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Biomedical subjects

Manuel Battegay

Publications and source records attributed to Manuel Battegay.

At least 37 records · Page 2Linked to original sources
PubMed2004

Is unsafe sexual behaviour increasing among HIV-infected individuals?

BACKGROUND: The number of new diagnoses of HIV infection is rising in the northwestern hemisphere and it is becoming increasingly important to understand the mechanisms behind this trend. OBJECTIVE: To evaluate whether reported unsafe sexual behaviour among HIV- infected individuals is changing over time. DESIGN: Participants in the Swiss HIV Cohort Study were asked about their sexual practices every 6 months for 3 years during regular follow-up of the cohort beginning on 1 April 2000. METHODS: : Logistic regression models were fit using generalized estimating equations assuming a constant correlation between responses from the same individual. RESULTS: At least one sexual behaviour questionnaire was obtained for 6545 HIV-infected individuals and the median number of questionnaires completed per individual was five. There was no evidence of an increase in reported unsafe sex over time in this population [odds ratio (OR), 1.0; 95% confidence interval (CI), 0.96-1.05]. Females (OR, 1.38; 95% CI, 1.19-1.60), 15-30 year olds (OR, 1.26; 95% CI, 1.09-1.47), those with HIV-positive partners (OR, 12.58; 95% CI, 10.84-14.07) and those with occasional partners (OR, 3.25; 95% CI, 2.87-3.67) were more likely to report unsafe sex. There was no evidence of a response bias over time, but individuals were less willing to leave questions about their sexual behaviour unanswered or ambiguous (OR, 0.93; 95% CI, 0.90-0.97). CONCLUSIONS: There was no evidence of a trend in unsafe sex behaviour over time. However, several subgroups were identified as being more likely to report unsafe sex and should be targeted for specific interventions.

Adolescent↗
PubMed2004

The role of CFTR and SPINK-1 mutations in pancreatic disorders in HIV-positive patients: a case-control study.

OBJECTIVE: Pancreatic disorders in HIV-positive patients are frequent. CFTR and SPINK-1 mutations have been reported to increase the risk of pancreatitis, but no data are available in HIV-positive patients. This study will evaluate the frequency of CFTR mutations and SPINK-1 polymorphisms in HIV-positive patients with clinical pancreatitis or asymptomatic elevation of serum pancreatic enzymes. METHOD: Cases (patients with hyperamylasemia) were identified during a toxicity study conducted in August 1999 among 1152 participants of the Swiss HIV Cohort Study. We designed a case-control study in which each case was matched one to one to an HIV-infected control according to sex, age, CD4 cell count, viraemia and medication use. CFTR mutations and SPINK-1 polymorphisms were studied using polymerase chain reaction techniques. RESULTS: Fifty-one HIV-positive patients with hyperamylasemia were detected among 1152 participants in the toxicity study (4.4%). There were 13 carriers of CFTR and SPINK-1 mutations (12.7%). Amylase levels were 316 +/- 130 U/l for the group with mutations, and 135 +/- 18 U/l for non-carriers (P = 0.79). However, among patients with hyperamylasemia, those with CFTR or SPINK-1 mutations had 648 +/- 216 U/l amylase levels compared with 232 +/- 28 U/l for those without (P = 0.025). Ten patients had acute pancreatitis, four of whom had CFTR mutations or SPINK-1 polymorphisms (40%) compared with seven of the control patients (14%) (P = 0.01). CONCLUSION: CFTR mutations and SPINK-1 polymorphisms are frequent among HIV-positive patients suffering from acute pancreatitis. These mutations may increase the susceptibility to pancreatitis when exposed to environmental risk factors.

Acute Disease↗
PubMed2004

Protease inhibitor-sparing simplified maintenance therapy: a need for perspective.

