Health care provider communication training in rural Tanzania empowers HIV-infected patients on antiretroviral therapy to discuss adherence problems.

OBJECTIVES: Self-reported adherence assessment in HIV-infected patients on antiretroviral therapy (ART) is challenging and may overestimate adherence. The aim of this study was to improve the ability of health care providers to elicit patients' reports of nonadherence using a "patient-centred" approach in a rural sub-Saharan African setting. METHODS: A prospective interventional cohort study of HIV-infected patients on ART for ≥ 6 months attending an HIV clinic in rural Tanzania was carried out. The intervention consisted of a 2-day workshop for health care providers on patient-centred communication and the provision of an adherence assessment checklist for use in the consultations. Patients' self-reports of nonadherence (≥ 1 missed ART dose/4 weeks), subtherapeutic plasma ART concentrations (< 2.5th percentile of published population-based pharmacokinetic models), and virological and immunological failure according to the World Health Organization definition were assessed before and after (1-3 and 6-9 months after) the intervention. RESULTS: Before the intervention, only 3.3% of 299 patients included in the study reported nonadherence. Subtherapeutic plasma ART drug concentrations and virological and immunological failure were recorded in 6.5%, 7.7% and 14.5% of the patients, respectively. Two months after the intervention, health care providers detected significantly more patients reporting nonadherence compared with baseline (10.7 vs. 3.3%, respectively; P < 0.001), decreasing to 5.7% after 6-9 months. A time trend towards higher drug concentrations was observed for efavirenz but not for other drugs. The virological failure rate remained unchanged whereas the immunological failure rate decreased from 14.4 to 8.7% at the last visit (P = 0.002). CONCLUSIONS: Patient-centred communication can successfully be implemented with a simple intervention in rural Africa. It increases the likelihood of HIV-infected patients reporting problems with adherence to ART; however, sustainability remains a challenge.

Emergence of Acquired HIV-1 Drug Resistance Almost Stopped in Switzerland: A 15-Year Prospective Cohort Analysis.

BACKGROUND: Drug resistance is a major barrier to successful antiretroviral treatment (ART). Therefore, it is important to monitor time trends at a population level. METHODS: We included 11 084 ART-experienced patients from the Swiss HIV Cohort Study (SHCS) between 1999 and 2013. The SHCS is highly representative and includes 72% of patients receiving ART in Switzerland. Drug resistance was defined as the presence of ≥1 major mutation in a genotypic resistance test. To estimate the prevalence of drug resistance, data for patients with no resistance test was imputed based on the patient's risk of harboring drug-resistant viruses. RESULTS: The emergence of new drug resistance mutations declined dramatically from 401 to 23 patients between 1999 and 2013. The upper estimated prevalence limit of drug resistance among ART-experienced patients decreased from 57.0% in 1999 to 37.1% in 2013. The prevalence of 3-class resistance decreased from 9.0% to 4.4% and was always <0.4% for patients who initiated ART after 2006. Most patients actively participating in the SHCS in 2013 with drug-resistant viruses initiated ART before 1999 (59.8%). Nevertheless, in 2013, 94.5% of patients who initiated ART before 1999 had good remaining treatment options based on Stanford algorithm. CONCLUSIONS: Human immunodeficiency virus type 1 drug resistance among ART-experienced patients in Switzerland is a well-controlled relic from the era before combination ART. Emergence of drug resistance can be virtually stopped with new potent therapies and close monitoring.

Validation of a treatment algorithm for orthopaedic implant-related infections with device-retention-results from a prospective observational cohort study.

