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B Hirschel

Publications and source records attributed to B Hirschel.

At least 19 recordsLinked to original sources
PubMed2006

Molecular biology of squamous cell carcinoma of the anus.

BACKGROUND: Squamous cell carcinoma of the anal canal provides a model for studying the contribution of human papillomavirus (HPV) and human immunodeficiency virus (HIV) infection to the development of neoplasia. This paper reviews the existing literature relating to the molecular biology of anal squamous cell carcinoma and proposes a theory of pathogenesis. METHODS: A Medline literature search was performed to identify English articles on the pathogenesis of squamous cell carcinoma of the anus; further articles were obtained from the references quoted in the literature initially reviewed. RESULTS: HPV infection and subsequent HPV DNA integration are necessary, but not sufficient, to cause cancer progression. Loss of heterozygosity at 11q23 is the most consistent genomic change observed. Loss of heterozygosity at 17p, 18q and 5q is frequently observed in tumours of HIV-negative patients, but not in those of HIV-positive patients. Current data suggest that mutations in p53, DCC and APC tumour suppressor genes contribute to the stepwise progression of anal squamous cell carcinoma in immunocompetent individuals. CONCLUSION: In comparison with immunocompetent individuals, HIV-positive patients have persistent HPV infection in the anal canal. In this population, microsatellite instability, rather than chromosomal instability, appears to be a preferred pathway for rapid progression towards invasive carcinoma.

Anus Neoplasms↗
PubMed2006

Prevalence of risk factors for cardiovascular disease in HIV-infected patients over time: the Swiss HIV Cohort Study.

OBJECTIVE: Metabolic changes caused by antiretroviral therapy (ART) may increase the risk of coronary heart disease (CHD). We evaluated changes in the prevalence of cardiovascular risk factors (CVRFs) and 10-year risk of CHD in a large cohort of HIV-infected individuals. METHODS: All individuals from the Swiss HIV Cohort Study (SHCS) who completed at least one CVRF questionnaire and for whom laboratory data were available for the period February 2000 to February 2006 were included in the analysis. The presence of a risk factor was determined using cut-offs based on the guidelines of the National Cholesterol Education Program (NCEP ATP III), the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), the American Diabetes Association, and the Swiss Society for Cardiology. RESULTS: Overall, 8,033 individuals completed at least one CVRF questionnaire. The most common CVRFs in the first completed questionnaire were smoking (57.0%), low high-density lipoprotein (HDL) cholesterol (37.2%), high triglycerides (35.7%), and high blood pressure (26.1%). In total, 2.7 and 13.8% of patients were categorized as being at high (>20%) and moderate (10-20%) 10-year risk for CHD, respectively. Over 6 years the percentage of smokers decreased from 61.4 to 47.6% and the percentage of individuals with total cholesterol >6.2 mmol/L decreased from 21.1 to 12.3%. The prevalence of CVRFs and CHD risk was higher in patients currently on ART than in either pretreated or ART-naive patients. CONCLUSION: During the 6-year observation period, the prevalence of CVRFs remains high in the SHCS. Time trends indicate a decrease in the percentage of smokers and individuals with high cholesterol.

Adult↗
PubMed2005

[HIV-AIDS 2004: New substances, new targets for treatment, future therapeutic strategies].

In developed countries, drug therapy has turned HIV infection into a chronic disease. Follow-up of patients who take antiretroviral therapy is becoming more and more complex and individualised, often multidisciplinary approach is warranted. Problems with compliance to treatment and viral drug resistance have encouraged research of new substances. More is known about viral replication and other targets for treatment are under investigation. Improvements to therapeutic strategies practised in the last few years provide new possibilities in the fight against HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Pharmacokinetic study of saquinavir hard gel caps/ritonavir in HIV-1-infected patients: 1600/100 mg once-daily compared with 2000/100 mg once-daily and 1000/100 mg twice-daily.

