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Background Antiretroviral (ART) drugs have been associated with higher triglycerides (TG), higher total cholesterol (TC) and lower high-density lipoprotein cholesterol (HDL-C) levels. Associations between lipid levels with HIV viraemia and immunosuppression in the presence of ART remain unclear. Methods Participants from the D:A:D study with at least one TG/TC/HDL-C measurement were included. Linear mixed effect models were used to determine the association of ART, viral load (VL), nadir and current CD4+ T-cell count and previous AIDS diagnosis with lipids. Results Of 49,717 participants, 90%, 92% and 80% contributed at least one TG/TC/HDL-C measurement (median follow-up 6.8, 6.8 and 5.0 years, respectively). Predicted mean (95% CI) baseline levels for TG, TC and HDL-C (mmol/l), were 2.10 (2.05, 2.14), 4.94 (4.91, 4.98) and 1.08 (1.07, 1.10), respectively. Lopinavir was associated with the worst TG profile, (27.2% higher levels compared to atazanavir; 95% CI 25.2%, 29.2%), and darunavir had a similar profile as atazanavir. The nucleoside pair lamivudine/tenofovir was associated with the most favourable TG profile (-2.8%; -3.5%, -2.0%) compared with emtricitabine/tenofovir, whereas lamivudine/abacavir (+10.2%; +9.3%, +11.2%) and lamivudine/ stavudine (+8.0%; +6.9%, +9.0%), were associated with the worst. Raltegravir was associated with lower TG (-5.2%; -6.4%, -3.9%), and nevirapine had a more favourable HDL-C profile (+11.3%; +10.8%, +11.7%) than efavirenz (+5.3%; 5.0%, 5.7%), compared to atazanavir. Higher VLs were associated with lower TG/TC/HDL-C, whereas higher CD4+ T-cell counts were associated with higher TG/TC/HDL-C. Conclusions TG, TC and HDL-C levels, which generally improved over time, are dependent on ART, viraemia and, to a lesser extent, immunosuppression.

OBJECTIVE To determine the effect of nonadherence to antiretroviral therapy (ART) on virologic failure and mortality in naive individuals starting ART. DESIGN Prospective observational cohort study. METHODS Eligible individuals enrolled in the Swiss HIV Cohort Study, started ART between 2003 and 2012, and provided adherence data on at least one biannual clinical visit. Adherence was defined as missed doses (none, one, two, or more than two) and percentage adherence (>95, 90-95, and 500 copies/ml) and mortality. RESULTS Of 3150 individuals followed for a median 4.7 years, 480 (15.2%) experienced viral failure and 104 (3.3%) died, 1155 (36.6%) reported missing one dose, 414 (13.1%) two doses and, 333 (10.6%) more than two doses of ART. The risk of viral failure increased with each missed dose (one dose: hazard ratio [HR] 1.15, 95% confidence interval 0.79-1.67; two doses: 2.15, 1.31-3.53; more than two doses: 5.21, 2.96-9.18). The risk of death increased with more than two missed doses (HR 4.87, 2.21-10.73). Missing one to two doses of ART increased the risk of viral failure in those starting once-daily (HR 1.67, 1.11-2.50) compared with those starting twice-daily regimens (HR 0.99, 0.64-1.54, interaction P = 0.09). Consistent results were found for percentage adherence. CONCLUSION Self-report of two or more missed doses of ART is associated with an increased risk of both viral failure and death. A simple adherence question helps identify patients at risk for negative clinical outcomes and offers opportunities for intervention.

Bovet P (Clinical Epidemiology Unit, Institute of Social and Preventive Medicine, University of Lausanne, Bugnon 17, CH-1005 Lausanne, Switzerland), Rickenbach M, Wietlisbach V, Riesen W, Shamlaye C, Darioli R and Burnand B. Comparison of lipoprotein(a) distribution and its correlates among black and white populations. International Journal of Epidemiology 1994; 23: 20-27. Background Epidemiological data on serum lipoprotein(a) (Lp(a)), a presumably strong risk factor for coronary artery disease in White populations, has mostly been derived, in Black populations, from small samples. This study compares the distribution and the determinants of serum Lp(a) in Blacks and in Whites using large representative samples and the same methods in both populations. Methods The distribution and the correlates of serum Lp(a) were investigated in population-based samples of 701 Blacks in the Seychelles and 634 Whites in Switzerland, aged 25-64 years. Serum Lp(a) was quantified using a commercial immunoradiometric assay. Results The distribution of serum Lp(a) was similarly skewed in both ethnic groups, but median Lp(a) concentration was about two fold higher in Blacks (210 mg/l) compared to Whites (100 mg/l). The proportions of individuals with elevated serum Lp(a) >300 mg/l) was about 50% higher in Blacks (37.5%) than in Whites (25.2%). In both ethnic groups, serum Lp(a) was found to correlate with total cholesterol, LDL-cholesterol and apoprotein B but not with HDL-cholesterol, alcohol intake, smoking, and body mass index. The variance in serum Lp(a) concentration explained by any combination of these factors was smaller than 5.3% in the two populations. Conclusions The measured factors did not explain the higher levels of serum Lp(a) found in Blacks compared to Whites. These findings are consistent with the hypothesis that genetic factors account for much of the variation of serum Lp(a) in both populations

BACKGROUND: Sequence data from resistance testing offer unique opportunities to characterize the structure of human immunodeficiency virus (HIV) infection epidemics. METHODS: We analyzed a representative set of HIV type 1 (HIV-1) subtype B pol sequences from 5700 patients enrolled in the Swiss HIV Cohort Study. We pooled these sequences with the same number of sequences from foreign epidemics, inferred a phylogeny, and identified Swiss transmission clusters as clades having a minimal size of 10 and containing >or=80% Swiss sequences. RESULTS: More than one-half of Swiss patients were included within 60 transmission clusters. Most transmission clusters were significantly dominated by specific transmission routes, which were used to identify the following patient groups: men having sex with men (MSM) (38 transmission clusters; average cluster size, 29 patients) or patients acquiring HIV through heterosexual contact (HETs) and injection drug users (IDUs) (12 transmission clusters; average cluster size, 144 patients). Interestingly, there were no transmission clusters dominated by sequences from HETs only. Although 44% of all HETs who were infected between 1983 and 1986 clustered with injection drug users, this percentage decreased to 18% for 2003-2006 (P

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.

Mortality among HIV-infected persons is decreasing, and causes of death are changing. Classification of deaths is hampered because of low autopsy rates, frequent deaths outside of hospitals, and shortcomings of International Statistical Classification of Diseases and Related Health Problems (ICD-10) coding.

