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Biomedical subjects

M Flepp

Publications and source records attributed to M Flepp.

At least 37 records · Page 2Linked to original sources
PubMed2000

Performance of five different assays for the quantification of viral load in persons infected with various subtypes of HIV-1. Swiss HIV Cohort Study.

Five methods for the assessment of plasma viral load (VL) were evaluated in 103 seropositive patients infected with various subtypes of HIV-1. The methods included three RNA-based assays (Amplicor Monitor 1.5, Quantiplex version 2.0, NucliSens), one ultrasensitive reverse transcriptase (PERT) assay and one "boosted" p24 antigen (Ag) enzyme immunoassay (EIA). Subtyping was based on sequencing in env. The sensitivities were, in decreasing order, Amplicor > PERT > p24 Ag > NucliSens > Quantiplex. The low sensitivity of NucliSens was related to the missing of several non-B (A, E, F, G) or recombinant strains, whereas that of Quantiplex did not depend on subtype. In the 1 group O sample and 4 group M samples, only PERT assay or p24Ag EIA produced a positive result. In the quantitative range, correlation was best between Amplicor and Quantiplex (r = 0.8848), fair between Amplicor and NucliSens (r = 0.7064) or PERT assay (r = 0.7266), lowest between Amplicor and p24Ag EIA (r = 0.3989). Amplicor underestimated VL in 1 subtype E sample. Thus, Amplicor performed best in terms of sensitivity (compared with all other assays) and accuracy (compared with NucliSens, PERT assay, and p24Ag) for non-B subtypes in group M samples. PERT assay appears useful for VL assessment in infections by group O or other highly divergent viruses.

HIV Infections↗
PubMed2000

Use of HIV-1 p24 as a sensitive, precise and inexpensive marker for infection, disease progression and treatment failure.

HIV RNA is an acknowledged marker of disease activity and predictive of progression, while the p24 antigen is considered unsuitable. This is at odds with the fact that viral pathogenesis is usually mediated by proteins. One might expect that p24, if analyzed properly, might even be superior to RNA. This hypothesis was investigated in clinical studies using a sensitive and precise p24 test (heat-mediated immune complex dissociation with signal amplification-boosted ELISA). This test was as sensitive and specific as the polymerase chain reaction (PCR) for viral RNA (200-400 copy detection), an overall better predictor of CD4 decline and survival, while RNA prevailed in predicting AIDS. The lower costs of p24 testing also permit a closer monitoring of patients with an earlier detection of anti-retroviral treatment failures.

Biomarkers↗
PubMed2000

A continuing concern: HIV and hepatitis testing and prevalence among drug users in substitution programmes in Zurich, Switzerland.

Phase I of the Zurich Prometheus Study is a cross-sectional study focusing on an up-to-date serology for HIV and hepatitis B/C and associated risk factors for all clients in four participating clinics offering opiate substitution in Zurich, Switzerland. The mean age of the 603 respondents is 30.7 years (SD = 6.2) and 38% of them are women. Seventy-five per cent of the respondents have a history of injecting drug use (IDU), and over half have injected within the past six months. Laboratory-confirmed seroprevalence for HBV (50%) and HCV (57%) is twice that of HIV (24%). There is an 80% risk reduction for all three viral infections among those starting IDU after 1991--when harm reduction efforts were in full swing--compared to those who began before 1988--before clean needles were widely available. These findings suggest a strongly protective effect of harm reduction measures. But while a stabilization in HIV prevalence at 15% can be seen among drug users who started injecting after 1991, prevalence rates for HBV and HCV still remain several times higher. The prevalence data in this study support data showing continued high incidence rates for HBV and HCV, even among new injectors in the harm reduction era.

Adult↗
PubMed1999

Incidence and predictors of virologic failure of antiretroviral triple-drug therapy in a community-based cohort.

Highly active antiretroviral therapy fails to reach its recommended goal of sustained suppression of viral replication in a substantial proportion of patients. We analyzed incidence and predictors of virologic failure of the first regimen of a triple-drug combination therapy, including a protease inhibitor and two nucleoside analog reverse transcriptase inhibitors (NRTIs), in 274 HIV-infected patients. Long-term virologic response to combination therapy including salvage regimens was assessed 2.5 years after treatment initiation. During an initial observation period of up to 1.8 years (median, 0.8 years) 152 patients (55%) experienced sustained suppression of HIV-1 RNA to <500 copies/ml. Failure to reduce viral load to <500 copies/ml within 6 months (initial failure) was observed in 51 patients (19%). Independent risk factors for initial failure included higher baseline viral load; addition of a protease inhibitor to an unchanged NRTI regimen; use of saquinavir hard-gel capsules; and longer duration of prior NRTI treatment. Within a median of 7 months viral load rebound above 500 copies/ml occurred in 71 of 223 patients (32%) whose viral load had initially decreased below this threshold. In proportional hazard analysis none of the potential risk factors was significantly associated with viral load rebound. However, in 40 patients (56%) with viral load rebound, incomplete adherence to therapy or treatment interruptions preceded the rebound. Virologic outcome after 2.5 years correlated with initial response to the first regimen: viral load was <500 copies/ml in 88, 55, and 21% of patients with sustained suppression, viral load rebound, and initial failure, respectively.