Body fat changes and metabolic abnormalities such as hyperlipidaemia and diabetes have been increasingly reported following the successful introduction of highly active antiretroviral therapy (HAART). These side effects were attributed initially to the use of protease inhibitors (PIs). As a consequence, a series of trials were conducted where patients with well-controlled HIV viraemia either continued on PIs or were switched to a simplified maintenance therapy (SMT) without PIs. Evidence from these trials is still insufficient to show that switching from PIs to either abacavir, nevirapine or efavirenz is safe. However, patients with suboptimal pre-HAART treatment are at increased risk of virological failure if switched to an SMT. Patients switched from PI regimens tend to stay longer on an SMT and those switched to abacavir show a reduction in total cholesterol, but there is no evidence of any additional benefit from non-PI-based SMT. There is a clear need for a better understanding of HAART-related lipodystrophy and metabolic toxicity, and pharmacogenetic tests to identify those patients most at risk. The advent of simpler formulations for all drug classes, and new PIs with less metabolic toxicity, is likely to reshape completely the role of SMT.

Antiretroviral Therapy, Highly Active↗
PubMed2004

Humoral immunity to HIV-1: kinetics of antibody responses in chronic infection reflects capacity of immune system to improve viral set point.

We analyzed the humoral immune response in 46 patients following structured treatment interruption (STI) to investigate the general potential of therapeutic vaccination in chronic HIV-1 infection. Evoked antibody titer increases to glycoprotein 120 (gp120) and p24 were low during 4 short-term STIs and only reached significance during a fifth long-term interruption. Although induction of binding antibodies to viral antigens was not associated with potent suppression of viremia, we observed that individuals with a rapid and high response to p24, and to a lesser extent also to gp120, lowered their viral set points significantly. Of note, the increase of the anti-p24 response correlated with specific CD4 T helper frequency to this antigen. Despite induction of binding antibody responses, which correlated with improved viral control, the increase in neutralizing activity was marginal and did not lead to this enhanced viral suppression. However, a subgroup of patients who potently suppressed viremia independently of STI had significantly higher pre-existing neutralization titers, suggesting a role of humoral immunity in conferring potent protection. In summary, measuring the kinetics of antibody responses provided a marker to validate the responsiveness and capacities of the immune system of HIV-1-infected individuals and reflected the patients' ability to decrease viral set points.

Adult↗
PubMed2004

Persistent apoptosis in HIV-1-infected individuals receiving potent antiretroviral therapy is associated with poor recovery of CD4 T lymphocytes.

CD4 T-cell depletion in HIV-1 infection is partly the result of T-cell apoptosis. Spontaneous apoptosis (SA) and apoptosis markers Fas-associated death-domain-like IL-1 beta converting enzyme (FLICE)-like inhibitory protein (FLIP), Bcl-2, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), TRAIL receptor 1, and Fas were determined in 55 HIV-1 infected persons treated with highly active antiretroviral therapy (HAART) for 48 months. Despite suppressive HAART, SA remained elevated. Increased SA of peripheral blood mononuclear cells (PBMCs) and CD8 T lymphocytes and increased TRAIL receptor 1 expression strongly predicted a poorer recovery of CD4 T-cell count. HAART did not significantly alter anti-or proapoptotic markers in cultured PBMCs and T lymphocytes. The significant relationship between residual T-lymphocyte apoptosis and CD4 T-cell recovery suggests that persistent apoptosis may impede immune restoration.

Adult↗
PubMed2004

Immune reconstitution in HIV-infected patients.

The prognosis of patients infected with human immunodeficiency virus (HIV) type 1 has dramatically improved since the advent of potent antiretroviral therapies (ARTs), which have enabled sustained suppression of HIV replication and recovery of CD4 T cell counts. Knowledge of the function of CD4 T cells in immune reconstitution was derived from large clinical studies demonstrating that primary and secondary prophylaxis against infectious agents, such as Pneumocystis jirovecii (Pneumocystis carinii), Mycobacterium avium complex, cytomegalovirus, and other pathogens, can be discontinued safely once CD4 T cell counts have increased beyond pathogen-specific threshold levels (usually >200 CD4 T cells/mm3) for 3-6 months. The downside of immune reconstitution is an inflammatory syndrome occurring days to months after the start of ART, with outcomes ranging from minimal morbidity to fatal progression. This syndrome can be elicited by infectious and noninfectious antigens. Microbiologically, the possible pathogenic pathways involve recognition of antigens associated with ongoing infection or recognition of persisting antigens associated with past (nonreplicating) infection. Specific antimicrobial therapy, nonsteroidal anti-inflammatory drugs, and/or steroids for managing immune reconstitution syndrome should be considered.

