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Biomedical subjects

Eva-Lena Fredriksson

Publications and source records attributed to Eva-Lena Fredriksson.

3 recordsLinked to original sources

Human immunodeficiency virus-type 1 specific cellular immunity in chronic infected patients on prolonged highly active antiretroviral treatment and on structured treatment interruption.

We have followed 15 HIV-1 chronically infected patients during prolonged highly active antiretroviral treatment (HAART) and subsequent long term structured treatment interruption (STI). We analyzed Nef, Tat, and p24 specific cellular immunity using IFN-gamma enzyme-linked immunospot assays and T cell proliferation assays. Eight HAART patients showed IFN-gamma responses to at least one antigen, but no positive responses were seen during STI. We observed retained or increased p24 specific IFN-gamma responses in most patients during HAART with viral suppression. These results showed persisting HIV-1 specific cellular immunity during HAART; however, in prolonged STI with viral rebound this immunity declined.

Anti-HIV Agents↗

Improved HIV-1 viral load determination based on reverse transcriptase activity recovered from human plasma.

A more sensitive version of ExaVir Load, a test that utilizes reverse transcriptase (RT) activity from virions in plasma to determine HIV-1 viral load, is described. The virions were immobilized on a gel that was washed, followed by lysis of the virions, elution of purified RT, and finally RT activity determination. The changes made to the original test were: (1) improved washing of the immobilized virions by addition of a non-lytic detergent to the wash buffer, (2) improved virion lysis procedure, including changes in salt, detergent and pH, (3) the use of larger sample volumes in the RT assay, and (4) prolonged RT reaction time. The alterations gave a tenfold increased sensitivity compared to the original version. The correlation between RT load by the current test and RNA PCR was the same as previously (r=0.90). Using colorimetric product detection, the average detection limit in a panel of 262 patient plasma from Stockholm was 0.5 fg RT/ml, corresponding to approximately 170 RNA copies/ml. None of 54 HIV-1 RNA negative samples exhibited RT. The amount of RT load positive samples were 19% for samples containing 50-400 RNA, 71% for samples with 400-1,500, and 100% among samples with >8,000 copies/ml (according to Roche Amplicor). The sensitivity could be increased further using fluorimetric detection. In conclusion, the modifications of the test described result in an important increase in sensitivity. It can now be regarded as a competitive alternative method for HIV viral load determinations.

Fluorometry↗

Long-term persistence of vaccination and HAART to human immunodeficiency virus (HIV).

The aim of this study was to monitor the immune responses in HIV-infected patients previously immunized with gp160 or DNA vaccines to analyze whether the introduction of highly active antiretroviral treatment (HAART) would affect the persistence of immunity. The immune responses were evaluated in patients who had participated in randomized trials of therapeutic vaccination. Immunization in conjunction with antiretroviral therapy was effective in inducing HIV-specific T-cell responses. Therapeutic immunizations with recombinant gp160 had a modest effect on CD4-cell counts, the treatment alone lead to a transient clinical benefit in the form of an improved survival after two years of immunization. Immunizations with HIV DNA during HAART treatment permitted persistence or development of innate (NK), CD4+ and/or CD8+ immune responses. HIV specific T-helper cell responses induced by immunization with gp160 were maintained at high levels up to 7 years after the last injection. Cells with HIV-specific interferon-gamma (IFN-gamma) production were retained or increased in long-term HAART treated patients. The impact of a single structured therapy interruption (STI) was analyzed in a small group of patients showing no obvious increase or decrease in the HIV-specific immune response during or after STI. The possibility to induce very long-term strong and persistent immune responses in HIV-infected individuals raises hopes that vaccination preceding therapy interruption might prolong the symptom-free period without HAART.

AIDS Vaccines↗