Success rates for treatment regimens involving retention of an infected implant are conflicting and failure rates of up to 80% have been reported. We aimed to validate a proposed treatment algorithm, based on strict selection criteria, by assessing long-term outcome of treatment for orthopaedic device-related infection (ODRI) with retention. From January 1999 to December 2009, all patients diagnosed with ODRI at the University Hospital Basel, Switzerland were eligible for treatment with open surgical debridement, implant-retention and antibiotics, if duration of clinical symptoms was ≤3 weeks, the implant was stable, the soft-tissue had no abscess or sinus tract, and the causative pathogen was susceptible to antimicrobial agents with activity against surface-adhering microorganisms. Antimicrobial treatment was administered according to a predefined algorithm. The primary outcome was treatment failure after 2-year follow up. A total of 455 patients were diagnosed with an ODRI, of whom 233 (51.2%) patients were eligible for treatment involving implant-retention. Causative pathogens were mainly Staphylococcus aureus (41.6%) and coagulase-negative staphylococci (33.9%). Among patients with ODRIs related to prostheses, failure was documented in 10.8% (12/111) and in patients with ODRIs related to osteosyntheses, failure occurred in 9.8% (12/122) after 2 years of follow up. In all, 90% of ODRIs were successfully cured with surgical debridement and implant-retention in addition to long-term antimicrobial therapy according to a predefined treatment algorithm: if patients fulfilled strict selection criteria and there was susceptibility to rifampin for Gram-positive pathogens and ciprofloxacin for Gram-negative pathogens.

HIV-1 Transmission During Recent Infection and During Treatment Interruptions as Major Drivers of New Infections in the Swiss HIV Cohort Study.

BACKGROUND: Reducing the fraction of transmissions during recent human immunodeficiency virus (HIV) infection is essential for the population-level success of "treatment as prevention". METHODS: A phylogenetic tree was constructed with 19 604 Swiss sequences and 90 994 non-Swiss background sequences. Swiss transmission pairs were identified using 104 combinations of genetic distance (1%-2.5%) and bootstrap (50%-100%) thresholds, to examine the effect of those criteria. Monophyletic pairs were classified as recent or chronic transmission based on the time interval between estimated seroconversion dates. Logistic regression with adjustment for clinical and demographic characteristics was used to identify risk factors associated with transmission during recent or chronic infection. FINDINGS: Seroconversion dates were estimated for 4079 patients on the phylogeny, and comprised between 71 (distance, 1%; bootstrap, 100%) to 378 transmission pairs (distance, 2.5%; bootstrap, 50%). We found that 43.7% (range, 41%-56%) of the transmissions occurred during the first year of infection. Stricter phylogenetic definition of transmission pairs was associated with higher recent-phase transmission fraction. Chronic-phase viral load area under the curve (adjusted odds ratio, 3; 95% confidence interval, 1.64-5.48) and time to antiretroviral therapy (ART) start (adjusted odds ratio 1.4/y; 1.11-1.77) were associated with chronic-phase transmission as opposed to recent transmission. Importantly, at least 14% of the chronic-phase transmission events occurred after the transmitter had interrupted ART. CONCLUSIONS: We demonstrate a high fraction of transmission during recent HIV infection but also chronic transmissions after interruption of ART in Switzerland. Both represent key issues for treatment as prevention and underline the importance of early diagnosis and of early and continuous treatment.

Strong Impact of Smoking on Multimorbidity and Cardiovascular Risk Among Human Immunodeficiency Virus-Infected Individuals in Comparison With the General Population.

