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1.
  • Eriksen, Jaran, et al. (författare)
  • Antiretroviral treatment for HIV infection: Swedish recommendations 2016.
  • 2017
  • Ingår i: Infectious diseases (London, England). - : Informa UK Limited. - 2374-4243 .- 2374-4235. ; 49:1, s. 1-34
  • Tidskriftsartikel (refereegranskat)abstract
    • The Swedish Medical Products Agency and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection on seven previous occasions (2002, 2003, 2005, 2007, 2009, 2011 and 2014). In February 2016, an expert group under the guidance of RAV once more revised the guidelines. The most important updates in the present guidelines are as follows: Tenofovir alafenamide (TAF) has recently been registered. TAF has several advantages over tenofovir disoproxilfumarate (TDF) and is recommended instead of TDF in most cases. First-line treatment for previously untreated individuals includes dolutegravir, boosted darunavir or efavirenz with either abacavir/lamivudine or tenofovir (TDF/TAF)/emtricitabine. Pre-exposure prophylaxis (PrEP) is recommended for high-risk individuals. As in the case of the previous publication, recommendations are evidence-graded in accordance with the Oxford Centre for Evidence Based Medicine ( http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/ ) ( Table 1 ). This document does not cover treatment of opportunistic infections and tumours. [Table: see text].
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2.
  • Shao, Xing-Wu, et al. (författare)
  • Use of HIV-1 reverse transcriptase recovered from human plasma for phenotypic drug susceptibility testing
  • 2003
  • Ingår i: AIDS. ; 17, s. 1463-1471
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To demonstrate the use of HIV-1 reverse transcriplase (RT) recovered directly fromplasma for phenotypic drug susceptibility testing. Methods: Plasma from HIV-1 infected individuals with and without drug resistance-associated mutations were selected for the study. The blind coded plasmas were treated to inactivate cellular enzymes. The virions were immobilized on a gel and washed to remove antiretroviral drugs and RT activity blocking antibodies. The immobilized virions were lysed; the viral RTeluted and quantified, all according to the ExaVir Load procedure. The drug sensitivity profiles of each RT were determined using serially diluted drugs and modified Cavidi HS Lenti RT kits. Results: The phenotypic drug sensitivity profiles of the RT and the patterns of drug resistance mutations were highly concordant. Plasma RT from virions devoid of mutations associated with drug resistance had average 50% inhibitory concentrations (IC50) of 1.5 +/- 0.93 muM for nevirapine, 0.21 +/- 0.099 muM forefavirenz, 7.1 +/- 3.2 muM for delavirdine, 0.42 +/- 0.15 muM for azidothymidine triphosphate and 0.059 +/- 0.018 muM for didehydrothymidine triphosphate. The increase in IC50 value for RT with drugresistance associated substitutions was from 3- to more than 65-fold for non-nucleoside inhibitors and between 2- and 30-fold for thymidine analogue drugs. Conclusion: RT derived from virions recovered from the plasma of HIV infected individuals can be used foranalysis of phenotypic drug susceptibility. The methods presented provide rapid alternatives for analysingphenotypic drug susceptibility especially when the therapy is based on non-nucleoside RT inhibitors and thymidine-analogue drugs. 
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3.
  • Abdurahman, Samir, 1965-, et al. (författare)
  • Pattern of microbial translocation in patients living with HIV-1 from Vietnam, Ethiopia and Sweden
  • 2014
  • Ingår i: Journal of the International AIDS Society. - 1758-2652. ; 17, s. 18841-
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: The role of microbial translocation (MT) in HIV patients living with HIV from low- and middle-income countries (LMICs) is not fully known. The aim of this study is to investigate and compare the patterns of MT in patients from Vietnam, Ethiopia and Sweden.METHODS: Cross-sectional samples were obtained from treatment-naïve patients living with HIV-1 and healthy controls from Vietnam (n=83; n=46), Ethiopia (n=9492; n=50) and Sweden (n=51; n=19). Longitudinal samples were obtained from a subset of the Vietnamese (n=24) in whom antiretroviral therapy (ART) and tuberculostatics were given. Plasma lipopolysaccharide (LPS), sCD14 and anti-flagellin IgG were determined by the endpoint chromogenic Limulus Amebocyte Assay and enzyme-linked immunosorbent assay.RESULTS: All three biomarkers were significantly increased in patients living with HIV-1 from all countries as compared to controls. No differences were found between males and females. Vietnamese and Ethiopian patients had significantly higher levels of anti-flagellin IgG and LPS, as compared to Swedes. ART reduced these levels for the Vietnamese. Vietnamese patients given tuberculostatics at initiation of ART had significantly lower levels of anti-flagellin IgG and higher sCD14. The biomarkers were lower in Vietnamese who did not develop opportunistic infection.CONCLUSIONS: Higher MT is common in patients living with HIV compared to healthy individuals, and in patients from LMICs compared to patients from a high-income country. Treatment with tuberculostatics decreased MT while higher levels of MT are associated with a poorer clinical outcome.
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4.
  • Ambikan, Anoop T., et al. (författare)
  • Genome-scale metabolic models for natural and long-term drug-induced viral control in HIV infection
  • 2022
  • Ingår i: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 5:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-scale metabolic models (GSMMs) can provide novel insights into metabolic reprogramming during disease progression and therapeutic interventions. We developed a context-specific system-level GSMM of people living with HIV (PLWH) using global RNA sequencing data from PBMCs with suppressive viremia either by natural (elite controllers, PLWHEC) or drug-induced (PLWHART) control. This GSMM was compared with HIV-negative controls (HC) to provide a comprehensive systems-level metabo-transcriptomic characterization. Transcriptomic analysis identified up-regulation of oxidative phosphorylation as a characteristic of PLWHART, differentiating them from PLWHEC with dysregulated complexes I, III, and IV. The flux balance analysis identified altered flux in several intermediates of glycolysis including pyruvate, a-ketoglutarate, and glutamate, among others, in PLWHART. The in vitro pharmacological inhibition of OXPHOS complexes in a latent lymphocytic cell model (J-Lat 10.6) suggested a role for complex IV in latency reversal and immunosenescence. Furthermore, inhibition of complexes I/III/IV induced apoptosis, collectively indicating their contribution to reservoir dynamics.
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5.
  • Bai, Xiangning, et al. (författare)
  • Whole-Genome Metagenomic Analysis of the Gut Microbiome in HIV-1-Infected Individuals on Antiretroviral Therapy
  • 2021
  • Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Gut microbiome plays a significant role in HIV-1 immunopathogenesis and HIV-1-associated complications. Previous studies have mostly been based on 16S rRNA gene sequencing, which is limited in taxonomic resolution at the genus level and inferred functionality. Herein, we performed a deep shotgun metagenomics study with the aim to obtain a more precise landscape of gut microbiome dysbiosis in HIV-1 infection. A reduced tendency of alpha diversity and significantly higher beta diversity were found in HIV-1-infected individuals on antiretroviral therapy (ART) compared to HIV-1-negative controls. Several species, such as Streptococcus anginosus, Actinomyces odontolyticus, and Rothia mucilaginosa, were significantly enriched in the HIV-1-ART group. Correlations were observed between the degree of immunodeficiency and gut microbiome in terms of microbiota composition and metabolic pathways. Furthermore, microbial shift in HIV-1-infected individuals was found to be associated with changes in microbial virulome and resistome. From the perspective of methodological evaluations, our study showed that different DNA extraction protocols significantly affect the genomic DNA quantity and quality. Moreover, whole metagenome sequencing depth affects critically the recovery of microbial genes, including virulome and resistome, while less than 5 million reads per sample is sufficient for taxonomy profiling in human fecal metagenomic samples. These findings advance our understanding of human gut microbiome and their potential associations with HIV-1 infection. The methodological assessment assists in future study design to accurately assess human gut microbiome.
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6.
  • Banerjee, Indradumna, 1986-, et al. (författare)
  • Microfluidic Centrifugation Assisted Precipitation based DNA Quantification
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Nucleic acid amplification methods are increasingly being used to detect trace quantities of DNA in samples for various diagnostic applications. However, quantifying the amount of DNA from such methods often require time consuming purification, washing or labeling step. Here, we report a novel microfluidic centrifugation assisted precipitation (uCAP) method for single-step DNA quantification. The method is based on formation of a visible precipitate, that can be quantified, when an intercalating dye (GelRed) is added to DNA sample and centrifuged for few seconds. We describe the mechanism leading to the precipitation phenomenon. We utilize centrifugal microfluidics to precisely control the formation of visible and quantifiable mass. Using a standard CMOS sensor for imaging, we report a detection limit of 45 ng/ul. Furthermore, using an integrated Lab-on-DVD platform we recently developed, the detection limit was lowered to 10 ng/ul, which is comparable to current commercially available instruments for DNA quantification. As a proof of principle, we demonstrate the quantification of LAMP products for a HIV-1B type genome containing plasmid on the Lab-on-DVD platform. The simple DNA quantification system could facilitate advanced molecular diagnosis at point of care.
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7.
