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Biomedical subjects

B Hirschel

Publications and source records attributed to B Hirschel.

At least 91 records · Page 5Linked to original sources
PubMed1997

Genetic polymorphism of CCR5 gene and HIV disease: the heterozygous (CCR5/delta ccr5) genotype is neither essential nor sufficient for protection against disease progression. Swiss HIV Cohort.

Homozygous (delta ccr5/delta ccr5) and heterozygous (CCR5/delta ccr5) deletions in the beta-chemokine receptor 5 (CCR5) gene, which encodes for the major co-receptor for macrophage-tropic HIV-1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/delta ccr5 genotype was found more frequently in long-term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p < 0.0001), in agreement with previous studies. Kaplan-Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4+ T cell counts > 500/microl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/delta ccr5 genotype. However, when LTNP were analyzed separately, no significant differences in CD4+ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild-type (69% of LTNP) and the heterozygous (31.0%) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/delta ccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/delta ccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.

HIV Infections↗
PubMed1997

Duration of hospitalization during the first two years after AIDS diagnosis: a descriptive study.

Has there been a change in the duration of periods of hospitalization during the first two years after diagnosis of AIDS between patients diagnosed before 1988, compared with patients diagnosed since 1988? A cohort of 212 AIDS patients was studied. They were diagnosed before December 31, 1990 and were hospitalized between January 1, 1981 and March 31, 1993 in the University Hospital of Geneva, Switzerland. Overall, the duration of hospitalization did not seem to differ according to the year of AIDS diagnosis, though the more recently diagnosed patients were hospitalized with a more advanced level of immunosuppression. However, the pattern of hospitalization was slightly different. The periods of hospitalization for subjects diagnosed before 1988 were relatively longer soon after the AIDS diagnosis and at a late stage in the course of the disease, whereas for the more recent patients the lengths of hospital stays were more uniform during the whole course of the disease.

Acquired Immunodeficiency Syndrome↗
PubMed1997

[Effect of antiretroviral treatment on early electroencephalographic and otoneurologic manifestations in HIV infection and prognostic importance of verified perturbations].

Electrophysiologic tests may be abnormal in asymptomatic HIV-1-infected individuals. Our study was aimed at determining whether these findings have a prognostic value and could be corrected by antiviral treatment. In 18 patients, followed for 34 or 43 months, these findings were not progressive. Only one patient developed Aids dementia complex (ADC). Three have died (one with normal, two with abnormal tests at baseline). To study the effect of antiviral treatment, another group of seven asymptomatic patients was included into a cross-over double-blind study with either eight weeks zidovudine or eight weeks placebo, separated by eight more weeks without treatment. Electrophysiological evaluation was also performed in a group of 15 patients before antiviral therapy with zidovudine or didanosine was started and again after a mean of three and 13 months treatment. Results did not suggest that treatment reverses early electroencephalographic and otoneurological changes seen in HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1997

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↗
PubMed1997

Acute human immunodeficiency virus type 1 disease as a mononucleosis-like illness: is the diagnosis too restrictive?

The purpose of this study was to describe the frequency and duration of clinical features at the time of acute human immunodeficiency virus type 1 (HIV-1) disease in 218 patients with documented symptomatic primary HIV-1 infection. The mean duration of acute HIV-1 disease was 25.1 days (median, 20.0 days) and did not differ by gender, age, and risk factor. The frequency and mean duration of clinical features occurring in >50% of patients were as follows: fever, 77.1% and 16.9 days; lethargy, 65.6% and 23.7 days; cutaneous rash, 56.4% and 15 days; myalgia, 54.6% and 17.7 days; and headache, 50.9% and 25.8 days. Only 15.6% of patients presented with a typical mononucleosis-like illness (MLI) defined as fever, pharyngitis or sore throat, and cervical adenopathy, and 10% had no features of an MLI. A meningitis-like syndrome occurred in 20 patients (9.2%). Acute HIV-1 disease is more diverse than previously reported, and the absence of fever or other MLI features does not rule out acute HIV-1 disease.

Acute Disease↗
PubMed1997

Toxicity, efficacy, plasma drug concentrations and protease mutations in patients with advanced HIV infection treated with ritonavir plus saquinavir. Swiss HIV Cohort Study.