OBJECTIVES: A pharmacokinetic comparison of three dosing regimens of saquinavir/ritonavir was carried out: 1600/100 mg once-daily with 1000/100 mg twice-daily, and 1600/100 mg once-daily with 2000/100 mg once-daily. METHODS: Twenty patients on saquinavir hard gel caps/ritonavir 1600/100 mg once-daily in combination with two nucleoside reverse transcriptase inhibitors for at least 4 weeks were enrolled and randomized to either saquinavir hard gel caps/ritonavir 1000/100 mg twice-daily or 2000/100 mg once-daily. Two pharmacokinetic curves were plotted, at baseline (day 0) and 7 days after the switch. Plasma concentrations were measured at 0, 2, 4, 6, 8, 10, 12 (and 24 for once-daily dosing) hours after drug intake by validated high-performance liquid chromatographic assay (HPLC). The area under the plasma concentration-time curve (AUC0-24 or AUC0-12), maximum and minimum concentration (Cmax and Cmin) and elimination half-life were calculated using a non-compartmental model. RESULTS: Compared with saquinavir/ritonavir 1600/100 mg once-daily dosing, the saquinavir AUC and Cmin improved significantly when dosed as 1000/100 mg twice-daily (53% and 299%, respectively), and as 2000/100 mg once-daily (71% and 65%, respectively). Low Cmin in three subjects at baseline was corrected after switch to the other dosages. Saquinavir/ritonavir 2000/100 mg once-daily was also associated with a significant increase in saquinavir Cmax (52%) compared with saquinavir/ritonavir 1600/100 mg once-daily. CONCLUSIONS: Saquinavir/ritonavir when dosed as 2000/100 mg once-daily or 1000/100 mg twice-daily achieves higher saquinavir plasma levels compared with saquinavir/ritonavir 1600/100 mg once-daily. Taking the convenience of once-daily dosing into consideration, dosage of 2000/100 mg once-daily may be preferred.

Adult↗
PubMed2004

[Treatment of cutaneous human papilloma virus, poxvirus and herpes simplex virus infections with topical cidofovir in HIV positive patients].

INTRODUCTION: Cidofovir (Vistide) is an antiviral marketed for the treatment of cytomegalovirus retinitis. Clinical efficacy has been reported with its broad antiviral spectrum that includes poxvirus, human papilloma virus and Herpes simplex. In immunodepressed patients, these infectious dermatoses are often recurrent and resistant. In an open study, we assessed the efficacy and clinical tolerance of cidofovir gel at 1 p. 100. PATIENTS AND METHODS: Twelve HIV-infected adults were included. Cidofovir gel at 1 p. 100 was applied directly on the lesions, once a day, for two weeks on the molluscum and condylomas, four weeks on the warts and one week on the chronic herpes. RESULTS: Four patients presented with warts and 3 of them with verruca plana. In 2 of the verruca plana patients, regression was complete although relapse was observed. Two failures were noted. Local application of the gel was not tolerated by one patient suffering from condylomas of the penis. Four patients presented with molluscum contagiosum. Two complete regressions with strong local reaction and two partial regressions were observed. The latter two patients exhibited severe immunodepression, one of them subsequently received infusions of cidofovir. Two women suffering from vulvar and perianal herpes resistant to acyclovir were treated for one week with cidofovir gel at 1 p. 100: no response was obtained. One of the patients stopped treatment because of local intolerance. A third, less immunodepressed, woman responded partially. COMMENTS: In HIV-positive patients, cidofovir in topical form appears to be indicated in extensive and confluent molluscum contagiosum. However, the effect occurs at the cost of local inflammation. The results are disappointing in papillomavirus lesions and in chronic acyclovir-resistant herpes ulcerations, efficacy is debatable.

Administration, Topical↗
PubMed2004

[Primary HIV infection].

Acute HIV infection presents as a mononucleosis-like disease with fever, lymphadenopathy, myalgias, rash and headache. Other symptoms are occurring at lower frequency. Since acute HIV infection is associated with high viral loads it is important to diagnose patients with this entity, in order to prevent transmission. It is still controversial whether very early therapy during acute seroconversion is beneficial on the long-run. Small studies may indicate that early therapy which is followed by a stop of antiretroviral therapy after one to two years may be followed by a better control of viremia.

Acute Disease↗
PubMed2004

[Simplified treatments for HIV infection].

The treatment of HIV infection is reputedly complicated. Indeed, in 1996 and 1997, the most widely used regimen implied five separate pill ingestions every day: A heavy burden even without side effects. Since then, however, treatment has been greatly simplified. The most widely used regimen in Switzerland is the combination of zidovudine, lamivudine and efavirenz, with 1 pill in the morning and 2 pills in the evening. The Swiss HIV Cohort has shown that simplifying therapy increases the success of HIV treatment. Once daily administration will soon be part of standard care, as clinical trials have shown promising results. In the future, many patients may well treat their HIV infection intermittently. Scheduled treatment interruptions are under intensive investigation in Switzerland and elsewhere. Large scale studies with long follow-up are necessary and the first results can not be expected before the end of 2005.

