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HIV-1-infected Individuals (hiv-1-infected + individual)
Selected AbstractsInterleukin-10-secreting T cells define a suppressive subset within the HIV-1-specific T-cell populationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2009Eirik A. Torheim Abstract Recent studies have indicated that Treg contribute to the HIV type 1 (HIV-1)-related immune pathogenesis. However, it is not clear whether T cells with suppressive properties reside within the HIV-1-specific T-cell population. Here, PBMC from HIV-1-infected individuals were stimulated with a 15-mer Gag peptide pool, and HIV-1-specific T cells were enriched by virtue of their secretion of IL-10 or IFN-, using immunomagnetic cell-sorting. Neither the IL-10-secreting cells nor the IFN-,-secreting cells expressed the Treg marker FOXP3, yet the IL-10-secreting cells potently suppressed anti-CD3/CD28-induced CD4+ as well as CD8+ T-cell proliferative responses. As shown by intracellular cytokine staining, IL-10- and IFN-,-producing T cells represent distinct subsets of the HIV-1-specific T cells. Our data collectively suggest that functionally defined HIV-1-specific T-cell subsets harbor potent immunoregulatory properties that may contribute to HIV-1-associated T-cell dysfunction. [source] Progressive CD127 down-regulation correlates with increased apoptosis of CD8 T cells during chronic HIV-1 infectionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2009Shu-Ye Zhang Abstract Chronic HIV-1 infection can induce a significant decrease in CD127 expression on CD8 T cells, but the underlying mechanisms and immunological consequences are unclear. In this study, we investigated CD127 expression on CD8 T cells from a total of 51 HIV-1-infected subjects and 16 healthy individuals and analyzed the association between CD127 expression and CD8 T-cell apoptosis in these HIV-1-infected subjects. We found that CD127 expression on total CD8 T cells was significantly down-regulated, which was correlated with the increased CD8 T-cell apoptosis and disease progression of chronic HIV-1 infection. The in vitro addition of IL-7 efficiently rescued the spontaneous apoptosis of CD8 T cells from HIV-1-infected individuals. IL-7 stimulation also transiently down-regulated CD127 expression, whereas some of the CD127, CD8 T cells regained CD127 expression soon after IL-7 was retracted from the incubation medium. Thus, IL-7 stimulation reduced apoptosis of both CD127+ and CD127,CD8 T cells to some degree. These data indicate that CD127 loss might impair IL-7 signaling and increase CD8 T-cell apoptosis during HIV-1 infection. This study, therefore, will extend the notion that IL-7 could be a good candidate for immunotherapy in HIV-1-infected patients. [source] Efficient mucosal delivery of the HIV-1 Tat protein using the synthetic lipopeptide MALP-2 as adjuvantEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2003Stefan Borsutzky Abstract A major requirement for HIV/AIDS research is the development of a mucosal vaccine that stimulates humoral and cell-mediated immune responses at systemic and mucosal levels, thereby blocking virus replication at the entry port. Thus, a vaccine prototype based on biologically active HIV-1 Tat protein as antigen and the synthetic lipopeptide, macrophage-activating lipopeptide-2 (MALP-2), asa mucosal adjuvant was developed. Intranasal administration to mice stimulated systemic and mucosal anti-Tat antibody responses, and Tat-specific T cell responses, that were more efficient than those observed after i.p. immunization with Tat plus incomplete Freund's adjuvant. Major linear B cell epitopes mapped within aa 1,20 and 46,60, whereas T cell epitopes were identified within aa 36,50 and 56,70. These epitopes have also been described in vaccinated primates and in HIV-1-infected individuals with better prognosis. Analysis of the anti-Tat IgG isotypes in serum, and the cytokine profile of spleen cells indicated that a dominant Th1 helper response was stimulated by Tat plus MALP-2, as opposed to the Th2 response observed with Tat plus incomplete Freund's adjuvant. Tat-specific IFN-,-producing cells were significantly increased only in response to Tat plus MALP-2. These data suggest that Malp-2 may represent an optimal mucosal adjuvant for candidate HIV vaccines based on Tat alone or in combination with other HIV antigens. [source] Prevalence of drug resistance and importance of viral load measurements in Honduran HIV-infected