OBJECTIVE: To assess the safety, efficacy and plasma drug levels of the combination of ritonavir plus saquinavir for the treatment of advanced HIV infection. DESIGN: Multicentre pilot study. PATIENTS: Eighteen protease inhibitor-naive patients, with intolerance or contraindication to reverse transcriptase inhibitors, a median CD4 cell count of 12 x 10(6)/l (range, 1-50 x 10(6)/l), and a median HIV viraemia of 5.25 log10 copies/ml (range, 4.00-6.13 log10 copies/ml). METHODS: Patients received 600 mg twice daily of both ritonavir and saquinavir. Viraemia was measured at baseline and at weeks 5, 9 and 13. Response was defined as a drop of viraemia of more than 1 log10 at week 5. Plasma drug levels were determined after at least 3 weeks of combined treatment: samples were collected before and 1, 2, and 4 h after the morning ingestion of both drugs. The protease gene was sequenced at baseline and under treatment. RESULTS: Among the 16 patients evaluable at week 5, 11 were responders, and among these patients, six remained responders at week 13 (two with undetectable viraemia). Study discontinuations were due to side-effects (n = 4), patient choice (n = 3), protocol violation (n = 1) and death (n = 1). Responders had higher drug levels than non-responders (P < 0.01 for saquinavir, P = 0.04 for ritonavir). In two non-responders, development of multiple new mutations at positions 10, 20, 48, 82, 84 and 90 was observed after 5-13 weeks. CONCLUSION: The response to ritonavir plus saquinavir in advanced HIV infection is unpredictable. A minority of patients respond with disappearance of HIV viraemia. In other patients, rapid cumulative emergence of protease mutations conferring resistance to treatment cannot always be prevented by good compliance and relatively high plasma drug levels.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Inhibitory effects of polyoxyethylene stearate, PANTA, and neutral pH on growth of Mycobacterium genavense in BACTEC primary cultures.

We report on the influences of polyoxyethylene stearate (POES), PANTA, and pH on primary cultures of Mycobacterium genavense in BACTEC vials. As a model for primary cultures from tissue, seven different strains first isolated from AIDS patients (five from Switzerland and two from the United States) were inoculated into nude mice in order to obtain large amounts of bacilli to test different conditions simultaneously. Our results demonstrate that the size of the inoculum (10[6] acid-fast bacilli/vial), an acid pH (pH 6.0), and the absence of additives (POES and PANTA) significantly (P < 0.001) increased the probability of a successful culture in 1 month, considering growth index (GI) of > or =100 or a GI of > or =999 as criterion of success. In logistic regression analysis, all factors maintained a significant (P < 0.001) independent effect, and no interactions were observed between them. The best conditions for the primary cultures of M. genavense were the use of Middlebrook 7H12 medium at pH 6.0 without any additives.

AIDS-Related Opportunistic Infections↗
PubMed1997

HIV-associated primary pulmonary hypertension. A case control study. Swiss HIV Cohort Study.

To assess the clinical and echocardiographic time course, prognosis, and possible etiology of HIV-associated primary pulmonary hypertension (PPH), we prospectively followed all 19 patients in whom PPH was diagnosed in our centers. Women (12 cases) and injecting drug use (16 cases) predominated; the median CD4 lymphocytes count was 83/microliter (range, 1 to 740). Matched control subjects without PPH were identified within the Swiss HIV Cohort Study. Frozen serum samples of both groups were then reanalyzed for autoimmune parameters, neopterin, beta-2-microglobulin, and thyroid-stimulating hormone. The median follow up of the patients was 1.3 yr. Follow-up Doppler echocardiography was available in 13 patients. The RVSP-RAP pressure gradient decreased by 3.2 mm Hg for those six patients who received antiretroviral treatment but increased by 19.0 mm Hg for untreated patients (p = 0.026). PPH was the cause of eight of 17 deaths. The probability of surviving was significantly decreased in patients with PPH in comparison with the control subjects; the median survival was 1.3 versus 2.6 yr (p < 0.05). Patients with PPH had significantly higher anticardiolipin IgM, anti SS-B, and neopterin, but all other laboratory values did not differ between cases and control subjects. In conclusion, HIV-associated PPH contributed significantly to mortality. Antiretroviral treatment may exert a beneficial effect on the pressure gradient. A possible role of an autoimmune phenomenon in the pathogenesis could not be substantiated.

Adult↗
PubMed1997

Zidovudine plus didanosine in primary HIV-1 infection.