  • Barqasho, Babilonia, et al. (författare)
  • Implications of the release of high-mobility group box 1 protein from dying cells during human immunodeficiency virus type 1 infection in vitro
  • 2010
  • Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 91:Pt 7, s. 1800-1809
  • Tidskriftsartikel (refereegranskat)abstract
    • Plasma levels of high-mobility group box 1 protein (HMGB1) are elevated during the course of human immunodeficiency virus type 1 (HIV-1) infection and the molecule has an impact on virus replication. This study investigated the mode of cell death and release of HMGB1 during HIV-1 infection in vitro. MT4 cells and primary CD4(+) T cells were infected with HIV-1 isolates, and HMGB1 release was monitored in relation to cytopathic effects (CPE) and apoptosis. HMGB1 release from cells was analysed by Western blotting. For MT4 cells, an enzyme-linked immunosorbent spot (ELISPOT) assay was adapted to measure the release during necrosis. Lactate dehydrogenase (LDH) activity was quantified using a commercial assay. Flow cytometry was used to determine the level of infection and apoptosis. MT4 cells were > or =90 % infected at 48 h post-infection (p.i.). CPE was first observed at 60 h and correlated with release of HMGB1, LDH activity and caspase-3 (C3) activation. HMGB1 spots were clearly detected by ELISPOT assay at 72 h p.i. Annexin V and C3 staining showed that apoptosis was substantially involved in HIV-1-related cell death. Addition of Z-VAD (a caspase inhibitor) in a single dose at 24 or 40 h p.i. decreased both the number of caspase-positive cells and the release of HMGB1. Infection of primary CD4(+) T cells showed a 22 % (median) infection rate at 96 h. Related CPE corresponded to LDH and HMGB1 release. Both necrosis and apoptosis contributed to HMGB1 liberation during HIV-1-induced cell death and the protein could induce tumour necrosis factor-alpha release from peripheral mononuclear blood cells. These data imply that passive HMGB1 release contributes to the excessive immune activation characteristic of HIV-1 pathogenesis.
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8.
  • Bergroth, T., et al. (författare)
  • Difference in drug resistance patterns between minor HIV-1 populations in cerebrospinal fluid and plasma
  • 2009
  • Ingår i: HIV Medicine. - 1468-1293. ; 10, s. 111-115
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective The aim of the study was to determine to what extent unique drug resistance patterns appear in minor and major HIV-1 quasispecies in cerebrospinal fluid (CSF) as compared with blood. Methods Forty-four plasma and CSF samples from 13 multi-treatment-experienced patients, seven of whom provided longitudinal samples, were included in the study. The subjects had failed antiretroviral therapy including lamivudine. The reverse transcriptase (RT) gene was examined by selective real-time polymerase chain reaction (SPCR), which can detect M184I/V mutants down to 0.2% of the viral population. Results SPCR revealed differences at amino acid position 184 in the plasma/CSF populations in 12 paired samples from eight patients. One plasma sample was positive by SPCR where direct sequencing showed wild-type M184. The other 11 paired samples showed quantitative differences in the mixed populations of the mutant or wild-type M184 quasispecies. Differences in other resistance-associated mutations between plasma and CSF viruses were also found by direct sequencing. Conclusions In multi-treatment-experienced patients with therapy failure, differences in drug resistance patterns were found frequently between plasma and CSF in both minor and major viral populations. To what extent this was a true biological phenomenon remains to be established, and the clinical relevance of these findings is yet to be determined.
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9.
  • Buggert, Marcus, et al. (författare)
  • Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease
  • 2018
  • Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 14:4
  • Tidskriftsartikel (refereegranskat)abstract
    • CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether effector CD4+ T cells expressing cytolytic molecules and β-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of β-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and eomesodermin (Eomes). This effector population is predominately found in peripheral blood and is limited in LNs regardless of HIV infection or treatment status. As a result, CD4+ T cells generally lack effector functions in LNs, including cytolytic capacity and IFNγ and β-chemokine expression, even in HIV elite controllers and during acute/early HIV infection. While we do find the presence of degranulating CD4+ T cells in LNs, these cells do not bear functional or transcriptional effector T cell properties and are inherently poor to form stable immunological synapses compared to their peripheral blood counterparts. We demonstrate that CD4+ T cell cytolytic function, phenotype, and programming in the peripheral blood is dissociated from those characteristics found in lymphoid tissues. Together, these data challenge our current models based on blood and suggest spatially and temporally dissociated mechanisms of viral control in lymphoid tissues.
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10.
  • Buggert, Marcus, et al. (författare)
  • T-bet and Eomes Are Differentially Linked to the Exhausted Phenotype of CD8+ T Cells in HIV Infection.
  • 2014
  • Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 10:7
  • Tidskriftsartikel (refereegranskat)abstract
    • CD8+ T cell exhaustion represents a major hallmark of chronic HIV infection. Two key transcription factors governing CD8+ T cell differentiation, T-bet and Eomesodermin (Eomes), have previously been shown in mice to differentially regulate T cell exhaustion in part through direct modulation of PD-1. Here, we examined the relationship between these transcription factors and the expression of several inhibitory receptors (PD-1, CD160, and 2B4), functional characteristics and memory differentiation of CD8+ T cells in chronic and treated HIV infection. The expression of PD-1, CD160, and 2B4 on total CD8+ T cells was elevated in chronically infected individuals and highly associated with a T-betdimEomeshi expressional profile. Interestingly, both resting and activated HIV-specific CD8+ T cells in chronic infection were almost exclusively T-betdimEomeshi cells, while CMV-specific CD8+ T cells displayed a balanced expression pattern of T-bet and Eomes. The T-betdimEomeshi virus-specific CD8+ T cells did not show features of terminal differentiation, but rather a transitional memory phenotype with poor polyfunctional (effector) characteristics. The transitional and exhausted phenotype of HIV-specific CD8+ T cells was longitudinally related to persistent Eomes expression after antiretroviral therapy (ART) initiation. Strikingly, these characteristics remained stable up to 10 years after ART initiation. This study supports the concept that poor human viral-specific CD8+ T cell functionality is due to an inverse expression balance between T-bet and Eomes, which is not reversed despite long-term viral control through ART. These results aid to explain the inability of HIV-specific CD8+ T cells to control the viral replication post-ART cessation.
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11.
  • Carlander, Christina, et al. (författare)
  • HPV Types in Cervical Precancer by HIV Status and Birth Region : A Population-Based Register Study
  • 2020
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : AMER ASSOC CANCER RESEARCH. - 1055-9965 .- 1538-7755. ; 29:12, s. 2662-2668
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Data are lacking regarding which human papillomavirus (HPV) types cause high-grade cervical neoplasia (CIN2+) in people with HIV in Europe. We assessed which HPV types are associated with CIN2+ in women living in Sweden by HIV status.Methods: The Swedish National HIV Registry, the Swedish Population Registry, and the Swedish National Cervical Screening Registry were linked. CIN2+ tissue blocks of 130 women living with HIV (WLWH) and 234 HIV-negative women, matched for country of birth (1:2), were retrieved from bio-banks and HPV genotyped. Adjusted ORs (adjOR), stratified by country of birth, were calculated using conditional logistic regression. Matching was broken for cross-group comparisons.Results: WLWH with CIN2 were less likely to have HPV16 [14% vs. 40%; adjOR 0.1; 95% confidence interval (CI), 0.04-0.56] than HIV-negative women, but among women with CIN3, there was no difference in HPV16 prevalence by HIV status (adjOR 0.9; 95% CI, 0.51-1.70). WLWH were six times more likely to have HPV35 in CIN3 than HIV-negative women (adjOR 6.2; 95% CI, 1.3-30.4). WLWH from sub-Saharan Africa (SSA) had less 9-valent vaccine types, compared with both HIV-negative women born in Sweden (adjOR 0.1; 95% CI, 0.02-0.44) and WLWH born in Sweden (adjOR 0.1; 95% CI, 0.01-0.73), mostly because of decreased HPV16 and increased HPV35.Conclusions: WLWH from SSA were less likely to be covered by the 9-valent vaccine, mostly due to less HPV16 and more HPV35. Impact: This could have implications for HPV vaccines, currently not including HPV35, and for HPV-screening algorithms in women with origin from SSA.
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12.
  • Carlander, Christina, et al. (författare)
  • Suppressive antiretroviral therapy associates with effective treatment of high-grade cervical intraepithelial neoplasia
  • 2018
  • Ingår i: AIDS. - : LIPPINCOTT WILLIAMS & WILKINS. - 0269-9370 .- 1473-5571. ; 32:11, s. 1475-1484
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To assess if women living with HIV (WLWH) have poorer outcome after treatment of cervical intraepithelial neoplasia grade 2, grade 3, adenocarcinoma in situ or cervical cancer (CIN2+) than HIV-negative women (HNW) and to identify predictors of CIN2+ treatment failure and recurrence in WLWH. Design: Population-based cohort study with follow-up between 1983 and 2015. Methods: The Swedish National HIV Registry, the Swedish Population Registry and the Swedish National Cervical Screening Registry were linked to identify all women in Stockholm and Gothenburg counties (Sweden) living with HIV and diagnosed with CIN2+ (n = 179) sometime between 1983 and 2014. For each WLWH, two HNW resident in the same counties and matched for country of birth, diagnosed with CIN2+, were chosen as controls. Treatment failure was defined as the presence of CIN2+ at initial follow-up. Recurrence was defined as the presence of CIN1+ subsequent to an initial normal follow-up. Results: WLWH were three times more likely to have treatment failure (odds ratio (OR) 3.7 [95% confidence interval (CI) 2.0-6.8]) and five times more likely to recur (hazard ratio 5.0 [95% CI 2.1-11.6]) than HNW. Suppressive antiretroviral therapy (ART) at time of treatment of CIN2+ was associated with reduced OR of treatment failure (OR 0.3 [95% CI 0.1-0.8]). Immunosuppression (CD4(+) cell count < 200 cells/mu l) associated strongly with treatment failure (OR compared with CD4 (+) cell count >= 500: 8.5 [95% CI 2.3-30.7]). Conclusion: Suppressive ART is associated with effective treatment of CIN2+. Early HIV diagnosis and ART are essential for successful CIN2+ treatment.
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13.