Antiretroviral Therapy, Highly Active↗
PubMed2004

Intranasal influenza vaccine in a working population.

In the present study, we assessed the incidence of adverse events and influenza-like symptoms in a working population in Switzerland that was vaccinated against influenza. A total of 12,582 individuals of working age (<65 years old) were offered a free influenza vaccine of their choice (injectable or intranasal vaccine) in October and November 2000. Of these individuals, 1600 were vaccinated against influenza. Ninety-seven percent of the vaccine recipients chose the intranasal vaccine, and 3% chose the injectable influenza vaccine. The incidence of influenza-like symptoms and side effects was 13% and 36%, respectively. Individuals who chose the intranasal vaccine were more likely to report side effects (OR, 3.23; 95% CI, 1.29-8.08). Facial paralysis was observed in 11 patients and was the most severe adverse event associated with the intranasal influenza vaccine. As a result of these adverse events, the intranasal vaccine was removed from the market in the fall of 2001.

Administration, Intranasal↗
PubMed2004

Acute renal failure on immune reconstitution in an HIV-positive patient with miliary tuberculosis.

Immune reconstitution syndrome following HAART in human immunodeficiency virus (HIV)-infected patients is characterized by inflammatory worsening of organ functions despite improvement in HIV surrogate markers of HIV infection. We describe a patient with miliary tuberculosis and urinary shedding of acid fast bacilli who developed acute renal failure 8 weeks after initiation of antituberculosis therapy and 6 weeks after initiation of HAART. The diagnostic workup and further course of disease implicated immune reconstitution syndrome as the cause of acute renal failure.

Acute Kidney Injury↗
PubMed2004

Optimising the performance of an outpatient setting.

BACKGROUND: An outpatient setting typically includes experienced and novice resident physicians who are supervised by senior staff physicians. The performance of this kind of outpatient setting, for a given mix of experienced and novice resident physicians, is determined by the number of senior staff physicians available for supervision. The optimum mix of human resources may be determined using discrete-event simulation. METHODS: An outpatient setting represents a system where concurrency and resource sharing are important. These concepts can be modelled by means of timed Coloured Petri Nets (CPN), which is a discrete-event simulation formalism. We determined the optimum mix of resources (i.e. the number of senior staff physicians needed for a given number of experienced and novice resident physicians) to guarantee efficient overall system performance. RESULTS: In an outpatient setting with 10 resident physicians, two staff physicians are required to guarantee a minimum level of system performance (42-52 patients are seen per 5-hour period). However, with 3 senior staff physicians system performance can be improved substantially (49-56 patients per 5-hour period). An additional fourth staff physician does not substantially enhance system performance (50-57 patients per 5-hour period). CONCLUSION: Coloured Petri Nets provide a flexible environment in which to simulate an outpatient setting and assess the impact of any staffing changes on overall system performance, to promote informed resource allocation decisions.

Ambulatory Care↗
PubMed2004

Stable partnership and progression to AIDS or death in HIV infected patients receiving highly active antiretroviral therapy: Swiss HIV cohort study.

OBJECTIVES: To explore the association between a stable partnership and clinical outcome in HIV infected patients receiving highly active antiretroviral therapy (HAART). DESIGN: Prospective cohort study of adults with HIV (Swiss HIV cohort study). SETTING: Seven outpatient clinics throughout Switzerland. PARTICIPANTS: The 3736 patients in the cohort who started HAART before 2002 (median age 36 years, 29% female, median follow up 3.6 years). MAIN OUTCOME MEASURES: Time to AIDS or death (primary endpoint), death alone, increases in CD4 cell count of at least 50 and 100 above baseline, optimal viral suppression (a viral load below 400 copies/ml), and viral rebound. RESULTS: During follow up 2985 (80%) participants reported a stable partnership on at least one occasion. When starting HAART, 52% (545/1042) of participants reported a stable partnership; after five years of follow up 46% (190/412) of participants reported a stable partnership. In an analysis stratified by previous antiretroviral therapy and clinical stage when starting HAART (US Centers for Disease Control and Prevention group A, B, or C), the adjusted hazard ratio for progression to AIDS or death was 0.79 (95% confidence interval 0.63 to 0.98) for participants with a stable partnership compared with those without. Adjusted hazards ratios for other endpoints were 0.59 (0.44 to 0.79) for progression to death, 1.15 (1.06 to 1.24) for an increase in CD4 cells of 100 counts/microl or more, and 1.06 (0.98 to 1.14) for optimal viral suppression. CONCLUSIONS: A stable partnership is associated with a slower rate of progression to AIDS or death in HIV infected patients receiving HAART.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Productivity costs and determinants of productivity in HIV-infected patients.

