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Biomedical subjects

B Hirschel

Publications and source records attributed to B Hirschel.

At least 55 records · Page 3Linked to original sources
PubMed2000

Delavirdine in combination with zidovudine in treatment of human immunodeficiency virus type 1-infected patients: evaluation of efficacy and emergence of viral resistance in a randomized, comparative phase III trial. The M/3331/0013B Study Group.

We compared the activity of delavirdine (DLV) plus zidovudine (AZT) (n = 300) with that of AZT (n = 297) against human immunodeficiency virus type 1 in a randomized, double-blind, placebo-controlled trial. DLV exerted a transient antiviral effect, and mutations for resistance to DLV were found in more than 90% of subjects at week 12. The K103N mutation, which confers nonnucleoside reverse transcriptase inhibitor cross-resistance, was found in 85% of the patients.

Anti-HIV Agents↗
PubMed2000

[Symptoms and clinical and radiological signs predicting the bacterial origin of acute rhinosinusitis].

A minority of patients with common cold and upper respiratory tract infections have a bacterial infection and may benefit from antibiotic therapy. The present analysis set out to determine whether there were clinical symptoms or signs which could help the clinician to identify a subset of patients with moderate forms of acute rhinosinusitis who are infected with pathogenic bacteria. Detailed clinical history and medical examination were obtained from 265 patients (mean age 35 years, 138 females and 127 males) presenting symptoms of upper respiratory tract infections but no fever above 38 degrees C. The presence of three pathogenic bacteria (S. pneumoniae, H. influenzae or M. catarrhalis) was determined in all patients by culture of nasopharyngeal secretions. Aggravating factors for severity of rhinosinusitis, such as severe nasal obstruction, inferior and/or middle turbinate hypertrophy, oedema of the middle meatus mucosa and septal defects, were not associated with the presence of bacteria. Pathogenic bacteria were found in 77 patients (29%). The clinical signs and symptoms which were significantly associated in a multivariate model with the presence of bacteria included facial pain (p < 0.003), coloured nasal discharge (p < 0.003) and radiological maxillary sinusitis (complete opacity, air-fluid level or mucosal thickening greater than 10 mm) (p < 0.002). This, the best predictive model, had a sensitivity of 69% and a specificity of 64% and therefore could not be used either as a screening tool or as a diagnostic criterion for bacterial rhinosinusitis. We conclude that signs and symptoms of acute rhinosinusitis in patients with a mild to moderate clinical presentation are poor predictors of the presence of bacteria. In agreement with previous studies, culture of nasopharyngeal secretions may identify patients who would benefit from antibiotic treatment. Thus, antibiotic therapy should not be prescribed in the absence of bacteriological evidence.

Adolescent↗
PubMed1999

AIDS-related opportunistic illnesses occurring after initiation of potent antiretroviral therapy: the Swiss HIV Cohort Study.

CONTEXT: Acquired immunodeficiency syndrome-related opportunistic illnesses (Ols) continue to occur after initiation of potent antiretroviral therapy in patients with human immunodeficiency virus (HIV) infection. Risk factors for clinical progression to Ols during potent therapy are not well defined. OBJECTIVE: To examine the incidence of and risk factors for Ols among patients treated with potent antiretroviral therapy in a population-based study. DESIGN: The Swiss HIV Cohort Study, a prospective cohort study of adult HIV-infected persons. SETTING: Seven study centers throughout Switzerland. PATIENTS: A total of 2410 cohort study participants with a potential follow-up of at least 15 months after starting potent therapy between September 1995 and December 1997. MAIN OUTCOME MEASURES: Disease-specific incidence of Ols during the 6 months preceding potent antiretroviral therapy and at 3 intervals after initiating therapy; risk factors for development of Ols during therapy. RESULTS: Of the 2410 participants, 143 developed 186 Ols after initiation of potent antiretroviral therapy. Incidence of any OI decreased from 15.1 per 100 person-years in the 6 months before therapy to 7.7 in the first 3 months after starting treatment, 2.6 in the following 6 months, and 2.2 per 100 person-years between 9 and 15 months. Reductions in incidence ranged from 38% per month for Kaposi sarcoma (P<.001) to 5% per month for non-Hodgkin lymphoma (P = .31). Baseline CD4 cell count continued to predict the risk of disease progression after initiating potent therapy. Compared with CD4 cell counts above 200 x 10(6)/L, the hazard ratio for developing Ols was 2.5 (95% confidence interval [CI], 1.4-4.5) for counts between 51 and 200 x 10(6)/L and 5.8 (95% CI, 3.2-10.5) for counts below 51 x 10(6)/L at baseline. Independent of baseline CD4 cell count, a rise in CD4 cell count by 50 x 10(6)/L or more and undetectable HIV-1 RNA in plasma (<400 copies/mL) by 6 months reduced risk of subsequent events, with hazard ratios of 0.32 (95% CI, 0.20-0.52) and 0.39 (0.24-0.65), respectively. CONCLUSIONS: Our data indicate that the risk of developing an OI for a person receiving potent antiretroviral therapy is highest during the initial months of therapy. Baseline CD4 cell count and immunologic and virologic response to treatment were strong predictors of disease progression in patients receiving potent therapy. Individuals with CD4 cell counts of 50 x 10(6)/L or below may need close clinical surveillance after initiation of potent therapy.

