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P Sudre

Publications and source records attributed to P Sudre.

At least 19 recordsLinked to original sources

Why is highly active antiretroviral therapy (HAART) not prescribed or discontinued? Swiss HIV Cohort Study.

In this cross-sectional survey conducted at the end of 1997 among the physicians of participants of the Swiss HIV Cohort Study (SHCS), 1487 of 2154 patients (69.0%) were treated with highly active antiretroviral treatment (HAART) defined as triple therapy with a combination of one or two reverse transcriptase inhibitors, and one or two protease inhibitors; 541 patients (25.1%) had never received such treatment. The physician's perception that the patient would not comply with treatment was one reason for not prescribing HAART to 20% of these patients (110). Physicians indicated that the most common reasons for the patient to refuse HAART were the fear of side effects (18%) and the patient's perception that treatment was too complicated (18%). Among 126 patients (5.8%) no longer receiving HAART, the most common reasons for discontinuing treatment were actual side effects (61%) or the fear of side effects (25%). Overall, 16% of patients did not receive therapy in accord with official Swiss guidelines. Multivariate logistic regression analysis indicated that patients with lower education, active intravenous drug users outside of a drug substitution program, and those who acquired HIV infection through intravenous drug use had a significantly higher risk of inadequate treatment. The physician's judgment of patient adherence and the physician's perception of the patient's fear of side effects are critical for the prescription of HAART. Physicians should address these issues to prevent unilateral withholding of treatment and increase the proportion of patients who may benefit from current antiretroviral therapy.

Anti-HIV Agents

Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort study. Swiss HIV Cohort Study.

BACKGROUND: The efficacy of highly active antiretroviral therapy (HAART) in suppression of HIV-1 is well documented. We investigated virological and clinical outcomes of HAART in routine practice. METHODS: We analysed prospective data from the Swiss HIV Cohort Study on suppression of viral load and progression to AIDS or death in 2674 outpatients (median age 36 years, 27.3% women) who started HAART in 1995-98. Viral rebound was defined as two consecutive HIV-1-RNA measurements of more than 400 copies/mL. We analysed separately outcomes in patients with a history of antiretroviral treatment and in treatment-naïve patients. FINDINGS: An estimated 90.7% of treatment-naïve patients reached undetectable viral load (<400 copies/mL) by 12 months. Among pretreated patients, estimates ranged from 70.3% treated with one new drug to 78.7% on three new drugs. 2 years after reaching undetectable concentrations, an estimated 20.1% of treatment-naïve patients and 35.7-40.1% of pretreated patients had viral rebound. At 30 months, an estimated 6.6% (95% CI 4.6-8.6) of patients who had maintained undetectable concentrations, 9.0% (5.5-12.5) who had viral rebound, and 20.1% (15.3-24.9) who had never reached undetectable concentrations developed AIDS or died. Compared with patients who maintained undetectable viral load, the adjusted relative hazard of AIDS or death was 1.00 (0.66-1.55) for patients with viral rebound, and 2.40 (1.72-3.33) for patients who failed to reach undetectable concentrations. INTERPRETATION: The rate of virological failure of HAART was high among these patients, but the probability of clinical progression was low even in patients with viral rebound.

Adult

Isoniazid prophylaxis for tuberculosis in HIV infection: a meta-analysis of randomized controlled trials.

OBJECTIVES: To evaluate the efficacy of isoniazid for the prevention of tuberculosis in tuberculin skin test-positive and negative individuals with HIV infection. DESIGN: Meta-analysis of randomized controlled trials. SETTING: Seven trials from Mexico, Haiti, the United States, Zambia, Uganda and Kenya. PATIENTS: Individuals free from tuberculosis, 2367 persons in the intervention and 2162 in the control groups. INTERVENTION: Comparison of isoniazid with placebo or no prophylaxis. METHODS: A systematic search of the literature was carried out from 1985 to October 1997 for randomized controlled trials of isoniazid prophylaxis in HIV-infected persons. Two reviewers evaluated the relevance of each candidate study and the validity of eligible trials. Studies were pooled using a random effect model, conducting secondary analyses for tuberculin skin test-positive and negative persons. RESULTS: Mean follow-up in trials varied between 0.4 and 3.2 years. Pooling all seven trials, a risk ratio was found for persons treated with isoniazid for developing tuberculosis of 0.58 [95% confidence interval (CI), 0.43-0.80] and 0.94 (95% CI, 0.83-1.07) for death. In groups of tuberculin skin test-positive and negative persons, the risk ratio of tuberculosis was 0.40 (95% CI, 0.24-0.65) and 0.84 (95% CI, 0.54-1.30), respectively, and the difference in the effectiveness of isoniazid versus placebo between these groups was statistically significant (P = 0.03, for the difference of summary estimates). Consistency of results was found across trials (P > 0.10, heterogeneity value) for all comparisons. CONCLUSIONS: Prophylaxis with isoniazid reduces the risk of tuberculosis in persons with HIV infection. The effect is restricted to tuberculin skin test-positive persons.

