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ABSTRACT: INTRODUCTION:: The Tim-3 receptor has been implicated as a negative regulator of adaptive immune responses, and has been linked to T cell dysfunction in chronic viral infections, such as HIV. Blocking Tim-3 has been proposed as a potential therapeutic intervention in HIV infection. However, a more detailed characterisation of Tim-3 expression in the presence of HIV is required before such strategies can be considered. METHODS:: In this study, we investigate Tim-3 expression on innate immune cell subsets in chronic HIV-infected individuals pre- and post-therapy. RESULTS:: We report that, pre-therapy, HIV infection is associated with elevated levels of Tim-3 on resting innate lymphocytes (NK, NKT, and ³´ T cells), but not resting monocytes. In the absence of HIV infection, stimulation with an inflammatory stimulus resulted in decreased Tim-3 on monocytes and increased Tim-3 on NK, NKT, and ³´ T cells. However, innate cells from HIV-infected donors were significantly less responsive to stimulation. Six months of combination antiretroviral therapy (cART) restored Tim-3 levels on resting NK cells but not NKT or ³´ T cells. The responses of all subsets to inflammatory stimuli were restored to some extent with cART, but only reached HIV-negative control levels in monocytes and NK cells. DISCUSSION:: These results demonstrate that, during HIV infection, Tim-3 expression on innate cells is dysregulated, and that this dysregulation is only partially restored following 6 months of cART. Our findings suggest that Tim-3 is differentially regulated on innate immune effector cells, and have direct implications for strategies designed to block Tim3-ligand interactions.
JAIDS Journal of Acquired Immune Deficiency Syndromes 01/2013; · 4.43 Impact Factor
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Sean B Rourke,
Sandra Gardner,
Ann N Burchell,
Janet Raboud,
Sergio Rueda,
Ahmed M Bayoumi, Mona Loutfy,
Curtis Cooper,
Marek Smieja,
Darien Taylor, [......],
Mark Fisher,
John Cairney,
Nicole Mittmann,
Irving E Salit,
Fred Crouzat,
Kevin Gough,
Edward Ralph,
Roger Sandre,
Don Kilby,
Anita Rachlis
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ABSTRACT: The Ontario HIV Treatment Network Cohort Study (OCS) is an observational, open dynamic cohort of people who are receiving medical care for human immunodeficiency virus (HIV) infection in Ontario, Canada. Established in the mid-1990s, the OCS has its roots in AIDS activists' demands for research that would improve the quality of life of people living with HIV while respecting their privacy. It is a collaborative and community-driven study, including a Governance Committee made up of people with HIV and other stakeholders that evaluates analysis project proposals for community relevance and ethics. From 1995 to 2010, a total of 5644 participants were enrolled and 27 720 person-years of observation were accumulated; follow-up will continue until at least 2015. In the initial years of study, the focus was on clinical data from medical chart reviews. It has since evolved into a comprehensive study that collects extensive de-identified information on clinical, laboratory and psychosocial and behavioural measures based on medical chart abstractions, interviews using a standardized questionnaire and linkage with external administrative health databases in Ontario. Interested collaborators are encouraged to submit analysis project proposals as instructed on the study website (www.ohtncohortstudy.ca).
International Journal of Epidemiology 02/2012; · 6.41 Impact Factor
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ABSTRACT: Objective: To compare the immunologic effectiveness of raltegravir-maraviroc (R+M+)-based regimens with raltegravir-based regimens that do not include maraviroc (R+M-) in treatment-experienced patients in clinical practice.
We conducted a retrospective study of treatment-experienced HIV-infected adults receiving either R+M+- or R+M--based therapy. Longitudinal CD4 counts were analyzed using a linear mixed model.
One hundred and fifty-six patients were included in the analysis, of whom 32 were receiving R+M+ and 124 R+M-. Mean baseline CD4 counts in patients on R+M+ and R+M- were 463.8 and 442.3 cells/mm(3), respectively (P = .67). In multivariable mixed models, a baseline viral load ≥50 copies/mL was significantly associated with CD4 change during follow-up (P < .0001). No difference between R+M+ and R+M- was observed during follow-up (P = .81).
CD4 cell recovery was similar among patients receiving either R+M+- or R+M--based therapy during a 24-month period of follow-up.
Journal of the International Association of Physicians in AIDS Care (JIAPAC) 01/2012; 11(3):192-7.