  • Ceña-Diez, Rafael, et al. (författare)
  • Novel Naturally Occurring Dipeptides and Single-Stranded Oligonucleotide Act as Entry Inhibitors and Exhibit a Strong Synergistic Anti-HIV-1 Profile
  • 2022
  • Ingår i: Infectious Diseases and Therapy. - : Springer Science and Business Media LLC. - 2193-8229 .- 2193-6382. ; 11:3, s. 1103-1116
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The availability of new classes of antiretroviral drugs is critical for treatment-experienced patients due to drug resistance to and unwanted side effects from current drugs. Our aim was therefore to evaluate the anti-HIV-1 activity of a new set of antivirals, dipeptides (WG-am or VQ-am) combined with a single-stranded oligonucleotide (ssON). The dipeptides were identified as naturally occurring and enriched in feces and systemic circulation in HIV-1-infected elite controllers and were proposed to act as entry inhibitors by binding to HIV-1 gp120. The ssON is DNA 35-mer, stabilized by phosphorothioate modifications, which acts on the endocytic step by binding to cell host receptors and inhibiting viruses through interference with binding to nucleolin.Methods: Chou–Talalay’s Combination Index method for quantifying synergism was used to evaluate the drug combinations. Patient-derived chimeric viruses encoding the gp120 (env region) were produced by transient transfection and used to evaluate the antiviral profile of the combinations by drug susceptibility assays.Results: We found that the combination WG-am:ssON or VQ-am:ssON had low combination index values, suggesting strong antiviral synergism. Of the two combinations, WG-am:ssON (1 mM:1 μM) had high efficacy against all prototype or patient-derived HIV-1 isolates tested, independent of subtype including the HIV-1-A6 sub-subtype. In addition, the antiviral effect was independent of co-receptor usage in patient-derived strains.Conclusion: WG-am and ssON alone significantly inhibited HIV-1 replication regardless of viral subtype and co-receptor usage, and the combination WG-am:ssON (1 mM:1 μM) was even more effective due to synergism.
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14.
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15.
  • Edén, Arvid, 1975, et al. (author)
  • Differential effects of efavirenz, lopinavir/r, and atazanavir/r on the initial viral decay rate in treatment naïve HIV-1-infected patients.
  • 2010
  • In: AIDS research and human retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 26:5, s. 533-40
  • Journal article (peer-reviewed)abstract
    • Initial viral decay rate may be useful when comparing the relative potency of antiretroviral regimens. Two hundred twenty-seven ART-naïve patients were randomized to receive efavirenz (EFV) (n = 74), lopinavir/ritonavir (LPV/r) (n = 77), or atazanavir/ritonavir (ATV/r) (n = 79) in combination with two NRTIs. The most frequently used NRTI combinations in the EFV and ATV/r groups were the nonthymidine analogues tenofovir and emtricitabine or lamivudine (70% and 68%, respectively) and, in the LPV/r group, lamivudine and the thymidine analogue zidovudine (89%). HIV-1 RNA was monitored during the first 28 days after treatment initiation. Phase 1 and 2 decay rate was estimated in a subset of 157 patients by RNA decrease from days 0 to 7, and days 14 to 28. One-way ANOVA and subsequent Tukey's post hoc tests were used for groupwise comparisons. Mean (95% CI) HIV-1 RNA reductions from days 0 to 28 were 2.59 (2.45-2.73), 2.42 (2.27-2.57), and 2.13 (2.01-2.25) log(10) copies/ml for the EFV-, LPV/r-, and ATV/r-based treatment groups, respectively, with a significantly larger decrease in the EFV-based group at all time points compared with ATV/r (p < 0.0001), and with LPV/r at days 7-21 (p < 0.0001-0.03). LPV/r gave a greater RNA decrease compared with ATV/r from day 14 (p = 0.02). Phase 1 decay rate was significantly higher in the EFV group compared with LPV/r (p = 0.003) or ATV/r (p < 0.0001). No difference was found in phase 2 decrease. EFV-based treatment gave a more rapid decline in HIV-1 RNA than did either of the boosted protease inhibitor-based regimens. The observed differences may reflect different inherent regimen potencies.
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16.
  • Elvstam, Olof, et al. (author)
  • All-Cause Mortality and Serious Non-AIDS Events in Adults with Low-Level HIV Viremia during Combination Antiretroviral Therapy: Results from a Swedish Nationwide Observational Study.
  • 2021
  • In: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 72:12, s. 2079-2086
  • Journal article (peer-reviewed)abstract
    • The impact of low levels of HIV RNA (low-level viremia; LLV) during combination antiretroviral therapy (cART) on clinical outcomes is unclear. We explored the associations between LLV and all-cause mortality, AIDS, and serious non-AIDS events (SNAE).We grouped individuals starting cART 1996-2017 (identified from the Swedish InfCare HIV register) as virologic suppression (VS; <50 copies/mL), LLV (repeated viral load 50-999 copies/mL), and non-suppressed viremia (NSV; ≥1000 copies/mL). Separately, LLV was subdivided into 50-199 and 200-999 copies/mL (reflecting different definitions of virologic failure). Proportional-hazard models (including sex, age, pre-ART CD4 count and viral load, country of birth, injection drug use, treatment experience and interruptions, and an interaction term between viremia and time) were fitted for the study outcomes.6,956 participants were followed for a median of 5.7 years. At the end of follow-up, 60% were categorized as VS, 9% as LLV, and 31% as NSV. Compared with VS, LLV was associated with increased mortality (adjusted hazard ratio [aHR] 2.2, 95% confidence interval [CI] 1.3-3.6). This association was also observed for LLV 50-199 copies/mL (aHR 2.2, 95% CI 1.3-3.8), but was not statistically significant for LLV 200-999 copies/mL (aHR 2.1, 95% CI 0.96-4.7). LLV 50-999 copies/mL was not linked to increased risk of AIDS or SNAE, but in subanalysis, LLV 200-999 copies/mL was associated with SNAE (aHR 2.0, 95% CI 1.2-3.6).In this population-based cohort, LLV during cART was associated with adverse clinical outcomes.
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17.
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18.
  • Elvstam, Olof, et al. (author)
  • Virologic failure following low-level viremia and viral blips during antiretroviral therapy: results from a European multicenter cohort
  • 2023
  • In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 76:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: It is unclear whether low-level viremia (LLV), defined as repeatedly detectable viral load (VL) of <200 copies/mL, and/or transient viremic episodes (blips) during antiretroviral therapy (ART), predict future virologic failure. We investigated the association between LLV, blips, and virologic failure (VF) in a multi-center European cohort.METHODS: People with HIV-1 who started ART 2005 or later were identified from the EuResist Integrated Database. We analyzed the incidence of VF (≥200 copies/mL) depending on viremia exposure, starting 12 months after ART initiation (grouped as suppression [≤50 copies/mL], blips [isolated VL of 51-999 copies/mL], and LLV [repeated VLs of 51-199 copies/mL]) using Cox proportional hazard models adjusted for age, sex, injecting drug use, pre-ART VL, CD4 count, HIV-1 subtype, type of ART, and treatment experience. We queried the database for drug resistance mutations (DRM) related to episodes of LLV and VF and compared those with baseline resistance data.RESULTS: During 81,837 person-years of follow-up, we observed 1,424 events of VF in 22,523 participants. Both blips (adjusted subhazard ratio [aHR], 1.7; 95% confidence interval [CI], 1.3-2.2) and LLV (aHR, 2.2; 95% CI, 1.6-3.0) were associated with VF, compared with virologic suppression. These associations remained statistically significant in sub-analyses restricted to people with VL <200 copies/mL and those starting ART 2014 or later. Among people with LLV and genotype data available within 90 days following LLV, 49/140 (35%) had at least one DRM.CONCLUSIONS: Both blips and LLV during ART are associated with increased risk of subsequent VF.
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19.
  • Gisslén, Magnus, 1962, et al. (author)
  • [Swedish guidelines for antiretroviral treatment of HIV. Good compliance is crucial for a good result]
  • 2002
  • In: Läkartidningen. ; 99:43, s. 4263-6
  • Research review (peer-reviewed)abstract
    • Antiretroviral combination therapy has markedly decreased the mortality and morbidity in HIV-disease during the last years. An increasing number of new antiretroviral agents has been introduced and there has been a rapid evolution of new information regarding treatment of HIV. Physicians and patients have to deal with medical associated side-effects, problems with adherence, and viral resistance. Recently a national expert group has prepared guidelines for antiretroviral treatment in HIV-infected adults and adolescents which are summarized in this report. The Swedish guidelines recommend initiation of treatment when the CD4-cell-count is in the range between 200 and 350 x 10(6)/l in asymptomatic HIV-infection. They emphasize that the patient should be carefully prepared before treatment initiation to avoid adherence difficulties which regularly leads to viral failure. As first line is suggested a therapy with 2 NRTIs (nucleoside reverse transcriptase inhibitors) in combination with either a NNRTI (non-nucleoside RTI) or a protease inhibitor. When protease inhibitors are chosen, ritonavir-boosted combinations are most often to prefer. The virological treatment goal is to achieve a decrease in HIV-RNA with 1.5-2 log after 4 weeks and to below 50 copies/ml after 3-4 months of therapy. If a therapy fails, the causes should be carefully investigated for adherence difficulties, medicine interactions, and viral resistance. Treatment change should be guided by a thorough drug treatment history and the results of resistance testing. Treatment of HIV is complex and it is recommended that it should be conducted by an expert in the field.
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20.
  • Häggblom, Amanda, et al. (author)
  • Virological failure in patients with HIV-1 subtype C receiving antiretroviral therapy : an analysis of a prospective national cohort in Sweden.
