2015

21st December funding 2016 and 2017 by SNSF - thanks to all

Dear all,

We want to inform you that the SHCS will be funded at the same level as before from the Swiss National Science Foundation (SNSF) for 2016 and 2017. This decision was based on a competitive intermediary evaluation by the SNSF that all cohorts in the cohort program had to undergo. The evaluation was very favorable.

At this time, we want first to thank

  • all the patients participating in the SHCS

We also thank all of you who are working tireless for the SHCS

  • study nurses, physicians at the cohort centers and HIV-practitioners
  • technicians, FAMH physicians taking care of the biobank
  • the data managers, the data center, the coordination center, all the administrative support we get at all levels
  • the Positivrat for actively participating in the SHCS Scientific Board
  • the many PhD, Postdocs and master students who work in the research labs and in front of their computers analyzing all the data that is being generated on the many exciting research projects that are ongoing in the SHCS
  • all the national and international collaborators with whom the SHCS works together
  • the SNSF for funding, the SHCS research foundation
  • pharmaceutical companies
    • AbbVie, Gilead, MSD, ViiV for support of the SHCS research foundation by unrestricted grants to support the SHCS core projects
    • AbbVie, BMS, Gilead, Janssen, MSD, ViiV for the collaboration with the SHCS association.
    • Some companies also support specific investigator initiated studies. We also thank you for this.

For 2016, we hope to finalize our negotiations with the FOPH (BAG) and hope that soon a very fruitful and synergistic collaboration between the SHCS and the FOPH will start with the ultimate goal to reduce HIV transmission, to get further insights into transmission of sexually transmitted diseases, to further optimize antiretroviral therapy and also to get insights what comorbidity means in the long run.

Thanks again for all your continuous support of the SHCS and we are looking forward to 2016: the 28th year the SHCS is alive!

Merry Christmas and a happy New Year!

Huldrych Günthard Andri Rauch Hansjakob Furrer

President of the SHCS

Chairman of the
Scientific Board

Chairman of the Clinical
and Laboratory Board

17th December Anagnostopoulos et al., Depression in the Swiss HIV Cohort Study


Frequency of and risk factors for depression among participants in the Swiss HIV Cohort Study (SHCS). PLoS ONE

Anagnostopoulos et al. aimed to assess the incidence and prevalence of, and co-factors for depression in the Swiss HIV Cohort Study and to determine the influence of depression on suicide rates and mortality. The incidence rate of new-onset depression was 3.85 per 100 patient-years. The incidence and cumulative prevalence were higher in injection drug users and women. One third of patients (28.7%) experienced a depressive disorder during follow-up. Prevalent depression was more likely among participants not on antiretroviral therapy (ART), and among participants with detectable viral load while on ART. Compared to participants free of depression, mortality was slightly elevated among participants with a history of depression (1.17 vs. 0.86).

The study-results show that the burden of depressive disorders among HIV-positive individuals in an economically wealthy environment is still substantial and underscore the need for interdisciplinary collaboration between HIV care providers, psychiatrists and other mental-health providers.

pdf publication

16th December Schmid et al., Liver fibrosis progression in HIV/HCV co-infection


Progression of liver fibrosis in HIV/HCV co-infection: A comparison between non-invasive assessment methods and liver biopsy. PLoS ONE

Schmid et al. aimed to compare the diagnostic accuracy of liver fibrosis staging by transient elastography (TE) and six serum biochemical markers in HIV/HCV co-infected patients and to assess changes in liver fibrosis over time. They found that TE was the non-invasive test with the highest diagnostic accuracy in detecting both significant liver fibrosis (METAVIR > = F2) and liver cirrhosis (METAVIR F4) compared to liver biopsy. Three indirect serum markers (APRI-Score, FIB-4 Index, Fibrotest) and one direct serum marker (ELF-Test) were secondary alternatives, whereas performance of the other two direct serum markers (hyaluronic acid and Hepascore) was worse. Non-invasive tests did not change significantly during the 3-year follow-up, suggesting slow liver disease progression in a majority of HIV/HCV co-infected patients on ART.

