Publications (118) View all
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Article: CD4 decline is associated with increased risk of cardiovascular disease, cancer and death in virally suppressed HIV patients.
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ABSTRACT: Background. The clinical implications of a considerable CD4 decline despite antiretroviral treatment and viral suppression are unknown. We aimed to test the hypothesis that a major CD4 decline could be a marker of cardiovascular disease or undiagnosed cancer. Methods. HIV patients were followed in the Danish nationwide, population-based cohort study in the period 1995-2010 with quarterly CD4 measurements. Associations between a CD4 decline of ≥30% and cardiovascular disease, cancer and death were analyzed using Poisson regression with date of CD4 decline as a time-updated variable. Results. We followed 2,584 virally suppressed HIV patients for 13,369 person-years, median observation time 4.7 years. Fifty-six patients developed CD4 decline (IR 4.2/1000PY (95%CI 3.2-5.4)). CD4 counts dropped from median 492 to 240 cells/µL. CD8, CD3 and total lymphocyte counts dropped concomitantly. No HIV-related factors, apart from treatment with didanosine, were associated with CD4 decline. The risk of cardiovascular disease, cancer and death increased markedly ≤6 months after CD4 decline (IRR 11.7 (95%CI 3.6-37.4), 13.7 (95%CI 4.3-43.6) and 4.3 (95%CI 1.1-17.6), respectively). Conclusion. A major decline in CD4 count is associated with a marked increased risk of cardiovascular disease, cancer and death among virally suppressed HIV patients.Clinical Infectious Diseases 04/2013; · 9.15 Impact Factor -
Article: Human Immunodeficiency Virus Type 1 infected individuals in anti-retroviral therapy react specifically with polyfunctional T-cell responses to Gag p24.
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ABSTRACT: BACKGROUND:: Still no effective Human Immunodeficiency Virus Type 1 (HIV-1) prophylactic or therapeutic vaccines are available. However, as the proportion of HIV-1 infected individuals on anti-retroviral treatment is increasing, knowledge about the residual immune response is important for the possible development of an HIV-1 vaccine. METHODS:: In this study, we determined the magnitude, breadth and quality of the HIV-1 specific T-cell response in HIV-1 infected viremic individuals (n=19) and individuals on highly active anti-retroviral treatment (HAART) (n=14) using multicolor flow cytometry. RESULTS:: We found that magnitude and breadth of the CD8 T-cell response was significantly higher in viremic individuals than individuals on HAART (p<0.0001 and p<0.0001, respectively) and that the functionality of the overall HIV-1 specific response was significantly different in individuals on HAART and viremic individuals (p=0.0020). In individuals on HAART, the remaining responses were primarily detected upon stimulation with overlapping peptides from Gag p24, integrase and Nef. The Gag p24 response was more polyfunctional than corresponding responses observed in viremic individuals. CONCLUSION:: Identification of highly immunogenic regions also recognized by individuals on HAART may be important for HIV-1 vaccine development. Irrespective of HLA haplotype, we have identified specific regions within the HIV-1 genome that is targeted more frequently in individuals on HAART. However, further studies are required to establish if these particular regions could be interesting for a future vaccine that might limit the time and opportunity for escape mutations.JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2013; · 4.43 Impact Factor -
Article: Anal carcinoma in HIV-infected patients in the period 1995-2009: A Danish nationwide cohort study.
