Pham Hong Thang

Karolinska Institutet, Stockholm, Stockholm, Sweden

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Publications (5)22.68 Total impact

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    ABSTRACT: : Decreased memory B-cell maintenance during HIV-1 infection has been associated with the viraemia-induced accumulation of activated memory B cells, sensitive to Fas-mediated apoptosis. We aimed at clarifying whether other B-cell subsets might also be affected by an increased Fas expression in HIV-1-infected patients, and we studied the possible contribution of viraemia, lymphopenia or T-cell activation in Fas upregulation on B cells. We analysed whether Fas upregulation might have collaborative effects with the dysregulation of other B-cell modulatory molecules, leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) and programmed cell death protein 1 (PD-1), on B-cell homeostasis. : Fas, LAIR1 and PD-1 were analysed on B-cell subpopulations in HIV-1-infected patients who were treatment naive, nonlymphopenic; antiretroviral therapy (ART)-treated, nonlymphopenic; or ART-treated, lymphopenic or in noninfected controls. : Flow cytometry was used to study B-cell subsets and Milliplex for serum cytokines. : Fas expression increased on all B-cell subpopulations of viraemic or lymphopenic individuals. The decreased ratio of resting memory B cells and their increased Fas expression were not normalized by ART. Cytokines associated with T-cell activation might influence Fas expression on the naive and transitional B cells. LAIR1 expression decreased in all HIV-1-infected patients, but only on memory B cells, whereas PD-1 increased on resting memory B cells in viraemic patients. : Fas is regulated by the concerted action of viraemia, lymphopenia and T-cell activation during HIV-1 infection, and Fas expression is altered on all peripheral B-cell subsets. Resting memory B-cell homeostasis shows the highest sensitivity to HIV-1-induced perturbations.
    AIDS (London, England) 01/2013; 27(2):155-62. · 4.91 Impact Factor
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    ABSTRACT: One important pathogenic feature of human immunodeficiency virus (HIV)-1 infection is chronic immune activation and impaired survival of T and B cells. A decline of resting memory B cells was reported to occur in both children and adults infected with HIV-1; these cells are responsible for maintaining an adequate serological response to antigens previously encountered in life through natural infection or vaccination. Further understanding of the mechanisms leading to impaired B cell differentiation and germinal center reaction might be essential to design new HIV vaccines and therapies that could improve humoral immune responses in HIV-1 infected individuals. In the present article we summarize the literature and present our view on critical mechanisms of B cell development impaired during HIV-1 infection. We also discuss the impact of microbial translocation, a driving force for persistent inflammation during HIV-1 infection, on survival of terminally differentiated B cells and how the altered expression of cytokines/chemokines pivotal for communication between T and B cells in lymphoid tissues may impair formation of memory B cells.
    Frontiers in Immunology 01/2011; 2:90.
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    ABSTRACT: Interleukin (IL)-7 is a key cytokine in T-cell homeostasis. Stromal cells, intestinal epithelial cells and keratinocytes are known to produce this cytokine. The mechanisms and cellular factors regulating IL-7 production are still unclear. We assessed whether IL-1beta and interferon (IFN)-gamma, cytokines produced during inflammatory conditions, may impact on IL-7 production. We used human intestinal epithelial cells (DLD-1 cell line) and bone marrow stromal cells (HS27 cell line), known to produce IL-7; IL-7 production was evaluated at the mRNA and protein levels. To assess whether treatment of HS27 cells with IL-1beta and/or IFN-gamma leads to changes in the gene expression of cytokines, Toll-like receptors (TLRs) and chemokines, we analysed gene expression profiles using the whole-genome microarray Human Gene 1.0 ST. We found that IFN-gamma enhanced the expression of IL-7 mRNA (P < 0.001) in both cell lines. IL-1beta treatment led to a significant down-regulation (P < 0.001) of IL-7 mRNA expression in both cell lines. The IL-7 concentration in supernatants collected from treated DLD-1 and HS27 cell cultures reflected the trend of IL-7 mRNA levels. The gene profiles revealed dramatic changes in expression of cytokines and their receptors (IL-7/IL-7R alpha; IL-1alpha,IL-1beta/IL-1R1; IFN-gamma/IFN-gammaR1), of IFN regulatory factors (IRF-1 and 2), of TLRs and of important chemo-attractants for T cells. The microarray results were verified by additional methods. Our results are discussed in the setting of inflammation and T-cell survival in the gut compartment during HIV-1 infection where stromal and epithelial cells may produce factors that contribute to impaired IL-7 homeostasis and homing of T cells.
    Journal of Internal Medicine 04/2010; 268(2):181-93. · 6.46 Impact Factor