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ABSTRACT: In recent years, the proportion of patients attending tertiary care HIV clinics who are recent immigrants to Canada has increased dramatically.
Among patients first seen at the Toronto Hospital Immunodeficiency Clinic (Toronto, Ontario) between January 1, 2000 and August 31, 2009, the time to death from the first positive HIV test was compared between individuals who had immigrated to Canada within 10 years of their first visit and individuals who were either Canadian-born or who had immigrated more than 10 years before their first clinic visit. In addition, for the antiretroviral-naive patients in these two groups who initiated combination antiretroviral therapy, the time to and the duration of virologic suppression were compared.
In a multivariable proportional hazards (PH) model, recent immigrant status was associated with decreased mortality (HR 0.11, P=0.03) after adjusting for age, CD4 count and the risk factor for men having sex with men. In multivariable PH models, recent female immigrants achieved virologic suppression more quickly (HR 1.51, P=0.02), while male immigrants (HR 1.14, P=0.44) and female nonimmigrants (HR 0.90, P=0.61) had similar times to virologic suppression as male nonimmigrants, respectively, after adjusting for the year of and viral load at combination antiretroviral therapy initiation. When pregnant women were removed from the analysis, there were no significant differences in the rates of virologic rebound according to sex or immigration status.
Despite the perceived barriers of newcomers to Canada, mortality was lower among recent immigrants and virologic suppression was achieved more quickly in recent female immigrants.
The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale / AMMI Canada 01/2012; 23(1):9-14. · 1.54 Impact Factor
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Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC 03/2011; 33(3):269-71.
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Duncan Chege,
Prameet M Sheth,
Taylor Kain,
Connie J Kim,
Colin Kovacs, Mona Loutfy,
Roberta Halpenny,
Gabor Kandel,
Tae-Wook Chun,
Mario Ostrowski,
Rupert Kaul
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ABSTRACT: Th17 cells play an important role in mucosal defence and repair and are highly susceptible to infection by HIV. Antiretroviral therapy (ART) suppresses HIV viremia and can restore CD4(+) numbers in the blood and gastrointestinal mucosa, but the resolution of systemic inflammation and gut microbial translocation is often incomplete. We hypothesized that this might relate to persistent dysregulation of gut CD4(+) Th17 subsets.
Blood and sigmoid biopsies were collected from HIV-uninfected men, chronically HIV-infected, ART-naive men, and men on effective ART for more than 4 years. Sigmoid provirus levels were assayed blind to participant status, as were CD4(+) Th17 subsets, systemic markers of microbial translocation, and cellular immune activation.
There was minimal CD4(+) Th17 dysregulation in the blood until later stage HIV infection, but gastrointestinal Th17 depletion was apparent much earlier, along with increased plasma markers of microbial translocation. Plasma lipopolysaccharide (LPS) remained elevated despite overall normalization of sigmoid Th17 populations on long-term ART, although there was considerable interindividual variability in Th17 reconstitution. An inverse correlation was observed between plasma LPS levels and gut Th17 frequencies, and higher plasma LPS levels correlated with an increased gut HIV proviral reservoir.
Sigmoid Th17 populations were preferentially depleted during HIV infection. Despite overall CD4(+) T-cell reconstitution, sigmoid Th17 frequencies after long-term ART were heterogeneous and higher frequencies were correlated with reduced microbial translocation.
AIDS (London, England) 03/2011; 25(6):741-9. · 4.91 Impact Factor
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Alexis K Palmer,
Marina B Klein,
Janet Raboud,
Curtis Cooper,
Sean Hosein, Mona Loutfy,
Nima Machouf,
Julio Montaner,
Sean B Rourke,
Marek Smieja,
Christos Tsoukas,
Benita Yip,
David Milan,
Robert S Hogg
International Journal of Epidemiology 02/2010; 40(1):25-32. · 6.41 Impact Factor
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Janet Raboud, Mona Loutfy,
DeSheng Su,
Ahmed Bayoumi,
Marina Klein,
Curtis Cooper,
Nima Machouf,
Sean Rourke,
Sharon Walmsley,
Anita Rachlis,
Harrigan P Richard,
Marek Smieja,
Christos Tsoukas,
Julio Montaner,
Robert Hogg
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ABSTRACT: Abstract
Background
Viral load (VL) monitoring is an essential component of the care of HIV positive individuals. Rates of VL monitoring have been shown to vary by HIV risk factor and clinical characteristics. The objective of this study was to determine whether there are differences among regions in Canada in the rates of VL testing of HIV-positive individuals on combination antiretroviral therapy (cART), where the testing is available without financial barriers under the coverage of provincial health insurance programs.