Anti-HIV Agents↗
PubMed2003

Caspofungin in the treatment of oropharyngeal candidiasis.

A patient with AIDS developed oropharyngeal candidiasis. Candida albicans and C. glabrata were isolated from the patient and found to be resistant to fluconazole and itraconazole in vitro. Voriconazole therapy was initiated, but discontinued when the C. albicans strain isolated from the patient was found to be resistant to it. The patient failed to respond to subsequent therapy with a combination of amphotericin B and 5-flucytosine. Therapy with caspofungin was then initiated (70 mg loading dose, followed by 50 mg/day). The patient responded favourably to caspofungin, with complete resolution of signs and symptoms.

AIDS-Related Opportunistic Infections↗
PubMed2002

Ritonavir plus saquinavir versus single protease inhibitor therapy in protease inhibitor-naive HIV-infected patients: the Swiss HIV Cohort Study.

OBJECTIVES: To compare the response to ritonavir (RTV) plus saquinavir (SQV) with single protease inhibitor (PI) therapies among PI-naive HIV-1 infected individuals. METHODS: Response to treatment was analysed according to the intent-to-treat principle in a prospective observational cohort study of 177 patients who between May 1995 and March 2000 started a double PI therapy with RTV and SQV (nonboosting dosages) plus at least one nucleoside reverse transcriptase inhibitor (NRTI) and 2,214 patients with a single PI therapy plus two NRTIs. We used survival analysis and Cox's proportional hazard regression methods. The primary endpoint was the time to a plasma viral load of < 400 copies/mL. Secondary endpoints were taken as a gain in the CD4 count of >100 cells/microL, and change of initial PI for any reason. RESULTS: Baseline characteristics in both treatment groups were balanced. Median follow-up in both groups was 10.4 months. Time to an HIV-1 viral load of < 400 copies/mL and an increase in the CD4 count of >100 x 10(6) cells/L was shorter for RTV plus SQV compared with single PI regimens (log rank test for each endpoint P < 0.05). The adjusted hazard ratios of RTV plus SQV compared with single PI regimens were 1.21 (95% confidence interval 0.99-1.47) for achieving an HIV-1 viral load of < 400 copies/mL, 1.12 (0.88-1.42) for an increase in the CD4 count of > 100 cells/microL, and 0.90 (0.73-1.11) for change of first PI regimen. CONCLUSIONS: Treatment with RTV plus SQV compared with single PI regimens appeared to give similar results for virological or immunological response.

Adolescent↗
PubMed2002

Response to antiretroviral therapy among patients exposed to three classes of antiretrovirals: results from the EuroSIDA study.

There is an increasing proportion of HIV-positive patients exposed to all licensed classes of antiretrovirals, and the response to salvage regimens may be poor. Among over 8500 patients in EuroSIDA, the proportion of treated patients exposed to nucleosides, protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitor (NNRTI) increased from 0% in 1996 to 47% in 2001. Four-hundred-and-thirteen patients, who had failed virologically two highly active antiretroviral therapy (HAART) regimens and experienced all three main drug classes, started a salvage regimen of at least three drugs, in which at least one new PI or NNRTI was included. Median viral load was 4.7 log copies/ml [Interquartile range (IQR) 4.2-5.2], CD4 lymphocyte count 150/mm3 (IQR 60-274/mm3) and follow-up 14 months. Of these patients, 283 (69%) subsequently experienced at least a 1 log decline in viral load and 202 (49%) achieved a viral load < 500 copies/ml. Conversely, the CD4 count halved from the baseline value in 88 (21%), and 45 (11%) experienced a new AIDS-defining disease. In multivariable analyses, a 1 log viral load reduction was related to baseline viral load [relative hazard (RH) 1.27 per 1 log higher; P = 0.008], a previous viral load of less than 500 copies/ml (RH 1.69; P = 0.002), more recent initiation of the regimen (RH 1.36 per year more recent; P = 0.02), number of new drugs in the regimen (RH 1.20 per drug; P = 0.02), time since start of antiretroviral therapy (RH 0.94 per extra year; P = 0.035) and time spent on HAART with viral load > 1000 copies/ml (RH 0.96 per extra month; P = 0.0001). Analysis of factors associated with CD4 count decline and new AIDS disease also indicated improved outcomes in more recent times and a tendency for a better response in those starting more new drugs, but no relationship with the total number of drugs. Outcomes in people starting salvage regimens appear to depend on the number of new drugs started but not on the total number of drugs being used.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Acute HIV infection: impact on the spread of HIV and transmission of drug resistance.