  • 2016
  • In: The lancet. HIV. - 2352-3018. ; 3:4
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: People with HIV-1 in low-income and middle-income countries increasingly need second-line regimens with boosted protease inhibitors. However, data are scarce for treatment response in patients with HIV-1 subtype C (HIV-1C), which is predominant in these regions. We aimed to examine factors associated with virological failure in patients in a standardised national health-care setting.METHODS: We analysed data for participants in InfCare HIV, a prospective national cohort that includes more than 99% of people with HIV in Sweden. We extracted data for the cohort from the InfCare HIV database on Jan 14, 2015. Baseline was initiation of antiretroviral therapy. We used logistic regression to assess factors associated with primary virological failure (failure to suppress HIV-1 within 9 months) in patients with HIV-1B and HIV-1C and calculated odds ratios (OR) for failure. We also used Cox regression models to calculate hazard ratios (HR) for time-to-secondary virological failure (detectable viral load after initial virological suppression). We did homology-based molecular modelling to assess docking.FINDINGS: We included 1077 patients with HIV-1B and 596 with HIV-1C. In multivariate regression analysis, pre-therapy higher viral load (OR 1·82, 95% CI 1·49-2·21; p<0·0001), subtype C infection (1·75, 1·06-2·88; p=0·028), and boosted protease inhibitor-based regimens (1·55, 1·45-2·11; p=0·004) were associated with increased risk of primary virological failure. Individuals with HIV-1C who were given therapy with boosted protease inhibitors had earlier time-to-secondary virological failure than did those with HIV-1B given similar regimens (adjusted HR 1·92, 95% CI 1·30-2·83; p=0·002). Molecular modelling suggested lower affinity for protease inhibitors to HIV-1C protease than to HIV-1B.INTERPRETATION: Our findings suggest an increased risk of virological failure in patients with HIV-1C, especially in those on boosted protease inhibitor-based regimens. Future studies should further dissect the biochemical and viral mechanisms of resistance to protease inhibitors in patients with non-B subtypes of HIV-1, including clinical studies to assess the efficacy of boosted protease inhibitor-based regimens in low-income and middle income countries.FUNDING: Karolinska Institutet Research Foundation, Swedish Research Council, Stockholm County Council, Swedish Physicians against AIDS, US National Institutes of Health, University of Missouri.
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21.
  • Josephson, Filip, et al. (author)
  • Antiretroviral treatment of HIV infection: Swedish recommendations 2007.
  • 2007
  • In: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 39:6-7, s. 486-507
  • Journal article (peer-reviewed)abstract
    • On 3 previous occasions, in 2002, 2003 and 2005, the Swedish Medical Products Agency (Läkemedelsverket) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection. An expert group, under the guidance of RAV, has now revised the text again. Since the publication of the previous treatment recommendations, 1 new drug for the treatment of HIV has been approved - the protease inhibitor (PI) darunavir (Prezista). Furthermore, 3 new drugs have become available: the integrase inhibitor raltegravir (MK-0518), the CCR5-inhibitor maraviroc (Celsentri), both of which have novel mechanisms of action, and the non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (TMC-125). The new guidelines differ from the previous ones in several respects. The most important of these are that abacavir is now preferred to tenofovir and zidovudine, as a first line drug in treatment-naïve patients, and that initiation of antiretroviral treatment is now recommended before the CD4 cell count falls below 250/microl, rather than 200/microl. Furthermore, recommendations on the treatment of HIV infection in children have been added to the document. As in the case of the previous publication, recommendations are evidence-graded in accordance with the Oxford Centre for Evidence Based Medicine, 2001 (see http://www.cebm.net/levels_of_evidence.asp#levels).
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22.
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23.
  • Josephson, Filip, et al. (author)
  • Treatment of HIV infection: Swedish recommendations 2009.
  • 2009
  • In: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 41:11-12, s. 788-807
  • Research review (peer-reviewed)abstract
    • On 4 previous occasions, in 2002, 2003, 2005 and 2007, the Swedish Medical Products Agency (Läkemedelsverket) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection. In November 2008, an expert group under the guidance of RAV once more revised the guidelines, of which this is a translation into English. The most important updates in the present guidelines include the following: (a) treatment initiation is now recommended at a CD4 cell count of approximately 350/microl; (b) new recommendations for first-line therapy: abacavir/lamivudine or tenofovir/emtricitabine in combination with efavirenz or a boosted protease inhibitor (PI/r); (c) an increased focus on reducing the use of antiretroviral drugs that may cause lipoatrophy; (d) an emphasis on quality assurance of HIV care through the use of InfCare HIV; (e) considerably altered recommendations for the initiation of antiretroviral therapy in children. All infants (<1 y) should start antiretroviral therapy, regardless of immune status. Also, absolute CD4+ cell counts, rather than percentage, may be used to guide treatment initiation in children above the age of 5 y.
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24.
  • Kalu, Amare Worku, et al. (author)
  • Monophylogenetic HIV-1C epidemic in Ethiopia is dominated by CCR5-tropic viruses-an analysis of a prospective country-wide cohort
  • 2017
  • In: BMC Infectious Diseases. - London, United Kingdom : BioMed Central. - 1471-2334. ; 17:1
  • Journal article (peer-reviewed)abstract
    • Background: CCR5 coreceptor using HIV-1 subtype C (HIV-1C) has been reported to dominate the Ethiopian epidemic. However, almost all data have been obtained from two large cities in the central and north-west regions and recent data is lacking.Methods: Plasma were obtained from 420 treatment-naïve patients recruited 2009-2011 to a large country-wide Ethiopian cohort. The V3 region was sequenced and the co-receptor tropism was predicted by the clinical and clonal models of the geno2pheno tool at different false positive rates (fpr) and for subtype. In an intention to treat analysis the impact of baseline tropism on outcome of antiretroviral therapy was evaluated.Results: V3 loop sequencing was successful in 352 (84%) patients. HIV-1C was found in 350 (99.4%) and HIV-1A in two (0.6%) patients. When comparing the geno2pheno fpr10% clonal and clinical models, 24.4% predictions were discordant. X4-virus was predicted in 17.0 and 19.0%, respectively, but the predictions were concordant in only 6%. At fpr5%, concordant X4-virus predictions were obtained in 3.1%. The proportion of X4-tropic virus (clonal fpr10%) increased from 5.6 to 17.3% (p < 0.001) when 387 Ethiopian V3 loop sequences dated from 1984 to 2003 were compared with ours. In an intention to treat analysis, 67.9% reached treatment success at month 6 and only 50% at month 12. Only age and not tropism predicted therapy outcome and no difference was found in CD4+ cell gain between R5-tropic and X4-tropic infected patients. At viral failure, R5 to X4 switch was rare while X4 to R5 switch occurred more frequently (month 6: p = 0.006; month 12: p = 0.078).Conclusion: The HIV-1C epidemic is monophylogenetic in all regions of Ethiopia and R5-tropic virus dominates, even in patients with advanced immunodeficiency, although the proportion of X4-tropic virus seems to have increased over the last two decades. Geno2pheno clinical and clonal prediction models show a large discrepancy at fpr10%, but not at fpr5%. Hence further studies are needed to assess the utility of genotypic tropism testing in HIV-1C. In ITT analysis only age and not tropism influenced the outcome.
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25.
  • Karlsson, Annika, et al. (author)
  • Low Prevalence of Transmitted Drug Resistance in Patients Newly Diagnosed with HIV-1 Infection in Sweden 2003-2010.
  • 2012
  • In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 7:3
  • Journal article (peer-reviewed)abstract
    • Transmitted drug resistance (TDR) is a clinical and epidemiological problem because it may contribute to failure of antiretroviral treatment. The prevalence of TDR varies geographically, and its prevalence in Sweden during the last decade has not been reported. Plasma samples from 1,463 patients newly diagnosed with HIV-1 infection between 2003 and 2010, representing 44% of all patients diagnosed in Sweden during this period, were analyzed using the WHO 2009 list of mutations for surveillance of TDR. Maximum likelihood phylogenetic analyses were used to determine genetic subtype and to investigate the relatedness of the sequences. Eighty-two patients showed evidence of TDR, representing a prevalence of 5.6% (95% CI: 4.5%-6.9%) without any significant time trends or differences between patients infected in Sweden or abroad. Multivariable logistic regression showed that TDR was positively associated with men who have sex with men (MSM) and subtype B infection and negatively associated with CD4 cell counts. Among patients with TDR, 54 (68%) had single resistance mutations, whereas five patients had multi-drug resistant HIV-1. Phylogenetic analyses identified nine significantly supported clusters involving 29 of the patients with TDR, including 23 of 42 (55%) of the patients with TDR acquired in Sweden. One cluster contained 18 viruses with a M41L resistance mutation, which had spread among MSM in Stockholm over a period of at least 16 years (1994-2010). Another cluster, which contained the five multidrug resistant viruses, also involved MSM from Stockholm. The prevalence of TDR in Sweden 2003-2010 was lower than in many other European countries. TDR was concentrated among MSM, where clustering of TDR strains was observed, which highlights the need for continued and improved measures for targeted interventions.
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26.