Background. Although acquired immune deficiency syndrome-associated morbidity has diminished due to excellent viral control, multimorbidity may be increasing among human immunodeficiency virus (HIV)-infected persons compared with the general population. Methods. We assessed the prevalence of comorbidities and multimorbidity in participants of the Swiss HIV Cohort Study (SHCS) compared with the population-based CoLaus study and the primary care-based FIRE (Family Medicine ICPC-Research using Electronic Medical Records) records. The incidence of the respective endpoints were assessed among SHCS and CoLaus participants. Poisson regression models were adjusted for age, sex, body mass index, and smoking. Results. Overall, 74 291 participants contributed data to prevalence analyses (3230 HIV-infected; 71 061 controls). In CoLaus, FIRE, and SHCS, multimorbidity was present among 26%, 13%, and 27% of participants. Compared with nonsmoking individuals from CoLaus, the incidence of cardiovascular disease was elevated among smoking individuals but independent of HIV status (HIV-negative smoking: incidence rate ratio [IRR] = 1.7, 95% confidence interval [CI] = 1.2-2.5; HIV-positive smoking: IRR = 1.7, 95% CI = 1.1-2.6; HIV-positive nonsmoking: IRR = 0.79, 95% CI = 0.44-1.4). Compared with nonsmoking HIV-negative persons, multivariable Poisson regression identified associations of HIV infection with hypertension (nonsmoking: IRR = 1.9, 95% CI = 1.5-2.4; smoking: IRR = 2.0, 95% CI = 1.6-2.4), kidney (nonsmoking: IRR = 2.7, 95% CI = 1.9-3.8; smoking: IRR = 2.6, 95% CI = 1.9-3.6), and liver disease (nonsmoking: IRR = 1.8, 95% CI = 1.4-2.4; smoking: IRR = 1.7, 95% CI = 1.4-2.2). No evidence was found for an association of HIV-infection or smoking with diabetes mellitus. Conclusions. Multimorbidity is more prevalent and incident in HIV-positive compared with HIV-negative individuals. Smoking, but not HIV status, has a strong impact on cardiovascular risk and multimorbidity.

Increases in Condomless Sex in the Swiss HIV Cohort Study.

Condomless sex is a key driver of sexually transmitted diseases. In this study, we assess the long-term changes (2000-2013) of the occurrence of condomless sex among human immunodeficiency virus (HIV)-infected individuals enrolled in the Swiss HIV Cohort study. The frequencies with which HIV-infected individuals reported condomless sex were either stable or only weakly increasing for 2000-2008. For 2008-2013, these rates increased significantly for stable relationships among heterosexuals and men who have sex with men (MSM) and for occasional relationships among MSM. Our results highlight the increasing public health challenge posed by condomless sex and show that condomless sex has been increasing even in the most recent years.

Incident Hepatitis C Virus Infections in the Swiss HIV Cohort Study: Changes in Treatment Uptake and Outcomes Between 1991 and 2013.

Background. The hepatitis C virus (HCV) epidemic is evolving rapidly in patients infected with human immunodeficiency virus (HIV). We aimed to describe changes in treatment uptake and outcomes of incident HCV infections before and after 2006, the time-point at which major changes in HCV epidemic became apparent. Methods. We included all adults with an incident HCV infection before June 2012 in the Swiss HIV Cohort Study, a prospective nationwide representative cohort of individuals infected with HIV. We assessed the following outcomes by time period: the proportion of patients starting an HCV therapy, the proportion of treated patients achieving a sustained virological response (SVR), and the proportion of patients with persistent HCV infection during follow-up. Results. Of 193 patients with an HCV seroconversion, 106 were diagnosed before and 87 after January 2006. The proportion of men who have sex with men increased from 24% before to 85% after 2006 (P < .001). Hepatitis C virus treatment uptake increased from 33% before 2006 to 77% after 2006 (P < .001). Treatment was started during early infection in 22% of patients before and 91% after 2006 (P < .001). An SVR was achieved in 78% and 29% (P = .01) of patients treated during early and chronic HCV infection. The probability of having a detectable viral load 5 years after diagnosis was 0.67 (95% confidence interval [CI], 0.58-0.77) in the group diagnosed before 2006 and 0.24 (95% CI, 0.16-0.35) in the other group (P < .001). Conclusions. In recent years, increased uptake and earlier initiation of HCV therapy among patients with incident infections significantly reduced the proportion of patients with replicating HCV.

Gender inequalities in the response to combination antiretroviral therapy over time: the Swiss HIV Cohort Study.