Methods
The Canadian Observational Cohort (CANOC) is a collaboration of nine Canadian cohorts of HIV-positive individuals who initiated cART after January 1, 2000. The study included participants with at least one year of follow-up. Generalized Estimating Equation (GEE) regression models were used to determine the effect of geographic region on (1) the occurrence of an interval of 9 months or more between two consecutive recorded VL tests and (2) the number of days between VL tests, after adjusting for demographic and clinical covariates. Overall and regional annual rates of VL testing were also reported.
Results
3,648 individuals were included in the analysis with a median follow-up of 42.9 months and a median of 15 VL tests. In multivariable GEE logistic regression models, gaps in VL testing >9 months were more likely in Quebec (Odds Ratio (OR) = 1.72, p < 0.0001) and Ontario (OR = 1.78, p < 0.0001) than in British Columbia and among injection drug users (OR = 1.68, p < 0.0001) and were less likely among older individuals (OR = 0.77 per 10 years, p < 0.0001), among men having sex with men (OR = 0.62, p < 0.0001), within the first year of cART (OR = 0.15, p < 0.0001), among individuals on cART at the time of the blood draw (OR = 0.34, p < 0.0001) and among individuals with VL < 50 copies/ml at the previous visit (OR = 0.56, p < .0001).
Conclusions
Significant variation in rates of VL testing and the probability of a significant gap in testing were related to geographic region, HIV risk factor, age, year of cART initiation, type of cART regimen, being in the first year of cART, AIDS-defining illness and whether or not the previous VL was below the limit of detection.
BMC Infectious Diseases. 01/2010;
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Prameet M Sheth,
Colin Kovacs,
Kimdar S Kemal,
R Brad Jones,
Janet M Raboud,
Richard Pilon,
Charles la Porte,
Mario Ostrowski, Mona Loutfy,
Harold Burger,
Barbara Weiser,
Rupert Kaul
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ABSTRACT: Effective antiretroviral therapy (ART) may reduce HIV sexual transmission by lowering genital HIV levels. A prospective study of men starting ART (n = 25) demonstrated rapid, substantial reductions in semen HIV RNA. However, despite an undetectable blood viral load, isolated semen HIV shedding was detected at more than one visit in 12 of 25 (48%) participants, with semen HIV RNA levels exceeding 5000 copies/ml in four of 25 (16%). Isolates were drug-sensitive, and this phenomenon was not associated with semen drug levels or regimen.
AIDS (London, England) 09/2009; 23(15):2050-4. · 4.91 Impact Factor
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R Brad Jones,
Lishomwa C Ndhlovu,
Jason D Barbour,
Prameet M Sheth,
Aashish R Jha,
Brian R Long,
Jessica C Wong,
Malathy Satkunarajah,
Marc Schweneker,
Joan M Chapman, [......],
Roberta Halpenny,
Desmond Persad,
Gerald Spotts,
Frederick M Hecht,
Tae-Wook Chun,
Joseph M McCune,
Rupert Kaul,
James M Rini,
Douglas F Nixon,
Mario A Ostrowski
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ABSTRACT: Progressive loss of T cell functionality is a hallmark of chronic infection with human immunodeficiency virus 1 (HIV-1). We have identified a novel population of dysfunctional T cells marked by surface expression of the glycoprotein Tim-3. The frequency of this population was increased in HIV-1-infected individuals to a mean of 49.4 +/- SD 12.9% of CD8(+) T cells expressing Tim-3 in HIV-1-infected chronic progressors versus 28.5 +/- 6.8% in HIV-1-uninfected individuals. Levels of Tim-3 expression on T cells from HIV-1-infected inviduals correlated positively with HIV-1 viral load and CD38 expression and inversely with CD4(+) T cell count. In progressive HIV-1 infection, Tim-3 expression was up-regulated on HIV-1-specific CD8(+) T cells. Tim-3-expressing T cells failed to produce cytokine or proliferate in response to antigen and exhibited impaired Stat5, Erk1/2, and p38 signaling. Blocking the Tim-3 signaling pathway restored proliferation and enhanced cytokine production in HIV-1-specific T cells. Thus, Tim-3 represents a novel target for the therapeutic reversal of HIV-1-associated T cell dysfunction.
