 weeks of treatment was evaluated.Results: The estimated median time from HIV-1 infection to ART onset was 63 days (IQR 53; 79.5) with 90% of patients at Fiebig V stage. No significant differences were observed in viral load decay, CD4 T cell recovery, immune response markers or the evolution of integrated DNA at week 8 (end of cyclosporine A) and week 36 between groups. However, non-integrated DNA significantly increased in the cyclosporine A arm between weeks 0 and 36. Cyclosporine A was well tolerated.Conclusions: Adding cyclosporine A to ART during acute/recent infection did not improve immune recovery. However, unintegrated DNA increased in the cyclosporine A group, suggesting an anti-integration effect, a point warranting further research (ClinicalTrials.gov Identifier: NCT00979706). [ABSTRACT FROM AUTHOR]

Background [ABSTRACT FROM AUTHOR]

Objectives Hepatitis C virus (HCV) antiviral therapy might lead to decreased chronic immune activation and endothelial dysfunction associated with cardiovascular risk. The aim was to evaluate the effect of HCV eradication on serum markers of inflammation and endothelial dysfunction markers in HIV/HCV co-infected patients. Methods We carried out a retrospective study of 69 HIV/HCV co-infected patients on interferon (IFN)-α plus ribavirin. In addition, 47 HIV-infected subjects were selected as a control group. A sustained virological response (SVR) was defined as an undetectable HCV viral load up to 24 weeks after the end of treatment. Tumour necrosis factor (TNF) receptor-1 (TNF-R1), soluble E-selectin (sE-selectin), soluble P-selectin (sP-selectin), soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured using a multiplex immunoassay kit. Results HIV/HCV co-infected patients had higher values of soluble TNF-R1 (sTNF-R1), sE-selectin and sICAM-1 than HIV mono-infected patients (P < 0.05). SVR patients had a decrease in sTNF-R1, sP-selectin, sE-selectin and sICAM-1 during anti-HCV treatment (P < 0.05) and, at the end of treatment, SVR patients had lower values of sTNF-R1, sE-selectin and sVCAM-1 than non-responder patients (P < 0.05), although the values of sTNF-R1, sP-selectin, sE-selectin and sICAM-1 remained higher than in HIV mono-infected patients (P < 0.05). Moreover, we found a significant positive relationship between an increase in sTNF-R1 and increases in sP-selectin, sE-selectin and sICAM-1 during anti-HCV therapy. Conclusions Chronic hepatitis C infection induces alterations of markers of inflammation and endothelial dysfunction. Eradication of HCV, following IFN-α and ribavirin therapy, reduces immune activation as well as markers of inflammation and endothelial dysfunction. [ABSTRACT FROM PUBLISHER]

Abstract: One of the primary limitations of RNA interference as a technique for gene regulation is effective delivery of siRNA into the target cells. Dendrimers are nanoparticles that are increasingly being used as oligonucleotide and drug delivery vehicles. We have developed amino-terminated carbosilane dendrimers (CBS) as a means to protect and transport siRNA. Initially, stability studies showed that CBS bind siRNA via electrostatic interactions. Dendrimer-bound siRNA was found to be resistant to degradation by RNase. Cytotoxicity assays of CBS/siRNA dendriplexes with peripheral blood mononuclear cells (PBMC) and the lymphocytic cell line SupT1 revealed a maximum safe dendrimer concentration of 25 µg/ml. Next, utilizing flow cytometry and confocal microscopy, lymphocytes were seen to be successfully transfected by fluorochrome-labeled siRNA either naked or complexed with CBS. Dendriplexes with +/− charge ratio of 2 were determined to have the highest transfection efficiency while maintaining a low level of toxicity in these systems including hard-to-transfect HIV-infected PBMC. Finally, CBS/siRNA dendriplexes were shown to silence GAPDH expression and reduce HIV replication in SupT1 and PBMC. These results point to the possibility of utilizing dendrimers such as CBS to deliver and transfect siRNA into lymphocytes thus allowing the use of RNA interference as a potential alternative therapy for HIV infection. [Copyright &y& Elsevier]