Viraemia levels in the months following primary HIV-1 infection (PHI) predict the subsequent course of the infection. Inhibition of viral replication in PHI patients might improve their clinical prognosis. In this study, we evaluated the antiviral efficacy of the association of two reverse transcriptase inhibitors--zidovudine at 250 mg twice daily and didanosine at 200 mg twice daily--in 12 patients treated for at least 6 months (median 10 months, range 6-15 months). We compared values for viraemia, proviral DNA and CD4:CD8 ratios in these patients with two historical control groups consisting of 16 untreated patients and 15 patients on zidovudine therapy. Significantly lower viraemia was observed between 3 and 12 months in patients on zidovudine-didanosine therapy. Viraemia levels lower than 200 HIV-1 RNA copies/ml were observed in 3/12 patients on zidovudine-didanosine therapy after 3 months, in 8/12 after 6 months and in 3/5 after 12 months. Only one of the 31 historical control patients had undetectable viraemia. For proviral DNA, smaller differences between groups were observed, although with time proviral DNA became undetectable (< 1 copy/7.5 x 10(5) lymphocytes) in four patients from the zidovudine-didanosine group versus one in the control groups. Finally, the CD4:CD8 ratio was significantly higher in the zidovudine-didanosine group and none of the patients in this group developed HIV-1-associated clinical complications. These data suggest a higher efficacy of combined therapy compared with zidovudine monotherapy in PHI patients and indicate that control of viraemia for at least 1 year is achievable in PHI patients.

Acquired Immunodeficiency Syndrome↗
PubMed1996

[Prevalence of transmission of zidovudine-resistant viruses in Switzerland. l'Etude suisse de cohorte VIH].

Zidovudine (ZDV) was the most widely used anti-HIV drug between 1987 and 1995, and, as already reported, transmission of ZDV-resistant viruses occurs. Several mutations of the reverse transcriptase gene have been identified; one of them affects the 215 codon and is associated with a high degree of resistance. We have determined, using selective PCR, the prevalence of transmission of 215 mutant isolates in 134 patients with primary HIV infection (PHI) and have identified 8 patients with 215 mutant virus between 1989 and 1995 in Switzerland. Mutant resistant viruses have been isolated from patients treated with most antiviral drugs. A systematic search for mutant viruses may provide useful information for the adaptation of treatment strategies.

Adolescent↗
PubMed1996

[Disseminated infection with Mycobacterium celatum].

A 29-year-old patient with AIDS was hospitalized with weight loss, fever and cough. Mycobacterial cultures from sputum, blood and bronchoalveolar lavage became positive after 3 weeks' incubation. When using a DNA probe for identification of Mycobacterium tuberculosis complex, a weakly positive signal was obtained. Tuberculosis was suspected and treatment was started with isoniazid, ethambutol and ciprofloxacin. Sequencing of the gene of the 16S rRNA, however, identified the isolates as belonging to a new, slow-growing atypical mycobacterial species, Mycobacterium celatum (M. celatum). Treatment was modified to take into account the previously described primary resistance of M. celatum to antituberculous drugs, whereupon the patient improved.

AIDS-Related Opportunistic Infections↗
PubMed1996

Effects of antibiotic treatment in the subset of common-cold patients who have bacteria in nasopharyngeal secretions.

BACKGROUND: Upper-respiratory-tract infection is one of the main causes of overuse of antibiotics. We have found previously that bacteria such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae can be isolated from the nasopharyngeal secretions of a substantial proportion of adults with upper-respiratory-tract infections. We have assessed the efficacy of co-amoxiclav in patients with common colds but no clinical signs of sinusitis or other indications for antibiotics. METHODS: Between January, 1992 and March, 1994, 314 patients who presented to our outpatient clinic with common colds were enrolled in the double-blind, placebo-controlled study. They were randomly assigned 5 days' treatment with co-amoxiclav (375 mg three times daily) or identical placebo. Clinical examinations were done at enrolment and on day 5-7 to assess outcome (cured, persistent symptoms, worse symptoms). Seven patients were excluded after randomisation, seven did not have nasopharyngeal aspiration, and 12 did not return for followup assessment. FINDINGS: Of 300 patients with nasopharyngeal aspirates, 72 had negative bacterial cultures, 167 had cultures positive only for bacteria unrelated to respiratory infections, and 61 had cultures positive for H influenzae, M catarrhalis, or S pneumoniae. At 5-day follow-up of these culture-positive patients, the distribution of outcome was significantly better among co-amoxiclav-treated (n=30) than placebo-treated (n=28) patients (cured 27 vs 4%; persistent symptoms 70 vs 60%; worse symptoms 3 vs 36%; p=0.001). Patients on co-amoxiclav also scored their symptoms significantly lower than patients on placebo (p=0.008). Among culture-negative patients (n=230), the outcome distribution did not differ between the treatment groups (p=0.392). INTERPRETATION: The majority of patients with upper-respiratory-tract infection do not benefit from antibiotics and side-effects are frequent. However, for the subgroup whose nasopharyngeal secretions contain H influenzae, M catarrhalis, or S pneumoniae, antibiotics are clinically beneficial.

Adult↗