  • Kieri, Oscar, et al. (author)
  • Incidence, Treatment, and Outcome of HIV-Associated Hematologic Malignancies in People Living with HIV in Sweden
  • 2022
  • In: AIDS Research and Human Retroviruses. - : Mary Ann Liebert. - 0889-2229 .- 1931-8405. ; 38:2, s. 135-142
  • Journal article (peer-reviewed)abstract
    • People living with HIV (PLHIV) have an increased risk of hematologic malignancies (HMs). We aimed to characterize HMs among PLHIV at Karolinska University Hospital, Stockholm, Sweden. We studied all PLHIV receiving care at our center between 2004 and 2018. Data were retrieved retrospectively from InfCareHIV database and medical records. Around 3,484 patients received HIV care for a total of 22,903 person-years (py) with median follow-up of 7.6 years. HMs were identified in 43 patients with 30 cases of non-Hodgkin lymphoma (NHL), 9 cases of Hodgkin lymphoma (HL), 2 multicentric Castleman's disease, and 1 case each of myeloma and myelodysplastic syndrome. The incidence rate of NHL was 88/10(5) py and HL 39.6/10(5) py. The incidence of NHL declined 2004-2010 versus 2011-2018 (180.8 vs. 40.1/10(5) py; p = .001). Median time from HIV diagnosis to malignancy was shorter in NHL compared with HL (1.2 years vs. 8.9 years; p = .01) and effective HIV treatment was less common in NHL (33% vs. 100%; p < .001). The 5-year survival rate of NHL was 59% and HL 43%, significantly lower compared with lymphoma survival in the general population in Sweden. In the era of effective antiretroviral therapy (ART), the incidence rate of lymphoma was more than five times higher in PLHIV and 5-year survival significantly inferior. Efforts for earlier identification of HIV-infected individuals are likely to affect the incidence of NHL. Additionally, an effective screening for clinical and laboratory signs of HL in PLHIV on ART should be introduced to improve identification and survival of HL in this population.
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27.
  • Krishnan, Shuba, et al. (author)
  • Metabolic Perturbation Associated With COVID-19 Disease Severity and SARS-CoV-2 Replication
  • 2021
  • In: Molecular & Cellular Proteomics. - : Elsevier BV. - 1535-9476 .- 1535-9484. ; 20
  • Journal article (peer-reviewed)abstract
    • Viruses hijack host metabolic pathways for their replicative advantage. In this study, using patient-derived multiomics data and in vitro infection assays, we aimed to understand the role of key metabolic pathways that can regulate severe acute respiratory syndrome coronavirus-2 reproduction and their association with disease severity. We used multiomics platforms (targeted and untargeted proteomics and untargeted metabolomics) on patient samples and cell-line models along with immune phenotyping of metabolite transporters in patient blood cells to understand viral-induced metabolic modulations. We also modulated key metabolic pathways that were identified using multiomics data to regulate the viral reproduction in vitro. Coronavirus disease 2019 disease severity was characterized by increased plasma glucose and mannose levels. Immune phenotyping identified altered expression patterns of carbohydrate transporter, glucose transporter 1, in CD8+ T cells, intermediate and nonclassical monocytes, and amino acid transporter, xCT, in classical, intermediate, and nonclassical monocytes. In in vitro lung epithelial cell (Calu-3) infection model, we found that glycolysis and glutaminolysis are essential for virus replication, and blocking these metabolic pathways caused significant reduction in virus production. Taken together, we therefore hypothesized that severe acute respiratory syndrome coronavirus-2 utilizes and rewires pathways governing central carbon metabolism leading to the efflux of toxic metabolites and associated with disease severity. Thus, the host metabolic perturbation could be an attractive strategy to limit the viral replication and disease severity.
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28.
  • Lindh, Magnus, 1960, et al. (author)
  • Treatment of chronic hepatitis B infection : an update of Swedish recommendations
  • 2008
  • In: Scandinavian Journal of Infectious Diseases. - London : Taylor & Francis. - 0036-5548 .- 1651-1980. ; 40:6-7, s. 436-450
  • Research review (peer-reviewed)abstract
    • The main goal for treatment of chronic hepatitis B is to prevent complications such as liver cirrhosis or hepatocellular carcinoma. Knowledge from population studies of the long-term risk of chronic HBV infection, as well as the recent introduction of pegylated interferon and additional nucleoside analogues has changed the therapeutic situation. Recently, a Swedish expert panel convened to update the national recommendations for treatment. The panel recommends treatment for patients with active HBV infection causing protracted liver inflammation or significant liver fibrosis, verified by liver histology. In general, pegylated interferon alpha-2a is recommended as first-line treatment, in particular for HBeAg-positive patients with HBV genotypes A or B. Among nucleoside analogues, entecavir is the first choice and adefovir or tenofovir can be used as alternatives. Lamivudine monotherapy is not recommended due to the high risk of resistance development. Combinations of nucleoside analogues such as tenofovir and lamivudine or emtricitabine are alternatives for patients with non-response or infection with resistant variants, or as first choice for patients with advanced liver disease. Nucleoside analogue treatment should be monitored to detect primary non-response and virological breakthrough. Special recommendations are given for HBV/HIV coinfected patients, immunosuppressed patients, children, and for treatment before and after liver transplantation. The present guideline is translated from Swedish, where it is published on the MPA and RAV websites (www.mpa.se and www.rav.nu.se) including 7 separate papers based on thorough literature search. The complete reference list can be received from the Medical Products Agency upon request.
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29.
  • Lindkvist, Annica, et al. (author)
  • Reduction of the HIV-1 reservoir in resting CD4+ T-lymphocytes by high dosage intravenous immunoglobulin treatment: a proof-of-concept study
  • 2009
  • In: AIDS research and therapy. - : Springer Science and Business Media LLC. - 1742-6405. ; 6:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The latency of HIV-1 in resting CD4+ T-lymphocytes constitutes a major obstacle for the eradication of virus in patients on antiretroviral therapy (ART). As yet, no approach to reduce this viral reservoir has proven effective. METHODS: Nine subjects on effective ART were included in the study and treated with high dosage intravenous immunoglobulin (IVIG) for five consecutive days. Seven of those had detectable levels of replication-competent virus in the latent reservoir and were thus possible to evaluate. Highly purified resting memory CD4+ T-cells were activated and cells containing replication-competent HIV-1 were quantified. HIV-1 from plasma and activated memory CD4+ T-cells were compared with single genome sequencing (SGS) of the gag region. T-lymphocyte activation markers and serum interleukins were measured. RESULTS: The latent HIV-1 pool decreased with in median 68% after IVIG was added to effective ART. The reservoir decreased in five, whereas no decrease was found in two subjects with detectable virus. Plasma HIV-1 RNA >or= 2 copies/mL was detected in five of seven subjects at baseline, but in only one at follow-up after 8-12 weeks. The decrease of the latent HIV-1 pool and the residual plasma viremia was preceded by a transitory low-level increase in plasma HIV-1 RNA and serum interleukin 7 (IL-7) levels, and followed by an expansion of T regulatory cells. The magnitude of the viral increase in plasma correlated to the size of the latent HIV-1 pool and SGS of the gag region showed that viral clones from plasma clustered together with virus from activated memory T-cells, pointing to the latent reservoir as the source of HIV-1 RNA in plasma. CONCLUSION: The findings from this uncontrolled proof-of-concept study suggest that the reservoir became accessible by IVIG treatment through activation of HIV-1 gene expression in latently-infected resting CD4+ T-cells. We propose that IVIG should be further evaluated as an adjuvant to effective ART.
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30.
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31.
  • Mellberg, Tomas, et al. (author)
  • Rebound of residual plasma viremia after initial decrease following addition of intravenous immunoglobulin to effective antiretroviral treatment of HIV
  • 2011
  • In: AIDS Research and Therapy. - : Springer Science and Business Media LLC. - 1742-6405. ; 8
  • Journal article (peer-reviewed)abstract
    • Abstract Background High dosage of intravenous immunoglobulin (IVIG) has been observed as a possible activator of HIV gene expression in latently infected resting CD4+ T-cells, leading to a substantial decrease in both the reservoir and the residual plasma viremia when added to effective ART. IVIG treatment has also been reported to expand T regulatory cells (Tregs). The aim of this study was to evaluate possible long-term effect of IVIG treatment on residual viremia and T-lymphocyte activation. Methods Nine HIV-infected subjects on effective ART included in a previously reported study on IVIG treatment were evaluated 48-104 weeks after therapy. In addition, 14 HIV-infected controls on suppressive ART were included. HIV-1 RNA was analyzed in cell-free plasma by using an ultrasensitive PCR-method with a detection limit of 2 copies/mL. T-lymphocyte activation markers and serum interleukins were measured. Results Plasma residual viremia rebounded to pre-treatment levels, 48-104 weeks after the initial decrease that was observed following treatment with high-dosage IVIG. No long-term effect was observed regarding T-lymphocyte activation markers, T-regulatory cells or serum interleukins. In a post-hoc analysis, a correlation between plasma HIV-1-RNA and CD4+ T-cell count was found in both IVIG-treated patients and controls. Conclusions These results indicate that the decrease in the latent HIV-1 pool observed during IVIG treatment is transient. Although not our primary objective, we found a correlation between HIV-1 RNA and CD4+ T-cell count suggesting the possibility that patients with a higher CD4+ T-cell count might harbor a larger residual pool of latently infected CD4+ T-cells.
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32.
