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B Ledergerber

Publications and source records attributed to B Ledergerber.

At least 55 records · Page 3Linked to original sources
PubMed1998

Levels of HIV-infected peripheral blood cells remain stable throughout the natural history of HIV-1 infection. Swiss HIV Cohort Study.

OBJECTIVE: To clarify the relationship between the number of provirus-bearing peripheral blood mononuclear cells (PBMC) and HIV-1 disease progression during the natural history of infection. DESIGN: Twenty-four HIV-1-infected subjects with known seroconversion dates and long-term follow-up were retrospectively identified using the Swiss HIV Cohort Database. PBMC specimens from this cohort were retrieved from storage for analysis. METHODS: Infected PBMC equivalents were determined by HIV-1 DNA quantitative competitive (QC)-PCR. The results were analysed with respect to HIV-1 disease stage and compared with a mathematical model of long-term HIV-1 disease progression. RESULTS: PBMC HIV-1 DNA did not correlate with major indices of disease progression, including time following primary infection, time before reaching a CD4 cell count less than 200 x 10(6)/l, and time before death. The number of PBMC harbouring HIV-1 provirus was relatively constant throughout the clinical stages of HIV-1 infection, consistent with simulated data from a mathematical model of long-term HIV-1 infection. We also showed that a biased interpretation of the QC-PCR data may arise when the values are expressed as HIV-1 DNA copies per PBMC or per CD4 cell. CONCLUSIONS: This analysis suggests that levels of provirus-bearing PBMC remain constant during the natural course of HIV-1 infection, whereas plasma virus load typically increases logarithmically during the same period. The hypothesis that plasma virus levels are directly related to the number of infected cells may deserve reconsideration.

Adult↗
PubMed1998

[The Swiss HIV Cohort Study--a link between clinical research and medical practice].

The prospective Swiss HIV Cohort Study (SHCS) documents since 1988 epidemiological, clinical and laboratory data of HIV-infected participants. Until the end of 1997, 9447 patients with a total follow-up of 25,584 patient-years have been included. The proportion of women is 27.3% and is rising. The proportion of heterosexually infected patients has been rising since 1992, this group was with 35.6% in 1997 the most frequent transmission category within the newly registered participants. The SHCS is representative for Switzerland since 73% of the 5532 nationwide registered AIDS cases are included in the study. Recently, the SHCS data could demonstrate an impressive reduction in morbidity and mortality due to the improvement in therapy and prophylaxis. The SHCS also serves as a basis for large multicenter studies that aim to evaluate new prophylactic treatments or new antiretroviral strategies. By introducing uniform guidelines for the diagnosis and the treatment of HIV infection, the SHCS has contributed significantly to the high quality of patient care, a goal that must be maintained and further improved in the future. Also important is the recognition of acute HIV infections because early treatment of such patients holds the promise to substantially improve the clinical course.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Regional differences in use of antiretroviral agents and primary prophylaxis in 3122 European HIV-infected patients. EuroSIDA Study Group.

Little is known about how widely HIV-related drugs are used outside controlled clinical trials. We therefore assessed factors associated with use of antiretroviral (ARV) therapy and primary prophylactic regimens to prevent HIV-associated opportunistic infections. Baseline data from a prospective study from May to August 1994, on 3122 consecutive HIV infected patients with a CD4 count <500 cells/microl, followed in 37 centers from 16 European countries, were analyzed. Two thousand and twenty patients (65%) were receiving at least 1 ARV drug at the time of the study. ARV therapy was more frequently used among patients from southern and central Europe as compared with patients from northern Europe, especially among patients with CD4 counts >200 cells/microl (73%, 57%, and 42%, respectively, p < 0.0001). Of patients on ARV therapy, 34% received open-label combination therapy. This proportion was higher in central Europe compared with other regions (27%, 50%, and 31% for southern, central, and northern Europe, respectively, p < 0.0001). Primary prophylaxis against Pneumocystis carinii pneumonia (PCP) was used by 85% of patients with a CD4 count <200 cells/microl, without marked regional differences. In patients without esophageal candidiasis or other invasive fungal infections, antifungal drugs were far less frequently used in patients from southern and central Europe compared with patients from northern Europe (10%, 10%, and 25%, respectively, p < 0.0001). Only 5% of patients with a CD4 count <100 cells/microl received rifabutine as primary prophylaxis against nontuberculous mycobacterioses. ARV and antifungal therapies are used differently in different parts of Europe, whereas primary PCP prophylaxis is uniformly administered to most at-risk patients. U.S. recommendations on the use of antimycobacterial prophylaxis have not been implemented in Europe.