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    ABSTRACT: To estimate the epidemic history of HIV-1 CRF01_AE in Vietnam and adjacent Guangxi, China, we determined near full-length nucleotide sequences of CRF01_AE from a total of 33 specimens collected in 1997–1998 from different geographic regions and risk populations in Vietnam. Phylogenetic and Bayesian molecular clock analyses were performed to estimate the date of origin of CRF01_AE lineages. Our study reconstructs the timescale of CRF01_AE expansion in Vietnam and neighboring regions and suggests that the series of CRF01_AE epidemics in Vietnam arose by the sequential introduction of founder strains into new locations and risk groups. CRF01_AE appears to have been present among heterosexuals in South-Vietnam for more than a decade prior to its epidemic spread in the early 1990s. In the late 1980s, the virus spread to IDUs in Southern Vietnam and subsequently in the mid-1990s to IDUs further north. Our results indicate the northward dissemination of CRF01_AE during this time.
    Virology. 01/2009;
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    ABSTRACT: A household-based population study interviewed 2,553 women and 1,984 men aged 15-49 years in urban (Ho Chi Minh City) and rural (Thai Binh) provinces in Viet Nam between July and August 2005. The survey response rate was high--approximately 97% of households and 93% of adults overall, with a >92% acceptance of HIV testing among eligible adults. The unadjusted estimated population HIV prevalence was 0.3% (confidence interval [CI]: 0.1-0.6%) in Thai Binh and 0.7% (CI: 0.3-1.3) in Ho Chi Minh City (HCMC), compared with the national estimates and projections of 0.352% and 1.250%, respectively, for 2005. The ratio of male-to-female prevalence was 10.5:1 in Thai Binh and 1.3:1 in HCMC. A low level of men reported purchasing sex in the last 12 months (2.4%) and there were low self-reports of sexually transmitted infections in all adults (5%). A correct knowledge of HIV/AIDS prevention methods was high in both provinces (83%), although only 24.8% of women knew of the use of antiretroviral therapy to prevent vertical transmission of HIV. The observed population prevalence was consistent with recent projections in Thai Binh, although lower than expected in HCMC, indicating the substantial downward revisions of projected population HIV prevalence may need to be extended. The unequal sex prevalence ratio is consistent with the projected trends of increasing male-to-female sexual transmission in urban areas. The results and experience of this study will inform future population based surveys in Viet Nam and the broader Asian region.
    AIDS research and human retroviruses 09/2008; 24(8):1017-26. · 2.18 Impact Factor
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    ABSTRACT: As CD8+CD28- T cells have been associated with dendritic and T cell suppression, we analyzed whether an increase in CD8+CD28- T cell numbers during HIV-1 infection could lead to impaired T cell responses. In contrast to the in-vitro generated CD8+CD28- suppressors, peripheral blood CD8+CD28- T cells of both HIV-infected and noninfected individuals promoted dendritic cell activation. The CD8+CD28- T cell accumulation during HIV-1 infection may thus contribute to accelerated inflammatory reactions and immune activation.
    AIDS (London, England) 05/2008; 22(9):1083-6. · 4.91 Impact Factor
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    ABSTRACT: Serum IL-7 levels correlate with T-cell depletion in HIV-infected individuals. In some patients, we observed that serum IL-7 decreases upon progression to AIDS, suggesting a role for IL-7 in T-cell maintenance in sporadic cases. Interestingly, IL-7 levels were significantly lower in stable long-term non-progressors (LTNP) than in patients who lost the LTNP status in a 3-year follow-up (P < 0.001), indicating that the serum IL-7 concentration might be a valuable marker for maintenance of the LTNP state.
    AIDS 05/2007; 21(8):1048-50. · 6.41 Impact Factor
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    ABSTRACT: To study patterns and determinants of HIV prevalence and risk-behaviour characteristics in different population groups in four border provinces of Viet Nam. We surveyed four population groups during April-June 2002. We used stratified random-cluster sampling and collected data concomitantly on HIV status and risk behaviours. The groups included were female sex workers (n = 2023), injecting drug users (n = 1391), unmarried males aged 15-24 years (n = 1885) and different categories of mobile groups (n = 1923). We found marked geographical contrasts in HIV prevalence, particularly among female sex workers (range 0-24%). The HIV prevalence among injecting drug users varied at high levels in all provinces (range 4-36%), whereas lower prevalences were found among both unmarried young men (range 0-1.3%) and mobile groups (range 0-2.5%). All groups reported sex with female sex workers. Less than 40% of the female sex workers had used condoms consistently. The strongest determinants of HIV infection among female sex workers were inconsistent condom use (adjusted odds ratio [OR], 5.3; 95% confidence interval [CI], 2.4-11.8), history of injecting drug use and mobility, and, among injecting drug users, sharing of injection equipment (adjusted OR, 7.3; 95% CI, 2.3-24.0) and sex with non-regular partners (adjusted OR 3.4; 95% CI 1.4-8.5). The finding of marked geographical variation in HIV prevalence underscores the value of understanding local contexts in the prevention of HIV infection. Although lacking support from data from all provinces, there would appear to be a potential for sex work to drive a self-sustaining heterosexual epidemic. That the close links to serious injecting drug use epidemics can have an accelerating effect in increasing the spread of HIV merits further study.
    Bulletin of the World Health Organisation 02/2007; 85(1):35-41. · 5.25 Impact Factor