AIDS-Related Opportunistic Infections↗
PubMed1999

Comprehensive classification of symptoms and signs reported among 218 patients with acute HIV-1 infection.

Acute HIV-1 illness presents a wide range of clinical manifestations. We assessed a classification and data reduction of clinical features among 218 patients with acute HIV-1 infection enrolled in four prospective seroincidence studies. Factor analysis allows the definition of eight factors based on groups of symptoms and signs: gastrointestinal transit disturbances, weight loss/abdominal pain, lymphadenopathy, myalgia/arthralgia, neurologic features, constitutional and mucocutaneous features, oral candidiasis, and anorexia/pharyngitis. These groups reflected the main target systems involved at the time of acute HIV-1 disease. Grouping of symptoms and signs based on groups of patients is potentially more informative than observations made on individual patients. It might facilitate diagnosis, suggest pathogenic mechanisms and reduce the number of variables for characterizing acute HIV-1 illness.

Acute Disease↗
PubMed1999

Discontinuation of primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1-infected adults treated with combination antiretroviral therapy. Swiss HIV Cohort Study.

BACKGROUND: It is unclear whether primary prophylaxis against Pneumocystis carinii pneumonia can be discontinued in patients infected with the human immunodeficiency virus (HIV) who are successfully treated with combination antiretroviral therapy. We prospectively studied the safety of stopping prophylaxis among patients in the Swiss HIV Cohort Study. METHODS: Patients were eligible for our study if their CD4 counts had increased to at least 200 cells per cubic millimeter and 14 percent of total lymphocytes while they were receiving combination antiretroviral therapy, with these levels sustained for at least 12 weeks. Prophylaxis was stopped at study entry, and patients were examined every three months thereafter. The development of P. carinii pneumonia was the primary end point, and the development of toxoplasmic encephalitis the secondary end point. RESULTS: Of the 262 patients included in our analysis, 121 (46.2 percent) were positive for IgG antibodies to Toxoplasma gondii at base line. The median CD4 count at study entry was 325 per cubic millimeter (range, 210 to 806); the median nadir CD4 count was 110 per cubic millimeter (range, 0 to 240). During a median follow-up of 11.3 months (range, 3.0 to 18.8), prophylaxis was resumed in nine patients, and two patients died. There were no cases of P. carinii pneumonia or toxoplasmic encephalitis. The one-sided upper 99 percent confidence limit for the incidence of P. carinii pneumonia was 1.9 cases per 100 patient-years (based on 238 patient-years of follow-up). The corresponding figure for toxoplasmic encephalitis was 4.2 per 100 patient-years (based on 110 patient-years of follow-up). CONCLUSIONS: Stopping primary prophylaxis against P. carinii pneumonia appears to be safe in HIV-infected patients who are receiving combination antiretroviral treatment and who have had a sustained increase in their CD4 counts to at least 200 cells per cubic millimeter and to at least 14 percent of total lymphocytes.

AIDS-Related Opportunistic Infections↗
PubMed1999

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↗
PubMed1999

Impact of drug resistance mutations on virologic response to salvage therapy. Swiss HIV Cohort Study.