AIDS-Related Opportunistic Infections↗
PubMed1997

Cytomegalovirus retinitis in patients with AIDS in Europe. AIDS in Europe Study Group.

The incidence of cytomegalovirus (CMV) retinitis and risk factors associated with the condition were studied in patients with the acquired immune deficiency syndrome (AIDS) in a multicenter retrospective cohort study of 6458 patients from 52 centers in 17 countries in Europe. Cytomegalovirus retinitis was diagnosed in 154 patients (2.4%) at the time of AIDS diagnosis, the probability of this diagnosis being significantly higher for those with CD4+ cell counts of < 100/mm3 (3.4%) than with counts of 100-200/mm3 (1.3%) or > 200/mm3 (0.8%). The rate of developing CMV retinitis after AIDS diagnosis was 9.4 per 100 patient years of follow-up. Multivariate analysis showed that risk behavior was significantly associated with the risk of developing CMV retinitis: lower for intravenous drug users [relative risk (RR) 0.47] and those engaged in "other risk behavior" (RR 0.58) than for homosexual men. The risk of developing CMV retinitis after AIDS diagnosis was significantly associated with CD4+ cell count at the time of AIDS diagnosis: for counts < 100/mm3 (RR 2.90) and from 100 to 200/mm3 (RR 2.13), there was a higher risk than for counts > 200/mm3. Patients with Pneumocystis carinii pneumonia, toxoplasmosis, or extraocular CMV infection at time of AIDS diagnosis exhibited an increased risk of developing CMV retinitis. Patients treated with zidovudine exhibited an increased rate of CMV retinitis: RR was 1.75 during and 2.87 after the second year of treatment as compared to those who had not received zidovudine. Median survival after CMV retinitis at time of AIDS diagnosis was eight months.

AIDS-Related Opportunistic Infections↗
PubMed1997

Survival of AIDS patients according to type of AIDS-defining event. The AIDS in Europe Study Group.

BACKGROUND: There are known to be wide differences in the prognosis of patients with a diagnosis of AIDS. In this study of 6578 patients with AIDS form 17 European centres, we develop a ranking of AIDS-defining illnesses, and determine how well this ranking holds after adjustment for potential confounding variables. METHODS: Survival from each AIDS-defining event was calculated and ranked using Kaplan-Meier estimation of median survival. Cox proportional hazards models with each disease modelled as a time dependant covariate were used to determine the risk of death after each diagnosis, before and after adjustment for potential confounders. RESULTS: Median survival after an initial AIDS-defining diagnosis of progressive multifocal leukoencephalopathy and malignant lymphoma was particularly poor (2 and 5 months respectively), while the longest median survival occurred after initial AIDS-defining illnesses of Kaposi's sarcoma and extrapulmonary tuberculosis (17 and 22 months respectively) Patients diagnosed with a primary brain lymphoma had shorter median survival times than patients with a peripheral lymphoma (median survival of 1 month and 4 months respectively P < 0.0001). In general, median survival in patients with cutaneous Kaposi's sarcoma (skin, oral) was between two and four times longer than patients with systemic involvement The ranking of diseases was found to be generally similar after adjustment for all potential confounders. CONCLUSIONS: AIDS-defining events can be grouped into three categories with median survival after diagnosis of < 6 months. 6-12 months and > 12 months. The assigned ranking of disease would not be altered by prognostic factors such as age or CD4 lymphocyte count. These results have important implications in the design of clinical trials and patient management.