AIDS-Related Opportunistic Infections

[Post-exposure HIV prevention: eligibility of patients recently infected by sexual exposure].

QUESTION: Post-exposure prophylaxis (PEP) is effective in preventing HIV infection after professional exposure. PEP is also recommended after inadvertent sexual exposure if two conditions are met: the source person is known to be HIV infected, and exposure to this person occurred only once or is accidental. The objective of this study is to describe the circumstances of sexual exposure and determine how frequently these conditions were present among patients diagnosed during primary HIV infection. METHODS: Physicians of 35 patients diagnosed with primary HIV infection provided detailed information on the circumstances of infection as well as on the patients and source persons. RESULTS: Most patients were homosexual (71%), and 91% were male. Only one patient (3%) had a single exposure with a known HIV-infected person and was therefore eligible for PEP. Eight patients (23%) who did not know the HIV status of their partner would have been eligible considering single exposure as a sufficient criterion for PEP. Oro-genital contact appears to account for transmission in four instances. Eleven persons (31%) were infected after sexual contact with their stable partner, of whom 7 did not known his/her HIV status. Twelve patients (34%) were infected after multiple unprotected sexual contact with unknown partners. CONCLUSION: The direct impact of PEP in terms of HIV infections prevented is likely to be small. PEP will not make up for the failure of other prevention methods. It may, however, contribute to the disclosure and the discussion of risk situations and help physicians provide individual counselling taking into account the precise context of risk behavior.

Adult

Prevalence and risk factors for nosocomial infections in four university hospitals in Switzerland.

OBJECTIVE: To determine the prevalence and risk factors for nosocomial infections (NIs) in four Swiss university hospitals. DESIGN AND SETTING: A 1-week period-prevalence survey conducted in May 1996 in medical, surgical, and intensive-care wards of four Swiss university hospitals (900-1,500 beds). Centers for Disease Control and Prevention definitions were used, except that asymptomatic bacteriuria was not categorized as NI. Study variables included patient demographics, primary diagnosis, comorbidities, exposure to medical and surgical risk factors, and use of antimicrobials. Risk factors for NIs were determined using logistic regression with adjustment for length of hospital stay, study center, device use, and patients' comorbidities. RESULTS: 176 NI were recorded in 156 of 1,349 screened patients (11.6%; interhospital range, 9.8%-13.5%). The most frequent NI was surgical-site infection (53; 30%), followed by urinary tract infection (39; 22%), lower respiratory tract infection (27; 15%), and bloodstream infection (23; 13%). Prevalence of NI was higher in critical-care units (25%) than in medical (9%) and surgical wards (12%). Overall, 65% of NIs were culture-proven; the leading pathogens were Enterobacteriaceae (44; 28%), Staphylococcus aureus (20; 13%), Pseudomonas aeruginosa (17; 11%), and Candida species (16; 10%). Independent risk factors for NI were central venous catheter (CVC) use (odds ratio [OR], 3.35; 95% confidence interval [CI95], 2.91-3.80), admission to intensive care (OR, 1.75; CI95, 1.30-2.21), emergency admission (OR, 1.57; CI95, 1.15-2.00), impaired functional status (Karnofsky index 1-4: OR, 2.56; CI95, 1.953.17), and McCabe classification of ultimately fatal (OR, 2.50; CI95, 2.04-2.96) or rapidly fatal (OR, 2.25; CI95, 1.52-2.98) underlying condition. CONCLUSIONS: According to the results of this survey, NIs are frequent in Swiss university hospitals. This investigation confirms the importance of CVCs as a major risk factor for NI. Patient comorbidities must be taken into account to adjust for case mix in any study comparing interhospital or intrahospital infection rates.

Adolescent

Objectives, methods and content of patient education programmes for adults with asthma: systematic review of studies published between 1979 and 1998.

