Publications by authors named "Jan Gerstoft"

270 Publications

Potential drug-drug interactions between antiretroviral drugs and comedications, including dietary supplements, among people living with HIV: A clinical survey.

HIV Med 2022 May 6. Epub 2022 May 6.

CREDID, Center for Research and Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark.

Objective: Age-related comorbidities, polypharmacy and thereby the risk of potential drug-drug interactions (PDDIs) among people living with HIV (PLWH) have increased over the years. We estimated the prevalence of comedications, including dietary supplements, and evaluated PDDIs among PLWH receiving antiretroviral therapy (ART) in Denmark in an outpatient setting.

Methods: Information on prescription medication, over-the-counter medication and dietary supplements was obtained from adult PLWH receiving ART attending two outpatient clinics in Denmark. The PDDIs were identified using the University of Liverpool's drug interaction database. Associations between PDDIs and relevant variables were compared using logistic regression models.

Results: A total of 337 PLWH receiving ART with a median age of 53 years (interquartile range: 45-61) were included; 77% were male and 96% had a HIV-RNA viral load < 50 copies/mL. Twenty-six per cent of participants received five or more comedications and 56% consumed dietary supplements. Co-administration of drugs requiring dose adjustment or monitoring was identified in the medication lists of 52% of participants, and 4.5% were on drugs that should not be co-administered. Male sex [odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.0-3.4], being on a protease inhibitor (OR = 4.3, 95% CI: 1.9-9.7), receiving five or more comedications (OR = 3.3, 95% CI: 1.5-7.2), taking over-the-counter medications (OR = 1.9, 95% CI: 1.1-3.3) and dietary supplements (OR = 2.0, 95% CI: 1.2-3.3) were independent predictors of PDDIs.

Conclusion: Potential drug-drug interactions were common among our study population Our study confirms that polypharmacy and being on a protease inhibitor-based regimen increase the risk of PDDIs considerably and highlights the importance of questioning PLWH about dietary supplement intake.
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http://dx.doi.org/10.1111/hiv.13321DOI Listing
May 2022

Risk of subarachnoid haemorrhages and aneurysms in Danish People Living With HIV, a nationwide cohort study.

AIDS 2022 May 24. Epub 2022 May 24.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen.

Objective: It remains unclear whether people with HIV (PWH) have increased risk of aneurysms. We aimed to investigate if the risk of subarachnoid haemorrhage, cerebral aneurysm, aortic aneurysm and other arterial aneurysms and dissections is increased in PWH compared with the general population.

Design: We performed a nationwide population-based matched cohort study.

Methods: We compared PWH with age-matched and sex-matched comparison cohort members to calculate incidence rate ratios (IRR) of subarachnoid haemorrhage, cerebral aneurysm, aortic aneurysm and other arterial aneurysms and dissections as well as surgery for these conditions.

Results: We included all PWH, who were Danish residents and treated at a HIV healthcare centre between January 1995 and February 2018 (n = 6935) and an age-matched and sex-matched comparison cohort (n = 55 480). PWH had increased risk of subarachnoid haemorrhage (IRR 1.7, 95% CI, 1.1-2.6), but no increased risk of surgery for this condition. PWH had no increased risk of cerebral aneurysm or aortic aneurysm or surgery for these conditions. The risk of other arterial aneurysms and dissections was increased in PWH (IRR 2.0, 95% CI, 1.4-2.9), but this only applied for PWH who reported intravenous substance use as route of HIV transmission (IRR 18.4, 95% CI, 9.3-36.6), and not for PWH without reported injection drug use (IRR 1.2, 95% CI, 0.73-1.7).

Conclusion: PWH were not at an increased risk of cerebral, aortic or other arterial aneurysms and dissections. Although PWH were at an increased risk of subarachnoid haemorrhage, subarachnoid haemorrhages were rare among PWH.
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http://dx.doi.org/10.1097/QAD.0000000000003260DOI Listing
May 2022

Epitope length variants balance protective immune responses and viral escape in HIV-1 infection.

Cell Rep 2022 03;38(9):110449

Nuffield Department of Clinical Neurosciences, Division of Clinical Neurology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headley Way, Oxford OX3 9DS, UK. Electronic address:

Cytotoxic T lymphocyte (CTL) and natural killer (NK) cell responses to a single optimal 10-mer epitope (KK10) in the human immunodeficiency virus type-1 (HIV-1) protein p24Gag are associated with enhanced immune control in patients expressing human leukocyte antigen (HLA)-B27:05. We find that proteasomal activity generates multiple length variants of KK10 (4-14 amino acids), which bind TAP and HLA-B27:05. However, only epitope forms ≥8 amino acids evoke peptide length-specific and cross-reactive CTL responses. Structural analyses reveal that all epitope forms bind HLA-B27:05 via a conserved N-terminal motif, and competition experiments show that the truncated epitope forms outcompete immunogenic epitope forms for binding to HLA-B27:05. Common viral escape mutations abolish (L136M) or impair (R132K) production of KK10 and longer epitope forms. Peptide length influences how well the inhibitory NK cell receptor KIR3DL1 binds HLA-B27:05 peptide complexes and how intraepitope mutations affect this interaction. These results identify a viral escape mechanism from CTL and NK responses based on differential antigen processing and peptide competition.
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http://dx.doi.org/10.1016/j.celrep.2022.110449DOI Listing
March 2022

Humoral response to two doses of BNT162b2 vaccination in people with HIV.

J Intern Med 2022 04 16;291(4):513-518. Epub 2021 Dec 16.

Viro-Immunology Research Unit, Department of Infectious Diseases, Section 8632, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.

Background: People with HIV (PWH) are at increased risk of severe COVID-19. We aimed to determine humoral responses in PWH and controls who received two doses of BNT162b2.

Methods: In 269 PWH and 538 age-matched controls, we measured IgG and neutralizing antibodies specific for the receptor-binding domain of SARS-CoV-2 at baseline, 3 weeks and 2 months after the first dose of BNT162b2.

Results: IgG antibodies increased from baseline to 3 weeks and from 3 weeks to 2 months in both groups, but the concentrations of IgG antibodies were lower in PWH than that in controls at 3 weeks and 2 months (p = 0.025 and <0.001), respectively. The IgG titres in PWH with a humoral response at 2 months were 77.9% (95% confidence interval [62.5%-97.0%], age- and sex-adjusted p = 0.027) of controls.