The study-results support the new recommendations by EASL to use non-invasive tests as first line tests to stage liver fibrosis.

pdf publication

10th December Harrison et al., Drug resistance in HIV-infected children


HIV-1 drug resistance and second-line treatment in children randomized to switch at low versus higher RNA thresholds. Journal of Acquired Immune Deficiency Syndrome

Harrison et al. explored resistance profiles after first-line antiretroviral therapy (ART) by randomized switch criteria based on RNA threshold (>1’000 copies/ml versus >30’000 copies/ml), and second-line treatment response in children. They found that children starting NNRTIs accumulated more NRTI mutations than those starting protease inhibitors (PIs). Children switching later on NNRTIs accumulated more NRTI mutations, whereas on PIs, NRTI mutations did not accumulate over the time. Children on first-line NNRTI-based ART who were randomized to switch at a higher virologic threshold developed the most resistance, yet resuppressed on second-line.

Overall, these data support WHO 2013 pediatric guidelines recommending abacavir + lamivudine as the first-line NRTI backbone with an NNRTI and provide reassurance that response to second-line with a boosted PI and zidovudine + lamivudine is expected to be good.

pdf publication

9th December Guidi et al., Vitamin D in HIV-infected individuals


Vitamin D time profile based on the contribution of non-genetic and genetic factors in HIV-infected individuals of European ancestry. Antiviral Therapy

Guidi et al. aimed at characterizing the kinetics of vitamin D [25(OH)D] in HIV-infected individuals to define the influence of genetic and non-genetic factors on 25(OH)D levels and to optimize vitamin D supplementation. They found that vitamin D deficiency ([25(OH)D]<20ng/ml) was present in 58% of all individuals. Seasonality and BMI had the strongest effect on 25(OH)D endogenous production. Eleven percent of the inter-individual variability in 25(OH)D levels was explained by non-genetic covariates, and 1% by genetics. Optimal supplementation for severe vitamin D deficiency (<10ng/ml) was 300’000 IU 2/year. A single vitamin D supplementation of 300’000 IU 1/year was appropriate for individuals with mild deficiency (<20ng/ml), independently of the season.

In conclusion, the study-results allow implementing a strategy for vitamin D supplementation dependent on the level of deficiency.

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3rd December Young et al., Blips and the risk of viral rebound


Transient detectable viremia and the risk of viral rebound in patients from the Swiss HIV Cohort Study. BMC Infectious Diseases

Young et al. investigated whether the level of transient HIV RNA in blood plasma (‘blip’ magnitude) is predictive of subsequent viral rebound. They found a gradual increase in the relative risk of viral rebound with increasing blip magnitude (hazard ratio 1.09 per 100 copies), corresponding to an estimated hazard ratio of nearly 1.5 using a threshold of 200 copies/mL. Reporting non-adherence and not responding to questions on adherence were associated with a higher risk of viral rebound. The risk of viral rebound increased with both the magnitude of the first blip and the number of blips per suppression episode.

In conclusion, this study suggests that blips in excess of 200 copies/mL are likely to be due to non-adherence rather than due to random variation in residual viremia and should prompt a discussion about adherence.

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2nd December Schultze et al., HIV resistance testing and prevalence


HIV resistance testing and detected drug resistance in Europe. AIDS

Schultze et al. on behalf of EuroSIDA aimed to describe regional differences and trends in resistance testing and in the prevalence of detected resistance among individuals experiencing virological failure. Compared to 74.19% of individuals in 1997, only 5.11% showed evidence of virological failure in 2012. Around one-third of the individuals received a resistance test within 12 months of virological failure, but this proportion decreased after 2004. Resistance was detected in 77.9% of the tests. The detection of resistance was less common in Northern and Central Eastern Europe, compared to Southern Europe. The odds of detecting resistance were lower in tests done in 1997–2000 and 2009–2010, compared to those carried out in 2003–2004.