BACKGROUND: Education programmes for adults with asthma vary widely. Such variability suggests a lack of consensus on what works and what does not. The objectives of this paper are to describe asthma education programmes and assess their variability. METHODS: A systematic review of reports published between 1979 and 1998 was conducted. Medline, the CINAHL database, the PsycINFO database, the Cochrane collaboration database, the Dissertation Index database, and cross referencing were used to identify educational interventions; 77 projects including 94 interventions that involved 7953 patients were analysed. A standard form was used to record characteristics of studies (design, setting, size, year, and country of publication), projects (theoretical framework, objectives), and education (methods, duration, intensity, educator, and content). RESULTS: Most reports did not specify the general (56%) and educational objectives (60%) of the intervention. Important training characteristics were often not available: duration of education (45%) and number of sessions (22%), who delivered education (15%), whether training was conducted in groups or was individualised (28%). When this information was available there were wide variations in training methods and content: training duration ranged from 0 (self-education) to 58 hours and the number of sessions from 0 to 36; training tools such as peak flow meters, diary cards or books were used in various proportions of interventions (19%, 27%, and 23%, respectively). The content of education also differed widely between programmes. CONCLUSIONS: Insufficient documentation of asthma education programmes for adults precludes their replication. This, together with excessive variability, reduces the possibility of identifying their most effective components. A more systematic description of asthma training programmes should be promoted.

Adult

Changes in renal function associated with indinavir.

BACKGROUND: Indinavir use is associated with a spectrum of renal and urinary tract complications including nephrolithiasis, renal colic and pain without recognizable lithiasis, and a picture of crystalluria-dysuria. A frank nephropathy has not been recognized as part of the spectrum. METHODS: A retrospective analysis of 106 HIV-infected individuals receiving indinavir was performed with the purpose of identifying the frequency and risk factors for indinavir-associated nephropathy and urinary complications. Individuals receiving ritonavir or nelfinavir served as controls. RESULTS: A sustained elevation of creatinine (>20%, into abnormal range) was identified in 20 (18.6%) subjects treated with indinavir but not with other protease inhibitors. Creatinine elevation was associated with treatment duration of more than 54 weeks [odds ratio (OR), 7.1; 95% confidence interval (CI), 1.8-27.7], low baseline body mass index < or = 20 kg/m2 (OR, 4.0; 95% CI, 1.0-16.6), and use of trimethoprim-sulphamethoxazole (TMP-SMX; OR, 4.6; 95% CI, 1.5-13.8). Lower urinary specific gravity (P = 0.015), and leukocyturia (P<0.001) were frequently associated features of indinavir nephropathy. No patient developed severe renal impairment and abnormalities were reversible upon discontinuation of the drug. Complications (renal colic, or pain and dysuria) occurred after a mean of 36 weeks (95% CI, 23-48) of indinavir treatment in 13 subjects (12.3%), eight of whom (62%) presented elevated creatinine during follow-up. Only long-term exposure to TMP-SMX (>160 weeks) was identified as a potential risk for the occurrence of a clinical event (OR, 4.7; 95% CI, 1.2-19.2). CONCLUSIONS: A crystal nephropathy, characterized by serum creatinine elevation, loss of concentrating ability of the kidney, leukocyturia, and renal parenchymal image abnormalities, is a frequent complication of indinavir therapy. Identification of individuals at risk, particularly those with low body mass index or receiving TMP-SMX prophylaxis, may help the decision to initiate indinavir or chose an alternative protease inhibitor in order to minimize renal and urinary tract adverse events.

Adult

A placebo-controlled trial of didanosine plus stavudine, with and without hydroxyurea, for HIV infection. The Swiss HIV Cohort Study.

OBJECTIVE: To explore the short-term effects on surrogate markers for HIV progression of didanosine (ddl) plus stavudine (d4T), with or without hydroxyurea. DESIGN: Randomized, double-blinded, prospective study. SETTING: Swiss HIV Cohort Study. PATIENTS: A total of 144 patients (75% antiretroviral-naive) were studied (mean baseline HIV-1 RNA, 4.53 log10 copies/ml; mean CD4 cell count, 370 x 10(6)/l). INTERVENTION: Patients received ddl (200 mg twice daily) plus d4T (40 mg twice daily), with additional hydroxyurea (500 mg twice daily) or placebo. MAIN OUTCOME MEASURES: The primary endpoint was a reduction of viraemia below 200 copies/ml after 12 weeks. At that time, patients who did not reach the primary endpoint were withdrawn in the hydroxyurea arm, whereas patients in the placebo group had the option of adding hydroxyurea to ddl and d4T. All patients were followed until week 24. RESULTS: After 12 weeks, 54% of the patients randomized to hydroxyurea had viraemia below 200 copies/ml, compared with 28% on placebo (P < 0.001). Using an ultrasensitive assay with a limit of detection of 20 copies/ml, 19% of patients receiving hydroxyurea had viraemia levels below 20 copies/ml, compared with 8% on placebo (P = 0.05). Mean decrease in HIV-1 RNA was 2.3 and 1.7 log10 copies/ml for hydroxyurea and placebo groups, respectively (P = 0.001). Hydroxyurea was found to induce lymphopenia (-124 x 10(6)/l). Increase in CD4 cell counts was +28 x 10(6)/l during hydroxyurea treatment compared with +107 x 10(6)/l on placebo (P = 0.001). CONCLUSIONS: Hydroxyurea improved the antiviral activity of d4T and ddl over a 12-week period, but was associated with a smaller increase in CD4 cell counts due to hydroxyurea-induced lymphopenia.