OBJECTIVES: Gender-specific data on the outcome of combination antiretroviral therapy (cART) are a subject of controversy. We aimed to compare treatment responses between genders in a setting of equal access to cART over a 14-year period. METHODS: Analyses included treatment-naïve participants in the Swiss HIV Cohort Study starting cART between 1998 and 2011 and were restricted to patients infected by heterosexual contacts or injecting drug use, excluding men who have sex with men. RESULTS: A total of 3925 patients (1984 men and 1941 women) were included in the analysis. Women were younger and had higher CD4 cell counts and lower HIV RNA at baseline than men. Women were less likely to achieve virological suppression < 50 HIV-1 RNA copies/mL at 1 year (75.2% versus 78.1% of men; P = 0.029) and at 2 years (77.5% versus 81.1%, respectively; P = 0.008), whereas no difference between sexes was observed at 5 years (81.3% versus 80.5%, respectively; P = 0.635). The probability of virological suppression increased in both genders over time (test for trend, P < 0.001). The median increase in CD4 cell count at 1, 2 and 5 years was generally higher in women during the whole study period, but it gradually improved over time in both sexes (P < 0.001). Women also were more likely to switch or stop treatment during the first year of cART, and stops were only partly driven by pregnancy. In multivariate analysis, after adjustment for sociodemographic factors, HIV-related factors, cART and calendar period, female gender was no longer associated with lower odds of virological suppression. CONCLUSIONS: Gender inequalities in the response to cART are mainly explained by the different prevalence of socioeconomic characteristics in women compared with men.

Evaluation of treatment outcomes for Stenotrophomonas maltophilia bacteraemia.

OBJECTIVE: The goal of this study was to retrospectively collect data about treatment outcomes in patients diagnosed with Stenotrophomonas maltophilia bacteraemia over a period of 20 years and evaluate these data with respect to the efficacy of treatment options. METHODS: The setting was a 700-bed tertiary care hospital in a large urban area. Hospital databases and medical records provided information about episodes of S. maltophilia, patient characteristics and treatment outcomes. Patients with at least one positive blood culture for S. maltophilia were included in the study. Data were analysed with respect to clinical improvement and mortality ≤30 days after the onset of infection. We compared patient characteristics, laboratory values and treatments by using the Chi-square or Fisher's exact tests and the Mann-Whitney test. RESULTS: We investigated 27 patients with S. maltophilia bacteraemia. The focus of infection was a central venous catheter in 18 (67 %) cases. The 30-day mortality rate was 11 %. All patients who were treated with an antibiotic that was effective in vitro against the pathogen recovered clinically and survived ≥30 days after the onset of infection. The most frequently used antibiotic was trimethoprim-sulfamethoxazole administered alone or in combination with a fluoroquinolone. CONCLUSIONS: Despite the fact that S. maltophilia is resistant to multiple antibiotics, the prognosis for patients with S. maltophilia bacteraemia is good when they are treated with antibiotics that are effective against this pathogen in vitro.

Obesity Trends and Body Mass Index Changes After Starting Antiretroviral Treatment: The Swiss HIV Cohort Study.

BACKGROUND: The factors that contribute to increasing obesity rates in human immunodeficiency virus (HIV)-positive persons and to body mass index (BMI) increase that typically occurs after starting antiretroviral therapy (ART) are incompletely characterized. METHODS: We describe BMI trends in the entire Swiss HIV Cohort Study (SHCS) population and investigate the effects of demographics, HIV-related factors, and ART on BMI change in participants with data available before and 4 years after first starting ART. RESULTS: In the SHCS, overweight/obesity prevalence increased from 13% in 1990 (n = 1641) to 38% in 2012 (n = 8150). In the participants starting ART (n = 1601), mean BMI increase was 0.92 kg/m(2) per year (95% confidence interval, .83-1.0) during year 0-1 and 0.31 kg/m(2) per year (0.29-0.34) during years 1-4. In multivariable analyses, annualized BMI change during year 0-1 was associated with older age (0.15 [0.06-0.24] kg/m(2)) and CD4 nadir <199 cells/µL compared to nadir >350 (P < .001). Annualized BMI change during years 1-4 was associated with CD4 nadir <100 cells/µL compared to nadir >350 (P = .001) and black compared to white ethnicity (0.28 [0.16-0.37] kg/m(2)). Individual ART combinations differed little in their contribution to BMI change. CONCLUSIONS: Increasing obesity rates in the SHCS over time occurred at the same time as aging of the SHCS population, demographic changes, earlier ART start, and increasingly widespread ART coverage. Body mass index increase after ART start was typically biphasic, the BMI increase in year 0-1 being as large as the increase in years 1-4 combined. The effect of ART regimen on BMI change was limited.