The study findings suggest a selective approach to resistance testing. Public health policy aimed at minimizing the emergence of drug resistance might benefit from targeting specific regions of Europe, notably in the countries in Eastern Europe.

PubMed

26th November Marzel et al., HIV-1 transmission during recent HIV-1 infection


HIV-1 transmission during recent infection and during treatment interruptions as major drivers of new infections in the Swiss HIV Cohort Study. Clinical Infectious Diseases

Marzel et al. aimed to determine the fraction of HIV-1 transmissions that occurs during recent HIV-1 infection. They found that the median fraction of transmission during recent infection (i.e., first year after seroconversion) ranged from a minimum of 41% to a maximum of 57%. HIV transmission in the chronic phase was strongly associated with higher area under the curve (AUC) of chronic-phase viral load and delayed initiation of antiretroviral therapy (ART). Additionally, at least 14% of the chronic-phase transmission events occurred after the transmitter had interrupted ART.

In conclusion, the study identified recent infections and HIV transmission during treatment interruptions as key issues for treatment as prevention and underlines the importance of early diagnosis and of early and continuous treatment.

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25th November Friis-Moller et al., Prediction of risk of cardiovascular disease in HIV-positive persons


An updated prediction model of the global risk of cardiovascular disease in HIV-positive persons: The Data-collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study. European Journal of Preventive Cardiology

Friis-Moller et al. on behalf of the D:A:D study developed prediction models for the risk of a composite cardiovascular disease (CVD) endpoint, specifically for patients with HIV. The performance of the models was superior to that of the Framingham CVD prediction model in this population. The full D:A:D CVD prediction model includes exposure to ART drugs (cumulative protease inhibitor and NRTI exposure, current abacavir use) and markers of immunodeficiency (CD4 lymphocyte count), in addition to conventional CVD risk factors, and more accurately estimated the risk of CVD outcomes in the cohort overall as well as in subgroups.

In conclusion, the estimated CVD risk can be used to quantify risk and to guide preventive care tailored to the HIV-positive population.

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19th November Kohler et al., HIV care cascade in Switzerland


The HIV care cascade in Switzerland: reaching the UNAIDS/WHO targets for patients diagnosed with HIV. AIDS

Kohler et al. aimed to describe the HIV care cascade for Switzerland in the year 2012. They estimated that 15’200 individuals (plausible range: 13’400–19’300) infected with HIV were living in Switzerland, corresponding to a prevalence of 0.19%. Of all 15’200 individuals, 81% had been diagnosed, 80% were linked to and 79% were retained in care. Eighty-eight percent of HIV-diagnosed patients were treated with antiretroviral therapy and of those 96% had had suppressed viral load, meeting recent UNAIDS/WHO targets.

Interventions aiming at improving the current situation of HIV care in Switzerland will most likely have the greatest impact if applied to individuals unaware of their HIV infection.

PubMed

18th November Edwards et al., HIV tropism by genosorting


A diagnostic HIV-1 tropism system based on sequence relatedness. Journal of Clinical Microbiology

Edwards et al. presented a new diagnostic HIV tropism test (XTrack) for complementing and improving the diagnostic genotype-based tropism determination of HIV for clinical use. They found a high concordance with the commercial TrofileES test (84.9%) and the Web-based tool Geno2Pheno (83.0%). Moreover, the new system reveals mixed virus populations, and it was successful on specimens with low virus loads or on provirus from leukocytes. Based on these data the XTrack test is favorably suitable for routine diagnostics.

The authors expect that the same test principle may also be applicable toward new pathogens, such as hepatitis viruses and other genetically highly variable entities.