Adult

Impact of methicillin resistance on the outcome of patients with bacteremia caused by Staphylococcus aureus.

BACKGROUND: Uncertainties remain about the contribution of methicillin resistance to morbidity and mortality associated with bacteremia caused by Staphylococcus aureus. OBJECTIVE: To assess the impact of methicillin resistance on patient outcome after staphylococcal bacteremia. METHODS: We investigated a cohort of 145 patients with methicillin-sensitive S aureus bloodstream infection (MSSA BSI) and 39 patients with methicillin-resistant S aureus bloodstream infection (MRSA BSI) and further performed a pairwise-matched (1:1) case-control study. All patients in the University Hospital of Geneva, Geneva, Switzerland, with clinically significant staphylococcal bacteremia between January 1, 1994, and December 31, 1995, were included in the study. For the case-control study, cases were defined as patients with MRSA BSI; control patients with MSSA BSI were selected in a stepwise manner according to the following matching variables: age, sex, number of comorbidities, severity of underlying illness, and prior length of stay in the hospital. Matching was successful for 97% of the cohort. MAIN OUTCOME MEASURE: The in-hospital mortality after staphylococcal bacteremia. RESULTS: In the population-based study, the relative hazard of death among patients with MRSA BSI (n = 39, 14 deaths, 36% fatality rate) compared with patients with MSSA BSI (n = 145, 40 deaths, 28% fatality rate) was 1.1 (95% confidence interval, 0.5-2.1), after adjusting for age and length of stay from admission to the onset of bloodstream infection. Following pairwise matching (n = 38), the in-hospital mortality was 34% in both groups (odds ratio, 1.0; 95% confidence interval, 0.4-2.5). Infection was the probable or definite cause of death in 54% of patients with MRSA BSI and 69% of patients with MSSA BSI who died. CONCLUSION: Methicillin resistance in patients with S aureus bacteremia had no significant impact on patient outcome as measured by in-hospital mortality after adjustment was made for major confounders.

Adult

A randomized double-blind controlled study of 6 months of oral nutritional supplementation with arginine and omega-3 fatty acids in HIV-infected patients. Swiss HIV Cohort Study.

OBJECTIVE: To evaluate the effects of an oral nutritional supplement enriched with two potentially immunostimulant compounds (arginine and omega-3 fatty acids) on the changes in food intake, body composition, immune parameters and viraemia in HIV-infected outpatients. DESIGN: Six-month prospective randomized double-blind controlled study. SETTING: University hospital outpatient nutrition clinic. PATIENTS: Sixty-four HIV-infected outpatients with CD4 lymphocyte count > or = 10O x 10(6)/l. INTERVENTION: All patients received a daily oral nutritional supplement (606 kcal supplemented with vitamins, trace elements and minerals). In addition, half of the patients were randomized to receive 7.4 g arginine plus 1.7 g omega-3 fatty acids. MAIN OUTCOME MEASURES: Disease progression measured by AIDS-defining events, CD4 and CD8 lymphocyte counts, viraemia, tumour necrosis factor soluble receptors, nutritional status determined by anthropometric, bioelectrical impedance and dietetic assessment. RESULTS: Fifty-five patients completed the protocol. Compliance with and tolerance of oral nutritional supplement during the 6-month period was excellent. In both groups of patients the following were found: total energy intake was transiently increased and then returned to baseline level; nitrogen/energy intake ratio was increased throughout the study; gain of body weight and fat mass were approximately 2 and 1kg, respectively, over 6 months, and were similar in both groups. In addition, CD4 and CD8 lymphocyte counts, viraemia, tumour necrosis factor soluble receptors remained statistically unchanged and were similar in both groups. CONCLUSIONS: Enrichment of an oral nutritive supplement with arginine and omega-3 fatty acids did not improve immunological parameters. However, body weight increased in both groups.