Prospective study of a panfungal PCR assay followed by sequencing, for the detection of fungal DNA in normally sterile specimens in a clinical setting: a complementary tool in the diagnosis of invasive fungal disease?

We prospectively analyzed 34 clinical biopsy samples from 23 patients with a suspected invasive fungal infection by fungal culture, histology and a panfungal PCR followed by sequencing. Results were compared to the composite diagnosis according the European Organization for Research and Treatment of Cancer (EORTC) criteria. In 34 samples, culture, histology and panfungal PCR were positive in 35%, 38% and 62%, respectively. On the sample level the panfungal PCR revealed a sensitivity of 69% and a specificity of 62.5% compared to proven IFI according postoperative EORTC criteria. On patient level, the sensitivity of the PCR approach was 100%, specificity 62.5%.

[Morbidity and mortality in HIV infection]. / Morbidität und Mortalität der HIV-Infektion.

Combination antiretroviral therapy (cART) has dramatically improved the prognosis of HIV-infected individuals, with a close to a normal life expectancy in a significant proportion of treated individuals. Upon start of cART, HIV-induced immune deficiency can be prevented or, if already present, reconstituted. Remaining morbidity and mortality is partly due to the late diagnosis of HIV infection or late presentation of patients, when CD4-T-cells have already fallen below 200 cells/µl and/or AIDS-defining conditions have manifested. Further reasons for remaining morbidity and mortality are related to co-morbidities such as viral hepatitis and tumors, particularly in older patients. As HIV-infected patients become older, increasing co-morbidities and socio-economic costs may become a challenge in the future.

How to discriminate contamination from bloodstream infection due to coagulase-negative staphylococci: a prospective study with 654 patients.

Coagulase-negative staphylococci (CoNS) are frequent contaminants of blood cultures. We aimed to evaluate the systemic inflammatory response syndrome (SIRS) criteria in patients with CoNS bacteraemia for discrimination between true bloodstream infection (BSI) and contamination. Prospective evaluation was carried out of clinical and laboratory parameters in adults with at least one positive blood culture with CoNS at the University Hospital of Basel between 2003 and 2007. Of 3060 positive blood cultures, 654 episodes of CoNS bacteraemia were identified. Of these, 232 (35%) were considered to be true BSI and 422 (65%) were considered to be contamination. Overall, 80% of study participants had at least one SIRS criterion, fever being the most common, and 49% had at least two SIRS criteria. In the multivariate analysis, independent predictors of BSI were fever or hypothermia (OR 2.93, 95% CI 1.91-4.5), tachycardia (OR 2.29, 95% CI 1.50-3.50), tachypnoea (OR 2.4, 95% CI 1.30-4.43), leucocytosis or leucopenia (OR 4.15, 95% CI 2.17-6.36) and the presence of a central venous line (OR 5.38, 95% CI 3.25-8.88). The probability of BSI increased with each additional SIRS criterion, ranging from 42.4% in patients with only one SIRS criterion to 56.7% for those with two criteria, and 72.3% for patients with three SIRS criteria. A positive blood culture with CoNS most likely represents true BSI if the patient has at least three SIRS criteria or two SIRS criteria and a central venous catheter. These simple bedside criteria may guide decision to treat, decreasing the use of glycopeptides.