Objectives: After structured treatment interruption (STI) of treatment for HIV-1, a fraction of patients maintain suppressed viral loads. Prospective identification of such patients might improve HIV-1 treatment, if selected patients are offered STI. Methods: We analysed the effect of previously identified genetic modulators of HIV-1 disease progression on patients' ability to suppress viral replication after STI. Polymorphisms in the genes killer cell immunoglobulin-like receptor 3DLI (KIR3DL1)/KIR3DS1, human leucocyte antigen B (HLA-B) and HLA Complex P5 (HCP5), and a polymorphism affecting HLA-C surface expression were analysed in 130 Swiss HIV Cohort Study patients undergoing STI. Genotypes were correlated with viral load levels after STI. Results: We observed a statistically significant reduction in viral load after STI in carriers of HLA-B alleles containing either the Bw480Thr or the Bw480Ile epitope (mean adjusted effect on post-STI viral load: -0.82 log HIV-1 RNA copies/ml, P

Darunavir was designed for activity against HIV resistant to other protease inhibitors (PIs). We assessed the efficacy, tolerability and risk factors for virological failure of darunavir for treatment-experienced patients seen in clinical practice.

The long-term outcome of antiretroviral therapy (ART) is not assessed in controlled trials. We aimed to analyse trends in the population effectiveness of ART in the Swiss HIV Cohort Study over the last decade.

To describe the effect of HAART on Kaposi sarcoma herpes virus (KSHV) antibody response and viremia among HIV-positive MSM.A follow-up study of 272 HIV-positive MSM (including 22 with Kaposi sarcoma) who first initiated HAART between January 1996 and July 2004 in the Swiss HIV Cohort Study.For each individual, two serum samples, one at HAART initiation and another 24 months later, were tested for latent and lytic KSHV antibodies using immunofluorescence assays, and for KSHV viremia using PCR. Factors associated with changes in KSHV antibody titers and viremia were evaluated.At HAART initiation, 69.1 and 75.0% of patients were seropositive to latent and lytic KSHV antibodies, respectively. Seropositivity was associated with the presence of Kaposi sarcoma, older age, lower CD8 cell count and higher CD4/CD8 ratio. Prevalence of KSHV viremia at HAART initiation was 6.4%, being significantly higher among patients with Kaposi sarcoma (35.0%), and those with HIV viral loads 100 000 copies/ml (11.7%) or higher. At 24-month follow-up, geometric mean titers (GMTs) among KSHV seropositive patients increased and antibody seroprevalence was higher. Having Kaposi sarcoma and/or CD4 cell counts less than 50 cells/microl at HAART initiation was associated both with higher probability for antibody titers to increase (including seroconversion) and larger increases in GMTs. Only one of 17 viremic patients at HAART initiation had viremia at 24-month follow-up.HAART increases KSHV-specific humoral immune response and clearance of viremia among HIV-infected MSM, consistent with the dramatic protection offered by HAART against Kaposi sarcoma.

Background There is an ongoing debate as to whether combined antiretroviral treatment (cART) during pregnancy is an independent risk factor for prematurity in HIV-1-infected women. Objective The aim of the study was to examine (1) crude effects of different ART regimens on prematurity, (2) the association between duration of cART and duration of pregnancy, and (3) the role of possibly confounding risk factors for prematurity. Method We analysed data from 1180 pregnancies prospectively collected by the Swiss Mother and Child HIV Cohort Study (MoCHiV) and the Swiss HIV Cohort Study (SHCS). Results Odds ratios for prematurity in women receiving mono/dual therapy and cART were 1.8 [95% confidence interval (CI) 0.85–3.6] and 2.5 (95% CI 1.4–4.3) compared with women not receiving ART during pregnancy (P=0.004). In a subgroup of 365 pregnancies with comprehensive information on maternal clinical, demographic and lifestyle characteristics, there was no indication that maternal viral load, age, ethnicity or history of injecting drug use affected prematurity rates associated with the use of cART. Duration of cART before delivery was also not associated with duration of pregnancy. Conclusion Our study indicates that confounding by maternal risk factors or duration of cART exposure is not a likely explanation for the effects of ART on prematurity in HIV-1-infected women.

Background Exposure to combination antiretroviral therapy (cART) can lead to important metabolic changes and increased risk of coronary heart disease (CHD). Computerized clinical decision support systems have been advocated to improve the management of patients at risk for CHD but it is unclear whether such systems reduce patients’ risk for CHD. Methods We conducted a cluster trial within the Swiss HIV Cohort Study (SHCS) of HIV-infected patients, aged 18 years or older, not pregnant and receiving cART for >3 months. We randomized 165 physicians to either guidelines for CHD risk factor management alone or guidelines plus CHD risk profiles. Risk profiles included the Framingham risk score, CHD drug prescriptions and CHD events based on biannual assessments, and were continuously updated by the SHCS data centre and integrated into patient charts by study nurses. Outcome measures were total cholesterol, systolic and diastolic blood pressure and Framingham risk score. Results A total of 3,266 patients (80% of those eligible) had a final assessment of the primary outcome at least 12 months after the start of the trial. Mean (95% confidence interval) patient differences where physicians received CHD risk profiles and guidelines, rather than guidelines alone, were total cholesterol -0.02 mmol/l (-0.09–0.06), systolic blood pressure -0.4 mmHg (-1.6– 0.8), diastolic blood pressure -0.4 mmHg (-1.5–0.7) and Framingham 10-year risk score -0.2% (-0.5–0.1). Conclusions Systemic computerized routine provision of CHD risk profiles in addition to guidelines does not significantly improve risk factors for CHD in patients on cART.

Background Data on a link between HCV or HBV infection and the development of cardiovascular disease among HIV-negative and HIV-positive individuals are conficting. We sought to investigate the association between HBV or HCV infection and myocardial infarction in HIV-infected individuals. Methods The prospective observational database of the D:A:D collaboration of 11 cohorts of HIV-infected individuals, including 212 clinics in Europe, the United States and Australia was used. Multivariate Poisson regression was used to assess the effect of HCV or HBV infection on the development of myocardial infarction after adjustment for potential confounders, including cardiovascular risk factors, diabetes mellitus and exposure to antiretroviral therapy. Results Of 33,347 individuals, 517 developed a myocardial infarction over 157,912 person-years, with an event rate of 3.3 events/1,000 person-years (95% confidence interval [CI] 3.0–3.6). Event rates (95% CIs) per 1,000 person-years in those who were HCV- seronegative and HCV-seropositive were 3.3 (3.0–3.7) and 2.7 (2.2–3.3), respectively, and for those who were HBV-seronegative, had inactive infection or had active infection were 3.2 (2.8–3.5), 4.2 (3.1–5.2) and 2.8 (1.8–3.9), respectively. After adjustment, there was no association between HCV seropositivity (rate ratio 0.86 [95% CI 0.62–1.19]), inactive HBV infection (rate ratio 1.07 [95% CI 0.79–1.43]) or active HBV infection (rate ratio 0.78 [95% CI 0.52–1.15]) and the development of myocardial infarction. Conclusions We found no association between HBV or HCV coinfection and the development of myocardial infarction among HIV-infected individuals.