  • Narayanan, Aswathy, et al. (author)
  • Exploring the interplay between antiretroviral therapy and the gut-oral microbiome axis in people living with HIV
  • 2024
  • In: Scientific Reports. - 2045-2322. ; 14
  • Journal article (peer-reviewed)abstract
    • The gut and oral microbiome is altered in people living with HIV (PLWH). While antiretroviral treatment (ART) is pivotal in restoring immune function in PLWH, several studies have identified an association between specific antiretrovirals, particularly integrase inhibitors (INSTI), and weight gain. In our study, we explored the differences in the oral and gut microbiota of PLWH under different ART regimens, and its correlation to Body Mass Index (BMI). Fecal and salivary samples were collected from PLWH (n = 69) and healthy controls (HC, n = 80). We performed taxonomy analysis to determine the microbial composition and relationship between microbial abundance and ART regimens, BMI, CD4+T-cell count, CD4/CD8 ratio, and ART duration. PLWH showed significantly lower richness compared to HC in both the oral and gut environment. The gut microbiome composition of INSTI-treated individuals was enriched with Faecalibacterium and Bifidobacterium, whereas non-nucleotide reverse transcriptase inhibitor (NNRTI)-treated individuals were enriched with Gordonibacter, Megasphaera, and Staphylococcus. In the oral microenvironment, Veillonella was significantly more abundant in INSTI-treated individuals and Fusobacterium and Alloprevotella in the NNRTI-treated individuals. Furthermore, Bifidobacterium and Dorea were enriched in gut milieu of PLWH with high BMI. Collectively, our findings identify distinct microbial profiles, which are associated with different ART regimens and BMI in PLWH on successful ART, thereby highlighting significant effects of specific antiretrovirals on the microbiome.Similar content being viewed by others
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33.
  • Navér, Lars, et al. (author)
  • Long-term pattern of HIV-1 RNA load in perinatally infected children
  • 1999
  • In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 31:4, s. 337-343
  • Journal article (peer-reviewed)abstract
    • The objective of this study was to describe the natural history of HIV-1 RNA load in vertically HIV-1-infected children. HIV-1 RNA in 156 plasma or serum samples (1-14, median 4 from each child) from 32 vertically HIV-1-infected children was detected with the NASBA® technique (Organon Teknika, The Netherlands). Twenty-one children were prospectively followed from birth, and 11 were identified and included at the age of 7-89 (median 61) months. The highest numbers of HIV-1 RNA copies were seen at 1.5-3 months of age. A quadratic curve model showed a reduction of HIV-1 RNA with increasing age up to approximately 8 years, and thereafter increasing numbers, p(age) = 0.002, p(age2) = 0.008, This pattern was not typical for individual children in whom a great variation in HIV-1 RNA numbers was seen over time. The interval from birth to the first HIV-1 RNA peak ranged from 1.5 months to more than 2 years. The HIV-1 RNA levels remained relatively high and fluctuating over the years in symptomatic as well as in long-term symptomatic children. This makes HIV-1 RNA determination in children more difficult to use than in adults, as the only tool for prediction of disease progression and for initiation of therapy.
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34.
  • Navér, Lars, et al. (author)
  • Prophylaxis and treatment of HIV-1 infection in pregnancy: Swedish recommendations 2013.
  • 2014
  • In: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 46:6, s. 401-11
  • Journal article (peer-reviewed)abstract
    • Prophylaxis and treatment with antiretroviral drugs and elective caesarean section delivery have resulted in very low mother-to-child transmission of HIV during recent years. Updated general treatment guidelines and increasing knowledge about mother-to-child transmission have necessitated regular revisions of the recommendations for the prophylaxis and treatment of HIV-1 infection in pregnancy. The Swedish Reference Group for Antiviral Therapy (RAV) updated the recommendations from 2010 at an expert meeting on 11 September 2013. The most important revisions are the following: (1) ongoing efficient treatment at confirmed pregnancy may, with a few exceptions, be continued; (2) if treatment is initiated during pregnancy, the recommended first-line therapy is essentially the same as for non-pregnant women; (3) raltegravir may be added to achieve rapid reduction in HIV RNA; (4) vaginal delivery is recommended if at > 34 gestational weeks and HIV RNA is < 50 copies/ml and no obstetric contraindications exist; (5) if HIV RNA is < 50 copies/ml and delivery is at > 34 gestational weeks, intravenous zidovudine is not recommended regardless of the delivery mode; (6) if HIV RNA is > 50 copies/ml close to delivery, it is recommended that the mother should undergo a planned caesarean section, intravenous zidovudine, and oral nevirapine, and the infant should receive single-dose nevirapine at 48-72 h of age and post-exposure prophylaxis with 2 drugs; (7) if delivery is preterm at < 34 gestational weeks, a caesarean section delivery should if possible be performed, with intravenous zidovudine and oral nevirapine given to the mother, and single-dose nevirapine given to the infant at 48-72 h of age, as well as post-exposure prophylaxis with 2 additional drugs.
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35.
  • Norda, Rut, et al. (author)
  • Transmission of hepatitis C virus by transfusion in Orebro County, Sweden, 1990-1992
  • 1995
  • In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 27:5, s. 449-452
  • Journal article (peer-reviewed)abstract
    • A retrospective study of hepatitis C virus (HCV) transmission by transfusion was conducted in Orebro county. Out of the 7,900 active, registered blood donors, 21 repeatedly anti-HCV reactive (RIVA 2 positive or indeterminate) donors were diagnosed. Their 84 recipients from January 1990 through June 1992 were identified and 41 (49%) were alive in December 1992. A total of 13 anti-HCV reactive (RIBA 2 positive or indeterminate) were diagnosed in 39 investigated recipients. Of these 11 were previously undiagnosed, and seven were HCV RNA-positive. In the donor population 1.03% were anti-HCV-positive by ELISA, but only 0.09% were RIBA and HCV RNA-positive. In 1990, 0.06% of the blood components came from the HCV RNA-positive donors, and none during the first 6 months of 1992. In order to identify transfusion-transmitted HCV infections that took place before the introduction of tests for anti-HCV antibodies, patients with a history of transfusion and symptoms and signs of liver dysfunction or damage should be thoroughly tested.
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36.
  • Nordqvist, Ola, et al. (author)
  • Assessing and achieving readiness to initiate HIV medication
  • 2006
  • In: Patient Education and Counseling. - : Elsevier BV. - 0738-3991 .- 1873-5134. ; 62:1, s. 21-30
  • Journal article (peer-reviewed)abstract
    • ObjectiveTo summarise published HIV-specific research on readiness theories, factors influencing readiness, instruments to measure readiness and interventions to increase readiness for treatment.MethodsMedline and PsychInfo were searched until August 2004.ResultsTwo HIV-specific readiness theories were identified. Fear of side effects, emotions emerging from the diagnosis and lack of trust in the physician were some barriers to overcome in order to reach readiness. Of the three measurement instruments found, the index of readiness showed the most promise. Multi-step intervention programs to increase readiness for HIV treatment had been investigated.ConclusionReadiness instruments may be useful tools in clinical practice but the predictive validity of the instruments needs to be further established in the HIV-infected population.Practice implicationsReadiness instruments and practice placebo trials may serve as complements to routine care, since health care providers currently have no better than chance probability in identifying those patients who are ready to adhere.
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37.
  • Nowak, Piotr, et al. (author)
  • Impact of HMGB1/TLR ligand complexes on HIV-1 replication : possible role for flagellin during HIV-1 infection
  • 2012
  • In: International Journal of Microbiology. - : Hindawi Limited. - 1687-918X .- 1687-9198. ; , s. 263836-
  • Journal article (peer-reviewed)abstract
    • Objective: We hypothesized that HMGB1 in complex with bacterial components, such as flagellin, CpG-ODN, and LPS, promotes HIV-1 replication. Furthermore, we studied the levels of antiflagellin antibodies during HIV-1-infection.Methods: Chronically HIV-1-infected U1 cells were stimulated with necrotic extract/recombinant HMGB1 in complex with TLR ligands or alone. HIV-1 replication was estimated by p24 antigen in culture supernatants 48-72 hours after stimulation. The presence of systemic anti-flagellin IgG was determined in 51 HIV-1-infected patients and 19 controls by immunoblotting or in-house ELISA.Results: Flagellin, LPS, and CpG-ODN induced stronger HIV-1 replication when incubated together with necrotic extract or recombinant HMGB1 than activation by any of the compounds alone. Moreover, the stimulatory effect of necrotic extract was inhibited by depletion of HMGB1. Elevated levels of anti-flagellin antibodies were present in plasma from HIV-1-infected patients and significantly decreased during 2 years of antiretroviral therapy.Conclusions: Our findings implicate a possible role of HGMB1-bacterial complexes, as a consequence of microbial translocation and cell necrosis, for immune activation in HIV-1 pathogenesis. We propose that flagellin is an important microbial product, that modulates viral replication and induces adaptive immune responses in vivo.
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38.
  • Ray, Shilpa, et al. (author)
  • Altered Gut Microbiome under Antiretroviral Therapy : Impact of Efavirenz and Zidovudine
  • 2021
  • In: ACS - Infectious Diseases. - : American Chemical Society (ACS). - 2373-8227. ; 7:5, s. 1104-1115
  • Journal article (peer-reviewed)abstract
    • Millions of individuals currently living with HIV globally are receiving antiretroviral therapy (ART) that suppresses viral replication and improves host immune responses. The involvement of gut microbiome during HIV infection has been studied, exposing correlation with immune status and inflammation. However, the direct effect of ART on gut commensals of HIV-infected individuals has been mostly overlooked in microbiome studies. We used 16S rRNA sequencing (Illumina MiSeq) for determining the microbiota composition of stool samples from 16 viremic patients before and one year after ART. We also tested the direct effect of 15 antiretrovirals against four gut microbes, namely, Escherichia coli, Enterococcus faecalis, Bacteroides, and Prevotella to assess their in vitro antibacterial effect. 16S rRNA analysis of fecal samples showed that effective ART for one year does not restore the microbiome diversity in HIV-infected patients. A significant reduction in α-diversity was observed in patients under non-nucleoside reverse transcriptase inhibitors; (NNRTI; 2 NRTI+NNRTI; NRTIs are nucleoside reverse transcriptase inhibitors) as compared to ritonavir-boosted protease inhibitors (PI/r; 2 NRTI+PI/r). Prevotella (P = 0.00001) showed a significantly decreased abundance in patients after ART (n = 16). We also found the direct effect of antivirals on gut microbes, where zidovudine (ZDV) and efavirenz (EFV) showed in vitro antimicrobial activity against Bacteroides fragilis and Prevotella. EFV also inhibited the growth of E. faecalis. Therefore, we observed that ART does not reverse the HIV-induced gut microbiome dysbiosis and might aggravate those microbiota alterations due to the antibacterial effect of certain antiretrovirals (like EFV, ZDV). Our results imply that restructuring the microbiota could be a potential therapeutic target in HIV-1 patients under ART.