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ABSTRACT: Background: Several studies have demonstrated an increased risk of non-AIDS cancers in HIV patients and, for some cancers, also in relatives of HIV patients. We aimed to estimate (1) the risk of anal carcinoma among HIV patients and their parents, and (2) the mortality after a diagnosis of anal carcinoma. Methods: We used Poisson regression to estimate the incidence rate ratios (IRR) of anal carcinoma in (1) a population of HIV patients identified from the Danish HIV Cohort Study (n = 4993) compared with a population control cohort matched on age and gender (n = 59,916) for the period 1995-2009, and (2) parents of HIV patients compared with parents of controls for the period 1978-2009. Cancer diagnoses were identified from The Danish Cancer Registry. We further estimated the mortality rate ratios (MRR) of HIV patients compared with controls after the diagnosis of anal carcinoma. Results: Thirty-six HIV patients versus 8 population controls were diagnosed with anal carcinoma. HIV patients had an increased risk of anal carcinoma (IRR 77.9, 95% CI 36.2-167.7), especially among men who have sex with men (MSM) (IRR 101.4, 95% CI 39.3-261.5). Fathers of HIV patients had an increased risk of anal carcinoma (IRR 7.4, 95% CI 1.4-38.3) compared to fathers of population controls. Mortality after diagnosis of anal carcinoma was increased in male HIV patients compared with the male control cohort (MRR 3.2, 95% CI 1.1-9.2). Conclusions: Danish HIV patients, especially MSM, have a considerably increased risk of anal carcinoma. We cannot exclude that fathers of HIV patients have an increased risk of anal carcinoma.Scandinavian Journal of Infectious Diseases 01/2013; · 1.72 Impact Factor -
Article: Statin Therapy and Mortality in HIV-Infected Individuals; A Danish Nationwide Population-Based Cohort Study.
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ABSTRACT: Recent studies have suggested that statins possess diverse immune modulatory and anti-inflammatory properties. As statins might attenuate inflammation, statin therapy has been hypothesized to reduce mortality in HIV-infected individuals. We therefore used a Danish nationwide cohort of HIV-infected individuals to estimate the impact of statin use on mortality before and after a diagnosis of cardiovascular disease, chronic kidney disease or diabetes. We identified all Danish HIV-infected individuals (1,738) who initiated HAART after 1 January 1998, and achieved virological suppression within 180 days. Date of first redemption of a prescription of statin was obtained from the Danish National Prescription Registry. We used Poisson regression analysis to assess adjusted mortality rate ratios (aMRR). First, time was censored at date of virological failure (VL >500 copies/ml). Second, time was not censored at virological failure. All analyses were adjusted for potential confounders. In the analyses confined to observation time without virological failure (+ censoring) statin therapy was associated with a non-statistically significant reduced rate of death (aMRR 0.75; 95% CI: 0.33-1.68). No difference was observed in the analysis with no censoring (aMRR 1.17; 95% CI: 0.66-2.07). Use of statin seemed to reduce mortality in individuals after a diagnosis of comorbidity {(+ censoring: aMRR: 0.34; 95% CI: 0.11-1.04), (-censoring: aMRR: 0.64; 95% CI: 0.32-1.29)}. No difference in rate of death could be detected before first date of diagnosis of comorbidity {(+ censoring: aMRR: 1.12; 95% CI: 0.34-3.62), (-censoring: aMRR: 0.90; 95% CI: 0.28-2.88)}. Statin therapy might reduce all-cause mortality in HIV-infected individuals, but the impact on individuals with no comorbidity seems small or absent. An unambiguous proof of a causal relation can only be obtained in a randomized controlled trial, but the sample size predicted may be prohibitive for its conduct.PLoS ONE 01/2013; 8(3):e52828. · 4.09 Impact Factor -
Article: Adjuvanted HLA-supertype restricted subdominant peptides induce new T-cell immunity during untreated HIV-1-infection.
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ABSTRACT: We investigated the potential of inducing additional T-cell immunity during chronic HIV-1 infection directed to subdominant HIV-1 epitopes from common HLA-supertypes. Ten treatment-naïve HIV-1-infected individuals were immunized with peptides in the adjuvant CAF01. One individual received placebo. T-cell immunogenicity was examined longitudinally by a flow cytometry (CD107a, IFNγ, TNFα, IL-2 and/or MIP1β expression) as well as IFNγ ELISPOT. Safety was evaluated by clinical follow up combined with monitoring of biochemistry, hematology, CD4 T-cell counts and viral load. New CD4 and CD8 T-cell responses specific for one or more vaccine epitopes were induced in 10/10 vaccinees. The responses were dominated by CD107a and MIP1β expression. There were no significant changes in HIV-1 viral load or CD4 T-cell counts. Our study demonstrates that the peptide/CAF01 vaccine is safe and that it is possible to generate new HIV-1 T-cell responses to defined epitopes in treatment-naïve HIV-1-infected individuals.Clinical Immunology 12/2012; 146(2):120-130. · 4.05 Impact Factor