Blood pressure (BP) levels may be classified as normal, borderline, or high with respect to the World Health Organization (WHO) criteria, but most studies like the MONICA project require at least two BP measurements and must tackle the problem of combining the results of the different readings into a single value for classification. The Swiss MONICA project measured the blood pressure of 1872 individuals in the areas of Vaud and Fribourg. Second BP readings were, on average, lower than the first by 3.2 mmHg for systolic and 1.1 mmHg for diastolic BP. These differences, while trivial at the individual level, nevertheless generate significant effects on prevalences of high BP. The first reading, the second, the mean, and the lowest yield prevalences of 14%, 10%, 11% and 9% respectively. Therefore, any published prevalence of high blood pressure should specify the method of measurement, the number of readings taken, and the way results were combined.

OBJECTIVE - It is much debated whether the metabolic syndrome contributes additional information over and above that provided by the individual components of the syndrome alone. Among HIV-infected individuals, we investigated whether any particular combinations of the components included in the definition of the metabolic syndrome are associated with a higher risk of cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS- We followed 33,347 HIV-infected individuals in a prospective observational study. The effect of combinations of components of the metabolic syndrome (low HDL cholesterol, high triglycerides, high BMI, hypertension, and diabetes) on the risk of CVD was assessed by Poisson regression incorporating interactions between each component pair and adjusting for age, sex, family history of CVD, smoking status, calendar year, and exposure to antiretroviral therapy. We reduced the risk of type 1 errors by randomly splitting the data set for training (70% of sample) and validation (remaining 30%). RESULTS- In the training data set, 671 patients experienced a CVD event over 110,652 person-years. Unadjusted, the presence of metabolic syndrome at study enrollment (≥ of the factors) was associated with a 2.89 higher risk of CVD (95% CI 2.34-3.59; P = 0.0001) compared with individuals without the metabolic syndrome. After adjustment for the individual components, the metabolic syndrome as an entity no longer predicted the risk of CVD (adjusted relative risk 0.85; 95% CI 0.61-1.17; P = 0.32). No significant positive interactions were found among the components of the metabolic syndrome. CONCLUSIONS - The presence of the metabolic syndrome in HIV-infected individuals did not appear to increase the CVD risk over and above that conferred by the components of the syndrome separately. © 2009 by the American Diabetes Association., SCOPUS: ar.j, info:eu-repo/semantics/published

Background Temporary increases in plasma HIV RNA ('blips') are common in HIV patients on combination antiretroviral therapy (cART). Blips above 500 copies/mL have been associated with subsequent viral rebound. It is not clear if this relationship still holds when measurements are made using newer more sensitive assays. Methods We selected antiretroviral-naive patients that then recorded one or more episodes of viral suppression on cART with HIV RNA measurements made using more sensitive assays (lower limit of detection below 50 copies/ml). We estimated the association in these episodes between blip magnitude and the time to viral rebound. Results Four thousand ninety-four patients recorded a first episode of viral suppression on cART using more sensitive assays; 1672 patients recorded at least one subsequent suppression episode. Most suppression episodes (87 %) were recorded with TaqMan version 1 or 2 assays. Of the 2035 blips recorded, 84 %, 12 % and 4 % were of low (50–199 copies/mL), medium (200–499 copies/mL) and high (500–999 copies/mL) magnitude respectively. The risk of viral rebound increased as blip magnitude increased with hazard ratios of 1.20 (95 % CI 0.89-1.61), 1.42 (95 % CI 0.96-2.19) and 1.93 (95 % CI 1.24-3.01) for low, medium and high magnitude blips respectively; an increase of hazard ratio 1.09 (95 % CI 1.03 to 1.15) per 100 copies/mL of HIV RNA. Conclusions With the more sensitive assays now commonly used for monitoring patients, blips above 200 copies/mL are increasingly likely to lead to viral rebound and should prompt a discussion about adherence. Electronic supplementary material The online version of this article (doi:10.1186/s12879-015-1120-8) contains supplementary material, which is available to authorized users.

BACKGROUND: Hepatitis B virus (HBV) genotypes can influence treatment outcome in HBV-monoinfected and human immunodeficiency virus (HIV)/HBV-coinfected patients. Tenofovir disoproxil fumarate (TDF) plays a pivotal role in antiretroviral therapy (ART) of HIV/HBV-coinfected patients. The influence of HBV genotypes on the response to antiviral drugs, particularly TDF, is poorly understood. METHODS: HIV/HBV-co-infected participants with detectable HBV DNA prior to TDF therapy were selected from the Swiss HIV Cohort Study. HBV genotypes were identified and resistance testing was performed prior to antiviral therapy, and in patients with delayed treatment response (>6 months). The efficacy of TDF to suppress HBV (HBV DNA

Objectives: To assess the long-term safety of discontinuation of secondary antiPneumocystis prophylaxis in HIV-infected adults treated with antiretroviral combination therapy and who have a sustained increase in CD4 cell counts. Design: Prospective observational multicentre study. Patients and methods: The incidence of P. jirovecii pneumonia after discontinuation of secondary prophylaxis was studied in 78 HIV-infected patients on antiretroviral combination therapy after they experienced a sustained increase in CD4 cell counts to at least 200 3 10 6 cells/l and 14% of total lymphocytes measured twice at least 12 weeks apart. Results: Secondary prophylaxis was discontinued at a median CD4 cell count of 380 3 10 6 cells/l. The median follow-up period after discontinuation of secondary prophylaxis was 40.2 months, yielding a total of 235 person-years of follow-up. No cases of recurrent P. jirovecii pneumonia occurred during this period. The incidence was thus 0 per 100 person-years with a 95% upper of confidence limit of 1.3 cases per 100 patient-years. Conclusions: Discontinuation of secondary prophylaxis against P. jirovecii pneumonia is safe even in the long term in patients who have a sustained immunologic response on antiretroviral combination therapy. & 2004 Lippincott Williams & Wilkins AIDS 2004, 18:2047–2053

Levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c), as well as the TC:HDL-c ratio, were compared in patients receiving different antiretroviral therapy regimens. Patients receiving first-line regimens including protease inhibitors (PIs) had higher TC and TG levels and TC : HDL-c ratios than did antiretroviral-naive patients; patients receiving 2 PIs had higher levels of each lipid. Ritonavir-containing regimens were associated with higher TC and TG levels and TC : HDL-c ratios than were indinavir-containing regimens; however, receipt of nelfinavir was associated with reduced risk of lower HDL-c levels, and receipt of saquinavir was associated with lower TC : HDL-c ratios. Patients receiving nonnucleoside reverse-transcriptase inhibitors had higher levels of TC and LDL-c than did antiretroviral-naive patients, although the risk of having lower HDL-c levels was lower than that in patients receiving a single PI. Efavirenz was associated with higher levels of TC and TG than was nevirapine.

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 (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. This study has been presented in part at the 10th Conference on Retroviruses & Opportunistic Infections. Boston, Mass., USA, 2003. Abstract #571.

BACKGROUND: Although studies have reported large reductions in the risks of AIDS and death since the introduction of potent anti-retroviral therapies, few have evaluated whether this has been similar for all AIDS-defining diseases. We wished to evaluate changes over time in the risk of specific AIDS-defining diseases, as first events, using data from individuals with known dates of HIV seroconversion. METHODS: Using a competing risks proportional hazards model on pooled data from 20 cohorts (CASCADE), we evaluated time from HIV seroconversion to each first AIDS-defining disease (16 groups) and to death without AIDS for four calendar periods, adjusting for exposure category, age, sex, acute infection, and stratifying by cohort. We compared results to those obtained from a cause-specific hazards model. RESULTS: Of 6,941, 2,021 (29%) developed AIDS and 437 (6%) died without AIDS. The risk of AIDS or death remained constant to 1996 then reduced; relative hazard = 0.89 (95% CI: 0.77-1.03); 0.90 (95% CI: 0.81-1.01); and 0.32 (95% CI: 0.28-0.37) for 1979-1990, 1991-1993, and 1997-2001, respectively, compared to 1994-1996. Significant risk reductions in 1997-2001 were observed in all but two AIDS-defining groups and death without AIDS in a competing risks model (with similar results from a cause-specific model). There was significant heterogeneity in the risk reduction across events; from 96% for cryptosporidiosis, to 17% for death without AIDS (P < 0.0001). CONCLUSION: These findings suggest that studies reporting a stable trend for particular AIDS diseases over the period 1979-2001 may not have accounted for the competing risks among other events or lack the power to detect smaller trends.

OBJECTIVE: To evaluate the efficacy of early initiation of highly active antiretroviral therapy (HAART), we compared the clinical course of two nested, matched cohorts within the Swiss HIV Cohort Study. METHODS: We selected all asymptomatic patients who started HAART between 1 January 1996 and 31 December 1999 with a CD4 cell count > 350 x 10(6)/l. We then matched them with asymptomatic participants who were seen at around the same time and who remained untreated during the following 12 months. This control group was further matched for age, sex, CD4 cell count, viral load, and HIV risk category, generating 283 pairs of treated versus untreated patients. RESULTS: During observation of median 3.19 versus 2.66 years, CDC stage B/C occurred in 6.4% versus 21.2%, AIDS in 1.8% versus 5.3%, death in 2.1% versus 6.4%, and AIDS or death of 'natural' causes in 2.8% versus 6.7% of the treated versus untreated patients. In multivariable Cox regression analysis, treatment reduced the risk of clinical progression by a factor of four- to five fold. During follow-up, the treated group had significantly higher CD4 counts and lower HIV-1 RNA levels. Intolerance/adverse events led to change or stop of at least one drug in 35% of treated patients. The entire regimen was interrupted at least once by 41% of patients, and 24% had no treatment anymore at the end of follow-up. CONCLUSIONS: The initiation of HAART in asymptomatic patients with CD4 cell count > 350 x 10(6)/l significantly delayed clinical progression. However, the risk of severe clinical events with deferred therapy was low and must be counter balanced against the burden and toxicity of HAART.

BACKGROUND: Transmitted human immunodeficiency virus type 1 (HIV) drug resistance (TDR) mutations are transmitted from nonresponding patients (defined as patients with no initial response to treatment and those with an initial response for whom treatment later failed) or from patients who are naive to treatment. Although the prevalence of drug resistance in patients who are not responding to treatment has declined in developed countries, the prevalence of TDR mutations has not. Mechanisms causing this paradox are poorly explored. METHODS: We included recently infected, treatment-naive patients with genotypic resistance tests performed ≤1 year after infection and before 2013. Potential risk factors for TDR mutations were analyzed using logistic regression. The association between the prevalence of TDR mutations and population viral load (PVL) among treated patients during 1997-2011 was estimated with Poisson regression for all TDR mutations and individually for the most frequent resistance mutations against each drug class (ie, M184V/L90M/K103N). RESULTS: We included 2421 recently infected, treatment-naive patients and 5399 patients with no response to treatment. The prevalence of TDR mutations fluctuated considerably over time. Two opposing developments could explain these fluctuations: generally continuous increases in the prevalence of TDR mutations (odds ratio, 1.13; P = .010), punctuated by sharp decreases in the prevalence when new drug classes were introduced. Overall, the prevalence of TDR mutations increased with decreasing PVL (rate ratio [RR], 0.91 per 1000 decrease in PVL; P = .033). Additionally, we observed that the transmitted high-fitness-cost mutation M184V was positively associated with the PVL of nonresponding patients carrying M184V (RR, 1.50 per 100 increase in PVL; P < .001). Such association was absent for K103N (RR, 1.00 per 100 increase in PVL; P = .99) and negative for L90M (RR, 0.75 per 100 increase in PVL; P = .022). CONCLUSIONS: Transmission of antiretroviral drug resistance is temporarily reduced by the introduction of new drug classes and driven by nonresponding and treatment-naive patients. These findings suggest a continuous need for new drugs, early detection/treatment of HIV-1 infection.