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12th November Cain et al., Clinical, virologic and immunologic outcomes of boosted atazanavir- versus boosted lopinavir-containing regimens


Boosted lopinavir- versus boosted atazanavir-containing regimens and immunologic, virologic, and clinical outcomes: a prospective study of HIV-infected individuals in high-income countries. Clinical Infectious Diseases

Cain et al. on behalf of the HIV-CAUSAL Collaboration aimed to provide evidence on clinical outcomes among patients who started a first-line regimen consisting of either ritonavir-boosted lopinavir or ritonavir-boosted atazanavir with an NRTI backbone. Compared with lopinavir, the hazard ratio for atazanavir was 0.70 for death, 0.67 for AIDS or death and 0.91 for virologic failure. Compared with lopinavir, the mean change in CD4 cell count for atazanavir was 8.15 cells/µl.

In conclusion, the authors estimated a 30% mortality reduction for atazanavir vs lopinavir and found that atazanavir had a beneficial but modest effect on immunologic and virologic outcomes. Future studies need to consider the effects of lopinavir and atazanavir on other clinical outcomes including non-AIDS-defining illnesses, when paired with specific backbones.

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11th November Achhra et al., ART, weight gain and cardiometabolic outcomes


Short-term weight gain after antiretroviral therapy initiation and subsequent risk of cardiovascular disease and diabetes: the D:A:D study. HIV Medicine

Achhra et al. analyzed the data from the D:A:D Study to assess the relationship between short-term body mass index (BMI) gain after antiretroviral therapy (ART) initiation and the subsequent risk of cardiovascular diseases (CVD) and diabetes mellitus (DM). Those with pre-ART BMI in the normal or middle two quartile categories experienced an increase of 20% in the risk of CVD per unit gain in BMI. Weight gain in underweight individuals had a minimal association with CVD. Unexpectedly, overweight patients did not experience any appreciable change in their already higher risk. For DM each unit gain in BMI was associated with a 12% increase in risk regardless of pre-ART BMI.

In conclusion, clinicians need to be aware that excess weight gain post ART initiation could be detrimental to future cardiometabolic health.

PubMed

5th November Carballo et al., Increased mortality after a first myocardial infarction in HIV+ patients


Increased mortality after a first myocardial infarction in human immunodeficiency virus-infected patients; a nested cohort study. AIDS Research and Therapy

Carballo et al. determined whether HIV infection is a risk factor for worse outcomes in patients with coronary artery disease (CAD). After adjustment for several traditional CAD risk-factors they found that HIV-positive individuals with a first episode of acute myocardial infarction had a higher risk of death from all causes at one year after acute myocardial infarction than their HIV-negative counterparts (hazard ratio 4.42). There was no statistically significant difference in the risk of recurrent acute myocardial infarction or hospital admission in this group.

These findings point out that HIV-infected individuals could benefit from better-informed cardiac risk stratifications as well as targeted secondary prevention measures.

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4th November Yang et al., Assessing efficacy of different nucleos(t)ide backbones


Assessing efficacy of different nucleos(t)ide backbones in NNRTI-containing regimens in the Swiss HIV Cohort Study. Journal of Antimicrobial Chemotherapy

Yang et al. compared different nucleos(t)ide backbones in NNRTI-containing regimens regarding virological responses and emergence of NNRTI resistance and evaluated the impact of pill burden and dosing frequency on treatment efficacy. They found that abacavir/lamivudine-, tenofovir/lamivudine- and zidovudine/lamivudine-containing regimens had a >2-fold high risk of virological failure (VF) than tenofovir/emtricitabine-containing regimens. Tenofovir/lamivudine was more often associated with emergence of NNRTI resistance than tenofovir/emtricitabine. A high number of pills but no dosing frequency was associated with VF and emergence of NNRTI resistance.

In conclusion, the study-results indicate a superiority of tenofovir/emtricitabine-containing regimens, but do not allow definitive determination of whether this effect is caused by the low pill burden or the substances themselves.