Acquired Immunodeficiency Syndrome

[National reference centers for surveillance of infectious diseases in Switzerland: results of a delphi study].

The national reference laboratories are one of the tools used by public health authorities to control infectious diseases. The Swiss Confederation supports 9 national reference centers (NC), each dealing with a limited number of infectious agents. The purpose of this study was to evaluate if this network meets present day needs, whether it has to be redefined, and how it can be improved. Using the Delphi technique, 34 experts in the field of infectious diseases were questioned to establish a concept for NC in Switzerland. The main result of this study is that official reference laboratories are considered necessary. However, depending on the type of infectious agent, the following types of laboratories should be used: national reference centers, specialized laboratories and laboratories abroad. The study also defined criteria for the designation of NC, their field of action (general objectives, tasks, duration of the mandate, infectious agent to be monitored), evaluation criteria, and the type of funding. Furthermore, possible improvements in the present system were identified and the establishment of good collaborations with reference centers abroad was proposed.

Communicable Diseases

Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study. Swiss HIV Cohort Study.

OBJECTIVES: To examine trends in disease progression and survival among patients enrolled in the Swiss HIV cohort study during 1988-96 and to assess the influence of new antiretroviral combination therapies. DESIGN: Prospective multicentre study, with follow up visits planned at six monthly intervals. SETTING: Seven HIV units at university centres and cantonal hospitals in Switzerland. PATIENTS: 3785 men (mean age 35.0 years) and 1391 women (30.3 years) infected with HIV. 2023 participants had a history of intravenous drug misuse; 1764 were men who had sex with men; 1261 were infected heterosexually; and 164 had other or unknown modes of transmission. 601 participants had had an AIDS defining illness. RESULTS: During more than 15,000 years of follow up, there were 1456 first AIDS defining diagnoses and 1903 deaths. Compared with those enrolled during 1988-90, the risk of progression to a first AIDS diagnosis was reduced by 18% (relative risk 0.82 (95% confidence interval 0.73 to 0.93)) among participants enrolled in 1991-2, by 23% (0.77 (0.65 to 0.91)) among those enrolled in 1993-4, and by 73% (0.27 (0.18 to 0.39)) among those enrolled in 1995-6. Mortality was reduced by 19% (0.81 (0.73 to 0.90)), 26% (0.74 (0.63 to 0.87)), and 62% (0.38 (0.25 to 0.97)) respectively. Compared with no antiretroviral treatment, the risk of an initial AIDS diagnosis after CD4 lymphocyte counts fell to < 200 cells x 10(6)/1 was reduced by 16% (0.84 (0.73 to 0.97)) with monotherapy, 24% (0.76 (0.63 to 0.91)) with dual therapy, and 42% (0.58 (0.37 to 0.92)) with triple therapy. Mortality was reduced by 23% (0.77 (0.68 to 0.88)), 31% (0.69 (0.60 to 0.80)), and 65% (0.35 (0.20 to 0.60)) respectively. CONCLUSIONS: The introduction of antiretroviral combination therapies outside the selected patient groups included in clinical trials has led to comparable reductions in disease progression and mortality.

Acquired Immunodeficiency Syndrome

Cytomegalovirus retinitis: decreased risk of bilaterality with increased use of systemic treatment. Swiss HIV Cohort Study Group.

Cytomegalovirus (CMV) retinitis may be treated systemically or intravitreally. We reviewed retrospectively patients with CMV retinitis, in order to determine whether systemic treatment was associated with less spread of CMV retinitis from one eye to the other. Of 222 cases, 92 patients had bilateral disease at onset of CMV retinitis, leaving 130 for analysis. Bilaterality occurred in 10 patients during 12,687 days of systemic treatment and in 34 during 14,791 days without systemic treatment (odds ratio [OR] = 2.92; confidence interval [CI], 1.44-5.90). Patients who had received systemic treatment for <50% of the follow-up period had a greater risk of bilaterality (OR = 3.7; CI, 2.79-4.54) than did the more intensively treated patients. CD4 cell levels also contributed to increased risk, but multivariate analysis showed that CD4 cell counts and treatment intensity were independent risk factors. CMV retinitis was more likely to become bilateral in patients who received less intravenous therapy. Local treatment can complete but does not replace systemically administered therapy.

Adult

[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