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39.
  • Ray, Shilpa, et al. (author)
  • Impact of the gut microbiome on immunological responses to COVID-19 vaccination in healthy controls and people living with HIV
  • 2023
  • In: npj Biofilms and Microbiomes. - 2055-5008. ; 9:1
  • Journal article (peer-reviewed)abstract
    • Although mRNA SARS-CoV-2 vaccines are generally safe and effective, in certain immunocompromised individuals they can elicit poor immunogenic responses. Among these individuals, people living with HIV (PLWH) have poor immunogenicity to several oral and parenteral vaccines. As the gut microbiome is known to affect vaccine immunogenicity, we investigated whether baseline gut microbiota predicts immune responses to the BNT162b2 mRNA SARS-CoV-2 vaccine in healthy controls and PLWH after two doses of BNT162b2. Individuals with high spike IgG titers and high spike-specific CD4 + T-cell responses against SARS-CoV-2 showed low α-diversity in the gut. Here, we investigated and presented initial evidence that the gut microbial composition influences the response to BNT162b2 in PLWH. From our predictive models, Bifidobacterium and Faecalibacterium appeared to be microbial markers of individuals with higher spike IgG titers, while Cloacibacillus was associated with low spike IgG titers. We therefore propose that microbiome modulation could optimize immunogenicity of SARS-CoV-2 mRNA vaccines.
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40.
  • Ripamonti, Enrico, et al. (author)
  • Longitudinal decline of plasma neurofilament light levels after antiretroviral initiation in people living with HIV.
  • 2023
  • In: Journal of internal medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 293:4, s. 445-456
  • Journal article (peer-reviewed)abstract
    • This retrospective follow-up study aims to investigate the dynamic longitudinal change of plasma neurofilament light (NfL) levels after antiretroviral therapy (ART) initiation in a cohort of people living with human immunodeficiency virus (HIV) (PWH).We tested a convenience sample of 116 patients from the NORTHIV study. Plasma NfL levels-measured using Single molecule array (Simoa) technology-as well as other laboratory parameters were collected at baseline, weeks 4, 48, 96, and 144. Linear mixed-effects models were estimated to evaluate longitudinal change over time. Baseline CD4+ T-cell levels, CDC classification, and HIV RNA levels were considered. Models were adjusted by age, sex, treatment regimen, and baseline serum creatinine levels.Plasma NfL levels were higher at baseline and also declined faster during the follow-up for participants with CD4+ count <100 cells/µl compared with >100 cells/µl. No significant difference was found between the CD4+ strata 100-199 and 200-499/µl. Participants with CDC classification stages B and C had higher levels of plasma NfL at baseline, as well as faster decline compared with participants with stage A. No significant main effects or change over time was found in baseline HIV RNA levels, treatment regimen, or sex.Plasma NfL is a sensitive biomarker to assess ongoing central nervous system injury in PWH. Plasma NfL concentrations decline relatively fast following ART initiation and then stabilize after 48 weeks. Plasma NfL concentrations are associated with CD4+ count and stage of HIV disease. No correlations were seen with different ART regimens.
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41.
  • Sandström, Eric, et al. (author)
  • Antiretroviral treatment of human immunodeficiency virus infection: Swedish recommendations
  • 2003
  • In: Scand J Infect Dis. - : Informa UK Limited. ; 35:3, s. 155-67
  • Research review (peer-reviewed)abstract
    • The Swedish guidelines (SwG) for treatment of human immunodeficiency virus (HIV) infection have several important roles. A major task involves the promotion of a uniformly high standard of care in all HIV treatment clinics in Sweden and the identification of strengths, weaknesses and relevance of recent research findings. CD4+ T-cell counts < 200 cells/microl are clear indications for the initiation of treatment, whereas high viral loads serve as an indication for increased vigilance rather than a criterion for therapy. It is recommended that the first regimen consists of 2 nucleoside reverse transcriptase inhibitors in combination with 1 protease inhibitor or 1 non-nucleoside reverse transcriptase inhibitor. The definition of treatment failure is rigorous. Treatment change should be considered if the viral load has not fallen by at least 1.5 log in 4 weeks or is undetectable within 3-4 months. Resistance testing is endorsed at primary infection, in the event of treatment failure and in pregnant women. Interaction with experts in HIV resistance testing is emphasized. Therapeutic drug monitoring is advocated. Patients with treatment failure should be handled individually and the decision on therapeutic strategy should be based on treatment history, resistance testing and other clinical facts. The SwG do not give recommendations for some important issues such as prolonged drug holidays and preferences in initial treatment regimens. More scientific data are likely to be available soon and the SwG will be refined accordingly. The present guidelines are translated from Swedish; they are published on the Medical Products Agency (MPA) and Swedish Reference Group for Antiviral Therapy (RAV) websites (www.mpa.se and www.rav.nu.se), including 7 separate papers based on a thorough literature search. A complete reference list is available on request from the MPA.
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42.
  • Sundén-Cullberg, Jonas, et al. (author)
  • Anakinra or tocilizumab in patients admitted to hospital with severe covid-19 at high risk of deterioration (IMMCoVA): A randomized, controlled, open-label trial
  • 2023
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:12
  • Journal article (peer-reviewed)abstract
    • Background: Anakinra and tocilizumab are used for severe Covid-19, but only one previous randomized controlled trial (RCT) has studied both. We performed a multi-center RCT comparing anakinra or tocilizumab versus usual care (UC) for adults at high risk of deterioration.Methods: The study was conducted June 2020 to March 2021. Eligibility required ≥ 5 liters/minute of Oxygen to maintain peripheral oxygen saturation at ≥ 93%, CRP > 70 mg/L, ferritin > 500 μg/L and at least two points where one point was awarded for lymphocytes < 1x 109/L; D-dimer ≥ 0.5 mg/L and; lactate dehydrogenase ≥ 8 microkatal/L. Patients were randomly assigned 1:1:1 to receive either a single dose of tocilizumab (8 mg/kg) or anakinra 100 mg IV QID for seven days or UC alone. The primary outcome was time to recovery.Results: Recruitment was ended prematurely when tocilizumab became part of usual care. Out of a planned 195 patients, 77 had been randomized, 27 to UC, 28 to anakinra and 22 to tocilizumab. Median time to recovery was 15, 15 and 11 days. Rate ratio for recovery for UC vs anakinra was 0.91, 0.47 to 1.78, 95% [CI], p = 0.8 and for UC vs tocilizumab 1.13, 0.55 to 2.30; p = 0.7. There were non-significant trends favoring tocilizumab (and to limited degree anakinra) vs UC for some secondary outcomes. Safety profiles did not differ significantly.Conclusion: Premature closure of trial precludes firm conclusions. Anakinra or tocilizumab did not significantly shorten time to clinical recovery compared to usual care. (IMMCoVA, NCT04412291, EudraCT: 2020-00174824).
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43.
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44.
  • Södergård, Björn, et al. (author)
  • A structural equation modeling approach to the concepts of adherence and readiness in antiretroviral treatment
  • 2007
  • In: Patient Education and Counseling. - : Elsevier BV. - 0738-3991 .- 1873-5134. ; 67:1-2, s. 108-116
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: The objective of this secondary analysis of data from a cross-sectional, nation-wide survey, was to test a hypothesized model with two latent concepts (readiness and adherence), based on the theory of trigger events. A secondary objective was to compare this model with two simpler models, without the concept of readiness. METHODS: Data consisted of a consecutive sample of 828 HIV patients > or = 18 years on antiretroviral treatment at 30 out of 32 HIV Clinics in Sweden (response rate 97.5%). Structural equation modeling (SEM) was used to test the models against the empirical data. Chi2 test was used to compare fit between models. RESULTS: The hypothesized model, with two latent concepts (readiness and adherence), fitted the data best (chi(2)=223.508, d.f.=129, p-value<0.0001, GFI=0.970, CFI=0.913, RMSEA=0.030), and significantly better than the models with adherence as the only latent concept. CONCLUSION: Although the SEM technique could not rule out that other models might also fit the data equally well, the hypothesized model, where readiness and adherence were two separate latent concepts, fitted data the best. This supports readiness as a distinct factor that influences adherence and hence treatment outcome. Increased attention should therefore be attached to interventions that focus on the individual' readiness for behavioural change, i.e. factors amendable to change and that can be addressed by the patients themselves. PRACTICE IMPLICATIONS: Based on these results it seems necessary to shift focus from adherence to readiness, especially in conditions where treatment can be postponed such as antiretroviral treatment.
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45.