Conclusions: Reduced IgG antibody response to vaccination with BNT162b2 was found in PWH, and thus increased awareness of breakthrough infections in PWH is needed.
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http://dx.doi.org/10.1111/joim.13419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011842PMC
April 2022

De novo electrocardiographic abnormalities in persons living with HIV.

Sci Rep 2021 10 21;11(1):20750. Epub 2021 Oct 21.

Viro-immunology Research Unit, Department of Infectious Diseases 8632, Copenhagen University Hospital, Rigshospitalet, University of Copenhagen, Blegdamsvej 9B, 2100, Copenhagen, Denmark.

Persons living with HIV (PLWH) may have increased incidence of cardiovascular events and longer QTc intervals than uninfected persons. We aimed to investigate the incidence and risk factors of de novo major electrocardiogram (ECG) abnormalities and QTc prolongation in well-treated PLWH. We included virologically suppressed PLWH without major ECG abnormalities, who attended the 2-year follow-up in the Copenhagen comorbidity in HIV infection (COCOMO) study. ECGs were categorized according to Minnesota Code Manual. We defined de novo major ECG abnormalities as new major Minnesota Code Manual abnormalities. Prolonged QTc was defined as QTc > 460 ms in females and QTc > 450 ms in males. Of 667 PLWH without major ECG abnormalities at baseline, 34 (5%) developed de novo major ECG abnormalities after a median of 2.3 years. After adjustment, age (RR: 1.57 [1.08-2.28] per decade older), being underweight (RR: 5.79 [1.70-19.71]), current smoking (RR: 2.34 [1.06-5.16]), diabetes (RR: 3.89 [1.72-8.80]) and protease inhibitor use (RR: 2.45 [1.27-4.74) were associated with higher risk of getting de novo major ECG abnormalities. Of PLWH without prolonged QTc at baseline, only 11 (1.6%) participants developed de novo prolonged QTc. Five percent of well-treated PLWH acquired de novo major ECG abnormalities and protease inhibitor use was associated with more than twice the risk of de novo major ECG abnormalities. De novo prolonged QTc was rare and did not seem to constitute a problem in well-treated PLWH.
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http://dx.doi.org/10.1038/s41598-021-00290-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531322PMC
October 2021

HIV Infection Is Associated With Type 2 Diabetes Mellitus.

J Acquir Immune Defic Syndr 2021 12;88(4):e32-e35

Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

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http://dx.doi.org/10.1097/QAI.0000000000002798DOI Listing
December 2021

HIV infection is associated with thoracic and abdominal aortic aneurysms: a prospective matched cohort study.

Eur Heart J 2021 08;42(30):2924-2931

Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Esther Møllers Vej 6, 2100 Kbh Ø, Copenhagen, Denmark.

Aims: Little is known about the prevalence of aortic aneurysms among people living with HIV (PLWH). We investigated whether HIV status is independently associated with having aortic aneurysms. Furthermore, we determined risk factors associated with aortic aneurysms in PLWH.

Methods And Results: PLWH aged ≥40 years (n = 594) were recruited from the Copenhagen Comorbidity in HIV Infection study and matched for age and sex with uninfected controls (n = 1188) from the Copenhagen General Population Study. Aortic dimensions were assessed using contrast enhanced computed tomography. Aortic aneurysms were defined according to the European Society of Cardiology guidelines, i.e. an aortic dilation of ≥50% or an infrarenal aortic diameter of ≥30 mm. Among PLWH and uninfected controls, the median (interquartile range) age was 52 (47-60) and 52 (48-61) and 88% and 90% were male, respectively. We found 46 aneurysms in 42 (7.1%) PLWH and 31 aneurysms in 29 (2.4%) uninfected controls (P < 0.001). PLWH had a significantly higher prevalence of ascending aortic aneurysms and infrarenal aortic aneurysms. In an adjusted model, HIV was independently associated with aortic aneurysms (adjusted odds ratio; 4.51 [95% confidence interval 2.56-8.08], P < 0.001). Within PLWH, obesity and hepatitis B co-infection were associated with aortic aneurysms.

Conclusion: PLWH had four-fold higher odds of aortic aneurysms compared to uninfected controls, and HIV status was independently associated with aortic aneurysms. Among PLWH, age, obesity and hepatitis B co-infection were associated with higher odds of aortic aneurysms. Our findings suggest that increased attention to aortic aneurysms in PLWH may be beneficial.
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http://dx.doi.org/10.1093/eurheartj/ehab348DOI Listing
August 2021

Independent Associations of Tumor Necrosis Factor-Alpha and Interleukin-1 Beta With Radiographic Emphysema in People Living With HIV.

Front Immunol 2021 14;12:668113. Epub 2021 Apr 14.

Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Background: People living with HIV (PLWH) have increased systemic inflammation, and inflammation has been suggested to contribute to the pathogenesis of emphysema. We investigated whether elevated cytokine concentrations (interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor-alpha (TNFα), interferon-gamma (IFNγ), soluble CD14 (sCD14) and sCD163 were independently associated with radiographic emphysema in PLWH.

Methods: We included PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study without hepatitis B and C co-infection and with a plasma sample and a chest computed tomography scan available. Emphysema plus trace emphysema was defined as the percentage of low attenuation area under -950 Houndsfield Unit (%LAA-950) using a cut-off at 5%. Cytokine concentrations were measured by ELISA or Luminex immunoassays. An elevated cytokine concentration was defined as above the 75 percentile.

Results: Of 783 PLWH, 147 (18.8%) had emphysema. PLWH were predominantly male (86.0%) and 743 (94.9%) had undetectable viral replication. PLWH with emphysema had higher concentrations of TNFα (median (IQR): 8.2 (6.4-9.8) versus 7.1 (5.7-8.6) pg/ml, p<0.001), IL-1β (0.21 (0.1-0.4) versus 0.17 (0.1-0.3) pg/ml, p=0.004) and IL-6 (3.6 (2.6-4.9) versus 3.1 (2.0-4.3) pg/ml, p=0.023) than PLWH without. In a logistic regression model adjusted for age, sex, ethnicity, smoking status, BMI and CD4 nadir, elevated TNFα (adjusted odds ratio (aOR): 1.78 [95%CI: 1.14-2.76], p=0.011) and IL-1β (aOR: 1.81 [95%CI: 1.16-2.81], p=0.009) were independently associated with emphysema. The association between IL-1β and emphysema was modified by smoking (p-interaction=0.020) with a more pronounced association in never-smokers (aOR: 4.53 [95%CI: 2.05-9.98], p<0.001).