OBJECTIVE: To assess the prognostic significance of drug-associated mutations in the protease and reverse transcriptase (RT) genes on virological response to salvage therapy. PATIENTS: All patients from four centres of the Swiss HIV Cohort Study who were switched, between February and October 1997, to nelfinavir plus other antiretroviral drugs following failure of highly active antiretroviral therapy (HIV-1 RNA >1000 copies/ml after > 3 months). METHODS: Direct sequencing of RT and protease genes derived from plasma RNA was performed in 62 patients before salvage therapy. Baseline predictors (drug-resistance mutations, drug exposure, clinical and biological parameters) of virological response after 4-12 weeks of therapy were assessed by linear regression analyses. RESULTS: Patients had been treated with RT inhibitors and protease inhibitors for a median duration of 35.6 and 12.2 months, respectively. Baseline median CD4 cell count was 113 x 10(6)/l and HIV-1 RNA 5.16 log10 copies/ml. The median decrease of HIV-1 RNA was 0.38 log10; 32% of the patients showed > 1 log10 decrease. At baseline, 90% of the patients had RT inhibitor-resistance mutations with a median number per patient of four (range, 0-7). Primary and secondary protease inhibitor-resistance mutations were detected in 69% and 89% of the patients, respectively. The median number of total protease inhibitor-resistance mutations per patient was four (range, 0-9). In univariate analysis, virological response to salvage therapy was associated with number of RT inhibitors, primary and secondary protease inhibitor-resistance mutations, history of protease inhibitor use (duration and number), but not with clinical stage, HIV-1 RNA level or CD4 cell count. After adjustment for all variables, the number of RT inhibitor plus protease inhibitor-resistance mutations was the only independent predictor. CONCLUSIONS: In patients with advanced HIV infection, the virological response to salvage therapy containing nelfinavir is best predicted by the number of baseline RT inhibitor plus protease inhibitor-resistance mutations.

Anti-HIV Agents↗
PubMed1999

Blood and charcoal added to acidified agar media promote the growth of Mycobacterium genavense.

Ten different agar media were tested for the in vitro growth of Mycobacterium genavense in primary cultures and in subcultures from BACTEC vials. These agar media were based on Middlebrook 7H9, 7H10 and 7H11, and supplemented with additives: mycobactin J, yeast extract, charcoal, or defibrinated sheep blood. Some media were acidified with phosphoric acid to a final pH of 6.2 +/- 0.2. Fourteen M. genavense strains from nude mouse organs as well as one decontaminated clinical specimen (from a bird) were tested. The optimal medium for primary cultures of M. genavense was Middlebrook 7H11 acidified to pH 6.2 +/- 0.2 and supplemented with charcoal and sheep blood: on this medium, all strains produced colonies within 6-12 weeks of incubation in numbers approaching the number of bacilli inoculated. It was also the only medium to support the growth of the decontaminated clinical specimen. Added blood and charcoal appeared not as essential for subcultures as for primary cultures. Three media supported the growth of all strains within 1 month incubation: they were acidified, and were supplemented with yeast extract or pancreatic digest of casein, and with either blood or charcoal.

AIDS-Related Opportunistic Infections↗
PubMed1999

Cell-associated HIV-1 RNA in blood as indicator of virus load in lymph nodes. The Swiss HIV Cohort Study.

We have developed sensitive assays for viremia and cell-associated human immunodeficiency virus type 1 (HIV-1) RNA and DNA to assess the predictive value of virological parameters determined in blood for virus load in lymph nodes (LNs). Eighteen patients were included; 13 received stavudine/didanosine/hydroxyurea and 5 stavudine/didanosine, and all had viremia <500 copies/mL for >3 months. At the time of LN biopsy (median, 10 months), the median viremia was 2.09 log copies/mL (range, <0.70-3.34). Cell-associated HIV-1 RNA and DNA were detectable in blood and LNs of all patients. The median cell-associated RNA and DNA were 2.16 log copies/106 cells and 2.60 log copies/106 cells in blood versus 4.31 log RNA copies/106 cells and 3.26 log DNA copies/106 cells in LNs. Regression analysis shows that, in treated patients with sustained low viremia, cell-associated RNA and DNA in blood are better predictors of virus load in LNs than viremia.

Acquired Immunodeficiency Syndrome↗
PubMed1999

A randomized, controlled trial of indinavir, zidovudine, and lamivudine in adults with advanced human immunodeficiency virus type 1 infection and prior antiretroviral therapy.