Participation, characteristics and retention rates of HIV-positive immigrants in the Swiss HIV Cohort Study.

OBJECTIVE: Data from observational cohorts may be influenced by population structure and loss to follow-up (LTFU). Quality of care may be associated with participation in cohort networks. We aimed to study the participation, characteristics and retention rates of immigrants in the Swiss HIV Cohort Study (SHCS). METHODS: We compared enrolment over time (1996-1999, 2000-2003 and 2004-2008) and LTFU between individuals from different geographical regions. In 2008, we performed a cross-sectional survey to investigate the proportion of individuals not participating in the SHCS but who were in care at SHCS institutions. Predictors for LTFU were analysed using Cox proportional hazard models, and those for nonparticipation using logistic regression. RESULTS: A total of 7840 individuals entered the SHCS during the observation period. The proportion of immigrants increased over time, especially the proportion of women from sub-Saharan Africa, which increased from 21 to 48% during the observation period. Overall LTFU was 3.76 [95% confidence interval (CI) 3.58-3.95]/100, with the highest hazard ratio in men from sub-Saharan Africa (2.82/100 patient-years; 95% CI 2.30-3.46/100), compared with men from northwestern countries. Other predictors for LTFU were age <30 years, lower education, injecting drug use, and higher baseline CD4 cell counts. Participants taking antiretroviral therapy had reduced LTFU. The survey showed that 84% of HIV-infected patients in care at SHCS institutions were enrolled in the cohort. Nonparticipation was more likely among men from non-European regions (odds ratio 2.73; 95% CI 2.29-3.24), women from sub-Saharan Africa (odds ratio 3.01; 95% CI 2.40-3.77) and women from Latin America/Caribbean (odds ratio 2.10; 95% CI 1.30-3.39). CONCLUSIONS: Numbers of HIV-infected immigrants are increasing but they are underrepresented in the SHCS, and immigrants are more likely to be lost to follow-up.

High specificity of line-immunoassay based algorithms for recent HIV-1 infection independent of viral subtype and stage of disease.

BACKGROUND: Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have shown that a patient's antibody reaction in a confirmatory line immunoassay (INNO-LIA HIV I/II Score, Innogenetics) provides information on the duration of infection. Here, we sought to further investigate the diagnostic specificity of various Inno-Lia algorithms and to identify factors affecting it. METHODS: Plasma samples of 714 selected patients of the Swiss HIV Cohort Study infected for longer than 12 months and representing all viral clades and stages of chronic HIV-1 infection were tested blindly by Inno-Lia and classified as either incident (up to 12 m) or older infection by 24 different algorithms. Of the total, 524 patients received HAART, 308 had HIV-1 RNA below 50 copies/mL, and 620 were infected by a HIV-1 non-B clade. Using logistic regression analysis we evaluated factors that might affect the specificity of these algorithms. RESULTS: HIV-1 RNA < 50 copies/mL was associated with significantly lower reactivity to all five HIV-1 antigens of the Inno-Lia and impaired specificity of most algorithms. Among 412 patients either untreated or with HIV-1 RNA ≥ 50 copies/mL despite HAART, the median specificity of the algorithms was 96.5% (range 92.0-100%). The only factor that significantly promoted false-incident results in this group was age, with false-incident results increasing by a few percent per additional year. HIV-1 clade, HIV-1 RNA, CD4 percentage, sex, disease stage, and testing modalities exhibited no significance. Results were similar among 190 untreated patients. CONCLUSIONS: The specificity of most Inno-Lia algorithms was high and not affected by HIV-1 variability, advanced disease and other factors promoting false-recent results in other STARHS. Specificity should be good in any group of untreated HIV-1 patients.

Survey of aspergillosis in non-neutropenic patients in Swiss teaching hospitals.

