Objectives: To assess the mortality in a cohort of HIV-infected patients starting highly active antiretroviral therapy (HAART) compared to the mortality of the general population, focusing on the influence of the CD4 cell count at the time of starting HAART.Methods: Patients in the HIV Cohort Study in Western Denmark starting HAART before 1 January 2002 were identified. For each patient, 100 population controls matched on age and gender were extracted from the Danish Civil Registration System. Mortality rates were compared between the two cohorts overall, and in four groups defined by baseline CD4 cell counts.Results: A total of 647 HIV-infected patients and 64 700 population controls were included, accounting for 53 and 815 deaths during follow-up. In-the HIV group, mortality rates were 70.0 per 1000 person-years at risk in the lowest CD4 cell group (< 50x10(6) cells/l), and 3.2 in the highest (>= 200x10(6) cells/l). Compared with population controls, mortality rate ratios declined with increasing CD4 cell counts, being 15.3 [95% confidence interval (CI), 9.8-23.8], 8.6 (95% CI, 4.3-16.8), 5.9 (95% CI, 3.0-11.4), and 3.6 (95% CI, 2.0-6.5) in the groups with CD4 cell count < 50, 50-99, 100-199, and greater than or equal to200x10(6) cells/l.Conclusion: In comparison with the general population, HIV-infected patients starting HAART with a CD4 cell count above 200x10(6) cells/l had low mortality rates that were comparable with the rates found in other chronic medical diseases. The mortality rates increased considerably when treatment was started at lower baseline CD4 cell counts. (C) 2004 Lippincott Williams Wilkins.

Saquinavir hard gel capsule (hgc), the first human immunodeficiency virus (HIV) protease inhibitor (PI) used in clinical practice, has been shown to have insufficient effectiveness. A population-based cohort study assessed the long-term consequences of using saquinavir hgc as initial PI in HIV-infected patients pre-exposed to nucleoside reverse transcriptase inhibitors. 121 patients starting a regimen with saquinavir hgc were compared with 91 starting with non-boosted indinavir (n = 72) or ritonavir (n = 19). Median follow-up time was 4.6 and 4.7 y for the 2 groups. Starting with saquinavir hgc was associated with a lower overall probability of achieving an undetectable viral load [risk ratio (RR) = 0.41, 95%, confidence interval (95% CI) 0.30-0.56]. However, the lower probability of having undetectable viral load during follow-up declined over time with odds ratios (OR) = 0.27 (95%, CI 0.14-0.54), 0.35 (951% CI 0.19-0.66), 0.47 (95% CI 0.24-0.91) and 0.73 (95% CI 0.34-1.55) at 60, 120, 180 and 240 weeks, respectively, after starting HAART. Starting with saquinavir hgc was correlated with a higher risk of having the initial PI discontinued (RR = 1.89, 95% CI 1.39-2.58). The insufficient suppression of viral load in patients starting with saquinavir hgc subsided during follow-up, probably owing to the earlier discontinuation of saquinavir hcg in favour of newer and more potent HAART regimens.

ObjectivesTo 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.MethodsThe 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.ResultsTwenty‐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/μL (P=0.062). The median IDV morning and evening Cmin were 434 ng/mL and 220 ng/mL, respectively.ConclusionsTreatment 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.

New antiretroviral drugs, expanding knowledge of their long-term toxic effects and the large number of patients with treatment failure have increased the demand for new strategies in the antiretroviral treatment of HIV-infected patients. The present study was conducted as part of the HIV Cohort Study in western Denmark to reveal trends in the use of antiretrovirals in the region. The cohort includes all patients attached to those centers treating HIV patients in western Denmark. A total of 537 patients who started highly active antiretroviral therapy (HAART) were included. The number of patients receiving HAART increased dramatically in 1996 and 1997 before leveling off, with 45-75 patients initiating treatment annually thereafter. Median follow-up time after initiation of HAART was 151 weeks. An estimated 45.1% of patients had the initial HAART regimen modified during the first year of follow-up. Side-effects and treatment failure were the main reasons for treatment modifications. Major new strategies implemented in the region in 1999 and 2000 included treatment with boosted protease inhibitors and non-nucleoside reverse transcriptase inhibitors.

We performed a population- based cohort study to assess the impact of nonwhite origin on the outcome of highly active antiretroviral therapy (HAART) for a Danish cohort of human immunodeficiency virus (HIV)- infected patients. A total of 389 whites and 135 nonwhites started receiving HAART before 1 April 2001. After 1 year of treatment, 78% of nonwhites and 76% of whites achieved a virus load of < 500 HIV RNA copies/ mL. No major differences were found between the 2 groups with respect to achievement of a virus load of < 500 copies/ mL (relative risk [RR], 0.94; 95% confidence interval [CI], 0.74- 1.18), risk of clinical progression (RR, 0.63; 95% CI, 0.32- 1.24), or response measured by total CD4(+) cell count. One year after fulfilling Danish recommendations for initiation of HAART, 91% of nonwhites and 93% of whites had started receiving HAART. Race and ethnic origin play no major role in the outcome associated with HAART if access to health care is free.

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.

Community-aquired pneumonia caused by atypical bacteria or viruses was studied in a double-blind trial comparing fleroxacin 400 mg od and doxycycline 100 mg bd for 10 days. The aetiology was confirmed in 258 of 411 cases (66%), of which 133 were caused by Mycoplasma spp., Chlamydia spp. or Legionella spp.; 30 patients had viral infection, nine had pneumococcal or Haemophilus influenzae infection and 93 had mixed aetiology. In intention-to-treat analyses clinical response rates in fleroxacin-treated patients were 86% (157/182) and 75% (137/182) 2-8 days and 3-5 weeks after therapy, respectively. Corresponding results with doxycycline were 93% (177/191) and 85% (162/190), respectively. Differences between treatments seemed to be due to the lower activity of fleroxacin compared with doxycycline against mycoplasma and pneumococci. Drug-related adverse events were reported in 39% of 204 fleroxacin patients and in 34% of 207 doxycycline patients. The null hypothesis that fleroxacin was <15% inferior to doxycycline was accepted at early follow-up but rejected at later review.

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.

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.

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.

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)

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 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.