A randomized, double-blind, multicenter study of indinavir, zidovudine, and lamivudine was conducted in 320 adults with human immunodeficiency virus type 1 (HIV-1) infection, </=50 CD4 cells/mm3, and extensive prior zidovudine therapy. Patients received indinavir, 800 mg every 8 h; zidovudine, 200 mg every 8 h, and lamivudine, 150 mg twice daily; or all 3 drugs for 24 weeks. In an intention-to-treat analysis, proportions of patients with HIV-1 RNA <500 and <50 copies/mL, respectively, at week 24 were 56% and 45% in the indinavir-zidovudine-lamivudine group, 3% and 2% in the indinavir group, and 0% in the zidovudine-lamivudine group. Observed mean CD4 cell increases were 95, 78, and 6 cells/mm3 in the three-, one-, and two-drug arms, respectively. Regimens were generally well tolerated. Patients with advanced HIV-1 infection benefit from triple therapy with indinavir, zidovudine, and lamivudine, although the proportion with optimal response appeared to be lower in patients with low CD4 cell counts.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Association between the rate of CD4+ T cell decrease and the year of human immunodeficiency virus (HIV) type 1 seroconversion among persons enrolled in the Swiss HIV cohort study.

The aim of this study was to investigate the early CD4+ T cell response among human immunodeficiency virus type 1 (HIV-1) seroconverters in relation to their year of seroconversion. Study participants were enrolled in the Swiss HIV Cohort Study between 1985 and 1995 and had not received antiretroviral treatment. The slope of the CD4+ T cell count within 2 years after seroconversion was significantly associated with the year of seroconversion, by sex and by use of injection drugs, when controlling for initial CD4+ cell count. These results show that the loss of CD4+ cells might be associated with the year of seroconversion, suggesting a change in the pathogenesis of HIV across the years. If these results are confirmed, they could have important implications for the pathogenesis of and therapeutic strategies for HIV-1 infection.

Adolescent↗
PubMed1999

Detection of mycobacterial nucleic acids by polymerase chain reaction in fixed tissue specimens of patients with human immunodeficiency virus infection. Swiss HIV Cohort Study.

A polymerase chain reaction (PCR) method, which amplifies a fragment of the 16S ribosomal RNA (rRNA) gene present in all mycobacterial species, was developed and tested on 84 formalin-fixed paraffin-embedded tissue specimens from 51 patients with human immunodeficiency (HIV) infection. The PCR products were characterized either by sequencing or by hybridization with nonradioactive oligonucleotide probes specific for Mycobacterium tuberculosis complex, M. avium, or M. genavense. Sequencing was successful for 26 samples compared with the 45 samples for probe hybridization. The sensitivity of DNA amplification compared with microscopic examination was 79.5%. A mixed infection was detected with M. genavense for only one patient who was infected with M. tuberculosis complex. In the group of 22 control patients, where no diagnosis of mycobacterial infection was made during life and no acid-fast bacteria were seen during the autopsy, four samples of one patient were positive by hybridization with the M. tuberculosis probe. This patient had a clinical history compatible with tuberculosis. This PCR method may be a powerful tool for the precise diagnosis of mycobacterial infections from histopathologic material, provided that several sections from the same specimen block are tested.

AIDS-Related Opportunistic Infections↗
PubMed1999

A randomized trial of interferon-alpha2a and zidovudine versus bleomycin and zidovudine for AIDS-related Kaposi's sarcoma. Swiss HIV Cohort Study.

The efficacy and toxicity of interferon-alpha2a (9MU/d) and bleomycin (15 mg every 2 weeks), each combined with zidovudine (2x250 mg/d), was compared in a randomized study in 26 men with progressing AIDS-related Kaposi's sarcoma (KS). The median CD4 count was 113/microl. Complete or partial response was achieved in one (8%) of 12 evaluable patients on interferon and in 2 (20%) of 10 patients on bleomycin (P = 0.43) during 4.7 and 5.3 months of treatment, respectively. The tolerability was comparable. During extended follow up, survival time was 24 and 13 months in the interferon and bleomycin arm, respectively. In a multivariate Cox regression analysis, CD4 lymphocytes <200/microl (relative risk 3.74; 95% CI: 1.30-10.8) and randomization to interferon (relative risk 0.37; 95% CI: 0.15-0.90) were significantly predictive of mortality. New AIDS-related events occurred more frequently in patients who had received bleomycin. The antiviral activity of interferon-alpha or the chemotherapy-mediated increase in the risk for opportunistic infections may explain these differences.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Antiretroviral therapies in pregnancy: maternal, fetal and neonatal effects. Swiss HIV Cohort Study, the Swiss Collaborative HIV and Pregnancy Study, and the Swiss Neonatal HIV Study.

