Low-dose indinavir in combination with low-dose ritonavir: steady-state pharmacokinetics and long-term clinical outcome follow-up.

OBJECTIVES: To evaluate the long-term efficacy and pharmacokinetics of indinavir (IDV)/ritonavir (RTV) 400/100 mg twice a day in combination with two nucleoside reverse transcriptase inhibitors. METHODS: The study was retrospective with a prospective pharmacokinetic study at a single centre. All HIV-1-infected patients who started the regimen in the period from January 1999 to February 2001 were included in the study. Plasma HIV RNA and CD4 cell counts were recorded from baseline to week 120. Results were evaluated as intention-to-treat and on-treatment analyses with separate analyses for protease inhibitor naive and experienced patients. Patients who were still on the regimen by August 2001 were asked to participate in a pharmacokinetic evaluation. RESULTS: Twenty-one patients started treatment with the regimen (median follow-up: 116 weeks). The percentage of patients with below 20 HIV-1 RNA copies/mL was 70.0% at week 120 and the median CD4 cell count increased from 320 to 607 cells/microL (P=0.062). The median IDV morning and evening Cmin were 434 ng/mL and 220 ng/mL, respectively. CONCLUSIONS: Treatment with the IDV/RTV 400/100 mg regimen appears to be efficacious for up to 2 years. However, rather low IDV Cmin suggests that the regimen should be evaluated further before its widespread use and that the regimen probably should be guided by pharmacokinetic evaluation.

Changing demographics in an HIV-infected population: results from an observational cohort study in Western Denmark.

We present demographic data from an observational database of HIV and AIDS in the Western part of Denmark, a region with a population of 2,935,156 individuals (55.1% of the population of Denmark). Five centers in the region treat HIV-positive adults; all patients attached to these centers since 1995 are included in this study. In total, 749 adult HIV-infected individuals were enrolled as of 31 December, 1999. Estimates of prevalence and incidence of HIV infection in the area were 25.9/100,000 and 2.6/100,000, respectively, which are lower than average for the country. The number of newly diagnosed HIV-infected patients remained constant during the period 1995-99, with an average of 62 diagnoses per year. The number of HIV-related deaths declined from 43 in 1995 to 15 in 1999. Of the enrolled patients, 70.9% were of Danish origin, 75% were Caucasians, 69.7% were male and 47.2% had heterosexual contact as their primary risk behavior. There seems to have been a shift in the HIV epidemic in recent years, with a higher proportion of newly diagnosed HIV patients having contracted the infection through heterosexual contact, a higher proportion being immigrants from less developed countries and newly diagnosed individuals getting older.

Trends in survival of Danish AIDS patients from 1981 to 1989.

Length of survival was analysed in relation to year of diagnosis, AIDS-indicative disease, age, risk behaviour, zidovudine therapy, and CD4 cell count and serum immunoglobulin (Ig) levels at the time of diagnosis in a group of 231 consecutive adult Danish AIDS patients reported before 1 January 1988. The cumulative survival rate was 53% (95% confidence interval 47-59%) at 1 year, 29% (22-36%) at 2 years and 18% (10-26%) at 3 years. Length of survival increased significantly (P less than 0.001) over time for patients who were initially diagnosed with Pneumocystis carinii pneumonia (PCP), 17% (3-31%) at 2 years prior to 1986, 32% (16-49%) in 1986 and 52% (34-69%) in 1987, whereas survival remained stable for patients with other AIDS-indicative diseases. Survival was similar for patients who were diagnosed with Kaposi's sarcoma alone and PCP alone. Independent predictors of a shortened survival were a CD4 cell count less than 200 x 10(6)/l, a serum IgA level greater than 4 g/l, and an initial diagnosis with opportunistic infections other than PCP. In addition, the multivariate analysis suggested an improved survival in recent years for patients diagnosed with PCP, independent of other factors examined. We conclude that length of survival in AIDS patients is highly variable. Determinants of progression include CD4 cell count, serum IgA level, and presenting disease. Survival has increased markedly for patients with PCP and median survival now exceeds 24 months.