Journal of Experimental Medicine 12/2008; 205(12):2763-79. · 13.85 Impact Factor
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ABSTRACT: This study examined the use of HIV postexposure prophylaxis (PEP) among sexually assaulted adolescent females.
We analyzed data from the HIV PEP Project, an implementation and evaluation of a program of universal offering of PEP to sexual assault victims of all ages. Baseline and follow-up data were collected prospectively from consecutive clients seen at 18 hospital-based sexual assault treatment centers in Ontario, Canada from September 2003 to January 2005. Among 386 at-risk female adolescents, we examined the provision and uptake of and adherence to PEP, and factors related to antiretroviral acceptance and completion.
Most adolescents were single (94.5%), living with family (68.0%), and attending school (67.4%). Slightly over two-fifths (42.7%) accepted and one-third (33.6%) completed the 28-day course of PEP. Factors associated with PEP acceptance were health care provider encouragement, being a student, and being moderately-to-highly anxious. PEP completion was associated with being white and an assailant known less than 24 hours.
Our findings highlight the importance of the health care provider's role in counseling sexually assaulted female adolescents about HIV PEP use. The results also suggest that at-risk adolescents not enrolled in school and those from culturally diverse backgrounds may require additional supports.
Sexually transmitted diseases 11/2008; 35(12):973-8. · 2.58 Impact Factor
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ABSTRACT: T(H)-17 cells have been shown to play a role in bacterial defense, acute inflammation, and autoimmunity. We examined the role of interleukin 17 (IL-17) production in human immunodeficiency virus type 1 (HIV-1) infection. Both HIV-1- and cytomegalovirus (CMV)-specific IL-17-producing CD4(+) T cells were detectable in early HIV-1 infection but were reduced to nondetectable levels in chronic and nonprogressive HIV-1 infection. IL-17-producing CMV-specific cells were not detected in blood from HIV-1-uninfected normal volunteers. Virus-specific T(H)-17 cells could coexpress other cytokines and could express CCR4 or CXCR3. Although the etiology of these cells has yet to be established, we propose that microbial translocation may induce them.
Journal of Virology 08/2008; 82(13):6767-71. · 5.40 Impact Factor
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Prameet M Sheth,
Sherzana Sunderji,
Lucy Y Y Shin,
Anuradha Rebbapragada,
Sanja Huibner,
Joshua Kimani,
Kelly S Macdonald,
Elizabeth Ngugi,
Job J Bwayo,
Stephen Moses,
Colin Kovacs, Mona Loutfy,
Rupert Kaul
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ABSTRACT: Chronic coinfection with herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) has been associated with an increased HIV viral load and more rapid disease progression, perhaps related to HSV-2-associated alterations in host immunity.
Studies were nested within (1) a cross-sectional study of men coinfected with HIV and HSV-2 and (2) women not infected with HIV, both before and after HSV-2 acquisition. HSV-2 infection status was determined by ELISA. HIV-specific CD8(+) T cell epitopes were mapped, and proliferation of HIV-specific cells was also assessed. Systemic inflammatory and regulatory T cell populations were assayed by flow cytometry.
The breadth of both the HIV-specific CD8(+) T cell interferon-gamma and proliferative responses was reduced in participants coinfected with HIV and HSV-2, independent of the HIV plasma viral load and CD4(+) T cell count, and the magnitude of the responses was also reduced. HSV-2 infection in this group was associated with increased T cell CD38 expression but not with differences in the proportion of CD4(+) FoxP3(+) regulatory T cells. However, in women not infected with HIV, acquisition of HSV-2 was associated with an increase in the proportion of regulatory T cells.
HSV-2 coinfection was associated with reduced HIV-specific T cell responses and systemic inflammation. The immune effects of HSV-2 may underlie the negative impact that this coinfection has on the clinical course of HIV infection.