HIV infection, even when well controlled, may be associated with important mental health problems. We sought to investigate anxiety, depression, and health-related quality of life using screening measurements in patients with HIV infection and to examine their dependency on biosocial parameters relating to HIV. Prospective clinical, virologic, and immunologic data were obtained in a cross-sectional study within the Swiss HIV Cohort Study. Four self-reported questionnaires were used in 397 HIV-infected individuals. The scores for anxiety and depression were high as measured by the Hospital Anxiety and Depression Scale (HADS) and the State Trait Anxiety Inventory (STAI). Half the population scored

Objectives: To assess the safety of discontinuation of primary prophylaxis in HIV-infected patients on antiretroviral combination therapy at high risk of developing Pneumocystis carinii pneumonia. Design: Prospective multicentre study. Patients and methods: The incidence of P. carinii pneumonia after discontinuation of primary prophylaxis was studied in 396 HIV-infected patients on antiretroviral combination therapy who experienced an increase in their CD4 cell count to at least 200 × 10 6 / and 14% of total lymphocytes; the study population included 191 patients with a history of CD4 cell counts below 100 × 10 6 /l (245 person-years) and 144 patients with plasma HIV RNA above 200 copies/ml (215 person-years). Results: There was one case of Pneumocystis pneumonia, an incidence of 0.18 per 100 person-years [95% confidence interval (CI), 0.005-1.0 per 100 person-years]. No case was diagnosed in groups with low nadir CD4 cell counts (95% Cl, 0-1.2 per 100 person-years) or detectable plasma HIV RNA (95% Cl, 0-1.4 per 100 person-years). Conclusions: Discontinuation of primary prophylaxis against Pneumocystis pneumonia is safe in patients who have responded with a sustained increase in their CD4 cell count to antiretroviral combination therapy, irrespective of the CD4 cell count nadir and the viral load at the time of stopping prophylaxis.

STUDY DESIGN: A cross-sectional survey was performed. OBJECTIVE: To estimate the extent of low back pain as a public health problem. SUMMARY OF BACKGROUND DATA: Health surveys converge on very high estimates of low back pain in general populations, but few studies have included severity criteria in their definition and conclusions. Because it is unlikely that interventions will influence the prevalence of minimal and infrequent symptoms, greater attention should be paid to characteristics of low back pain that indicate some impact on the life of survey respondents. METHODS: Two regions participated in the MONICA (MONitoring of trends and determinants in CArdiovascular disease) project in Switzerland. Participants randomly selected from the general population completed a standard self-administered questionnaire on cardiovascular risk factors. A special section on low back pain was added in the third (1992-1993) MONICA survey and completed by 3227 participants. RESULTS: A regional difference found in the 12-month prevalence rate disappeared with the inclusion of severity criteria. Low back pain over more than seven cumulated days was reported among men by 20.2% (age range, 25-34 years) to 28.5% (age range, 65-74 years), respectively, among women by 31.1% to 38.5%. Similar rates of reduction in activity (professional, housekeeping, and leisure time) and medical consultation (conventional and nonconventional) motivated by low back pain characterized the two participating regions. The cumulative duration of pain was related to all the indicators showing the impact of low back pain on everyday life. CONCLUSIONS: Determining the cumulative duration of low back pain over the preceding year is a straightforward task, and a cutoff at 1 week seems appropriate for distinguishing between low- and high-impact low back pain.

Summary Background We used data from Europe, North America, and Australia to assess the effect of exposure category on the AIDS incubation period and HIV-1 survival and whether the effect of age at seroconversion varies with exposure category and with time since seroconversion. Methods 38 studies of HIV-1-infected individuals whose dates of seroconversion could be reliably estimated were included in the analysis. Individual data on 13 030 HIV-1-infected individuals from 15 countries were collated, checked, and analysed centrally. We calculated estimates of mortality and AIDS incidence rates and estimated the proportions of individuals surviving and developing AIDS at each year after seroconversion from the numbers of observed deaths or cases of AIDS and the corresponding person-years at risk. Analyses were adjusted for age at seroconversion, time since seroconversion, and other factors as appropriate. Findings Mortality and AIDS incidence increased strongly with time since seroconversion and age at seroconversion. Median survival varied from 12·5 years (95% Cl 12·1–12·9) for those aged 15–24 years at seroconversion to 7·9 years (7·4–8·5) for those aged 45–54 years at seroconversion, whereas for development of AIDS the corresponding values were 11·0 years (10·7–11·7) and 7·7 years (7·1–8·6). There was no appreciable effect of exposure category on survival. For AIDS incidence, the exposure category effect that we noted was explained by the high incidence of Kaposi's sarcoma in those infected through sex between men. We estimated that among people aged 25–29 years at seroconversion 90% (89–91) and 60% (57–62) survived to 5 years and 10 years, respectively, after seroconversion, whereas 13% (12–15) and 46% (44–49), respectively, developed AIDS (excluding Kaposi's sarcoma). Interpretation Before widespread use of highly-active antiretroviral therapy (before 1996), time since seroconversion and age at seroconversion were the major determinants of survival and development of AIDS in Europe, North America, and Australia.

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 co...

Three acute coronary care surveys (1986, 1990, and 1993) were conducted in the Swiss region of Vaud-Fribourg on all men aged 25 to 64 years hospitalized for a definite myocardial infarction (218, 224, and 167 cases). Nearly all patients received anticoagulants and nitrates. The proportion of patients treated increased significantly, between 1986 and 1990, for antiplatelet drugs (from 51% to 96%) and thrombolytics (from 9% to 44%) and, between 1990 and 1993, for beta-blockers (from 57% to 78%) and angiotensin-converting enzyme inhibitors (from 26% to 43%). The use of calcium antagonists and antiarrhythmics dropped over time. Coronary arteriography and angioplasty were increasingly performed (53% and 18% in 1993), although progressively postponed in-hospital stay. The observed trends reflect a rapid translation of clinical trials into medical practice. However the use of thrombolytics could be raised further by shortening the hospitalization delay (median: 3 hours in 1993) and door-to-needle time (median: 47 minutes) which remained stable over time.