SUMMARY The objective of this study was to study immune system status in long-term asymptomatic (LTA) HIV-1-infected children. A cross-sectional study was used, involving HIV-1-infected children over 7 years of age who were rated into two groups according to their clinical and immunological classification: (a) LTA: 7 asymptomatic HIV-1-infected children in A1; (b) Rapid progressor (RP): 14 age-matched C3 HIV-1-infected children. The control group consisted of 17 age-matched uninfected children. The characterization of CD4+ T-cell subsets was determined by three-colour flow cytometry. The proliferative response and cytokine production by activated peripheral blood T-cells were also measured. IL-7 levels were measured in serum. Thymic production of T-cells was quantified by TCR rearrangement excision circles (TRECs). The LTA children showed similar proliferative responses to PHA, PWM and anti-CD3+ anti-CD28, but lower responses to tetanus toxoid and streptokinase, in comparison with the controls but always higher responses in comparison with the RP group. The production of TNF-α and IFN-γ was similar in the LTA and control groups, and both were higher than the levels in the RP group. The LTA group showed a lower percentage of memory CD4+ T-cells (CD4+ CD45RO+, CD4+ CD45RA-CD62L+) than the control and RP groups. The LTA group also showed lower percentages of CD4+ CD7- cells than the controls. As for naïve CD4+ T-cells (CD4+ CD45RA+ CD62L+), CD4+ CD45RA+ and CD4+ CD62L+ cells, the LTA group showed higher values than the control and RP groups. The LTA group showed higher percentages of CD4+ HLA-DR+ CD38+ than the controls, but lower values than the RP group. In contrast, the LTA group had percentages of CD4+ HLA-DR-CD38+ T-cells higher than both the control and RP groups, whereas CD4+ CD38+ levels were only higher in the LTA group in comparison with the controls. CD4+ HLA-DR+ CD38- and CD4+ HLA-DR+ cell numbers were lower in the LTA group in... [ABSTRACT FROM AUTHOR]

SUMMARY The objective of the study was to investigate the relationship between various CD4+ T cell subsets and the ability of peripheral blood mononuclear cells (PBMC) to proliferate to several stimuli in vertically human immunodeficiency virus type 1 (HIV-1)-infected children. We studied 29 HIV-1-infected children on highly active antiretroviral therapy (HAART) (median duration: 12·3 months). T cell subsets were determined by flow cytometry. Plasma viral load (VL) was quantified using a standardized molecular method. Proliferative responses were evaluated by [3 H]-thymidine incorporation. Decreased proliferative responses of PBMC to pokeweed mitogen (PWM) were found for HIV-1-infected children in Centers for Disease Control (CDC) clinical categories B and C when compared to the control group (P < 0·05). Similarly, children with ≤ 15% CD4+ T cells showed a decrease in proliferative responses to PWM (P < 0·01), anti-CD3 + anti-CD28 (P < 0·01) and phytohaemagglutinin (PHA) (P < 0·05) with respect to the control group and to children with CD4+ T cells ≥ 25%. Proliferative responses to PWM, anti-CD3+ , anti-CD28 and PHA had a statistically significant positive correlation with CD3+ /mm3 , CD4+ /mm3 , % CD4 T cells, CD4/CD8 ratio and the percentage of naive T cell subsets (CD4+ CD45RO– HLA-DR– , CD4+ CD45RA+ CD62L+ , CD4+ CD45RA+ ), CD4+ CD62L+ and CD4+ T cells co-expressing CD38+ (CD4+ HLA-DR- CD38+ , CD4+ CD38+ ). Moreover, we found a negative correlation between PBMC proliferative responses and % CD8 T cells, memory, memory-activated and activated CD4+ T cell subsets. Lower proliferative responses to PWM (P <... [ABSTRACT FROM AUTHOR]

The human immunodeficiency virus 1 (HIV-1) envelope regulates the initial attachment of viral particles to target cells through its association with CD4 and either CXCR4 or CCR5. Although F-actin is required for CD4 and CXCR4 redistribution, little is known about the molecular mechanisms underlying this fundamental process in HIV infection. Using CD4+ CXCR4+ permissive human leukemic CEM T cells and primary lymphocytes, we have investigated whether HIV-1 Env might promote viral entry and infection by activating ERM (ezrin-radixin-moesin) proteins to regulate F-actin reorganization and CD4/CXCR4 co-clustering. The interaction of the X4-tropic protein HIV-1 gp120 with CD4 augments ezrin and moesin phosphorylation in human permissive T cells, thereby regulating ezrin-moesin activation. Moreover, the association and clustering of CD4-CXCR4 induced by HIV-1 gp120 requires moesin-mediated anchoring of actin in the plasma membrane. Suppression of moesin expression with dominant-negative N-moesin or specific moesin silencing impedes reorganization of F-actin and HIV-1 entry and infection mediated by the HIV-1 envelope protein complex. Therefore, we propose that activated moesin promotes F-actin redistribution and CD4-CXCR4 clustering and is also required for efficient X4-tropic HIV-1 infection in permissive lymphocytes. [ABSTRACT FROM AUTHOR]