Adult↗
PubMed1999

Enteric infections and diarrhea in human immunodeficiency virus-infected persons: prospective community-based cohort study. Swiss HIV Cohort Study.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) are at increased risk for diarrhea and enteric infections. We studied (1) the epidemiology of enteric pathogens associated with diarrhea, (2) the diagnostic yield of stool examination and endoscopic evaluation, (3) risks to develop diarrhea, and (4) the impact of diarrhea on patients' survival. METHODS: A total of 1933 participants in the Swiss HIV Cohort Study were prospectively followed up for a median of 25.5 months. A total of 560 diarrheal episodes were evaluated by standardized stool examination. Endoscopic evaluation was performed in 25% of patients with chronic diarrhea. RESULTS: The incidence of diarrhea was 14.2 per 100 person-years (95% confidence interval, 13.0-15.4). Among patients with CD4 cell counts below 0.05 x 10(9)/L, the probability to develop diarrhea within 1, 2, and 3 years was 48.5%, 74.3%, and 95.6%, respectively. The risk to develop diarrhea was increased among patients with severe immunodeficiency, homosexual men, and patients taking antiretroviral therapy. Pneumocystis carinii chemoprophylaxis did not reduce the risk of diarrhea. Diarrhea was an independent negative predictor of survival. Enteric pathogens were detected in 16.5% of 212 acute diarrheal episodes and in 46% of 348 chronic diarrheal episodes. The sensitivity of histological and stool examination was similar except for the diagnosis of intestinal cytomegalovirus infection and leishmaniasis, which required invasive evaluation. CONCLUSIONS: Intestinal infections were diagnosed in less than 50% of chronic diarrheal episodes. The prevalence of enteric pathogens tended to decrease during the observation period, possibly because of improved antiretroviral therapy. Endoscopic evaluation did not improve the diagnostic yield compared with stool examination except for the diagnosis of cytomegalovirus enteritis and leishmaniasis.

AIDS-Related Opportunistic Infections↗
PubMed1999

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↗
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↗
PubMed1997

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↗
PubMed1997

[Fever and dry cough in a construction worker from Portugal].

A 33-year-old Portugese worker presented with a one-week history of nonproductive cough and fever. A presumptive diagnosis "viral infection of the respiratory tract" was made. However, because of persisting cough and fever further investigations were necessary, and finally Brucella melitensis was isolated in blood cultures. Three months before admission to the hospital the man was dressing the carcasses of a goat in Portugal and consumpted fresh goats milk cheese. Antibiotic therapy with Rifampicin and Trimethoprim/Sulfamethoxazol over 6 weeks improved the signs and symptoms of the infection.

Adult↗
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

Effect of antiviral treatment on the shedding of HIV-1 in semen.

OBJECTIVE: The potential role of antiretroviral treatment on the infectiousness of HIV-1-infected men was examined by studying the effect of antiviral treatment on the shedding of HIV-1 in semen. METHODS: Forty-four patients enrolled in various treatment protocols were asked to donate a semen sample before they began a new antiviral treatment and at a follow-up visit after 6 to 15 weeks of treatment. Since most patients were on blinded protocols, patients were stratified by response of blood viral load. The effect of each patient's treatment was classified as good (n = 24), fair (n = 8) and marginal (n = 13) by measurement of the HIV RNA reduction in blood plasma (> 1.0 log10; 0.5-1.0 log10 and < 0.5 log10 HIV RNA copies/ml reduction, respectively). The effect of treatment on shedding of HIV-1 in semen was documented by the reduction of HIV RNA concentration in seminal plasma and by quantitative HIV-1 seminal cell culture. RESULTS: Overall, antiviral treatment resulted in a significant fall in the viral load in semen (RNA and culture) that paralleled the reduction of viral load in blood. More pronounced reductions of HIV RNA in semen were observed as the effectiveness of treatment on blood HIV RNA levels increased (median drop from baseline 0, 0.3 log10 and 0.8 log10 RNA copies/ml in patients with marginal, fair and good treatment effect, respectively). Thirteen patients lost detectable HIV RNA in blood on treatment and all of these had undetectable levels of HIV-1 in semen by culture and RNA analysis at follow-up. In 19 of the 31 patients (62%) who still had HIV RNA in their blood during treatment, semen HIV levels were below detection in semen at follow-up. CONCLUSIONS: Treatment-induced changes of HIV RNA concentration in blood are generally associated with a corresponding change in seminal HIV RNA: If confirmed in larger studies, potent antiretroviral therapy might reduce the spread of HIV-1.

Anti-HIV Agents↗
PubMed1996

Reasons for failure of prevention of Toxoplasma encephalitis. Swiss HIV Cohort Study.