BACKGROUND: In HIV-infected patients, reduced ability to work may be an important component of the societal costs of this disease. Few data about productivity costs in HIV-infected patients are available. OBJECTIVE: The goals of this study were to estimate productivity costs in the HIV-infected population in Switzerland and to identify characteristics that may influence patient productivity. METHODS: This cross-sectional study included all patients younger than retirement age (65 years for men and 62 years for women) who were enrolled in the Swiss HIV Cohort Study in 2002. Measures of productivity losses in this population were based on patients' ability to work and the median monthly wage rates adjusted for age, sex, and educational level in Switzerland. Factors associated with ability to work were analyzed in a multivariate ordinary logistic regression (proportional odds) model. As of July 1, 2002, the exchange rate for US dollars to Swiss francs (CHF) was US $1.00 approximately equal to CHF 1.48. RESULTS: A total of 5319 HIV-infected patients (3665 men [68.9%] and 1655 women [31.1%]; mean [SD] age, 40.6 [8.4] years; range, 17-64 years) were included in the study. The mean annual productivity loss per patient was estimated at CHF 22,910 (95% CI, CHF 22,064-CHF 23, 756). Ability to work was independently associated with the following (P < 0.001 for all): age (10-year increase: odds ratio [OR], 0.60 [95% CI, 0.54-0.62]), sex (female/male: OR, 0.73 [95% CI, 0.63-0.84]), history of IV drug use (OR, 0.22 [95% CI, 0.19-0.26]), time since first positive HIV test (>10 years vs < or = 10 years: OR, 0.66 [95% CI, 0.58-0.76]), CD4 cell count (201-500 vs 0-200 cells/microL: OR, 1.68 [95% CI, 1.38-2.46]; > or =501 vs 0-200 cells/microL: OR, 2.01 [95%, CI, 1.64-2.46]), history of AIDS-indicator disease (OR, 0.47 [95% CI, 0.41-0.55]), stable partnership during the last 6 months (OR, 1.63 [95% CI, 1.43-1.86]), and educational level (higher vs basic: OR, 1.68 [95% CI, 1.45-1.95]). CONCLUSIONS: Productivity losses to society for the HIV-infected population appeared to be substantial in this analysis. Given a patient's clinical health status, a higher education level and a stable partnership were associated with greater ability to work. Socioeconomic characteristics may influence the cost-effectiveness of health care interventions in HIV-infected patients.

Adolescent↗
PubMed2004

Carriage of Staphylococcus aureus among injection drug users: lower prevalence in an injection heroin maintenance program than in an oral methadone program.

OBJECTIVES: To compare the prevalence of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) carriage among injection drug users (IDUs) treated in an injection heroin maintenance program with that among IDUs treated in an oral methadone program, and to determine predictors of S. aureus carriage. DESIGN: Survey. SETTING: Two opiate maintenance programs at a psychiatric university clinic. PARTICIPANTS: A volunteer sample consisting of 94 (74%) of 127 IDUs treated in an injection opiate maintenance program with at least twice daily injections of heroin, and 70 (56%) of 125 IDUs treated in an oral methadone program. RESULTS: Addicts treated in the intravenous heroin substitution program had a significantly lower overall rate of S. aureus carriage (37 of 94 [39.4%] vs 42 of 70 [60%]; P = .009) and a significantly lower rate of nasal carriage (21 of 94 [22.3%] vs 30 of 70 [42.9%]; P = .005) than did addicts treated in the oral methadone program. Being treated in the oral methadone program was the only independent predictor of S. aureus carriage (odds ratio, 2.27; 95% confidence interval, 1.19-4.31; P = .012). All S. aureus isolates were susceptible to oxacillin. CONCLUSIONS: The regular use of needles under aseptic conditions did not increase the rate of S. aureus carriage among IDUs. Further studies are necessary to investigate whether the lower rate of S. aureus carriage among IDUs treated with intravenous heroin leads to a lower incidence of S. aureus infections in these patients.