AIDS-Related Opportunistic Infections↗
PubMed1996

[Sex differences in disease course: analysis of the Swiss HIV cohort study].

The Swiss HIV Cohort Study (SHCS) is a prospective multicentre study of HIV-infected adults. Participants have been followed up at six-monthly intervals since 1988. The purpose of the present study was to examine sex differences in developing AIDS-defining events and in survival among participants of the SHCS (1042 women, 1507 men). A statistically significant higher risk of Pneumocystis carinii pneumonia (PCP) was evident among women. This difference was particularly pronounced in 1989 (hazard ratio 2.11, p = 0.01). Other opportunistic events and survival showed no statistically significant sex differences. The results are compatible with slower introduction of PCP prophylaxis among women. A reason for this may be that women were less likely to be enrolled in clinical trials than men. This hypothesis will be examined in a further study.

AIDS-Related Opportunistic Infections↗
PubMed1996

[HIV infection, tuberculosis and tuberculin test in Switzerland. The Swiss HIV Cohort Study].

BACKGROUND: The usefulness of the tuberculin skin test (TST) for HIV-infected subjects may be questioned because false-negative results are increasingly common with advanced immune deficiency. The objectives of this research were thus to describe the use and the results of TST among patients with HIV infection in Switzerland and to measure the usefulness of isoniazid preventive chemotherapy and the incidence of tuberculosis (TB) relative to TST and CD4 cell count at the time of TST. DESIGN: Prospective multicentric cohort study of HIV infected patients; comparison of patients tested and non-tested, and of those with positive and negative TST. Multivariate comparison (Cox model) of TB incidence taking into account TST results and CD4 cell count at the time of TST. RESULTS: Out of 5802 patients followed up in the Swiss HIV cohort study as of September 1994, 34.6% were tested. Native Swiss were more likely to be tested than patients from high TB prevalence countries (36% vs 21% of native Africans). Patients registered after 1990 were more often tested than before (50% vs 26%). Of 2010 tested patients, 6.8% had a > 5 mm induration. African patients were more frequently TST positive (26%) than Swiss nationals (6%). Among patients with CD4 > 500 per mm3 at the time of the test, 16% were TST positive compared to 1% of those with CD4 < 200 per mm3. Out of 25 cases of tuberculosis among tested patients, 84% (21) occurred among TST-negative patients. Tuberculosis incidence among TST-negative patients with CD4 > or = 200 per mm3 at the time of the test was 0.3 per person-year. In comparison, the adjusted relative risk of tuberculosis among TST-positive patients with CD4 > or = 200 per mm3 was 5.5 (95% confidence interval [CI]: 1.2-23.9) and 6.6 (CI: 2.3-19.0) among TST-negative patients with CD4 < 200 per mm3. CONCLUSION: Despite its usefulness, TST is often performed too late and is therefore difficult to interpret. TST should be done as early as possible. TST should be done as early as possible. Among patients with CD4 < 200 per mm3, a negative TST should not preclude the use-of preventive chemotherapy, particularly in those originally from countries with a high incidence of tuberculosis.

AIDS-Related Opportunistic Infections↗
PubMed1996

Tuberculosis among European patients with the acquired immune deficiency syndrome. The AIDS in Europe Study Group.