Invasive aspergillosis (IA) is a live-threatening opportunistic infection that is best described in haematological patients with prolonged neutropenia or graft-versus-host disease. Data on IA in non-neutropenic patients are limited. The aim of this study was to establish the incidence, disease manifestations and outcome of IA in non-neutropenic patients diagnosed in five Swiss university hospitals during a 2-year period. Case identification was based on a comprehensive screening of hospital records. All cases of proven and probable IA were retrospectively analysed. Sixty-seven patients were analysed (median age 60 years; 76% male). Sixty-three per cent of cases were invasive pulmonary aspergillosis (IPA), and 17% of these were disseminated aspergillosis. The incidence of IPA was 1.2/10 000 admissions. Six of ten cases of extrapulmonary IA affected the brain. There were six cases of invasive rhinosinusitis, six cases of chronic pulmonary aspergillosis, and cases three of subacute pulmonary aspergillosis. The most frequent underlying condition of IA was corticosteroid treatment (57%), followed by chronic lung disease (48%), and intensive-care unit stays (43%). In 38% of patients with IPA, the diagnosis was established at autopsy. Old age was the only risk factor for post-mortem diagnosis, whereas previous solid organ transplantation and chronic lung disease were associated with lower odds of post-mortem diagnosis. The mortality rate was 57%.

Changing patterns of cancer incidence in the early- and late-HAART periods: the Swiss HIV Cohort Study.

BACKGROUND: The advent of highly active antiretroviral therapy (HAART) in 1996 led to a decrease in the incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL), but not of other cancers, among people with HIV or AIDS (PWHA). It also led to marked increases in their life expectancy. METHODS: We conducted a record-linkage study between the Swiss HIV Cohort Study and nine Swiss cantonal cancer registries. In total, 9429 PWHA provided 20,615, 17,690, and 15,410 person-years in the pre-, early-, and late-HAART periods, respectively. Standardised incidence ratios in PWHA vs the general population, as well as age-standardised, and age-specific incidence rates were computed for different periods. RESULTS: Incidence of KS and NHL decreased by several fold between the pre- and early-HAART periods, and additionally declined from the early- to the late-HAART period. Incidence of cancers of the anus, liver, non-melanomatous skin, and Hodgkin's lymphoma increased in the early- compared with the pre-HAART period, but not during the late-HAART period. The incidence of all non-AIDS-defining cancers (NADCs) combined was similar in all periods, and approximately double that in the general population. CONCLUSIONS: Increases in the incidence of selected NADCs after the introduction of HAART were largely accounted for by the ageing of PWHA.

Secular trend and risk factors for antimicrobial resistance in Escherichia coli isolates in Switzerland 1997-2007.

BACKGROUND: Antibacterial resistance in Escherichia coli isolates of urinary infections, mainly to fluoroquinolones, is emerging. The aim of our study was to identify the secular trend of resistant E. coli isolates and to characterize the population at risk for colonization or infections with these organisms. PATIENTS AND METHODS: Retrospective analysis of 3,430 E.coli first isolates of urine specimens from patients admitted to the University Hospital Basel in 1997, 2000, 2003, and 2007. RESULTS: Resistance to ciprofloxacin, trimethoprim/sulfamethoxazole, and amoxicillin/clavulanate has increased over the 10-year study period (from 1.8% to 15.9%, 17.4% to 21.3%, and 9.5% to 14.5%, respectively). A detailed analysis of the 2007 data revealed that independent risk factors for ciprofloxacin resistance were age (5.3% < 35 years of age to 21.9% in patients > 75 years; odds ratio [OR] 1.29 per 10 years, 95% confidence interval [CI] 1.15-1.45, p < 0.001) and male gender (OR 1.59, 95% CI 1.05-2.41, p = 0.04). In contrast, nosocomial E. coli isolates were associated with lower odds of ciprofloxacin resistance (OR 0.51, 95% CI 0.28-0.67, p < 0.001). The frequency of resistant isolate rates was not influenced by the clinical significance (i.e., colonization vs urinary tract infection, UTI) or by whether the urine was taken from a urinary catheter. Importantly, the increase in ciprofloxacin resistance paralleled the increase in ciprofloxacin consumption in Switzerland (Pearson's correlation test R(2)= 0.998, p = 0.002). Of note, resistance was less frequent in isolates sent in by general practitioners. However, after adjustment for age and gender, only resistance against amoxicillin/clavulanate was found to be less frequent (OR 0.34, 95% CI 0.16-0.92, p = 0.03). CONCLUSION: Our study reveals that resistance rates have been increasing during the last decade. Published resistance rates may lack information due to important differences regarding age, gender, and probable origin of the isolates. Empirical therapy for UTI should be guided more on individual risk profile and local resistance data than on resistance data banks.