Conclusion: Two markers of systemic inflammation, TNFα and IL-1β, were independently associated with emphysema in PLWH and may contribute to the pathogenesis of emphysema. Importantly, the effect of IL-1β seems to be mediated through pathways that are independent of excessive smoking.

Clinical Trial Registration: clinicaltrials.gov, identifier NCT02382822.
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http://dx.doi.org/10.3389/fimmu.2021.668113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080065PMC
October 2021

A simple, safe and sensitive method for SARS-CoV-2 inactivation and RNA extraction for RT-qPCR.

APMIS 2021 Jul 17;129(7):393-400. Epub 2021 Mar 17.

Division of Clinical Neurology, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.

The SARS-CoV-2 pandemic has created an urgent need for diagnostic tests to detect viral RNA. Commercial RNA extraction kits are often expensive, in limited supply, and do not always fully inactivate the virus. Together, this calls for the development of safer methods for SARS-CoV-2 extraction that utilize readily available reagents and equipment present in most standard laboratories. We optimized and simplified a RNA extraction method combining a high molar acidic guanidinium isothiocyanate (GITC) solution, phenol and chloroform. First, we determined the GITC/RNA dilution thresholds compatible with an efficient two-step RT-qPCR for B2M mRNA in nasopharyngeal (NP) or oropharyngeal (OP) swab samples. Second, we optimized a one-step RT-qPCR against SARS-CoV-2 using NP and OP samples. We furthermore tested a SARS-CoV-2 dilution series to determine the detection threshold. The method enables downstream detection of SARS-CoV-2 by RT-qPCR with high sensitivity (~4 viral RNA copies per RT-qPCR). The protocol is simple, safe, and expands analysis capacity as the inactivated samples can be used in RT-qPCR detection tests at laboratories not otherwise classified for viral work. The method takes about 30 min from swab to PCR-ready viral RNA and circumvents the need for commercial RNA purification kits.
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http://dx.doi.org/10.1111/apm.13123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250463PMC
July 2021

Independent Association of Interleukin 6 With Low Dynamic Lung Function and Airflow Limitation in Well-Treated People With Human Immunodeficiency Virus.

J Infect Dis 2021 05;223(10):1690-1698

Viro-immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Background: Human immunodeficiency virus (HIV) infection is associated with an increased risk of chronic pulmonary diseases. We compared cytokine concentrations (interleukin 6 [IL-6], interleukin 1β, 2, 4, 10, and 17A, tumor necrosis factor α, interferon γ, soluble CD14 [sCD14] and soluble CD163 [sCD163]) in people with HIV (PWH) and uninfected controls and investigated whether elevated cytokine concentrations were independently associated with lung function indices in PWH.

Methods: We performed spirometry and measured cytokine concentrations by Luminex immunoassays or enzyme-linked immunoassay in 951 PWH and 79 uninfected controls from the Copenhagen Comorbidity in HIV Infection study. Regression analyses were used to explore associations between elevated cytokine concentrations and lung function indices.

Results: PWH were predominantly male (84.6%) and 94.2% had undetectable viral replication. In PWH, elevated IL-6 was associated with lower forced expiratory volume in 1 second (-212 mL [95% confidence interval, -308 to -116 mL]), lower forced vital capacity (-208 mL [-322 to -93 mL]), and airflow limitation (aOR, 2.62 [1.58-4.36]) (all P < .001) in models adjusted for age, sex, ethnicity, smoking status, body mass index, and CD4 T-cell nadir. The association between IL-6 and dynamic lung function was modified by smoking (P for interaction = .005).

Conclusion: IL-6 levels were elevated and independently associated with low dynamic lung function and airflow limitation in well-treated PWH, suggesting that systemic inflammation may contribute to the pathogenesis of chronic pulmonary diseases.
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http://dx.doi.org/10.1093/infdis/jiaa600DOI Listing
May 2021

Global evolutionary analysis of chronic hepatitis C patients revealed significant effect of baseline viral resistance, including novel non-target sites, for DAA-based treatment and retreatment outcome.

J Viral Hepat 2021 02 25;28(2):302-316. Epub 2020 Nov 25.

Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.

Direct-acting antivirals (DAAs) have proven highly effective against chronic hepatitis C virus (HCV) infection. However, some patients experience treatment failure, associated with resistance-associated substitutions (RASs). Our aim was to investigate the complete viral coding sequence in hepatitis C patients treated with DAAs to identify RASs and the effects of treatment on the viral population. We selected 22 HCV patients with sustained virologic response (SVR) to match 21 treatment-failure patients in relation to HCV genotype, DAA regimen, liver cirrhosis and previous treatment experience. Viral-titre data were compared between the two patient groups, and HCV full-length open reading frame deep-sequencing was performed. The proportion of HCV NS5A-RASs at baseline was higher in treatment-failure (82%) than matched SVR patients (25%) (p = .0063). Also, treatment failure was associated with slower declines in viraemia titres. Viral population diversity did not differ at baseline between SVR and treatment-failure patients, but failure was associated with decreased diversity probably caused by selection for RAS. The NS5B-substitution 150V was associated with sofosbuvir treatment failure in genotype 3a. Further, mutations identified in NS2, NS3-helicase and NS5A-domain-III were associated with DAA treatment failure in genotype 1a patients. Six retreated HCV patients (35%) experienced 2nd treatment failure; RASs were present in 67% compared to 11% with SVR. In conclusion, baseline RASs to NS5A inhibitors, but not virus population diversity, and lower viral titre decline predicted HCV treatment failure. Mutations outside of the DAA targets can be associated with DAA treatment failure. Successful DAA retreatment in patients with treatment failure was hampered by previously selected RASs.
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http://dx.doi.org/10.1111/jvh.13430DOI Listing
February 2021

Impact of Age and HIV Status on Immune Activation, Senescence and Apoptosis.

Front Immunol 2020 30;11:583569. Epub 2020 Sep 30.

Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Introduction: Residual immune dysfunctions, resembling those that occur during normal aging, may persist even in well-treated people with HIV (PWH), and accelerated aging has been proposed. We aimed to determine if HIV infection is an independent risk factor for T-cell immune dysfunctions including increased immune activation, senescence and apoptosis. Moreover, in PWH we aimed to identify the associations between age and immune activation, senescence and apoptosis.

Materials And Methods: We included 780 PWH with suppressed viral replication (<50 copies/mL) and absence of hepatitis B and hepatitis C co-infection and 65 uninfected controls from the Copenhagen Co-morbidity in HIV Infection (COCOMO) Study. Flow cytometry was used to determine T-cell activation (CD38+HLA-DR+), senescence (CD28-CD57+), and apoptosis (CD28-CD95+). T-cell subsets are reported as proportions of CD4+ and CD8+ T-cells. We defined an elevated proportion of a given T-cell subset as above the 75th percentile. Regression models were used to determine the association between HIV status and T-cell subset and in PWH to determine the association between age or HIV-specific risk factors and T-cell subsets. Furthermore, an interaction between HIV status and age on T-cell subsets was investigated with an interaction term in models including both PWH and controls. Models were adjusted for age, sex, BMI, and smoking status.

Results: In adjusted models a positive HIV status was associated with elevated proportions of CD8+ activated ( = 0.009), CD4+ senescent ( = 0.004), CD4+ apoptotic ( = 0.002), and CD8+ apoptotic ( = 0.003) T-cells. In PWH a 10-year increase in age was associated with higher proportions of CD4+ and CD8+ senescent ( = 0.001 and < 0.001) and CD4+ and CD8+ apoptotic T-cells ( < 0.001 and < 0.001). However, no interaction between HIV status and age was found. Furthermore, in PWH a CD4+/CD8+ ratio < 1 was associated with elevated proportions of T-cell activation, senescence, and apoptosis.

Discussion: We found evidence of residual T-cell immune dysfunction in well-treated PWH without HBV or HCV co-infection, and age was associated with T-cell senescence and apoptosis. Our data supports that HIV infection has similar effects as aging on T-cell subsets. However, since no interaction between HIV status and age was found on these parameters, we found no evidence to support accelerated immunological aging in PWH.
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http://dx.doi.org/10.3389/fimmu.2020.583569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561401PMC
June 2021

Implementation of treatment recommendations for chronic hepatitis B in patients attending specialized hospital care in Denmark - a region wide study.

Scand J Gastroenterol 2020 Jul 22;55(7):843-847. Epub 2020 Jun 22.

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.

To evaluate implementation of national guideline recommendations on treatment initiation for chronic hepatitis B (CHB) in Denmark. Using DANHEP, a nationwide cohort of chronic hepatitis B and C patients attending specialized hospital care in Denmark, we performed a descriptive cohort study from January 2002 through December 2017. We identified patients with CHB in 3 of 5 Danish regions, with at least two hospital/outpatient clinic visits during the study period. We identified 990 CHB patients who remained untreated throughout the study period, and 265 who initiated treatment. At their last visit 952/990 (96%, 95% CI 95-97) untreated patients did not meet current national criteria for treatment initiation while 198/265 (75%, 95% CI 69-80) who initiated treatment met the national criteria. Overall, 198/236 (84%, 95% CI 79-88) who met national treatment criteria, initiated treatment. The majority of CHB patients received care in line with national guideline recommendations for treatment initiation. We found that only few patients eligible for treatment remained untreated. However, a fourth of patients who received treatment were not eligible according to national guidelines.
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http://dx.doi.org/10.1080/00365521.2020.1779803DOI Listing
July 2020

Cytomegalovirus-specific CD8+ T-cell responses are associated with arterial blood pressure in people living with HIV.

PLoS One 2020 13;15(1):e0226182. Epub 2020 Jan 13.

Department of Infectious Diseases, Viro-immunology Research Unit, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.

People living with HIV (PLHIV) are at increased risk for cardiovascular disease (CVD), and immunity against cytomegalovirus (CMV) may be a contributing factor. We hypothesized that enhanced T-cell responses against CMV and CMV-IgG antibody-levels are associated with higher arterial blood pressure in PLHIV. We assessed serum CMV-IgG, systolic- (SBP) and diastolic- (DBP) blood pressure, pulse pressure (PP), traditional risk factors, activated CD8+ T-cells (CD38+HLA-DR+), senescent CD8+ T-cells (CD28-CD57+) and interleukin-6 (IL-6) in 60 PLHIV and 31 HIV-uninfected controls matched on age, gender, education and comorbidity. In PLHIV, expression of interleukin-2, tumor necrosis factor-α and interferon-γ was measured by intracellular-cytokine-staining after stimulation of T-cells with CMV-pp65 and CMV-gB. Associations between CMV-specific immune responses and hypertension, SBP, DBP or PP were assessed by multivariate logistic and linear regression models adjusted for appropriate confounders. The median age of PLHIV was 47 years and 90% were male. Prevalence of hypertension in PLHIV was 37% compared to 55% of HIV-uninfected controls. CMV-specific CD8+ T-cell responses were independently associated with higher PP (CMV-pp65; β = 2.29, p = 0.001, CMV-gB; β = 2.42, p = 0.001) in PLHIV. No significant differences were found with regard to individual measures of SBP and DBP. A possible weak association was found between CMV-IgG and hypertension (β = 1.33, p = 0.049) after adjustment for age, smoking and LDL-cholesterol. HIV-related factors, IL-6, CD8+ T-cell activation or CD8+ T-cell senescence did not mediate the associations, and no associations were found between CMV-specific CD4+ T-cell responses and blood pressure in PLHIV. In conclusion, increased arterial blood pressure in PLHIV may be affected by heightened CMV-specific CD8+ T-cell responses.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226182PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957152PMC
April 2020

Fraction of Exhaled Nitric Oxide Levels Are Elevated in People Living With Human Immunodeficiency Virus Compared to Uninfected Controls, Suggesting Increased Eosinophilic Airway Inflammation.

Clin Infect Dis 2020 12;71(12):3214-3221

Department of Infectious Diseases 8632, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Background: Increased risk of asthma and chronic obstructive pulmonary disease has been reported in people living with human immunodeficiency virus (PLWH). Fraction of exhaled nitric oxide (FeNO) is a marker of eosinophilic airway inflammation. We assessed FeNO levels in PLWH and matched uninfected controls and investigated whether human immunodeficiency virus (HIV) status is independently associated with elevated FeNO.