OBJECTIVES: To describe the characteristics of acquired immune deficiency syndrome (AIDS) patients with tuberculosis in Europe; to assess the incidence and risk factors of tuberculosis after AIDS; to compare survival of AIDS patients with and without extra-pulmonary tuberculosis (EPTB) at the time of AIDS diagnosis. DESIGN: Multicentric retrospective cohort study of 6544 AIDS patients diagnosed in 52 clinical centres and 17 European countries. METHODS: Description of patient characteristics and comparisons of tuberculosis incidence and mortality after AIDS with multivariate Cox proportional hazard models. RESULTS: 14.6% of AIDS patients had tuberculosis and 78% of those with tuberculosis had EPTB. EPTB was the AIDS-defining condition in 8.7% of the patients. Tuberculosis incidence after AIDS was 3.1 per 100 person-years. Age, gender and HIV-transmission category were not significantly associated with an increased risk of tuberculosis and the strongest risk factor for both EPTB and pulmonary tuberculosis (PTB) was the region of origin. The adjusted hazard ratio of EPTB and PTB in Southern Europe compared to Northern Europe were 5.5 (95% confidence interval [CI]: 5.0-6.1) and 2.0 (CI: 1.4-2.7) respectively. The apparent survival advantage of AIDS patients with EPTB compared to patients diagnosed with other conditions (median survival time: 22 vs 16 months) was statistically not significant when confounding variables were adjusted for (Hazard ratio: 0.85; CI: 0.62-1.07). CONCLUSIONS: In Europe, there are large differences in the incidence of tuberculosis among AIDS patients in different countries. They do not seem to be due to differences in age or in the prevalence of injecting drug use and likely reflect differences in the prevalence of tuberculosis infection. The role of recent transmission should also be considered, and national tuberculosis control efforts and Europe-wide surveillance need to be reinforced accordingly.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Risk factors for tuberculosis among HIV-infected patients in Switzerland. Swiss HIV Cohort Study.

The aim of this study was to determine the risk factors associated with tuberculosis among human immunodeficiency virus (HIV)-infected persons living in Switzerland, a country with low prevalence of tuberculous infection. We performed a nested case-control study and logistic regression. Cases (n = 239) were patients participating in the Swiss-HIV Cohort study (n = 7,103), diagnosed with bacteriologically confirmed tuberculosis. The rest of the cohort population was used as control. Patients from industrialized countries had a risk of tuberculosis similar to those from Switzerland (adjusted odds ratio (OR) 1.1; 95% confidence interval (95% CI) 0.7-1.5); whereas the risk among patients from Eastern Europe (OR 2.8, 95% CI 1.9-3.7), Brazil (OR 10.6; 95% CI 9.6-11.5), and Africa (OR 3.0; 95% CI 2.4-3.6) was markedly higher. Immune suppression, as indicated by low CD4 + cell count, was an independent risk factor for tuberculosis (OR 7.8; 95% CI 7.3-8.3 for patients with CD4 + < 50 cells.mm-3 compared to those with CD4 + > 500 cells.mm-3). Age, sex and HIV-transmission category did not appear to increase the risk of tuberculosis after adjustment for other patient characteristics. In conclusion, in countries of low prevalence of Mycobacterium tuberculosis infection, to originate from a country with high prevalence of tuberculosis infection and to have advanced immunodeficiency are significant risk factors for tuberculosis. They may be used to complement the tuberculin skin test in targeting patients for preventive chemotherapy.

Adult↗
PubMed1995

Changes in survival over time after a first episode of Pneumocystis carinii pneumonia for European patients with acquired immunodeficiency syndrome. Multicentre Study Group on AIDS in Europe.

BACKGROUND: Factors associated with improved survival over time for patients with the acquired immunodeficiency syndrome (AIDS) who have Pneumocystis carinii pneumonia at diagnosis are not clearly defined. METHODS: An inception cohort of 2533 patients with AIDS, diagnosed from 1979 to 1989, from 52 centers in 17 European countries was studied. Survival 3 months and 3 years after diagnosis was estimated by Kaplan-Meier life tables. Independent predictors of survival were analyzed by construction of Cox proportional hazards models. RESULTS: Patients in whom AIDS and P carinii pneumonia had been diagnosed before 1988 had a poorer 3-month (ie, short-term) survival, whereas the survival 1 and 2 years after P carinii pneumonia was lower only for patients whose disease was diagnosed before 1987 compared with those with more recent diagnoses. Other variables associated with poorer outcome were greater age, infection via blood transfusion, diagnosis made in south Europe, and coexisting illnesses. After controlling for these prognostic markers in multivariate analysis, improvement in survival over time was still evident. For patients who survived the P carinii pneumonia episode, both zidovudine and secondary prophylaxis for P carinii pneumonia initiated around the time of diagnosis were associated with improved survival, and, after controlling for these treatment variables, no statistically significant improvement in survival over time was observed. CONCLUSIONS: Survival after an episode of P carinii pneumonia has improved within recent years. Increased awareness of early symptoms of P carinii pneumonia and better treatment of the pneumonia may have led to improvement in short-term survival over time, whereas the introduction of zidovudine and increased use of secondary P carinii pneumonia prophylaxis may have resulted in the recent increase in survival 1 and 2 years after the diagnosis. However, 3-year survival remained unchanged over time, implying that the underlying human immunodeficiency virus infection and other complications are not effectively controlled.