The Journal of Infectious Diseases 06/2008; 197(10):1394-401. · 6.41 Impact Factor
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ABSTRACT: Sustained recruitment over time of tens of thousands of clinical trial volunteers is essential to the development of safe and efficacious HIV vaccines. This study explored, in depth, reasons for declining to enroll among persons screened in as eligible for a Phase IIb prophylactic HIV vaccine trial. Thirteen non-enrollees completed a self-administered questionnaire; of those, 11 completed a 1-h follow-up interview. Interviews were transcribed verbatim and themes derived using narrative thematic analysis and NVivo software. Concerns about negative social consequences of false HIV-positive tests, trial uncertainties, side effects, double-blind assignment, trial duration, uncertain efficacy, behavioral disinhibition and stigma emerged as reasons for declining to enroll. Social, psychological and emotional dimensions of HIV vaccine trial participation--including false-positives and anticipated stigma and discrimination, possible impact on intimate relationships, and concerns about behavioral disinhibition--suggest that provision of voluntary trial-related psychosocial counseling, a trial ombudsperson, alternate trial sites, and systematic community engagement in trial planning, recruitment and evaluation may facilitate informed participation in safe and ethically conducted HIV vaccine trials.
Vaccine 03/2008; 26(8):1091-7. · 3.77 Impact Factor
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Bahareh Vali,
Feng Yun Yue,
R Brad Jones,
Prameet M Sheth,
Rupert Kaul,
Michael R Betts,
David Wong,
Colin Kovacs, Mona Loutfy,
Andrew Common,
Roberta Halpenny,
Mario A Ostrowski
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ABSTRACT: Hepatitis C Virus (HCV)-related liver disease progresses more rapidly in individuals co-infected with Human Immunodeficiency Virus-1 (HIV), although the underlying immunologic mechanisms are unknown. We examined whether HIV-specific T-cells are identified in the liver of HCV/HIV co-infected individuals and promote liver inflammation through bystander immune responses.
Ex-vivo intra-hepatic lymphocytes from HCV mono-infected and HCV/HIV co-infected individuals were assessed for immune responses to HIV and HCV antigens by polychromatic flow cytometry.
HCV/HIV liver biopsies had similar frequencies of lymphocytes but lower percentages of CD4+ T-cells compared to HCV biopsies. In co-infection, intra-hepatic HIV-specific CD8+ and CD4+ T-cells producing IFN-gamma and TNF-alpha were detected and were comparable in frequency to those that were HCV-specific. In co-infected individuals, viral-specific CD8+ T-cells produced more of the fibrogenic cytokine, TNF-alpha. In both mono- and co-infected individuals, intra-hepatic HCV-specific T-cells were poorly functional compared to HIV-specific T-cells. In co-infection, HAART was not associated with a reconstitution of intra-hepatic CD4+ T-cells and was associated with reduction in both HIV and HCV-specific intra-hepatic cytokine responses.
The accumulation of functional HIV-specific T-cells in the liver during HCV/HIV co-infection may represent a bystander role for HIV in inducing faster progression of liver disease.
PLoS ONE 02/2008; 3(10):e3454. · 4.09 Impact Factor
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ABSTRACT: Abstract
Background
The advantage of treatment interruptions (TIs) in salvage therapy remains controversial. Regardless, characterizations of the correlates of CD4 count fall during TI are important to identify since patients with virologic failure commonly stop antiretroviral (ARV) therapy. The objective of this study was to determine the predictive value of pre-TI proliferative capacity and cell surface markers for CD4 count change in HIV-infected patients experiencing virologic failure before undergoing TI.
Methods
Peripheral blood mononuclear cells (PBMCs) from 13 HIV-infected patients experiencing virologic failure at baseline time points before the TI were tested for proliferation using the 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution assay and a Gag p55 peptide pool, staphylococcus enterotoxin B (SEB), cytomegalovirus (CMV) recall antigen, and anti-CD3 antibody as stimuli. CD28 and CD57 expression on CD4+ and CD8+ T-cells was measured.
Results
The median changes in the CD4+ T-cell count and viral load from baseline to the TI time point corresponding to the CD4 count nadir were -44 cells/mm<sup>3 </sup>{Interquartile range (IQR) -17, -104} and +85,332 copies/mL (IQR +11,198, +283,327), respectively. CD4+ T-cell proliferation to CMV, pre-TI CD4+ T-cell count, and percent CD4+CD57+ cells correlated negatively with CD4 count change during TI (r = -0.59, p = 0.045, r = -0.61, p = 0.030 and r = -0.69, p = 0.0095, respectively; Spearman correlation). The presence of HIV-specific proliferative responses was not associated with a reduced decline in CD4 count during TI.
Conclusion
The use of pre-TI immune proliferative responses and cell surface markers may have predictive value for CD4 count decline during TI.