Methods: FeNO was quantified by NIOX Vero and pulmonary function was assessed by spirometry in 432 PLWH from the Copenhagen Comorbidity in HIV Infection Study and in 1618 age- and sex-matched uninfected controls from the Copenhagen General Population Study. Elevated FeNO was defined as ≥25 parts per billion. Associations between FeNO and HIV status were adjusted for known potential confounders.

Results: Mean age of PLWH was 50.7 (standard deviation [SD], 11.1) years and 97.4% received combination antiretroviral therapy. PLWH had higher FeNO than uninfected controls (median, 17.0 [interquartile range {IQR}, 11.0-26.0] vs 13.0 [IQR, 9.0-19.0]; P < .001). Also, PLWH had a higher prevalence of elevated FeNO than uninfected controls (27.5% vs 12.3%; P < .001). This association remained after adjusting for age, sex, height, smoking status, use of airway medication, blood eosinophils, and immunoglobulin E (adjusted OR [aOR], 3.56 [95% CI, 2.51-5.04]; P < .001). Elevated FeNO was associated with self-reported asthma (aOR, 2.65 [95% CI, 1.66-4.24]; P < .001) but not with airflow limitation (aOR, 1.07 [95% CI, .71-1.62]; P = .745).

Conclusions: HIV status was independently associated with elevated FeNO, suggesting increased eosinophilic airway inflammation. The potential impact on chronic lung disease pathogenesis needs further investigation.
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http://dx.doi.org/10.1093/cid/ciz1223DOI Listing
December 2020

Impact of Human Immunodeficiency Virus-Related Gut Microbiota Alterations on Metabolic Comorbid Conditions.

Clin Infect Dis 2020 11;71(8):e359-e367

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Background: We aimed to identify a human immunodeficiency virus (HIV)-related microbiota signature, independent of sexual preferences and demographic confounders, in order to assess a possible impact of the microbiome on metabolic comorbid conditions.

Methods: Bacterial 16S ribosomal RNA analyses were performed on stool samples from 405 HIV-infected and 111 uninfected participants of the Copenhagen Comorbidity in HIV Infection (COCOMO) study. Individuals were stratified according to sexual behavior (men who have sex with men [MSM] vs non-MSM).

Results: After excluding MSM-associated microbiota traits and adjusting for confounders, we identified an HIV-related microbiota signature, consisting of lower biodiversity, increased relative abundance of the bacterial clades Gammaproteobacteria and Desulfovibrionaceae and decrease in several Clostridia. This microbiota profile was associated with a 2-fold excess risk of metabolic syndrome, driven by increase in Desulfovibrionaceae and decrease in Clostridia (Butyrivibrio, Coprococcus 2, Lachnospiraceae UCG-001 and CAG-56). This association was accentuated (5-fold excess risk) in individuals with previous severe immunodeficiency, which also modified the association between HIV-related microbiota signature and visceral adipose tissue (VAT) area (P for interaction = .01). Accordingly, HIV-related microbiota was associated with 30-cm2 larger VAT in individuals with history of severe immunodeficiency, but not in those without.

Conclusion: The HIV-related microbiota was associated with increased risk of metabolic syndrome and VAT accumulation, particularly in individuals with previous severe immunodeficiency, driven by increased Desulfovibrionaceae and lower abundance of several Clostridia. Our findings suggest a potential interplay between HIV-related microbiota, immune dysfunction and metabolic comorbid conditions. Interventions targeting the gut microbiome may be warranted to reduce cardiovascular risk, particularly in individuals with previous immunodeficiency.
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http://dx.doi.org/10.1093/cid/ciz1235DOI Listing
November 2020

"Development in well-being and social function among Danish hemophilia patients with HIV: a three-wave panel study spanning 24 years".

BMC Public Health 2019 Dec 19;19(1):1714. Epub 2019 Dec 19.

Department of Public Health Section of Social Medicine, University of Copenhagen, Oester Farimagsgade 5, 1014 K, Copenhagen, Denmark.

Background: Between 1975 and 1985 a total of 91 Danish patients with moderate and severe hemophilia (PWH) was infected with HIV constituting a major scandal in the Danish health care system. This study describes the burden of HIV infection among Danish PWH by evaluating changes from 1988 to 2012 in well-being, social function, experiencing stigma and openness about disease among Danish HIV PWH.

Methods: Three anonymous surveys were conducted in 1988, 2001 and 2012 targeting all Danish patients with moderate to severe hemophilia. Survey responses were received from 53, 21 and 18 HIV PWH respectively. A matched comparison sample of HIV PWH was identified for each survey-year, using propensity score matching. Differences for each survey-year and trends over time were analyzed using ordinal logistic regression.

Results: In 1988, HIV PWH had more psychosomatic symptoms than HIV PWH, but in 2001 life satisfaction was higher among HIV PWH than among HIV PWH. Tests of differences in trend over time showed larger improvements in life satisfaction among HIV PWH than HIV PWH, while HIV PWH showed an increase in educational level compared to HIV PWH. Analysis restricted to HIV PWH showed an increase in perceived stigmatization.

Conclusions: Differences between Danish HIV and HIV PWH regarding well-being and psychosomatic symptoms seem to have evened out between 1988 and 2012. However, results suggest that HIV PWH still experience stigmatization and lower levels of education.
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http://dx.doi.org/10.1186/s12889-019-8062-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923887PMC
December 2019

Impact of early antiretroviral treatment on sexual behaviour: a randomised comparison.

AIDS 2019 12;33(15):2337-2350

Institute for Global Health, University College London, London, UK.

Background: Antiretroviral treatment (ART) reduces HIV infectiousness but the effect of early ART on sexual behaviour is unclear.

Methods: We assessed, within the START randomized trial that enrolled HIV-positive adults with CD4 cell count greater than 500 cells/μl, the effect of early (immediate) versus deferred ART on: condomless sex with HIV-serodifferent partners (CLS-D); all condomless sex (CLS); HIV transmission-risk sex (CLS-D-HIV risk, defined as CLS-D and: not on ART or started ART <6 months ago or viral load greater than 200 copies/ml or no viral load in past 6 months), during 2-year follow-up. Month-12 CLS-D (2010-2014) was the primary outcome.

