HIV therapies : from health-related quality of life to DNA levels

Abstract: The treatment of people infected with HIV was revolutionised with the introduction of protease inhibitor based antiretroviral combination therapy. The therapy has greatly reduced the incidence of AIDS and AIDS-related mortality in the industrialised world. However, the necessity of strict adherence to the complicated regimes and the long-term adverse effects have a negative impact on the patient. The aims of this thesis were to study the longitudinal influence of vaccination therapy, antiretroviral therapy and therapy interruption on the health-related quality of life and biomedical variables of HIV-positive patients. Further, to develop methods to monitor HIV DNA during different treatment conditions. The five-year impact of recombinant envelope glycoprotein 160 (rgpl60) vaccination was investigated in 40 HIV-infected patients. During the first six months of therapy, the immunisations were followed by two weeks of double-blind azidothymidine or placebo therapy. Treatment with rgp160 was safe and temporarily improved the levels of CD4+ cells but had no apparent long-term effect on disease progression. In a subsequent study of the rgpl60 vaccine, the impact on the health-related quality of life of 72 men was investigated, using the Swedish Health-Related Quality of Life Questionnaire (SWEDQUAL) and the Health Index. Before the initiation of treatment there was a negative effect on quality of life compared with random population groups. The most affected parameters were those related to emotional well-being. During two years of treatment the physical domains deteriorated, unrelated to treatment arm (rgp 160 or placebo). Moreover, 54 patients were measured by the SWED-QUAL before and after two years of protease inhibitor based antiretroviral therapy. We constructed two new comprehensive scores to facilitate evaluation of data obtained by SWED-QUAL. Initiation of therapy improved immune and viral parameters but induced a decrease in the emotional health domain while 'the physical and social domains remained unchanged. The experience of adverse effects contributed most to the deterioration of emotional health. Further, physical health domains before the start of therapy predicted experiences of adverse effects and adherence. That is why it could be important to consider health- related quality of life when planning strategies and care for antiretroviral therapy. For the first time, the viral content of CD4+ cells was studied during long-term therapy interruption. In order to accomplish this, we developed an unorthodox assay, comparing two viral genomes by realtime PCR. A multiplex PCR was established for measuring the HIV DNA load in CD4+ cells by simultaneously amplifying a conserved region of the HIV-1 pol gene, an EBV gene and a section of the human albumin gene. The HIV DNA load was monitored in 15 patients undergoing long-term supervised therapy interruption. HIV DNA seemed to decrease unceasingly during efficient treatment. When therapy was interrupted, HIV DNA increased in all patients with an average doubling time of two months. The change in the HIV DNA load (slope) was positively related to the HIV RNA maximum load, the RNA steady state level and the baseline HIV DNA value. The HIV DNA slope was also inversely related to the decrease in CD4+ cells both before the start of therapy and during the therapy interruption. The health-related quality of life in the patients undergoing long- term supervised therapy interruption seemed to remain stable or improved slightly after two years of interrupted therapy. The progression rate of the HIV infection before initiation of antiretroviral combination therapy and the health-related quality of life may thus be important considerations when assessing patients for supervised therapy interruption.

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