BACKGROUND: Therapies containing two reverse transcriptase inhibitors (RTI) with or without protease inhibitors are used with increasing frequency in pregnant HIV-infected women. OBJECTIVE: To assess the safety of antiretroviral therapy in pregnant women and their newborns. METHODS: All clinical events and laboratory abnormalities in pregnant women on RTI with or without protease inhibitors and in their newborns were collected through an observational study. RESULTS: A total of 37 HIV-infected pregnant women have given birth to 30 children (by 30 April 1998). All received RTI, which were combined with protease inhibitors in 16 cases. Twelve women became pregnant while on treatment. Drugs used were as follows: zidovudine (n = 33), lamivudine (n = 33), stavudine (n = 4), indinavir (n = 9), ritonavir (n = 4), nelfinavir (n = 2) and saquinavir (n = 2). Adverse events during pregnancy were anaemia (n = 15), elevation of transaminases (n = 4), nausea/vomiting (n = 4), glucose intolerance (n = 2), nephrolithiasis (n = 2), diarrhoea (n = 2), hypertension (n = 1), insulin-requiring diabetes (n = 1). Adverse events in neonates were prematurity (n = 10), anaemia (n = 8), cutaneous angioma (n = 2), cryptorchidism (n = 2), transient hepatitis (n = 1). Non-life-threatening intracerebral haemorrhage occurred in a premature baby (33 weeks gestation) exposed during fetal life to zidovudine-lamivudine-indinavir, and in a term baby exposed to stavudine-lamivudine-indinavir. Extrahepatic biliary atresia occurred in one newborn exposed to zidovudine-lamivudine-indinavir. Maternal viral load was below 400 copies/ml in 18 out of 30 patients who delivered. One case of mother-to-child HIV transmission was identified. CONCLUSIONS: In HIV-infected pregnant women treated with two RTI with or without protease inhibitors, one or more adverse events occurred in 29 out of 37 women and in 14 out of 30 babies. In newborns, frequent prematurity, one case of biliary malformation and one intracerebral haemorrhage in a term baby are of concern. These observations do not preclude combination therapies during pregnancy but emphasize the necessity to maintain updated registers on their safety.

Anti-HIV Agents↗
PubMed1998

Prevalence and incidence rate of HIV, hepatitis B and C among drug users on methadone maintenance treatment in Geneva between 1988 and 1995.

OBJECTIVES: To evaluate the prevalence and incidence rates of infection with HIV, hepatitis B (HBV) and hepatitis C (HCV), in a cohort of drug users (DU) in Geneva, Switzerland. DESIGN: Prospective open cohort study. SETTING: Private methadone maintenance treatment (MMT) programme. PATIENTS, PARTICIPANTS: Over 700 DU in treatment between 1988 and 1995 were tested biannually for HIV, HBV and HCV infection. INTERVENTION: None. MAIN OUTCOME MEASURE: Prevalence for HIV, HBV and HCV at study entry, determined by gender, by injection behaviour, by year of start of MMT and incidence rates for HIV, HBV and HCV, assuming equal risk of seroconversion on each day of the interval between last negative and first positive test. RESULTS: The prevalence at entry into treatment declined dramatically over time for all three viruses. Comparing DU entering treatment before 1988 to those entering treatment after 1993, the prevalence of HIV was 38.2% versus 4.5%, of HBV 80.5% versus 20.1%, and of HCV 91.6% versus 29.8%, respectively. Follow-up rate was 80%. The incidence rates for HIV and HBV were 0.6% and 2.1% per person-year of follow-up, respectively. For HCV the rate was higher (4.2%) especially among women (9.6%). CONCLUSION: These data suggest that DU have changed HIV risk-taking behaviour in response to HIV prevention campaigns. Current prevention efforts should focus on improvement of HCV prevention, identification of high-risk individuals and maintaining safe behaviour.

Cohort Studies↗