Results: Among 2562 MSM, there was no difference between immediate and deferred arms in CLS-D at month 12 [12.6 versus 13.1%; difference (95% CI): -0.4% (-3.1 to 2.2%), P = 0.75] or month 24, or in CLS. Among 2010 heterosexual men and women, CLS-D at month 12 tended to be higher in the immediate versus deferred arm [10.8 versus 8.3%; difference:2.5% (-0.1 to 5.2%), P = 0.062]; the difference was greater at month 24 [9.3 versus 5.6%; difference: 3.7% (1.0 to 6.4%), P = 0.007], at which time CLS was higher in the immediate arm (20.7 versus 15.7%, P = 0.013). CLS-D-HIV risk at month 12 was substantially lower in the immediate versus deferred arm for MSM [0.2 versus 11%; difference: -10.7% (-12.5 to -8.9%), P < 0.001] and heterosexuals [0.6% versus 7.7%; difference: -7.0% (-8.8 to -5.3%), P < 0.001], because of viral suppression on ART.

Conclusion: A strategy of early ART had no effect on condomless sex with HIV-serodifferent partners among MSM, but resulted in modestly higher prevalence among heterosexuals. However, among MSM and heterosexuals, early ART resulted in a substantial reduction in HIV-transmission-risk sex, to a very low absolute level.
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http://dx.doi.org/10.1097/QAD.0000000000002359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882545PMC
December 2019

Clinical Outcomes in Persons Coinfected With Human Immunodeficiency Virus and Hepatitis C Virus: Impact of Hepatitis C Virus Treatment.

Clin Infect Dis 2020 05;70(10):2131-2140

Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, Copenhagen, and Department of Infectious Diseases, Copenhagen.

Background: A hepatitis C (HCV) cure is associated with changes in lipids and inflammatory biomarkers, but its impact on clinical endpoints among treated human immunodeficiency virus (HIV)/HCV coinfected persons is unclear.

Methods: People living with HIV from EuroSIDA with a known HCV status after January 2001 were classified into strata based on time-updated HCV RNA measurements and HCV treatment, as either HCV antibody-negative; spontaneously resolved HCV; chronic, untreated HCV; cured HCV (HCV RNA-negative); or HCV treatment failures (HCV RNA-positive). Poisson regression was used to compare incidence rates between HCV groups for end-stage liver disease (ESLD; including hepatocellular carcinoma [HCC]), non-acquired immunodeficiency virus defining malignancy (NADM; excluding HCC), and cardiovascular disease (CVD).

Results: There were 16 618 persons included (median follow-up 8.3 years, interquartile range 3.1-13.7). There were 887 CVD, 902 NADM, and 436 ESLD events; crude incidence rates/1000 person-years follow-up were 6.4 (95% confidence interval [CI] 6.0-6.9) for CVD, 6.5 (95% CI 6.1-6.9) for NADM, and 3.1 (95% CI 2.8-3.4) for ESLD. After adjustment, there were no differences in incidence rates of NADM or CVD across the 5 groups. HCV-negative individuals (adjusted incidence rate ratio [aIRR] 0.22, 95% CI 0.14-0.34) and those with spontaneous clearance (aIRR 0.61, 95% CI 0.36-1.02) had reduced rates of ESLD compared to cured individuals. Persons with chronic, untreated HCV infections (aIRR 1.47, 95% CI 1.02-2.13) or treatment failure (aIRR 1.80, 95% CI 1.22-2.66) had significantly raised rates of ESLD, compared to those who were cured.

Conclusions: Incidences of NADM or CVD were independent of HCV group, whereas those cured had substantially lower incidences of ESLD, underlining the importance of successful HCV treatment for reducing ESLD.
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http://dx.doi.org/10.1093/cid/ciz601DOI Listing
May 2020

[Management of Staphylococcus aureus bacteraemia].

Ugeskr Laeger 2019 08;181(33)

In this review, we discuss Staphylococcus aureus bac-teraemia (SAB), which is a frequent and severe condition associated with high morbidity and mortality. Despite these facts, high-quality data on diagnostic approach, treatment and management of SAB remain scarce. Consequently, evidence-based guidelines concerning antibiotic therapy including the optimal choice of antibiotic drug, route of administration and treatment duration are not available. Thus, controlled clinical trials are urgently needed to increase evidence and to potentially improve the outcome for patients with SAB.
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August 2019

[Corneal graft due to an overlooked gonorrhoeal conjunctivitis].

Ugeskr Laeger 2019 May;181(21)

In this case report, a 42-year-old man who had sex with other men presented with conjunctivitis, which later was diagnosed as gonorrhoeal conjunctivitis. Gonorrhoeal conjunctivitis is associated with a high risk of severe eye infections and resulting complications. It is important to perform swabs for gonorrhoea from all relevant anatomical locations. Through complete microbiological diagnostics and treatment with recommended antibiotics, a gonorrhoeal conjunctivitis infection can be effectively treated.
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May 2019

Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study.

Lancet 2019 06 2;393(10189):2428-2438. Epub 2019 May 2.

Aarhus University Hospital, Skejby, Denmark.

Background: The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. The aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships.

Methods: The PARTNER study was a prospective observational study done at 75 sites in 14 European countries. The first phase of the study (PARTNER1; Sept 15, 2010, to May 31, 2014) recruited and followed up both heterosexual and gay serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex, whereas the PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only. At study visits, data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner). If a seroconversion occurred in the HIV-negative partner, anonymised phylogenetic analysis was done to compare HIV-1 pol and env sequences in both partners to identify linked transmissions. Couple-years of follow-up were eligible for inclusion if condomless sex was reported, use of pre-exposure prophylaxis or post-exposure prophylaxis was not reported by the HIV-negative partner, and the HIV-positive partner was virally suppressed (plasma HIV-1 RNA <200 copies per mL) at the most recent visit (within the past year). Incidence rate of HIV transmission was calculated as the number of phylogenetically linked HIV infections that occurred during eligible couple-years of follow-up divided by eligible couple-years of follow-up. Two-sided 95% CIs for the incidence rate of transmission were calculated using exact Poisson methods.

Findings: Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1-3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33-46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4-2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76 088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up).

Interpretation: Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV.

Funding: National Institute for Health Research.
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http://dx.doi.org/10.1016/S0140-6736(19)30418-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584382PMC
June 2019

Syphilitic hepatitis and neurosyphilis: an observational study of Danish HIV-infected individuals during a 13-year period.