In Switzerland where AIDS reporting is mandatory surveillance reports indicated the first decline since the onset of the epidemic: from 545 new cases in 1995 to 459 new cases in 1996. Through use of data from the Swiss HIV Cohort Study--a prospective multicenter study that includes about 70% of all people with AIDS in Switzerland the impact of the introduction of antiretroviral combination therapy on this declining HIV prevalence was assessed. A total of 4915 asymptomatic HIV-positive men and women with a CD4 cell count below 200 (clinical stage B) contributed 10755 person-years and 2366 initial AIDS events. The mid-year prevalence of use of combination therapies in this cohort was 6% in 1994 13% in 1995 and 48% in 1996. The difference between expected AIDS cases in 1994-96 in the absence of combination therapies estimated through a parametric statistical survival model and observed cases per half-year increased from 12 in the first 6 months of 1994 to 69 in the second half of 1996. Taking reporting delays into account it was estimated that 43 (50%) of the deficit of 86 reports could be attributed to combination therapies. The contribution of the introduction of combination therapies to the decline of AIDS reports between 1995 and 1996 corresponds to the difference between the number of reports prevented in the 2 years. Monitoring of the use and effectiveness of antiretroviral therapy should become a standard component of AIDS surveillance systems.

Introduction : HIV-infected pregnant women are very likely to engage in HIV medical care to prevent transmission of HIV to their newborn. After delivery, however, childcare and competing commitments might lead to disengagement from HIV care. The aim of this study was to quantify loss to follow-up (LTFU) from HIV care after delivery and to identify risk factors for LTFU. Methods : We used data on 719 pregnancies within the Swiss HIV Cohort Study from 1996 to 2012 and with information on follow-up visits available. Two LTFU events were defined: no clinical visit for >180 days and no visit for >360 days in the year after delivery. Logistic regression analysis was used to identify risk factors for a LTFU event after delivery. Results : Median maternal age at delivery was 32 years (IQR 28–36), 357 (49%) women were black, 280 (39%) white, 56 (8%) Asian and 4% other ethnicities. One hundred and seven (15%) women reported any history of IDU. The majority (524, 73%) of women received their HIV diagnosis before pregnancy, most of those (413, 79%) had lived with diagnosed HIV longer than three years and two-thirds (342, 65%) were already on antiretroviral therapy (ART) at time of conception. Of the 181 women diagnosed during pregnancy by a screening test, 80 (44%) were diagnosed in the first trimester, 67 (37%) in the second and 34 (19%) in the third trimester. Of 357 (69%) women who had been seen in HIV medical care during three months before conception, 93% achieved an undetectable HIV viral load (VL) at delivery. Of 62 (12%) women with the last medical visit more than six months before conception, only 72% achieved an undetectable VL (p=0.001). Overall, 247 (34%) women were LTFU over 180 days in the year after delivery and 86 (12%) women were LTFU over 360 days with 43 (50%) of those women returning. Being LTFU for 180 days was significantly associated with history of intravenous drug use (aOR 1.73, 95% CI 1.09–2.77, p=0.021) and not achieving an undetectable VL at delivery (aOR 1.79, 95% CI 1.03–3.11, p=0.040) after adjusting for maternal age, ethnicity, time of HIV diagnosis and being on ART at conception. Conclusions : Women with a history of IDU and women with a detectable VL at delivery were more likely to be LTFU after delivery. This is of concern regarding their own health, as well as risk for sexual partners and subsequent pregnancies. Further strategies should be developed to enhance retention in medical care beyond pregnancy. (Published: 2 November 2014) Citation : Abstracts of the HIV Drug Therapy Glasgow Congress 2014 Aebi-Popp K et al. Journal of the International AIDS Society 2014, 17(Suppl 3) :19535 http://www.jiasociety.org/index.php/jias/article/view/19535 | http://dx.doi.org/10.7448/IAS.17.4.19535

Background.This study attempted to assess the time trends in lifestyle and cardiovascular risk factors in the Swiss region of Vaud-Fribourg (population 784,000). Methods.Three surveys (1984/1985, 1988/1989, and 1992/1993), based on independent representative samples (n = 3,300) of the population ages 25 to 74, were conducted within the framework of the international WHO–MONICA Project. Results.The most favorable changes were observed in reported behaviors: increased physical activity in leisure time, healthier dietary habits (switch from unskimmed milk, butter, and meat to skimmed milk, margarine, and fish, with no change for fruits and vegetables), and lower prevalence of regular smoking among men (from 32 to 28%). Body mass index did not vary significantly, apart from an increase in the prevalence of obesity among men (from 11 to 15%). Total cholesterol varied only slightly, while the HDL cholesterol levels decreased steadily (from 1.37 to 1.19 mmol/L among men; from 1.59 to 1.51 among women). Average systolic blood pressure regressed among women (from 127.2 to 124.4 mm Hg), while the prevalence of untreated hypertension increased among older men. Conclusion.The self-reported changes in lifestyle were only partially reflected by favorable trends in objective measurements. Physical activity, even at moderate intensity, and consumption of fruits, vegetables, and fiber in general should be promoted.

