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- Elvstam, O., et al.
(författare)
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Is low-level HIV-1 viraemia associated with elevated levels of markers of immune activation, coagulation and cardiovascular disease?
- 2019
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Ingår i: HIV Medicine. - : Wiley. - 1464-2662 .- 1468-1293. ; 20:9, s. 571-580
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The clinical significance of low-level viraemia (LLV) during antiretroviral therapy (ART) is debated. We retrospectively investigated longitudinal levels of plasma markers associated with inflammation, altered coagulation and cardiovascular disease in Swedish HIV-positive adults in relation to LLV or permanent virological suppression during long-term ART. Methods: Plasma levels of C-reactive protein (CRP), D-dimer, vascular cell adhesion molecule 1 (VCAM-1), suppression of tumorigenicity 2 (ST2), growth differentiation factor 15 (GDF-15), soluble CD14 (sCD14), soluble CD163 (sCD163), interferon-γ-induced protein 10 (IP-10) and β-2-microglobulin were measured in 34 individuals with LLV (viral load 50–999 HIV-1 RNA copies/mL) and in matched controls with persistent virological suppression. Biomarker levels were analysed in samples obtained during episodes of LLV and follow-up samples obtained 1year later (with similar timing for controls). All biomarkers were analysed using an independent sample t-test and analysis of covariance (ANCOVA) after logarithmic transformation. Log-rank analysis was applied for markers with concentration values out of range. Results: Compared with controls, patients with LLV had significantly higher levels of GDF-15 [geometric mean 3416 (95% confidence interval (CI) 804–14516) pg/mL versus 2002 (95% CI 355–11295) pg/mL in controls; P=0.026] and D-dimer [mean 1114 (95% CI 125–9917) ng/mL versus 756 (95% CI 157–3626) ng/mL; P=0.038] after adjustment for age, CD4 count nadir and type of ART. In the unadjusted t-test, only GDF-15 was significantly higher and in the log-rank test, both GDF-15 and D-dimer were significantly elevated. No significant differences were observed for the other biomarkers analysed. Conclusions: Although levels of inflammation markers were similar in ART recipients with and without LLV, persons with LLV had significantly higher levels of GDF-15 and D-dimer. These findings suggest a potential link between LLV and cardiovascular outcomes. © 2019 British HIV Association
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| 3. |
- Esbjornsson, J., et al.
(författare)
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HIV-1 transmission between MSM and heterosexuals, and increasing proportions of circulating recombinant forms in the Nordic Countries
- 2016
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Ingår i: Virus Evolution. - : Oxford University Press (OUP). - 2057-1577. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Increased knowledge about HIV-1 transmission dynamics in different transmission groups and geographical regions is fundamental for assessing and designing prevention efforts against HIV-1 spread. Since the first reported cases of HIV infection during the early 1980s, the HIV-1 epidemic in the Nordic countries has been dominated by HIV-1 subtype B and MSM transmission. HIV-1 pol sequences and clinical data of 51 per cent of all newly diagnosed HIV-1 infections in Sweden, Denmark, and Finland in the period 2000-2012 (N = 3,802) were analysed together with a large reference sequence dataset (N = 4,537) by trend analysis and phylogenetics. Analysis of the eight dominating subtypes and CRFs in the Nordic countries (A, B, C, D, G, CRF01_AE, CRF02_AG, and CRF06_cpx) showed that the subtype B proportion decreased while the CRF proportion increased over the study period. A majority (57 per cent) of the Nordic sequences formed transmission clusters, with evidence of mixing both geographically and between transmission groups. Detailed analyses showed multiple occasions of transmissions from MSM to heterosexuals and that active transmission clusters more often involved single than multiple Nordic countries. The strongest geographical link was between Denmark and Sweden. Finally, Denmark had a larger proportion of heterosexual domestic spread of HIV-1 subtype B (75 per cent) compared with Sweden (49 per cent) and Finland (57 per cent). We describe different HIV-1 transmission patterns between countries and transmission groups in a large geographical region. Our results may have implications for public health interventions in targeting HIV-1 transmission networks and identifying where to introduce such interventions.
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| 10. |
- Boswell, M. T., et al.
(författare)
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Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS
- 2022
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Ingår i: Virus Evolution. - : Oxford University Press (OUP). - 2057-1577. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10-3 versus 1.4x10-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors – synonymous rates: 4.6x10-3 vs. 2.3x10-3; and nonsynonymous rates: 6.9x10-4 vs. 2.7x10-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.
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