Sex Transm Infect 2019 09 28;95(6):416-418. Epub 2019 Mar 28.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Objective: Syphilis is an STI that potentially affects any organ. Syphilitic hepatitis and neurosyphilis have been reported in both HIV-uninfected and HIV-infected individuals. The aim of this study was to investigate syphilitic hepatitis and neurosyphilis among HIV-infected individuals during a 13-year period.

Methods: This retrospective study included all HIV-infected individuals ≥18 years diagnosed with syphilis between 1 May 2004 and 31 December 2016 in Copenhagen, Denmark. We used the unique 10-digit personal identification number assigned to all individuals in Denmark to link data from two nationwide registers to identify the patients. Patient files were revised to obtain clinical and laboratory data.

Results: A total of 509 episodes of syphilis were diagnosed in 427 HIV-infected individuals attending three hospitals in Copenhagen, Denmark. The majority of the patients were men (99.5%), and the majority of men were men who have sex with men (96%). Twenty-seven patients (6%) met the criteria for neurosyphilis, and the neurological symptoms included ocular and auditory abnormalities, headache, paraesthesia, vertigo, facial paresis, motor weakness and unexplained pain in the legs. The patients with neurosyphilis were diagnosed in the secondary stage (84%) and in the early latent (8%) or late latent (8%) stage. Among the patients tested for liver affection, 41% met the criteria for syphilitic hepatitis. The patients with syphilitic hepatitis were diagnosed in the secondary stage (82%), primary stage (10%), and in the early latent (5%) or late latent (3%) stage.

Conclusions: The study emphasises that patients with syphilis, also those seen at STI clinics, should undergo a thorough clinical examination and questioning to reveal neurological symptoms. Identification of patients with neurosyphilis is crucial since these patients undergo a different treatment. The study also emphasises that syphilis should be considered as a diagnosis in sexually active patients with liver .
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http://dx.doi.org/10.1136/sextrans-2018-053921DOI Listing
September 2019

Retired Nurses Can Improve Retention in Prevention of Mother-to-Child Transmission Programmes.

East Afr Health Res J 2019 29;3(2):88-95. Epub 2019 Nov 29.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Background: The success of prevention of mother-to-child transmission (PMTCT) programmes depends on retention of mothers throughout the PMTCT cascade.

Methods: In a clinical trial of short-course combination antiretroviral therapy (cART) for PMTCT in Tanzania, senior nurses were employed to reduce the substantial loss-to-follow up (LTFU) rate.

Results: Following intervention, the relative risk (RR) of receiving a CD4 count result and antiretroviral therapy was 1.16 (95% confidence interval [CI], 1.05 to 1.27), the RR of delivery at clinic was 2.51 (95% CI, 2.06 to 3.06), the RR for reporting for follow-up at 6 to 8 weeks postpartum was 4.63 (95% CI, 3.41 to 6.27), and the RR for being retained until 9 months postpartum was 28.19 (95% CI, 11.81 to 67.28). No significant impact on transmission was found.

Conclusion: Significantly higher retention was found after senior nurses were employed. No impact on transmission was found. Relatively low transmission was found in both study arms.
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http://dx.doi.org/10.24248/EAHRJ-D-19-00011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279289PMC
November 2019

The Prevalence of Human Immunodeficiency Virus Coinfection Among Patients Newly Diagnosed With Chronic Hepatitis B or C in Denmark: A Nationwide Cohort Study.

Open Forum Infect Dis 2018 Dec 21;5(12):ofy310. Epub 2018 Nov 21.

Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.

Background: Early identification of patients with chronic viral hepatitis coinfected with human immunodeficiency virus (HIV) is essential for optimal care. The objectives of this study were to estimate the prevalence of HIV coinfection among patients newly diagnosed with chronic viral hepatitis, HIV testing prevalence, and identify factors associated with coinfection.

Methods: Patients with chronic viral hepatitis newly enrolled in The Danish Database for Hepatitis B and C between 2002 and 2015 were identified. The HIV coinfection prevalence was calculated, and risk factors associated with HIV coinfection were estimated by logistic regression.

Results: In total, 8490 patients were included: 3091 had chronic hepatitis B (CHB), 5305 had chronic hepatitis C (CHC), and 94 had CHB and CHC. The prevalence of HIV coinfection was 4.4% (95% confidence interval [CI], 4.0-4.9) and was higher among CHC and CHB-CHC patients than CHB patients with a prevalence of 5.3% (95% CI, 4.7-5.9), 6.4% (95% CI, 2.4-13.4), and 2.9 (95% CI, 2.3-3.5), respectively ( < .0001). The HIV testing prevalence increased from 65% to 88% between 2002 and 2014 concurrently with a decrease in the HIV coinfection prevalence from 7.8% (95% CI, 5.5-10.7) to 1.6% (95% CI, 0.7-3.2). Age 35-50 years, male sex, and sexual route of viral hepatitis transmission were associated with HIV coinfection with odds ratios of 4.42 (95% CI, 1.40-13.94), 2.21 (95% CI, 1.74-2.81), and 8.81 (95% CI, 6.30-12.33), respectively.

Conclusions: The prevalence of HIV coinfection among patients with newly diagnosed chronic viral hepatitis decreased concurrently with an increase in HIV testing prevalence.
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http://dx.doi.org/10.1093/ofid/ofy310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297860PMC
December 2018

A modeling study of the Danish HIV epidemic in men who have sex with men: travel, pre-exposure prophylaxis and elimination.

Sci Rep 2018 10 30;8(1):16003. Epub 2018 Oct 30.

Center for Biomedical Modeling, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, 90024, USA.

UNAIDS has identified the Danish HIV epidemic in men who have sex with men (MSM) as a priority for elimination. Incidence is close to the elimination threshold of one new infection per year per 1,000 individuals. However, surveillance data show that HIV strains are being imported into Denmark, mainly due to travel. We use a transmission model to predict (from 2018 to 2030) the impact of pre-exposure prophylaxis (PrEP) on incidence. Our model reflects the current epidemic and diagnosis rates in the Danish MSM community. We conduct a sensitivity analysis based on 20,000 simulations, and assume that PrEP coverage could range from zero to 50% and diagnosis rates increase up to three-fold. We predict that incidence will fall below the elimination threshold, even without the introduction of PrEP, reaching 0.87 (median, 95% Confidence Interval: 0.65-1.23) new infections per 1,000 MSM by 2030. PrEP could reduce incidence to well below the threshold, if it results in a significant increase in diagnosis rates and reduces the number of infections occurring abroad. The Danish Medicine Agency and Danish Health Authority have recommended introducing PrEP. Our study provides strong support for this recommendation, and shows the importance of Danish MSM using PrEP when abroad.
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http://dx.doi.org/10.1038/s41598-018-33570-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207710PMC
October 2018

Whole Exome Sequencing of HIV-1 long-term non-progressors identifies rare variants in genes encoding innate immune sensors and signaling molecules.