Family studies of hereditary hemochromatosis in Denmark and the Faroe Islands.

Pedigree studies were performed based on one Faroese and four Danish probands with overt idiopathic hemochromatosis (IH). The study consisted of HLA typing and determination of biochemical iron status indicators (serum transferrin saturation, serum ferritin). In total, 130 persons were evaluated. The screening identified 6 homozygous (h/h) subjects with preclinical IH, 46 heterozygous (h/n), and 8 normal (n/n) subjects, while 39 subjects were classified as normal or heterozygous (n/h?). One family demonstrated both a homozygous x heterozygous as well as a heterozygous x heterozygous mating. Recombination between the HLA region and IH locus occurred possibly in three subjects in three different families. The significance of detailed screening in families with probands with IH is discussed.

Opportunistic infections and malignancies in 231 Danish AIDS patients.

We analysed cumulative disease frequencies in the first 231 adult Danish AIDS patients with life tables. There was a certain hierarchical pattern in the occurrence of complicating diseases. Herpes zoster, Kaposi's sarcoma and Pneumocystis carinii pneumonia were early manifestations, whereas diseases caused by cytomegalovirus and atypical mycobacteria tended to occur later in the course of AIDS. Compared with all other AIDS patients, homosexual men were more likely to develop Kaposi's sarcoma, cytomegalovirus chorioretinitis and mucocutaneous herpes simplex virus infection. The proportion of patients who developed particular diseases changed with calendar time. Most striking was a three to fourfold decrease in diseases caused by cytomegalovirus. In conclusion, the study showed that disease frequencies in patients with AIDS may vary with the patients risk behaviour and duration of AIDS, and that the frequencies of particular diseases may change with calendar time.

Short-term curative treatment of Aspergillus fumigatus pneumonia with fluconazole.

A 67-year-old previously healthy female presented with fever, malaise and bilateral pulmonary infiltrates. Serology and culture were positive for Aspergillus fumigatus. After 15 days of treatment with fluconazole, clinical cure and regression of the infiltrates were obtained. No side-effects were observed during or after treatment.

[Knowledge of AIDS and of transmission risks of HIV infection in a group of homosexual people. A questionnaire study]. / En gruppe homoseksuelles viden om AIDS og smitterisikoen ved HIV-infektion. En spørgeskemaundersøgelse.

A questionnaire investigation among 430 homosexual persons all of whom were members of an organization for homosexuals was completed by 144 (33%). These replies showed that they knew about HIV infection, risk behaviour and "safe sex". Their knowledge about the signs of HIV infection and AIDS was, however, more limited. The replies were compared with an age-matched group of the male population. The results of the investigation provide reasons to suppose that the information campaigns have been of value but information to prevent spread of infection is still necessary. In addition, further information is necessary about the subjective signs of HIV-infection so that persons in whom these signs develop may be offered the best possible treatment as early as possible.

[A group of homosexuals change their sex habits after information about AIDS. A questionnaire survey]. / En gruppe homoseksuelles aendringer i seksualvaner efter information om AIDS. En spørgeskemaundersøgelse.

A questionnaire investigation to which 144 homosexual persons replied anonomously revealed alterations in the sexual habits after information about AIDS. Significant reduction in the annual number of partners and significantly fewer employ the more dangerous sexual practices which now occur particularly in more permanent partnerships are among the alterations started. An unchanged number still employ active anal and orogenital coitus. Employment of condoms has increased significantly, particularly in anal coitus and "casual" partners (from 3% to 82%). The majority accept the use of condoms and state that they employ more "safe sex" than prior to information about AIDS. 12% stated that they had sex with both sexes and the possibility of spread of infection from homosexual to heterosexual groups is present. The intensive informative work from the homosexuals own organisation and from public health authorities appear to have had some effect but further information and influencing are necessary if the spread of HIV infection is to be stopped.