AIDS-Related Opportunistic Infections↗
PubMed1994

Survival differences in European patients with AIDS, 1979-89. The AIDS in Europe Study Group.

OBJECTIVES: To examine the pattern of survival and factors associated with the outcome of disease in patients with AIDS. DESIGN: Inception cohort. Data collected retrospectively from patients' charts. SETTING: 52 clinical centres in 17 European countries. SUBJECTS: 6578 adults diagnosed with AIDS from 1 January 1979 to 31 December 1989. MAIN OUTCOME MEASURES: Survival after the time of diagnosis. RESULTS: The median survival after diagnosis was 17 months, with an estimated survival at three years of 16% (95% confidence interval 15% to 17%). Patients diagnosed in southern Europe had a shorter survival, particularly immediately after the time of diagnosis, compared with patients diagnosed in central and northern Europe (survival at one year (95% confidence interval) 54% (52% to 56%) 66% (64% to 68%), 65% (63% to 66%), respectively. The three year survival, however, was similar for all regions. The regional differences in survival were less pronounced for patients diagnosed in 1989 compared with earlier years. Improved survival in recent years was observed for patients with a variety of manifestations used to define AIDS but was significant only for patients diagnosed with Pneumocystis carinii pneumonia. The three year survival, however, remains unchanged over time. CONCLUSIONS: Survival of AIDS patients seems to vary within Europe, being shorter in southern than central and northern Europe. The magnitude of these differences, however, has declined gradually over time. Short term survival has improved in recent years, but the long term prognosis has remained equally poor, reflecting the fact that the underlying infection with HIV and many of the complicating diseases remains essentially uncontrolled.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Comparison of long-term prognosis of patients with AIDS treated and not treated with zidovudine. AIDS in Europe Study Group.

OBJECTIVE: To determine the association between elapsed time since starting zidovudine and survival in patients with acquired immunodeficiency syndrome (AIDS). DESIGN: Inception cohort and observational study of patients treated and not treated with zidovudine. SETTING: Fifty-one centers in 17 European countries. PATIENTS: A total of 4484 patients diagnosed as having AIDS from 1979 to 1989 who survived their initial AIDS-defining event and who had not started zidovudine before AIDS diagnosis. MAIN OUTCOME MEASURES: Use of zidovudine and mortality. RESULTS: Among patients who did not receive zidovudine, the death rate was approximately constant for the first 5 years after AIDS diagnosis. For patients treated with zidovudine, the death rate within the first year since starting zidovudine was markedly lower than for untreated patients who had developed AIDS at the same time (relative rate, 0.47; 95% confidence interval [CI], 0.42 to 0.51). For longer times since starting zidovudine, the association with reduced mortality rate was diminished, and for patients surviving more than 2 years since starting zidovudine, the death rate was greater than for untreated patients who had developed AIDS at the same time (relative rate, 1.35; 95% CI, 1.15 to 1.58). Adjustment for other prognostic factors failed to substantially affect this observation. CONCLUSIONS: When initiated after the time of AIDS diagnosis, zidovudine was associated with improved prognosis but for no more than 2 years after starting therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1994

The Swiss HIV Cohort Study: rationale, organization and selected baseline characteristics.