patients failing antiretroviral treatmentHIV MEDICINE, Issue 2 2010W Murillo Objective The Honduran HIV/AIDS Program began to scale up access to HIV therapy in 2002. Up to May 2008, more than 6000 patients received combination antiretroviral therapy (cART). As HIV drug resistance is the major obstacle for effective treatment, the purpose of this study was to assess the prevalence of antiretroviral drug resistance in Honduran HIV-1-infected individuals. Methods We collected samples from 138 individuals (97 adults and 41 children) on cART with virological, immunological or clinical signs of treatment failure. HIV-1 pol sequences were obtained using an in-house method. Resistance mutations were identified according to the 2007 International AIDS Society (IAS)-USA list and predicted susceptibility to cART was scored using the anrs algorithm. Results Resistance mutations were detected in 112 patients (81%), 74% in adults and 98% in children. Triple-, dual- and single-class drug resistance was documented in 27%, 43% and 11% of the study subjects, respectively. Multiple logistic regression showed that resistance was independently associated with type of treatment failure [virological failure (odds ratio (OR)=1) vs. immunological failure (OR=0.11; 95% confidence interval (CI) 0.030,0.43) vs. clinical failure (OR=0.037; 95% CI 0.0063,0.22)], route of transmission (OR=42.8; 95% CI 3.73,491), and years on therapy (OR=1.81; 95% CI 1.11,2.93). Conclusion The prevalence of antiretroviral resistance was high in Honduran HIV-infected patients with signs of treatment failure. A majority of study subjects showed dual- or triple-class resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Virologically defined treatment failure was a strong predictor of resistance, indicating that viral load testing is needed to correctly identify patients with treatment failure attributable to resistance. [source] Effect of nucleoside reverse transcriptase inhibitors on CD4 T-cell recovery in HIV-1-infected individuals receiving long-term fully suppressive combination antiretroviral therapyHIV MEDICINE, Issue 3 2009H Byakwaga Objective The aim of the study was to determine the effect of nucleoside reverse transcriptase inhibitors (NRTIs) on CD4 recovery in HIV-1-infected individuals receiving long-term suppressive combination antiretroviral therapy (cART). Methods A retrospective cohort study was carried out. The mean time-weighted CD4 change from baseline was determined at weeks 48, 96 and 144: its associations with exposure to NRTIs were assessed using linear regression. Results One hundred and five patients were included. Their median baseline CD4 count was 225 (interquartile range 91,362) cells/,L. A trend of greater CD4 change from baseline was observed for individuals who at baseline had CD4 counts >200 cells/,L (138 vs. 113, 176 vs. 134 and 204 vs. 173 cells/,L), or were ,40 years old (136 vs. 118, 182 vs. 150, 208 vs. 174) at weeks 48, 96 and 144, respectively; however, all P -values were >0.05. Lower CD4 increases were observed in patients exposed to didanosine (ddI) or a combination of ddI and stavudine, although the difference was not statistically significant. For patients that commenced cART with CD4 count ,200 cells/,L, a trend towards a CD4 count response <250 cells/,L at weeks 48, 96 and 144 was observed in patients receiving zidovudine. Conclusion Exposure to different NRTIs in initial cART was not significantly associated with variable rises in CD4 cell count. However, these findings need to be confirmed in larger studies. [source] Effect of food on the antiviral activity of didanosine enteric-coated capsules: a pilot comparative study,HIV MEDICINE, Issue 4 2008B Hernández-Novoa Objectives To determine the effect of food on the antiviral activity of enteric-coated (EC) capsules of didanosine (ddI). Methods We conducted a pilot, randomized, open-label study of 28-day ddI-EC capsules monotherapy-administered in a fasted state (group 1, n=11) or with food (group 2, n=10) to treatment-naïve chronically HIV-1-infected individuals. To assess the antiviral efficacy, HIV-1 RNA was determined at baseline, day 3, day 7 and weekly thereafter. The area under the HIV-1 RNA curve minus baseline weighted by time (AUCMB/day) was calculated. Results Mean baseline HIV-1 RNA was 4.2 log10 copies/mL in group 1 and 3.8 log10 copies/mL in group 2. After 28 days, the mean HIV-1 RNA reduction was 0.99 log10 copies/mL [95% confidence interval (CI) 0.45,1.53] for