  • Södergård, Björn, 1973- (author)
  • Adherence and Readiness to Antiretroviral Treatment
  • 2006
  • Doctoral thesis (other academic/artistic)abstract
    • Antiretroviral therapy places extraordinarily high demands on adherence, since non-adherence affects both individuals and society due to the spread of resistant viral strains. The aims of the thesis were to investigate the prevalence of adherence in Swedish HIV-infected patients, changes in adherence over time, and factors associated with adherence, including patients’ readiness to adhere. Further, to investigate the collaboration between nurses, doctors and pharmacists after the introduction of a HIV-clinic satellite pharmacy. Data were collected via two cross-sectional patient surveys in 1998 and 2002, qualitative interviews with health care personnel at a major HIV clinic, and a nation-wide, cross-sectional patient survey in 2003-2004. The level of adherence improved from 28% in 1998 to 57% in 2002, possibly due to simplified treatment and a new multi-professional treatment model at the clinic. The proportion of adherent patients was 63% in the nationwide survey. Factors associated with adherence were high age, high quality patient-provider relationships, no drug or alcohol problems and shorter time on treatment. A hypothesized structural equational model, using readiness and adherence as separate latent concepts, was tested and found to support readiness as a distinct factor influencing adherence. The health care personnel believed that conventional pharmacies had several disadvantages in serving the HIV infected population. They found the HIV-clinic satellite pharmacy valuable, since it contributed to increased communication and trust between the health care professions, and improved teamwork in medication management.In conclusion, the level of adherence increased over time, and several factors associated with adherence were identified. Improved collaboration between health care professionals may enhance treatment support, and increased attention should be given to interventions that focus on the individual’s readiness for behavioural change in order to optimize treatment outcomes.
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46.
  • Södergård, Björn, et al. (author)
  • Adherence to treatment in Swedish HIV infected patients
  • 2006
  • In: Journal of Clinical Pharmacy and Therapeutics. - : Hindawi Limited. - 0269-4727 .- 1365-2710. ; 31:6, s. 605-616
  • Journal article (peer-reviewed)abstract
    • Objectives: The objectives were to assess the prevalence of adherence to antiretroviral treatment in Swedish human immunodeficiency virus (HIV)-infected patients and to evaluate factors associated with adherence. Methods: All HIV-treated patients, who attended one of 30 (of a total of 32) Swedish infectious diseases clinics, during 7 months, were asked to complete an anonymous questionnaire containing the 9-item Morisky Medication Adherence Scale (MMAS) and questions about other factors potentially affecting adherence. The summary score of MMAS ranges from 1 to 13, where 13 indicates perfect adherence; patients scoring 11 or above (corresponding to 95% adherence level) were classified as 'adherent'. Results and discussion: In total 946 patients participated (response rate 97.5%). The proportion of patients who reported not missing a dose during the day prior to the completion of the questionnaire was 97% and the proportion classified as 'adherent' was 63%. 'Adherent' patients were more likely to have a good relationship with their health care professionals (P < 0.05) and not have problems with drugs or alcohol (P < 0.01). Being older (P < 0.01) and having a shorter time on current treatment (P < 0.01) and on treatment in total (P < 0.05) were factors also associated with good adherence. Conclusion: Factors modifiable for interventions by health care professionals are patient-provider relationship, drug or alcohol problems and patients with long treatment periods.
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47.
  • Södergård, Björn, et al. (author)
  • Differences in adherence and motivation to HIV therapy : Two independent assessments in 1998 and 2002
  • 2006
  • In: Pharmacy World & Science. - : Springer Science and Business Media LLC. - 0928-1231 .- 1573-739X. ; 28:4, s. 248-256
  • Journal article (peer-reviewed)abstract
    • Objective: The aim of this study was to compare the level of adherence and motivation in two independent cross-sectional samples of HIV-infected patients conducted in 1998 and 2002, and to investigate the relationship between adherence and motivation. Method: Consecutive HIV-infected patients on treatment at a Swedish clinic were asked to complete an anonymous questionnaire. In 1998, 60 patients participated and in 2002, 53 participated. In 2002, the 9-item Morisky Medication Adherence Scale (MMAS) was added to the questionnaire set. Main outcome measure: Self-reported adherence and motivation. Results: In 1998, 28.1% of the respondents were considered adherent, while the corresponding proportion was 57.4% in 2002 (P = 0.002). The mean summary score for MMAS was 10.7 in 2002 (13 = perfect adherence). The proportion considered motivated were 22.4% in the 1998 survey and 41.3% in 2002 (P = 0.038). Of the respondents considered motivated in the 2002 survey, 46.7% scored the maximum summary score on the MMAS, while 8.7% of the non-motivated respondents did so (P = 0.016). Conclusion: The respondents in 2002 were more adherent and motivated than the respondents in 1998 and a relationship between motivation and adherence was found. The difference in adherence and motivation might be due to a new treatment model at the clinic.
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48.
  • Trøseid, Marius, et al. (author)
  • Elevated plasma levels of lipopolysaccharide and high mobility group box-1 protein are associated with high viral load in HIV-1 infection : reduction by 2-year antiretroviral therapy
  • 2010
  • In: AIDS. - 0269-9370 .- 1473-5571. ; 24:11, s. 1733-1737
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To investigate plasma levels of high mobility group box-1 protein (HMGB1), a marker of tissue necrosis and immune activation, as well as lipopolysaccharide (LPS), a marker of bacterial translocation, in HIV-1-infected patients.DESIGN: We studied 32 HIV-1-positive patients who had responded to antiretroviral therapy with undetectable viremia after 2 years, 10 nonresponders and 19 healthy controls.METHODS: HMGB1 was analyzed by ELISA, and LPS by Lamilus colometric assay. Nonparametric statistics were applied.RESULTS: In naive HIV-1 patients, HMGB1 and LPS were elevated as compared with controls (P < 0.001). LPS levels were higher in African and Oriental patients compared with whites (P = 0.007). Notably, viral load was two-fold higher in patients with LPS, and HMGB1 was above median as compared with other patients (P = 0.005). This association was largely driven by African patients, who had a five-fold increased viral load in the presence of elevated LPS and HMGB1. After 2 years of effective antiretroviral therapy, LPS was reduced to the same median level as in the control group (P < 0.001), and HMGB1 was also reduced (P = 0.001), whereas no reductions were seen in nonresponders.CONCLUSION: The new findings are the association of elevated plasma levels of LPS and HMGB1 with high viral load, as well as the normalized levels of LPS, and the reduction of HMGB1 after 2 years of effective antiretroviral therapy. As LPS and HMGB1 tend to form immunologically active complexes in vitro, we propose that such complexes may be involved in the immune activation and pathogenesis of HIV-1 infection.
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49.
  • Vesterbacka, Jan, et al. (author)
  • Kinetics of microbial translocation markers in patients on efavirenz or lopinavir/r based antiretroviral therapy
  • 2013
  • In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1, s. e55038-
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: We investigated whether there are differences in the effects on microbial translocation (MT) and enterocyte damage by different antiretroviral therapy (ART) regimens after 1.5 years and whether antibiotic use has impact on MT. In a randomized clinical trial (NCT01445223) on first line ART, patients started either lopinavir/r (LPV/r) (n = 34) or efavirenz (EFV) containing ART (n = 37). Lipopolysaccharide (LPS), sCD14, anti-flagellin antibodies and intestinal fatty acid binding protein (I-FABP) levels were determined in plasma at baseline (BL) and week 72 (w72).RESULTS: The levels of LPS and sCD14 were reduced from BL to w72 (157.5 pg/ml vs. 140.0 pg/ml, p = 0.0003; 3.13 ug/ml vs. 2.85 ug/ml, p = 0.005, respectively). The levels of anti-flagellin antibodies had decreased at w72 (0.35 vs 0.31 [OD]; p<0.0004), although significantly only in the LPV/r arm. I-FABP levels increased at w72 (2.26 ng/ml vs 3.13 ng/ml; p<0.0001), although significantly in EFV treated patients only. Patients given antibiotics at BL had lower sCD14 levels at w72 as revealed by ANCOVA compared to those who did not receive (Δ = -0.47 µg/ml; p = 0.015).CONCLUSIONS: Markers of MT and enterocyte damage are elevated in untreated HIV-1 infected patients. Long-term ART reduces the levels, except for I-FABP which role as a marker of MT is questionable in ART-experienced patients. Why the enterocyte damage seems to persist remains to be established. Also antibiotic usage may influence the kinetics of the markers of MT.TRIAL REGISTRATION: ClinicalTrials.gov NCT01445223.
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50.
  • Weibull Wärnberg, Anna, et al. (author)
  • The molecular epidemiology of HIV-1 in Sweden 1996 to 2022, and the influence of migration from Ukraine.
  • 2023
  • In: Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. - 1560-7917. ; 28:48
  • Journal article (peer-reviewed)abstract
    • BackgroundThe global distribution of HIV-1 subtypes is evolving, which is reflected in the Swedish HIV cohort. The subtype HIV-1A6, which may be prone to developing resistance to cabotegravir, is the most common subtype in Ukraine.AimWe aimed to examine trends in HIV-1 subtype distribution in Sweden, with a special focus on HIV-1A6, and to describe the virology, demography and treatment of Ukrainian people living with HIV (PLWH) who migrated to Sweden in 2022.MethodsData about PLWH in Sweden are included in a national database (InfCareHIV). We used the online tool COMET to establish HIV-1 subtypes and the Stanford database to define drug resistance mutations. We investigated the relation between virological characteristics and demographic data.ResultsThe early epidemic was predominated by HIV-1 subtype B infections in people born in Sweden. After 1990, the majority of new PLWH in Sweden were PLWH migrating to Sweden, resulting in an increasingly diverse epidemic. In 2022, HIV-1A6 had become the sixth most common subtype in Sweden and 98 of the 431 new PLWH that were registered in Sweden came from Ukraine. We detected HIV RNA in plasma of 32 Ukrainian patients (34%), of whom 17 were previously undiagnosed, 10 had interrupted therapy and five were previously diagnosed but not treated. We found HIV-1A6 in 23 of 24 sequenced patients.ConclusionThe molecular HIV epidemiology in Sweden continues to diversify and PLWH unaware of their HIV status and predominance of HIV-1A6 should be considered when arranging care directed at PLWH from Ukraine.
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