Dear Editor: As recently published in your Journal, the LILAC prospective cohort study showed a decrease in self-reported adherence between pregnancy and postpartum in South America.1 Interestingly, our smaller study with a longitudinal measure and analysis of adherence to antiretroviral treatment confirms these findings. Antiretroviral therapy (ART) during pregnancy and postpartum involves two issues: prophylaxis of perinatal transmission and treatment of maternal infection.2 Adherence, defined as “the process by which patients take their medications as prescribed,” is crucial to address these concerns.3,4 Pregnancy and the first months of motherhood cause important changes in a women's life, which might impact ART adherence. Most frequently cited barriers to adherence were competition with other issues including family obligation and hectic lifestyle. Conversely, the baby's health was cited as a motivator for adherence.5 During postpartum, women tend to miss more medical visits, and adherence tends to be lower than during pregnancy.1,6–10 Between 10% and 50% of the women stopped their ART after childbirth, part of them on their own without physician's approval.7–10 Most of published studies are based on pill count or self-reported adherence. To our knowledge this is the first study assessing electronically the dynamics of adherence in a continuum from pregnancy to postpartum along with clinical data. This exploratory, retrospective study was approved by the Swiss Ethic Commission (Vaud) for clinical research. It aimed at comparing adherence to the entire ART—during pregnancy and postpartum—using continuous electronic drug monitoring data. The community Pharmacy of the Department of ambulatory care and community medicine in Lausanne has been running an adherence-enhancing program since 2004, which combines electronic drug monitoring and semistructured, repeated motivational interviews.4 All pregnant HIV-positive women having taken part in the program between 2004 and 2012 were retrieved. The maximal observation period extended from first adherence visit after last menstruation to 6 months after childbirth. Sociodemographic and clinical data were collected from the Swiss HIV Cohort Study database. Percent of attended visits were compared between pregnancy and postpartum using the McNemar test. Electronic data on medication adherence, extracted from the adherence-enhancing program database, were reconciled with pill count and interview notes in order to include reported pocket doses. For each woman, adherence was described with a binary variable (1=correct number of daily opening(s) of all electronic monitors; 0=less daily openings than prescribed). Data were analyzed via a piecewise logistic mixed effect model. Mixed effect models are methods of choice for analyzing data with repeated measures for each participant. They take into account the interindividual variability of the measures and can deal with unbalanced data due to missing values. In particular, a piecewise logistic mixed effect model allowed us to estimate the probability of taking ART as prescribed, for each day d of pregnancy and postpartum periods.11 Adherence at days 0–3 from childbirth has been replaced by missing values before entering the model, because of the bias due to hospitalization. Analysis of change in CD4 over time was performed using a piecewise polynomial mixed effect model. A qualitative inspection of viral RNA individual trajectories was made only graphically, as the large interindividual variability and the small number of data prevented the application of a mixed effect model. We used the Stata/IC software (v12.0, StataCorp, College Station, TX) for data description and the R system for computation and graphic of mixed effect models (v2.12.1, www.r-project.org/, library “nlme”). Among 400 patients referred to the adherence program, 29 pregnant women (7%) were screened and 25 (86%) were included. Three women who did not use electronic monitors were excluded, and one underwent an early pregnancy interruption. Median age was 29 (interquartile range [IQR]: 26.5, 32.0). Seventeen women (68%) were black and 11 (44%) were ART naive. ART included protease and nucleoside reverse transcriptase inhibitors (n=24; 96%). Six women (24%) stopped the program during pregnancy, 3 (12%) at childbirth and 4 (16%) during the postpartum period. Among these 13 women, 8 (62%) were kept on ART, 3 stopped ART after childbirth according to guidelines, and 2 stopped ART without physician's agreement. All these women were considered in the analysis. The percentage of unattended visits increased from 17% during pregnancy to 38% during postpartum (p=0.001). Probability of correct ART intake was continuously high during pregnancy (97% [95% CI: 0.94–0.98]), decreased to 93% (95% CI: 0.87–0.96) at childbirth (p of the difference=0.006), and increased again during postpartum (p of the slope coefficient=0.009) (Fig. 1A) to reach the same probability than during pregnancy after 164 days. A sensitivity analysis with the 10 women who were continuously monitored during pregnancy and postpartum confirmed the decrease in ART intake after childbirth. FIG. 1. Change in drug intake, viral load, and CD4 count over time. (A) Percentage of women with correct number of daily opening(s) of the electronic monitors over time. Curves in bold represent the prediction±95% confidence interval, (days 0–3 ... CD4 count increased during pregnancy, decreased around 40 days after childbirth then increased again (p of the linear, quadratic and cubic coefficient

This study analyzes the trend and determinants of blood lead levels in a Swiss region (population 770,000) over the 10-year period following the introduction of unleaded gasoline in 1985. The consumption of unleaded fuel increased rapidly, accounting in 1988 for 36% and in 1992 for 65% of all gasoline sales. Blood lead levels were measured in three representative samples (n = 1700) of the adult population within the framework of a health examination survey carried out in 1984/1985, 1988/1989, and 1992/1993. The geometric mean blood lead levels were, respectively, 0.59, 0.42, and 0.33 mumole/liter in men, 0.41, 0.29, and 0.25 mumole/liter in women. Similar trends have been observed across all age groups, occupational classes, and categories based on smoking, drinking, and dietary habits. The overexposure of city residents, in comparison to village residents, fades out over the observation period. These findings suggest that the changeover from leaded to unleaded gasoline has been the major cause of the blood lead decline. Wine drinking, cigarette smoking, and age appear to be significant determinants of blood lead for both sexes in all three surveys. In contrast, the association is inverse for milk consumption. The multivariate regression analysis shows that wine drinking remains the most important predictor of blood lead, whereas the influence of age increases with time and overcomes the effect of smoking in the third survey.

Purpose of the study: To investigate the impact of ART, HIV viremia and immunosuppression on triglyceride (TG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) levels. Methods: We considered the cross-sectional associations between TG, TC and HDL-C (mmol/l; first available measurement on/after enrolment in the D:A:D study) and use of ART, HIV viral load (VL; copies/ml), and CD4 count (cells/mm 3 ) measured at the same time. TG was log 10 transformed to ensure normality. Analyses were performed using linear regression and adjusted for other factors known to impact lipid levels (table footnote). ART and VL status were combined (off ARTV IQR 1.52; 1.00-2.45), 45,169 (90.8%) a TC measurement (4.80; 4.00-5.70) and 38,604 (77.6%) a HDL-C measurement (1.12; 0.90-1.40). Most participants were male (74%), of white ethnicity (51%), without AIDS (78%), were not receiving lipid-lowering drugs (4%) and were ART experienced (61%) with 47% previously exposed to PIs, 61% previously exposed to NRTIs and 29% previously exposed to NNRTIs. The median (IQR) age, current CD4 count and CD4 nadir were 38 (36-45) years, 400 (242-590) cells/μl and 240 (100-410) cells/μl respectively. Compared to those on ART with a suppressed VL, all lipids were lower for those off ART (Table); non-suppressive ART was also associated with lower TC and HDL-C levels (no impact on TG). A low current CD4 count was associated with lower lipid levels, whereas a low nadir CD4 count was associated with higher TC and TG levels. Prior AIDS diagnosis was associated with higher TG and TC, but lower HDL-C levels Conclusion: Although specific drug classes were not considered, lipid levels are considerably higher in those on a suppressive ART regimen. The higher TC/TG and lower HDL-C levels seen among those with low nadir CD4 count and with a prior AIDS diagnosis suggests severe immunosuppression may be associated with dyslipidaemia over the long-term. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Kamara D et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18280 http://www.jiasociety.org/index.php/jias/article/view/18280 | http://dx.doi.org/10.7448/IAS.15.6.18280