Sci Rep 2018 10 15;8(1):15253. Epub 2018 Oct 15.

Department of Infectious Diseases, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.

Common CCR5-∆32 and HLA alleles only explain a minority of the HIV long-term non-progressor (LTNP) and elite controller (EC) phenotypes. To identify rare genetic variants contributing to the slow disease progression phenotypes, we performed whole exome sequencing (WES) on seven LTNPs and four ECs. HLA and CCR5 allele status, total HIV DNA reservoir size, as well as variant-related functional differences between the ECs, LTNPs, and eleven age- and gender-matched HIV-infected non-controllers on antiretroviral therapy (NCARTs) were investigated. Several rare variants were identified in genes involved in innate immune sensing, CD4-dependent infectivity, HIV trafficking, and HIV transcription mainly within the LTNP group. ECs and LTNPs had a significantly lower HIV reservoir compared to NCARTs. Furthermore, three LTNPs with variants affecting HIV nuclear import showed integrated HIV DNA levels below detection limit after in vitro infection. HIV slow progressors with variants in the TLR and NOD2 pathways showed reduced pro-inflammatory responses compared to matched controls. Low-range plasma levels of fibronectin was observed in a LTNP harboring two FN1 variants. Taken together, this study identified rare variants in LTNPs as well as in one EC, which may contribute to understanding of HIV pathogenesis and these slow progressor phenotypes, especially in individuals without protecting CCR5-∆32 and HLA alleles.
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http://dx.doi.org/10.1038/s41598-018-33481-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189090PMC
October 2018

Limited anti-HIV neutralizing antibody breadth and potency before and after HIV superinfection in Danish men who have sex with men.

Infect Dis (Lond) 2019 Jan 14;51(1):56-61. Epub 2018 Oct 14.

a Laboratory of Immunoregulation, Division of Intramural Research, NIAID, NIH , Bethesda , USA.

Background: The role of the anti-HIV neutralizing antibody response in protecting against HIV superinfection, and changes in neutralizing antibody potency and breadth after HIV superinfection have not been fully elucidated. This study examined the rate of HIV superinfection in men who have sex with men (MSM) also diagnosed with syphilis in Denmark, and the anti-HIV neutralizing antibody response in men who became superinfected.

Materials And Methods: MSM enrolled in the Danish HIV cohort who acquired syphilis were examined longitudinally for HIV superinfection using a validated next-generation sequencing assay. HIV superinfection cases were matched 3:1 to controls, and neutralizing antibody responses before (cases/controls) and after (cases) HIV superinfection were determined using a 20-pseudovirus panel.

Results: Four cases of HIV superinfection were identified from 95 MSM screened for a rate of HIV superinfection of 1.56/100 pys (95% CI = 0.43-4.01). Prior to HIV superinfection neutralizing antibody responses were low in breadth and potency, and did not differ between cases and controls (p = 1.0). In cases, neutralizing antibody responses increased modestly after HIV superinfection.

Conclusions: These data support the theory that the natural neutralizing antibody response to HIV infection may not be the controlling factor in protecting against a subsequent HIV challenge.
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http://dx.doi.org/10.1080/23744235.2018.1500708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319735PMC
January 2019

HIV Status Is a Greater Determinant of Low Self-perceived Life Expectancy Than Cigarette Smoking in a Well-resourced Setting.

J Acquir Immune Defic Syndr 2018 10;79(2):e81-e84

Department of Infectious Diseases 8632, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

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http://dx.doi.org/10.1097/QAI.0000000000001784DOI Listing
October 2018

Classification of death causes after transplantation (CLASS): Evaluation of methodology and initial results.

Medicine (Baltimore) 2018 Jul;97(29):e11564

Department of Infectious Diseases Centre of Excellence for Health, Immunity and Infections (CHIP) Department of Hematology Department of Cardiology, Copenhagen University Hospital/Rigshospitalet, Copenhagen Department of Nephrology, Copenhagen University Hospital/Herlev Hospital, Herlev Department of Pediatrics Department of Surgery, Copenhagen University Hospital/Rigshospitalet, Copenhagen Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, United Kingdom Department of Hematology, Aarhus University Hospital/Skejby Hospital, Aarhus N Department of Nephrology, Copenhagen University Hospital/Rigshospitalet, Copenhagen, Denmark.

Correct classification of death causes is an important component of transplant trials.We aimed to develop and validate a system to classify causes of death in hematopoietic stem cell (HSCT) and solid organ (SOT) transplant recipients.Case record forms (CRF) of fatal cases were completed, including investigator-designated cause of death. Deaths occurring in 2010 to 2013 were used for derivation; and were validated by deaths occurring in 2013 to 2015. Underlying cause of death (referred to as recorded underlying cause) was determined through a central adjudication process involving 2 external reviewers, and subsequently compared with the Danish National Death Cause Registry.Three hundred eighty-eight recipients died 2010 to 2015 (196 [51%] SOT and 192 [49%] HSCT). The main recorded underlying causes of death among SOT and HSCT were classified as cancer (20%, 48%), graft rejection/failure/graft-versus-host-disease (35%, 28%), and infections (20%, 11%). Kappa between the investigator-designated and the recorded underlying cause of death was 0.74 (95% CI 0.69-0.80) in derivation and comparable in the validation cohort. Death causes were concordant with the Danish National Death Cause Registry in 37.2% (95% CI 31.5-42.9) and 38.4% (95% CI 28.8-48.0) in the derivation and validation cohorts, respectively.We developed and validated a method to systematically and reliably classify the underlying cause of death among transplant recipients. There was a high degree of discordance between this classification and that in the Danish National Death Cause Registry.
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http://dx.doi.org/10.1097/MD.0000000000011564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086480PMC
July 2018
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