BMC Infectious Diseases. 01/2008;
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ABSTRACT: Changes in T-cell function are a hallmark of human immunodeficiency virus type 1 (HIV-1) infection, but the pathogenic mechanisms leading to these changes are unclear. We examined the gene expression profiles in ex vivo human CD4+ and CD8+ T cells from untreated HIV-1-infected individuals at different clinical stages and rates of disease progression. Profiles of pure CD4+ and CD8+ T-cell subsets from HIV-1-infected nonprogressors with controlled viremia were indistinguishable from those of individuals not infected with HIV-1. Similarly, no gene clusters could distinguish T cells from individuals with early infection from those seen in chronic progressive HIV-1 infection, whereas differences were observed between uninfected individuals or nonprogressors versus early or chronic progressors. In early and chronic HIV-1 infection, three characteristic gene expression signatures were observed. (i) CD4+ and CD8+ T cells showed increased expression of interferon-stimulated genes (ISGs). However, some ISGs, including CXCL9, CXCL10, and CXCL11, and the interleukin-15 alpha receptor were not upregulated. (ii) CD4+ and CD8+ T cells showed a cluster similar to that observed in thymocytes. (iii) More genes were differentially regulated in CD8+ T cells than in CD4+ T cells, including a cluster of genes downregulated exclusively in CD8+ T cells. In conclusion, HIV-1 infection induces a persistent T-cell transcriptional profile, early in infection, characterized by a dramatic but potentially aberrant interferon response and a profile suggesting an active thymic output. These findings highlight the complexity of the host-virus relationship in HIV-1 infection.
Journal of Virology 05/2007; 81(7):3477-86. · 5.40 Impact Factor
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ABSTRACT: For full HIV virological suppression, three fully active antiretroviral agents are required. New drug classes should be included to ensure that agents are fully active. The addition of enfuvirtide and efavirenz to the present patient's new antiretroviral regimen ensured that two fully active agents were in use in the setting of a moderate degree of nucleoside resistance and a high level of protease resistance, and where non-nucleoside reverse transcriptase inhibitors were still fully active. Both viral load and CD4 count responded favourably to this regimen. The patient received support from physicians and clinic staff in the introduction and use of enfuvirtide. To reduce injection site reactions, a needle-free injection system (Biojector) proved effective.
The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale / AMMI Canada 01/2007; 18(Suppl A):10A-1A. · 1.54 Impact Factor
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ABSTRACT: Globally, at least 60 million people have been infected with the human immunodeficiency virus type 1 (HIV-1), the majority of whom will develop the acquired immunodeficiency syndrome (AIDS) leading to tremendous morbidity and the mortality. Understanding the immunopathogenesis of AIDS and the immune correlates of viral protection are necessary to develop effective vaccines and immunotherapies. A major focus of our laboratory has been to understand the CD4+ T cell immune response directed against HIV- 1, and to determine mechanisms of T cell dysfunction that lead to viral escape. In addition, we are interested in evaluating the TNF-TNFR family members as potential molecular adjuvants that could be incorporated into vaccines which could be used to further boost T cell immunogenicity in healthy or HIV-1-infected individuals, as many of these molecules have been shown to replace the functions of CD4+ T cell help.
Immunologic Research 02/2006; 35(1-2):89-102. · 3.03 Impact Factor
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Michael D Christian, Mona Loutfy,
L Clifford McDonald,
Kennth F Martinez,
Mariana Ofner,
Tom Wong,
Tamara Wallington,
Wayne L Gold,
Barbara Mederski,
Karen Green,
Donald E Low
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ABSTRACT: Infection of healthcare workers with the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is thought to occur primarily by either contact or large respiratory droplet transmission. However, infrequent healthcare worker infections occurred despite the use of contact and droplet precautions, particularly during certain aerosol-generating medical procedures. We investigated a possible cluster of SARS-CoV infections in healthcare workers who used contact and droplet precautions during attempted cardiopulmonary resuscitation of a SARS patient. Unlike previously reported instances of transmission during aerosol-generating procedures, the index case-patient was unresponsive, and the intubation procedure was performed quickly and without difficulty. However, before intubation, the patient was ventilated with a bag-valve-mask that may have contributed to aerosolization of SARS-CoV. On the basis of the results of this investigation and previous reports of SARS transmission during aerosol-generating procedures, a systematic approach to the problem is outlined, including the use of the following: 1) administrative controls, 2) environmental engineering controls, 3) personal protective equipment, and 4) quality control.
Emerging infectious diseases 03/2004; 10(2):287-93. · 6.17 Impact Factor