Uptake of and virological response to antiretroviral therapy among HIV-infected former and current injecting drug users and persons in an opiate substitution treatment programme: the Swiss HIV Cohort Study.

OBJECTIVES: The aim of the study was to investigate the influence of continued injecting drug use, enrolment in an opiate substitution treatment programme (OSTP), or cessation of injecting drug use on the uptake and course of antiretroviral therapy (ART). Design A prospective observational study of all participants in the Swiss HIV Cohort Study followed between 1997 and 2006 was carried out. METHODS: We distinguished four groups of former or current injecting drug users (IDUs): (i) abstinent former IDUs; (ii) persons in OSTPs without concomitant injecting drug use; (iii) persons in OSTPs with concomitant injecting drug use; (vi) current IDUs. These groups were compared with a group of patients who had never been IDUs. Factors related to ART uptake and virological endpoints were analysed using logistic generalized estimating equations. RESULTS: We followed 8660 participants for 48 477 person-years; 29.7% were in the IDU HIV transmission group. The likelihood of being on ART at biannual visits was lower among individuals in OSTPs with concomitant injecting drug use [odds ratio (OR) 0.79; 95% confidence interval (CI) 0.71-0.89] and current IDUs (OR 0.80; 95% CI 0.67-0.96), compared with those who had never been IDUs (reference), abstinent former IDUs (OR 1.13; 95% CI 1.02-1.25) and individuals in OSTPs without injecting drug use (OR 1.18; 95% CI 1.06-1.31). The likelihood of suppressed viral replication on ART was similar among those who had never been IDUs, abstinent former IDUs and individuals in an OSTP without injecting drug use, and lower among those in OSTPs with concomitant drug use (OR 0.82; 95% CI 0.72-0.93) and current IDUs (OR 0.81; 0.65-1.00). Adherence to ART was decreased among persons with continued injecting drug use, and correlated with virological outcome. CONCLUSIONS: Uptake of and virological response to ART were improved among abstinent former IDUs and persons in OSTPs without concomitant injecting drug use, compared with persons with continued injecting drug use.

Kaposi sarcoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy.

Between 1984 and 2006, 12 959 people with HIV/AIDS (PWHA) in the Swiss HIV Cohort Study contributed a total of 73 412 person-years (py) of follow-up, 35 551 of which derived from PWHA treated with highly active antiretroviral therapy (HAART). Five hundred and ninety-seven incident Kaposi sarcoma (KS) cases were identified of whom 52 were among HAART users. Cox regression was used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (CI). Kaposi sarcoma incidence fell abruptly in 1996-1998 to reach a plateau at 1.4 per 1000 py afterwards. Men having sex with men and birth in Africa or the Middle East were associated with KS in both non-users and users of HAART but the risk pattern by CD4 cell count differed. Only very low CD4 cell count (<50 cells microl(-1)) at enrollment or at HAART initiation were significantly associated with KS among HAART users. The HR for KS declined steeply in the first months after HAART initiation and continued to be low 7-10 years afterwards (HR, 0.06; 95% CI, 0.02-0.17). Thirty-three out of 52 (63.5%) KS cases among HAART users arose among PWHA who had stopped treatment or used HAART for less than 6 months.