OBJECTIVE: To assess the impact of primary HIV infection (PHI) on the spread of HIV and the temporal trends in transmission of HIV drug resistance between 1996 and 1999 in Switzerland. METHODS: Sequencing of the genes for reverse transcriptase (RT) and protease was performed for 197 individuals with documented PHI. Phylogenetic analyses were confronted with epidemiological data. RESULTS: Significant clustering was demonstrated for 29% of the RT sequences. All these cases occurred closely together in place and time; contact tracing demonstrated transmission at the time of PHI in 30% of them. Genotypic drug resistance was detected in 8.6% of PHI individuals in 1996, 14.6% in 1997, 8.8% in 1998 and 5.0% in 1999. Drug-resistant variants were identified in 11.3% of individuals infected by homosexual contacts, 6.1% by heterosexual contacts, 13% of intravenous drug users and more frequently in men (10.4%) than women (2.6%). Potential factors involved in the recent decrease of transmission of drug-resistant variants include increase of HIV non-B subtypes from 23% in 1996 to 35% in 1999 (only one non-B subtype had resistance mutations) and a steady increase of patients with undetectable viraemia as documented in Swiss HIV Cohort Study (10% in 1996 vs 53% in 1999). CONCLUSIONS: Phylogenetic and epidemiological analyses underline the impact of PHI in the spread of HIV. Moreover, this study indicates that drug resistance transmission may have decreased recently in Switzerland through the increased frequency of infection with HIV non-B subtypes and the steady increase of patients with undetectable viraemia.

Acute Disease↗
PubMed2001

Hyperlactatemia and antiretroviral therapy: the Swiss HIV Cohort Study.

The prevalence, clinical presentation, and risk factors for hyperlactatemia among patients receiving antiretroviral therapy was determined during a 1-month period for patients in the Swiss HIV Cohort Study. Overall, 73 (8.3%) of 880 patients presented an increase in serum lactate of >1.1 times the upper normal limit (UNL). For 9 patients (1%), lactate elevation was moderate or severe (>2.2 times the UNL). Patients who presented with hyperlactatemia were more likely to be receiving stavudine with or without didanosine (odds ratio, 2.7; 95% confidence interval, 1.5-4.8), as compared with patients who received zidovudine-based regimens. The risk increased with increasing time receiving stavudine with or without didanosine. The association between hyperlactatemia and stavudine with or without didanosine was not biased by these medications being more recently available and, therefore, being given preferentially to patients who had prolonged use of nucleoside analog reverse-transcriptase inhibitors. Hyperlactatemia was associated with lipoatrophy, hyperlipidemia, and hyperglycemia. Age, sex, or stage of infection with human immunodeficiency virus were not predictive of hyperlactatemia. Determination of lactate levels may prove useful in the screening for mitochondrial toxicity.

Acidosis, Lactic↗
PubMed2001

Prevalence of adverse events associated with potent antiretroviral treatment: Swiss HIV Cohort Study.

BACKGROUND: Data on adverse events to antiretroviral treatment have been recorded in clinical trials, post-marketing analyses, and anecdotal reports. Such data might not be an up-to-date or comprehensive assessment of all possible treatment combinations defined as potent antiretroviral treatment. METHODS: Using a standard clinical and laboratory method, we assessed prevalence of adverse events in 1160 patients who were receiving antiretroviral treatment. We measured the toxic effects associated with the drug regimen (protease inhibitor [PI], non-nucleoside and nucleoside analogue reverse transcriptase inhibitor) and specific compounds using multivariate analyses. FINDINGS: 47% (545 of 1160) of patients presented with clinical and 27% (194 of 712) with laboratory adverse events probably or definitely attributed to antiretroviral treatment. Among these, 9% (47 of 545) and 16% (30 of 194), respectively, were graded as serious or severe. Single-PI and PI-sparing-antiretroviral treatment were associated with a comparable prevalence of adverse events. Compared with single-PI treatment, use of dual-PI-antiretroviral treatment and three-class-antiretroviral treatment was associated with higher prevalence of adverse events (odds ratio [OR] 2.0 [95% CI 1.0-4.0], and 3.9 [1.2-12.9], respectively). Compound specific associations were identified for zidovudine, lamivudine, stavudine, didanosine, abacavir, ritonavir, saquinavir, indinavir, nelfinavir, efavirenz, and nevirapine. INTERPRETATION: We recorded a high prevalence of toxic effects attributed to antiretroviral treatment for HIV-1. Such data provides a reference for regimen-specific and compound-specific adverse events and could be useful in postmarketing analyses of toxic effects.