OBJECTIVE: To study whether absence of prophylaxis is a risk factor for cerebral toxoplasmosis, and to determine the reasons for absence of prophylaxis among AIDS patients diagnosed with Toxoplasma encephalitis (TE). DESIGN: Retrospective chart review and matched case-control study. PATIENTS: Patients (104 first episodes and 26 relapses of TE) were registered in the Swiss HIV Cohort Study from three centres from July 1992 to December 1994; 91 matched controls were included for 52 patients with a first episode, and 17 matched controls for 17 patients with relapse of TE. RESULTS: Prophylaxis was prescribed to 17 patients (16%) with a first episode and 19 patients (73%) with a relapse of TE. Reasons for the absence of prophylaxis included patient refusal (25%), non-proposal by physicians (17%), and drug intolerance (17%). Reduced absorption due to non-compliance, diarrhoea or vomiting was identified among 12 patients with a first episode and 14 patients with a relapse of TE. Absence of prescription of prophylaxis was associated with a 10-fold increased risk of a first episode of TE (odds ratio, 9.8; 95% confidence interval, 2.7-35.4) in the matched case-control study. CONCLUSIONS: TE continues to occur among patients not receiving prophylaxis. At least one-half of the cases may be prevented with better motivation of physicians and increased compliance of patients.

AIDS-Related Opportunistic Infections↗
PubMed1996

Heat-mediated immune complex dissociation and enzyme-linked immunosorbent assay signal amplification render p24 antigen detection in plasma as sensitive as HIV-1 RNA detection by polymerase chain reaction.

OBJECTIVE: To compare heat denaturation and acidification as immune complex dissociation (ICD) methods in adult HIV-1 infection and to increase the sensitivity by a signal-amplification-boosted HIV-1 p24 antigen enzyme-linked immunosorbent assay (ELISA). DESIGN: Prospective and retrospective blinded study of paired serum and plasma samples from 245 patients (112 of class A, 66 of B, 67 of C of the Centers for Disease Control and Prevention 1993 classification). METHODS: Plasma and sera were prospectively tested for antigen by ELISA using native, acidified, or heat-denatured material. Retrospective tests included batch analysis of heat-denatured samples for antigen by the signal-amplification-boosted ELISA and for viral RNA. RESULTS: With serum, native antigen was reactive in 26.5%. Acidification increased the rate to 53.1% (P < or = 0.0001), but was inefficient at a CD4+ count > or = 500 x 10(6)/l. Heat denaturation further elevated the rate to 67.8% (P < or = 0.0007) and the use of plasma to 78.0% (P < or = 0.008). The boosted ELISA, performed with plasma samples diluted 1 :6, which eliminated the problem of heat-induced sample coagulation, was confirmed positive in 89.5% of serum and 97.8% of plasma samples. RNA was detected in 95.7%. CONCLUSION: Heat-mediated ICD combined with a signal-amplification-boosted ELISA detects HIV-1 expression as sensitively as a polymerase chain reaction kit for viral RNA, but at only a fraction of the cost. The procedure uses a 50 microliters plasma sample and should be fully automatable.

Adult↗
PubMed1995

Pregnancy, immunosuppression and reactivation of latent toxoplasmosis.

Toxoplasmosis is a chronic, latent infection which can be reactivated in the presence of immunosuppression. The critical question in obstetrics is whether toxoplasmosis may be reactivated in the presence of the physiological "immunosuppression" of pregnancy. Standard in vitro tests, done in 24 healthy pregnant women and compared with the literature, show no significant changes in humoral and cellular immunity during pregnancy. However, the fact that some infections occur more frequently and more severely than in non-pregnant women (e.g. those due to cytomegalovirus (CMV) and human papilloma virus (HPV) points to a degree of pregnancy-associated immunosuppression. Non-rejection of the semiallogenic fetus is achieved in presence of maternal immunocompetence and is explained mainly by local changes in immune function, mediated by inhibitors of decidual, placental and fetal origin, and by the absence of class II histocompatibility antigens at the fetomaternal interface. Immune status allowing reactivation of toxoplasmosis was studied in a selected group of (predominantly male) AIDS patients from the Swiss HIV Cohort study. Shortly before (cerebral) reactivation of toxoplasmosis, 92% of these patients had very low CD4 lymphocyte counts (mean 50 cells/microliters, i.e. lower than ever recorded in a normal uncomplicated pregnancy). In a larger population of 48 women receiving immunosuppressive therapy after organ transplantation, not a single case of cerebral toxoplasmosis was observed during pregnancy, while in the 105 HIV-positive women in the Swiss HIV and Pregnancy study, there was only one case of cerebral toxoplasmosis during pregnancy and the puerperium (20 CD4/microliters), even though some 17% of those sampled (18/105) had CD4 levels below 200 cells/microliters on at least one occasion during pregnancy. These findings explain why latent toxoplasmosis is not reactivated in normal pregnancy, and why it is only likely in an immunosuppressed mother when her CD4 lymphocyte count is very low (< 200 cells/microliters). In such cases, a prophylactic treatment to prevent maternal reactivation and vertical transmission of toxoplasmosis may be useful.

AIDS-Related Opportunistic Infections↗