Administration, Oral↗
PubMed2004

Long-term virological response to multiple sequential regimens of highly active antiretroviral therapy for HIV infection.

OBJECTIVE: Information about the virological response to sequential highly active antiretroviral therapy (HAART) for HIV infection is limited. The virological response to four consecutive therapies was evaluated in the Swiss HIV Cohort. DESIGN: Retrospective analysis in an observational cohort. METHODS: 1140 individuals receiving uninterrupted HAART for 4.8 +/- 0.6 years were included. The virological response was classified as success (<400 copies/ml), low-level (LF: 400-5000 copies/ml) or high-level failure (HF: >5000 copies/ml). Potential determinants of the virological response, including patient demographics, treatment history and virological response to previous HAART regimens were analysed using survival and logistic regression analyses. RESULTS: 40.1% failed virologically on the first (22.0% LF; 18.1% HF), 35.1% on the second (14.2% LF; 20.9% HF), 34.2% on the third (9.9% LF; 24.3% HF) and 32.7% on the fourth HAART regimen (9% LF; 23.7% HF). Nucleoside pre-treatment (OR: 2.34; 95% CI: 1.67-3.29) and low baseline CD4 T-cell count (OR: 0.79/100 cells rise; 95% CI: 0.72-0.88) increased the risk of HF on the first HAART. Virological failure on HAART with HIV-1 RNA levels exceeding 1000 copies/ml predicted a poor virological response to subsequent HAART regimens. A switch from a protease inhibitor- to a non-nucleoside reverse transcriptase inhibitor-containing regimen significantly reduced the risk of HF. Multiple switches of HAART did not affect the recovery of CD4 T lymphocytes. CONCLUSION: Multiple sequential HAART regimens do not per se reduce the likelihood of long-term virological suppression and immunological recovery. However, early virological failure increases significantly the risk of subsequent unfavourable virological responses. The choice of a potent initial antiretroviral drug regimen is therefore critical.

Adult↗
PubMed2004

Infrequent transmission of HIV-1 drug-resistant variants.

Transmission of drug-resistant variants is influenced by several factors, including the prevalence of drug resistance in the population of HIV-1-infected patients, HIV-1 RNA levels and transmission by recently infected patients. In order to evaluate the impact of these factors on the transmission of drug-resistant variants, we have defined the population of potential transmitters and compared their resistance profiles to those of newly infected patients. Sequencing of pol gene was performed in 220 recently infected patients and in 373 chronically infected patients with HIV-1 RNA >1000 copies/ml. Minimal and maximal drug-resistance profiles of potential transmitters were estimated by weighting resistance profiles of chronically infected patients with estimates of the Swiss HIV-1-infected population, the prevalence of exposure to antiviral drugs and the proportion of infections attributed to primary HIV infections. The drug-resistance prevalence in recently infected patients was 10.5% (one class drug resistance: 9.1%; two classes: 1.4%; three classes: 0%). Phylogenetic analysis revealed significant clustering for 30% of recent infections. The drug-resistance prevalence in chronically infected patients was 72.4% (one class: 29%; two classes: 27.6%; three classes: 15.8%). After adjustment, the risk of transmission relative to wild-type was reduced both for one class drug resistance (minimal and maximal estimates: odds ratio: 0.39, P<0.001; and odds ratio: 0.55, P=0.011, respectively), and for two to three class drug resistance (odds ratios: 0.05 and 0.07, respectively, P<0.001). Neither sexual behaviour nor HIV-1 RNA levels explained the low transmission of drug-resistant variants. These data suggest that drug-resistant variants and in particular multidrug-resistant variants have a substantially reduced transmission capacity.

Adolescent↗