Adult↗
PubMed2001

Response to first protease inhibitor- and efavirenz-containing antiretroviral combination therapy. The Swiss HIV Cohort Study.

OBJECTIVE: To compare the response to protease inhibitor (PI) and efavirenz-containing combination therapy among treatment-naive HIV-infected persons. DESIGN: Prospective observational cohort study. METHODS: Response to treatment was analysed according to the intent-to-treat principle among antiretroviral-naive patients who started either efavirenz (n = 89) or PI (n = 183) plus two nucleoside reverse transcriptase inhibitors between February 1999 and March 2000 using Kaplan-Meier and multivariable Cox proportional hazard regression methods. Primary endpoint was time to undetectable plasma viral load. Secondary endpoints included the number of CD4 cells gained, virological rebound, treatment change, and clinical progression. RESULTS: Patients on PI regimens had lower median CD4 counts (165 versus 216 x 5 106/l; P = 0.15) and were more likely to have AIDS at initiation of treatment (25% versus 15% P = 0.048) than patients starting efavirenz regimens. The probability of reaching plasma HIV-1 RNA < 400 copies/ml was higher with efavirenz- than with PI-containing regimens [adjusted hazard ratio, 1.75; 95% confidence interval (CI), 1.34-2.29]. Median times to undetectable viral load were 58 days (95% CI, 44-70 days) for efavirenz-treated and 88 days (95% CI, 79-98 days) for PI-treated patients. The median number of CD4 cells gained in the first 6 months (90 x 10(6) cells/l with efavirenz, 10(7) x 10(6) cells/l with PI; P = 0.63), time to and reasons for treatment change, time to viral rebound, drug intolerance and clinical progression rates were similar in the two treatment groups. CONCLUSIONS: Treatment with efavirenz-, compared with PI-based regimens, appeared to result in a superior virological response but no difference in immunological or clinical efficacy. The relevance of these observations remains to be determined in studies with longer follow-up.

Adult↗
PubMed2001

Antiretroviral prophylaxis for community exposure to the human immunodeficiency virus in Switzerland, 1997-2000.

OBJECTIVE: To analyse the data from Swiss nationwide voluntary reporting on non-occupational HIV-postexposure prophylaxis (HIV-PEP) by prescribing physicians. METHODS: One hundred and seventy-six persons, who received antiretroviral prophylaxis for community exposure to HIV between December 1997 and March 2000, were included in this prospective cohort study with standardised data collection. Information on the source, the exposed person, type of exposure, treatment, and outcome was reported by physicians on a voluntary basis to three co-ordinating centers. RESULTS: HIV-PEP was prescribed predominantly following sexual exposure (69%). Needle injury was the second most common type of exposure (19% of all exposures), mostly occurring in a non-healthcare related "professional" setting (i.e., housekeepers, concierges [caretakers], and policemen). Needle sharing accounted for only 4% of all cases of exposure. The HIV status of the source often remained unknown (56%). Most patients received a combination of three antiretroviral drugs (zidovudine/lamivudine/nelfinavir in 34.1%; zidovudine/lamivudine/indinavir in 22.8%; zidovudine/lamivudine/nevirapine in 18.6%; various triple combinations in 13.8%). Follow-up information was available for 86 patients. In this group 78 (91%) completed at least one week of prophylaxis. Side-effects were common (70.9%), particularly diarrhoea (29.6%) and nausea (20.9%). Two patients experienced severe side effects, nephrolithiasis with sepsis, and toxic hepatitis, respectively. CONCLUSIONS: In most of the cases where HIV-PEP was prescribed the indication was questionable, with the HIV status of the source unknown. The role of HIV-PEP as part of HIV prevention programs should be well defined in view of the cost and potential for causing severe side-effects.

Adolescent↗