group 1 and 0.89 log10 copies/mL (95% CI 0.38,1.40) for group 2. AUCMB/day values were 0.775 log10 copies/mL (95% CI 0.33,1.22) and 0.774 log10 copies/mL (95% CI 0.48,1.07), respectively, showing no difference in the rate of decrease of HIV-1 RNA (P=0.995). Mean ddI plasma levels at day 28 were 0.0234 mg/L for group 1 and 0.0227 mg/L for group 2 (P=0.96). Conclusions In this pilot study, the administration of food did not have any significant effect on the antiviral activity of ddI-EC capsules. [source] Sequence-specific detection method for reverse transcription, loop-mediated isothermal amplification of HIV-1,,JOURNAL OF MEDICAL VIROLOGY, Issue 6 2009Kelly A. Curtis Abstract HIV diagnosis at the point-of-care or in resource-limited settings poses considerable challenges due to time and cost limitations. Currently, nucleic acid-based tests are the only reliable method for diagnosing recent infections during the window period post-infection and pre-seroconversion, but these tests are only suitable for well-equipped laboratory settings. The reverse transcription loop-mediated isothermal amplification (RT-LAMP) technology exhibits characteristics that are ideal for the development of a rapid, cost-effective nucleic acid-based test for detection of HIV DNA and RNA. In this study, a sequence-specific detection method was developed for immediate, naked-eye visualization of RT-LAMP products with high sensitivity and specificity. The rapid detection method was incorporated into the HIV-1-specific RT-LAMP assay and validated using minute volumes of whole blood from HIV-1-infected individuals. Together with the minimal sample preparation time and one-step, isothermal amplification reaction, the sequence-specific detection method adds to the overall versatility of the RT-LAMP assay and enhances the applicability for use at point-of-care or resource-limited sites. J. Med. Virol. 81:966,972, 2009. Published 2009 Wiley-Liss, Inc. [source] A novel CD4-conjugated ultraviolet light-activated photocatalyst inactivates HIV-1 and SIV efficiently,JOURNAL OF MEDICAL VIROLOGY, Issue 8 2008Koushi Yamaguchi Abstract In this study, we found that the electric potential derived from the redox reaction of ultraviolet (UV)-illuminated CD4-conjugated titanium dioxide (TiO2) inactivated a wide range of high-titered primary HIV-1 isolates, regardless of virus co-receptor usage or genetic clade. In vitro incubation of HIV-1 isolates with CD4-conjugated TiO2 (CD4-TiO2) followed by UV illumination led to inhibition of viral infectivity in both H9 cells and peripheral blood mononuclear cells as well as to the complete inactivation of plasma virions from HIV-1-infected individuals. Treatment with a newly established extra-corporeal circulation system with the photocatalyst in rhesus macaques completely inactivated plasma virus in the system and effectively reduced the infectious plasma viral load. Furthermore, plasma viremia and infectious viral loads were controlled following a second therapeutic photocatalyst treatment during primary SIVmac239 infection of macaques. Our findings suggest that this therapeutic immunophysical strategy may help control human immunodeficiency viral infection in vivo. J. Med. Virol. 80:1322,1331, 2008. © 2008 Wiley-Liss, Inc. [source] RANKL/OPG/TRAIL plasma levels and bone mass loss evaluation in antiretroviral naive HIV-1-positive menJOURNAL OF MEDICAL VIROLOGY, Issue 10 2007Davide Gibellini Abstract Osteopenia and osteoporosis are common in HIV-1-infected individuals and represent a challenge in clinical and therapeutic management. This report investigated osteopenia/osteoporosis in a group of 31 antiretroviral naive HIV-1-positive men and the role of specific molecules belonging to TNF and the TNF-receptor family in HIV-1-related bone mass loss. Osteoprotegerin (OPG), the receptor activator of NF-,b-ligand (RANKL), and the TNF-related apoptosis-inducing ligand (TRAIL) were significantly increased in the plasma of antiretroviral naive HIV-1-positive patients compared to a control group of healthy blood donors. In addition, TRAIL and RANKL plasma concentrations were positively correlated to HIV-1-RNA viral load. Measurement of bone mineral density in 20 out of 31 HIV-1-positive subjects disclosed osteopenia/osteoporosis in 40% of these patients. The antiretroviral naive HIV-1-positive subjects with low bone mineral density had a decreased plasma OPG/RANKL ratio and a plasma RANKL concentration >500 pg/ml. Together, these data indicate that plasma concentrations of specific factors involved in bone homeostasis were increased during HIV-1 infection and that RANKL and OPG/RANKL ratio deregulation may be involved in osteopenia/osteoporosis occurring in antiretroviral naive HIV-1 individuals. J. Med. Virol. 