Biomedical subjects

Annette Alaeus

Publications and source records attributed to Annette Alaeus.

5 recordsLinked to original sources

PubMed2006

Therapeutic immunization for HIV.

Vaccines have entered into human clinical trials against infectious diseases and as therapies against cancer. The HIV virus establishes a latent infection at a very early stage and the T cell memory of the infected patient is rapidly destroyed. However, results of immunotherapy after DNA and protein immunization show that vaccine-induced immune responses might be present for a long period of time. Patients subjected to therapeutic immunization appear to do well, and to have a small immunological advantage, which, however, will have to be improved. The vaccine therapy should start early, while adequate reservoirs of appropriate T helper cells are available and still inducible. The DNA vaccines induce a relatively long-lived immunological memory, and gene-based immunization is effective in inducing cytotoxic CD8(+) T cells and CD4+ helper cells. Protein vaccines, on the other hand, primarily give T cell help. It thus appears that DNA and protein approaches to HIV immunization complement each other. A surprisingly broad reactivity to peptides from different subtypes of HIV was identified in individuals infected with several subtypes of HIV.

AIDS Vaccines↗

PubMed2005

Impact of HIV type 1 genetic subtype on the outcome of antiretroviral therapy.

The objective of this study was to investigate the short-term virological outcome of antiretroviral combination therapy (ART) in relation to infection with different HIV-1 genetic subtypes. Antiretroviral drug-naive patients in Sweden were prospectively enrolled and followed for 6 months when starting ART in the period from January 1998 to January 2002. Plasma-HIV-1 RNA levels, CD4 counts, and type of ART regimen were recorded. The HIV-1 subtype was determined by direct sequencing of regions of the env or pol genes. Data from 172 patients who harbored subtypes A, B, C, D, G, and CRF01_AE were analyzed (32 A, 44 B, 34 C, 18 D, 5 G, and 19 CRF01_AE). Of all patients 84% had undetectable plasma HIV-1 RNA levels after 6 months of ART. Patients infected with CRF01_AE more often had undetectable HIV-1 RNA plasma levels than patients infected with subtypes A or D. However, the possibility that this difference is due to ethnicity cannot be ruled out. Of patients of African origin, 77% had undetectable viral load after 6 months of treatment, while the corresponding figures for Caucasians and Asians were 91% and 100%, respectively. Thus, we have found an overall good short-term virological outcome after the initiation of ART in a cohort of ARV-naive patients of diverse ethnic background infected with different HIV-1 genetic subtypes. In univariate analysis ethnicity, but not genetic subtype, correlated with virological response. However, the impact of ethnicity was moderate. Patients of African origin, who had the poorest outcome, showed a 77% virological response rate.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Effects of potent antiretroviral therapy on the immune activation marker soluble CD27 in patients infected with HIV-1 subtypes A-D.

HIV-1 genetic subtypes might have a different impact on disease progression and response to antiretroviral therapy (ART). Few data are available on the immune activation profile in patients with different HIV-1 subtypes. We have tested by ELISA the plasma levels of an immune activation marker, soluble CD27 (sCD27), in a cohort of 64 patients infected with HIV-1 subtypes A-D, at baseline and after 1 year of virologically successful ART. Plasma sCD27 was significantly higher in the whole HIV-1-infected population as compared to healthy subjects [522 U/ml (188-1,307) vs. 285 U/ml (174-397), P < 0.001]. Among the four different HIV-1 subtypes, patients with subtype C virus had significantly higher plasma sCD27 [684 U/ml, (188-1228)] as compared to patients with subtype A [428 U/ml (247-1307), P < 0.05] and B [454 (211-925), P < 0.05]. After 1 year of ART, plasma sCD27 significantly decreased in all groups but patients with subtype C viruses had the largest reduction of sCD27 from baseline. The data indicate that a similar immune activation profile is present in patients infected with HIV-1 subtypes A, B, and D and that in presence of successful ART these subtypes respond similarly in terms of immune activation. Intriguingly, subtype C infection seems to be associated with higher levels of plasma sCD27, suggesting that HIV-1 genetic subtype C may have a different impact on disease outcome and response to therapy.

Adolescent↗

PubMed2003

Chronic hepatitis C: updated Swedish consensus.

In 1999 a Swedish national expert panel published recommendations for the treatment of chronic hepatitis C (HCV) infection. Recently, pegylated interferon (peg-IFN) products have been introduced, and an increased knowledge concerning treatment of acute HCV and HCV-human immunodeficiency virus (HIV) coinfection has been gained. As a result of this, an update of the Swedish recommendations was developed following an expert meeting in October 2002. The panel now recommends the use of peg-IFN together with ribavirin as the standard treatment. Owing to the excellent response rates in HCV genotype 2 and 3 infections, these patients can be treated for 24 weeks without preceding liver biopsy. For patients with genotype 1 infection (with a slightly below 50% sustained response rate after 48 weeks treatment) and only mild histological disease, treatment can be postponed until future better treatment options become available. In patients who fail to achieve a 99% reduction (2 log drop) in viral titre after 12 weeks of treatment, discontinuation of therapy is recommended. Patients previously treated with IFN monotherapy and not having achieved a sustained virological response are recommended the same combination treatment as treatment-naive patients. IFN monotherapy is recommended in patients with acute hepatitis C. For children with chronic HCV infection, combination treatment is mainly recommended in clinical trials. For HCV-HIV coinfected patients, combination treatment is recommended and preferably given when blood CD4 counts are above 350/ml and before antiretroviral treatment (ART) is needed. Concurrent ART or prominent liver fibrosis requires frequent monitoring because of the increased risk for mitochondrial toxicity and liver failure.

Adult↗

PubMed2003

Limited transmission of drug-resistant HIV type 1 in 100 Swedish newly detected and drug-naive patients infected with subtypes A, B, C, D, G, U, and CRF01_AE.

The prevalence of genetic drug resistance in newly diagnosed HIV-1 cases and potential subtype-specific mutation patterns were studied. Samples from 100 newly diagnosed patients were randomly chosen from three HIV clinics in Sweden, prospectively collected during the period June 1998 to August 2001. Viral RNA was extracted from plasma and an approximately 2000-bp fragment covering the protease (PR) and reverse transcriptase (RT) genes was sequenced. Subtypes A, B, C, D, G, U, and CRF01_AE were found. All 100 sequences had mutations reported to be involved in some drug resistance, revealing naturally occurring subtype-specific amino acid patterns. Such patterns may be important to consider when treating patients infected with nonsubtype B viruses. While many drug resistance mutations seem to be naturally occurring, 9% of the newly detected patients in Sweden may have been infected with virus from antiviral-treated patients. Among the individuals infected with resistant virus, the majority were infected with subtype B virus and belonged to the homosexual risk group. It may be important to routinely test for resistance in newly infected cases to improve the choice of drugs for treatment because the virus may revert and resistant forms can become latent.

Anti-HIV Agents↗