Effects of 3'-azido-3'-deoxythymidine (AZT) on short-term cultured human peripheral blood lymphocytes.

Although an optimal dose-regimen has still not been established, the antiviral drug 3'-azido-3'-deoxythymidine is known to improve the clinical condition of patients suffering from acquired immunodeficiency syndrome and acquired immunodeficiency syndrome-related complex. The drug effect has mainly been assessed in terms of survival time and/or immunological parameters. One of the most prominent immunological features associated with immunodeficiency virus infection is a persistant hypergammaglobulinaemia due to in vivo polyclonal B-lymphocyte activation. In vitro this is reflected by a hyporesponsiveness of peripheral blood B-lymphocytes to mitogen and antigen induced activation. The present paper deals with the in vitro impact of 3'-azido-3'-deoxythymidine on the immunoglobulin secretion in short-term cultures of peripheral blood lymphocytes. Twenty-four human immunodeficiency virus antibody positive (seropositive) and 24 antibody negative (seronegative) individuals were studied. In addition, T- and B-cell proliferation and the distribution of cell surface markers were determined in 3'-azido-3'-deoxythymidine-supplemented cultures of peripheral blood lymphocytes from eight seronegative subjects. At concentrations similar to those reported in clinical trials, 3'-azido-3'-deoxythymidine was found to suppress the mitogen and antigen induced proliferation of T-cells from seronegative subjects. In contrast, B-cell proliferation and the distribution of membrane markers appeared to be unaffected by the drug. Furthermore, 3'-azido-3'-deoxythymidine did not alter the in vivo immunoglobulin secretion capacity in autologous or allogeneic cultures of lymphocytes from seropositive subjects. In human immunodeficiency virus-infected individuals the number of unactivated, circulating B-cells is significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Lymphocyte immunoglobulin secretion during short-term treatment with cephalosporins in vivo and in vitro: effects on plaque-forming cell response of human peripheral blood lymphocytes.

The influence of 4 cephalosporins on the plaque-forming cell (PFC) generation in mitogen-activated cultures of human lymphocytes (PBL) was assessed. In vitro, suprapharmacological concentrations of the drug resulted in a decreased PFC response, while pharmacological concentrations did not influence the generation of PFC. Cells exposed to drugs for 24 h in vivo and propagated in autologous serum in vitro showed a decreased PFC response.

Plaque-forming cell capability in the senescent.

The number of plaque-forming cells (PFC) developed in pokeweed mitogen (PWM)-activated unfractionated or T/B separated, 4:1 reconstituted cultures of peripheral blood lymphocytes (PBL) with well-characterized subpopulations obtained from healthy, aged subjects was compared to that of young blood donors. The absolute number of PBL in the aged was reduced by 36%, and the percentage of sheep erythrocyte-rosette-forming cells (E-RFC) by 27%, compared to the percentage obtained in young donors. The IgM-, IgG- and IgA-immunoglobulin (Ig) secretion was monitored with a protein A PFC assay. The number of PFC in PBL cultures of the aged was 58% of the number found in cultures of the young controls. The number of PFC generated in cultures of autologous irradiated T and untreated B cells showed a 104% increase in the aged whereas a 63% increase was obtained using cells from young individuals. Co-cultures of young B cells with untreated or irradiated young or aged T cells showed a significant rise in the PFC response in cultures with irradiated aged T cells, while an equal number of PFC was generated in cultures of young B cells with young or aged untreated T cells. Our results demonstrate a decreased number of PBL, especially T cells, an impaired B cell function and a pronounced enhancement of the PFC response in cultures of irradiated aged T cells and young or aged B cells, whereas the T helper function of untreated cells was found to be normal. The influence of monocytes on the PFC response did not differ in the two groups.