This study compared adherence (persistence and execution) during pregnancy and postpartum in HIV-positive women having taken part in the adherence-enhancing program of the Community Pharmacy of the Department of Ambulatory Care and Community Medicine in Lausanne between 2004 and 2012. This interdisciplinary program combined electronic drug monitoring and semi-structured, repeated motivational interviews. This was a retrospective, observational study. Observation period spread over from first adherence visit after last menstruation until 6 months after childbirth. Medication-taking was recorded by electronic drug monitoring. Socio-demographic and delivery data were collected from Swiss HIV Cohort database. Adherence data, barriers and facilitators were collected from pharmacy database. Electronic data were reconciled with pill-count and interview notes in order to include reported pocket-doses. Execution was analyzed over 3-day periods by a mixed effect logistic model, separating time before and after childbirth. This model allowed us to estimate different time slopes for both periods and to show a sudden fall associated with childbirth. Twenty-five pregnant women were included. Median age was 29 (IQR: 26.5, 32.0), women were in majority black (n=17,68%) and took a cART combining protease and nucleoside reverse transcriptase inhibitors (n=24,96%). Eleven women (44%) were ART-naive at the beginning of pregnancy. Twenty women (80%) were included in the program because of pregnancy. Women were included at all stages of pregnancy. Six women (24%) stopped the program during pregnancy, 3 (12%) at delivery, 4 (16%) during postpartum and 12 (48%) stayed in program at the end of observation time. Median number of visits was 4 (3.0, 6.3) during pregnancy and 3 (0.8, 6.0) during postpartum. Execution was continuously high during pregnancy, low at beginning of postpartum and increased gradually during the 6 months of postpartum. Major barriers to adherence were medication adverse events and difficulties in daily routine. Facilitators were motivation for promoting child-health and social support. The dramatic drop and very slow increase in cART adherence during postpartum might result in viral rebound and drug resistance. Although much attention is devoted to pregnant women, interdisciplinary care should also be provided to women in the community during first trimester of postpartum to support them in sustaining cART adherence. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Michel O et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18149 http://www.jiasociety.org/index.php/jias/article/view/18149 | http://dx.doi.org/10.7448/IAS.15.6.18149

Im Rahmen der WHO-MONICA Studie wurde der Zusammenhang zwischen Sozialschicht und Pravalenz kardiovaskularer Risikofaktoren in der Tessiner Bevolkerung untersucht. Gegenstand der Untersuchung ist eine reprasentative Stichprobe von 984 Mannern und 1014 Frauen der Altersgruppen 35 bis 64 Jahre. Die Teilnahmerate (beider Geschlechter), der 1985/1986 durchgefuhrten Studie lag bei 78%. Die Sozialschicht wurde mit dem Beruf und Anzahl der Ausbildungsjahre bestimmt. In der univariaten Analyse ergeben sich fur beide Geschlechter schlechter statistisch signifikante Unterschiede (p

CD4 expression in HIV replication is paradoxical: HIV entry requires high cell-surface CD4 densities, but replication requires CD4 down-modulation. However, is CD4 density in HIV+ patients affected over time? Do changes in CD4 density correlate with disease progression? Here, we examined the role of CD4 density for HIV disease progression by longitudinally quantifying CD4 densities on CD4+ T cells and monocytes of ART-naive HIV+ patients with different disease progression rates. This was a retrospective study. We defined three groups of HIV+ patients by their rate of CD4+ T cell loss, calculated by the time between infection and reaching a CD4 level of 200 cells/microl: fast (7.5 years), intermediate (7.5-12 years), and slow progressors (12 years). Mathematical modeling permitted us to determine the maximum CD4+ T cell count after HIV seroconversion (defined as "postseroconversion CD4 count") and longitudinal profiles of CD4 count and density. CD4 densities were quantified on CD4+ T cells and monocytes from these patients and from healthy individuals by flow cytometry. Fast progressors had significantly lower postseroconversion CD4 counts than other progressors. CD4 density on T cells was lower in HIV+ patients than in healthy individuals and decreased more rapidly in fast than in slow progressors. Antiretroviral therapy (ART) did not normalize CD4 density. Thus, postseroconversion CD4 counts define individual HIV disease progression rates that may help to identify patients who might benefit most from early ART. Early discrimination of slow and fast progressors suggests that critical events during primary infection define long-term outcome. A more rapid CD4 density decrease in fast progressors might contribute to progressive functional impairments of the immune response in advanced HIV infection. The lack of an effect of ART on CD4 density implies a persistent dysfunctional immune response by uncontrolled HIV infection.

AIM OF THE STUDY: To assess the impact of international consensus conference guidelines on the attitude of Swiss specialists when facing the decision to treat chronic hepatitis C patients. METHODS: Questionnaires focusing on the personal situation and treatment decisions were mailed to 165 patients who were newly diagnosed with hepatitis C virus (HCV) infection and enrolled into the Swiss Hepatitis C Cohort Study during the years 2002-2004. RESULTS: Survey respondents (n = 86, 52.1%) were comparable to non-respondents with respect to severity of liver disease, history of substance abuse and psychiatric co-morbidities. Seventy percent of survey respondents reported having been offered antiviral treatment. Patients deferred from treatment had less advanced liver fibrosis, were more frequently infected with HCV genotypes 1 or 4 and presented more often with a history of depression. There were no differences regarding age, socio-economic background, alcohol abuse, intravenous drug abuse or methadone treatment when compared with patients to whom treatment was proposed. Ninety percent of eligible patients agreed to undergo treatment. Overall, 54.6% of respondents and 78.3% of those considered eligible had actually received antiviral therapy by 2007. Ninety-five percent of patients reported high satisfaction with their own hepatitis C management. CONCLUSIONS: Consistent with latest international consensus guidelines, patients enrolled in the Swiss Hepatitis C Cohort with a history of substance abuse were not withheld antiviral treatment. A multidisciplinary approach is warranted to provide antiviral treatment to patients suffering from depression.

BACKGROUND: Adherence to combination antiretroviral therapy (cART) is a dynamic process, however, changes in adherence behavior over time are insufficiently understood. METHODS: Data on self-reported missed doses of cART was collected every 6 months in Swiss HIV Cohort Study participants. We identified behavioral groups associated with specific cART adherence patterns using trajectory analyses. Repeated measures logistic regression identified predictors of changes in adherence between consecutive visits. RESULTS: Six thousand seven hundred nine individuals completed 49,071 adherence questionnaires [median 8 (interquartile range: 5-10)] during a median follow-up time of 4.5 years (interquartile range: 2.4-5.1). Individuals were clustered into 4 adherence groups: good (51.8%), worsening (17.4%), improving (17.6%), and poor adherence (13.2%). Independent predictors of worsening adherence were younger age, basic education, loss of a roommate, starting intravenous drug use, increasing alcohol intake, depression, longer time with HIV, onset of lipodystrophy, and changing care provider. Independent predictors of improvements in adherence were regimen simplification, changing class of cART, less time on cART, and starting comedications. CONCLUSIONS: Treatment, behavioral changes, and life events influence patterns of drug intake in HIV patients. Clinical care providers should routinely monitor factors related to worsening adherence and intervene early to reduce the risk of treatment failure and drug resistance.