OBJECTIVES: This paper describes the rationale and design features of the Swiss HIV Cohort Study (SHCS) and the baseline characteristics of participants enrolled up to March 31st 1993. The objectives include epidemiological, clinical and laboratory research. DESIGN: The SHCS is a prospective cohort study of HIV infected adolescents and adults seen at the outpatient clinics of the Swiss University Hospitals in Basle, Berne, Geneva, Lausanne and Zurich and the Cantonal Hospital St. Gall. The multicentre collaboration was initiated in September 1988 by the Swiss Federal Office of Public Health. Data collected prior to this date by several participating centers using a similar protocol were included, the earliest records dating back to 1982. Follow-up visits are scheduled every 6 months. ENROLLMENT: As of March 31st 1993, 6253 participants (M: 4580, F: 1675) were included with a total of 16015 person-years of follow-up (mean 2.6 years). HIV transmission categories were 46% intravenous drug users (IDU), 32% men who had sex with men (MSM), 18% heterosexual contacts (HET) and 4% other. The proportion of MSM among male participants decreased from 62% in 1985 to 40% in 1987, to remain stable thereafter. The proportion of IDU among males was around 40% throughout, whereas in females, there was a pronounced decline from 90% IDU in 1985 to 50% in 1992. Conversely, there was a striking increase in registrations of women presumably infected by HET, from 8% in 1985 to 50% in 1992. Among men, the proportion classified as HET increased from 2% to 15%. It is estimated, that a large proportion of all Swiss AIDS patients (70%) and HIV infected individuals (32%-47%) are enrolled in the Swiss HIV Cohort Study. Losses to follow-up, however, are common. CONCLUSIONS: The SHCS serves multiple purposes as a research project, as infrastructure for multidisciplinary research and as a tool to improve patient care. Several international and national trials, post-marketing surveillances and expanded access protocols were or still are based upon its infrastructure. The large number of female participants and of participants AIDS-free at entry, make the database especially valuable.

Adolescent↗
PubMed1994

Survival in HIV infection: do sex and category of transmission matter? Swiss HIV Cohort Study.

OBJECTIVE: To examine survival differences in HIV-infected individuals between the sexes and the categories of transmission. PATIENTS AND SETTING: Subjects assumed to have been infected by injecting drug use, by male homosexual contact or by heterosexual contact and enrolled in the Swiss HIV Cohort Study, a national multicentre cohort study of adult HIV-infected patients. METHODS: Kaplan-Meier lifetable and Cox regression analyses were performed (time 0 = date of study entry) and survivors were censored at their last follow-up visit. RESULTS: A total of 4428 patients (mean duration of follow-up, 2.1 years) were considered. At entry, men were older and had lower CD4+ counts than women (P < 0.0001). Homosexual men were the oldest group with the lowest CD4+ counts and the most advanced disease at study entry (P < 0.0001). Crude hazard ratios indicated a 28% lower mortality from all causes in women compared with men (P < 0.0001) and, among men but not in women, a 28 and 32% higher mortality in homosexuals and heterosexuals compared with injecting drug users (IDU) (P = 0.0002 and P = 0.008, respectively). After adjusting for differences at entry, the mortality difference between the sexes disappeared (P = 0.5) and differences across transmission categories were reversed. Mortality in homosexual men was an estimated 13% (P = 0.057) lower than in male IDU; mortality was 22% lower in heterosexual women than in female IDU (P = 0.098). In stratified analysis the increased risk in IDU was confined to subjects with CD4+ cell counts > 500 x 10(6)/l cells at study entry. CONCLUSIONS: These results indicate a uniform mortality risk across the sexes but indicate an increased risk in IDU without CD4+ cell depletion at entry, the latter probably attributable to causes not related to progression of HIV infection. This study underscores the importance of adjusting for prognostic factors when comparing survival between different patient groups.

Adult↗