79:1446,1454, 2007. © Wiley-Liss, Inc. [source] Inhibition of Hematopoietic Progenitor Cell Proliferation by Ethanol in Human Immunodeficiency Virus Type 1 Tat-Expressing Transgenic MiceALCOHOLISM, Issue 3 2001Om Prakash Background: A number of hematological abnormalities are associated with both human immunodeficiency virus type 1 (HIV-1) infection and alcohol abuse. There is little information on how alcohol abuse might further influence the survival and growth of hematopoietic progenitors in HIV-infected individuals in the presence of immune system abnormalities and anti-HIV drugs. Because there is evidence that viral transactivator Tat itself can induce hematopoietic suppression, in this study we examined the role of ethanol as a cofactor in transgenic mice that expressed HIV-1 Tat protein. Methods: Tat transgenic mice and nontransgenic littermates were given ethanol (20% v/v) and the anti-HIV drug 3,-azido-3,-deoxythymidine (AZT; 1 mg/ml) in drinking water. Immunosuppression in mice was induced by weekly intraperitoneal injections of anti-CD4 antibody. Hematopoiesis was examined by erythroid colony forming unit (CFU-E) and granulocyte/macrophage colony-forming unit (CFU-GM) assays of the bone marrow progenitor cells. Results: Administration of ethanol for 7 weeks resulted in a 50% decrease in the proliferative capacity of CFU-E- and CFU-GM-derived progenitors from transgenic mice compared with that of ethanol-treated nontransgenic controls. Similar decreases also were observed in transgenic mice treated with AZT or a combination of AZT and ethanol. Furthermore, ethanol and AZT were significantly more toxic to the granulopoietic progenitors (40,50% inhibition) than to the erythropoietic progenitors (10,20% inhibition) in Tat transgenic mice. Although a 10 day exposure of Tat transgenic and nontransgenic mice to a combination of ethanol and AZT had no suppressive effect on the erythropoietic and granulopoietic progenitor cells, there was a marked decrease (40,60%) in CFU-GM in mice made immunodeficient by CD4+ T-lymphocyte depletion. The ethanol-treated Tat transgenic mice but not the nontransgenic littermates also showed a significant decrease (25%) in CFU-GM. Conclusion: Our in vivo study strongly suggests that ethanol ingestion in HIV-1-infected individuals, particularly those on antiretroviral drugs, might increase bone marrow toxicity and contribute to HIV-1-associated hematopoietic impairment. [source] Cytokine profiles in parotid saliva from HIV-1-infected individuals: changes associated with opportunistic infections in the oral cavityMOLECULAR ORAL MICROBIOLOGY, Issue 2 2000K. P. Black The purpose of this study was to quantitate levels of cytokines in parotid saliva of subjects infected with human immunodeficiency virus-1 (HIV-1) and to determine if the cytokine profiles differ in subjects with an oral opportunistic infection, i.e., candidiasis or oral hairy leukoplakia. Parotid saliva samples were obtained from HIV-infected individuals with or without candidiasis or oral hairy leukoplakia and from healthy controls and were assessed by ELISA for levels of interleukin (IL)-1, IL-2, IL-4, IL-5, IL-10, transforming growth factor-,, tumor necrosis factor-, and interferon (IFN)-,. Saliva from HIV-infected subjects with oral candidiasis had significantly higher levels of IFN-, than that seen in HIV-infected individuals with no oral disease and significantly higher levels of IL-2, IL-5 and IFN-, than saliva of healthy controls. No significant difference was seen in cytokine levels in saliva from HIV-infected subjects with no oral infections and healthy controls. The HIV-infected subjects with oral hairy leukoplakia displayed significantly higher levels of both IL-1, and IFN-, compared with the HIV and no oral disease group and a higher level of IFN-, than seen in saliva from the healthy control group. In comparing cytokine levels from both HIV and oral disease groups, significant differences were detected in levels of IL-5 and IL-10. These results indicate that the profile of salivary cytokines is altered as a result of the oral opportunistic infection candidiasis or oral hairy leukoplakia and also by concurrent HIV infection. [source] | ||||||||||