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29th October Young et al., Abacavir and cardiovascular disease events


Effect of cumulating exposure to abacavir on the risk of cardiovascular disease events in patients from the Swiss HIV Cohort Study. J Acquir Immune Defic Syndr

Young et al. assessed the effect of abacavir on the risk of cardiovascular disease (CVD) events in the SHCS. They found that in the new marginal structural Cox model continued exposure to abacavir during the past 4 years increased the risk of a CVD event (hazard ratio = 2.06). Exposure during the past 6-36 months caused the greatest increase in risk. Both, current exposure and exposure more than 3 years ago, showed little additional increase in risk.

In conclusion, abacavir can increase the risk for a CVD event. However, the study results suggest that a rapidly acting mechanism such as acute inflammation is unlikely for the increased risk observed.

PubMed

28th October Wagner et al., Comparison of three genotypic HIV-1 drug resistance interpretation algorithms


Algorithm evolution for drug resistance prediction: comparison of systems for HIV-1 genotyping. Antiviral Therapy

Wagner et al. assessed the concordance of the three genotypic HIV-1 drug resistance interpretation algorithms ANRS, Rega and Stanford-HIVdb and their evolution over time. The algorithm versions of 2004 on the analyzed sequences classified 55% of viruses as resistant to at least one antiretroviral drug compared to 63% when the 2013 version was used. Discordant results were obtained for 24% of all samples with the 2004 version compared to 26% of samples with the 2013 version. Most deviations reflected differences between the ANRS and the other two algorithms.

The study results emphasize the need for further adjustment and improvement of the existing interpretation algorithms.

PubMed

22nd October Lodi et al., Effectiveness of immediate ART versus CD4-based initiation in high-income settings


Comparative effectiveness of immediate antiretroviral therapy versus CD4-based initiation in HIV-positive individuals in high-income countries: observational cohort study. The Lancet HIV

Lodi et al. aimed to compare immediate initiation of antiretroviral therapy (ART) with strategies for starting ART based on CD4 thresholds of 500 cells/µl and 350 cells/µl in HIV-positive individuals from high-income countries. Median CD4 count at diagnosis of HIV was 376 cells/µl. Immediate initiation of ART increased survival and AIDS-free survival compared with initiation strategies based on CD4 count. However, compared with immediate initiation of ART, the mean survival time at 7 years was only 2 days shorter at a CD4 count less than 500 cell/µl and 5 days shorter at a CD4 count less than 350 cells/µl.

In conclusion, the benefits of a strategy of immediate ART initiation might be small in high-income settings with relatively low CD4 count at HIV diagnosis. A focus on better and innovative HIV testing strategies might be as important as discussions about early initiation of ART.

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21st October Kohler et al., Influenza antibodies in HIV-infected individuals


The impact of vaccination on the breadth and magnitude of the antibody response to influenza A viruses in HIV-infected individuals. AIDS

Kohler et al. investigated the impact of influenza vaccination and HIV-disease parameters on the breadth and magnitude of antibody responses in HIV-infected individuals. They found that both homo and heterosubtypic antibody titers were lower in HIV-positive individuals. Vaccination increased homosubtypic but had no impact on heterosubtypic serum antibodies. There was no HIV-related parameter that could be used as reliable predictor for the breadth or magnitude of the humoral response to influenza A viruses.

The results clearly support the importance of vaccination of HIV-infected individuals against influenza viruses.

PubMed

14th October Podlekareva et al., Time trends in d4T utilization in Europe


Changing utilization of Stavudine (d4T) in HIV-positive people in 2006–2013 in the EuroSIDA study. HIV Medicine

Podlekareva et al. aimed to describe temporal patterns of Stavudine (d4T) use across Europe from 2006 to 2013 in HIV-positive patients. Of note, d4T is associated with serious long-term side effects, e.g. mitochondrial toxicity resulting in lactic acidosis, polyneuropathy and lipodystrophy. The proportion of patients on d4T-based antiretroviral therapy decreased from 11.2% to 0.7% over the study-period. However, 2.3% of patients in Eastern Europe were still treated with d4T in 2013, reflecting a 4-fold higher risk being treated with d4T compared to other regions in Europe. Having a HIV RNA > 400 copies/mL was associated with initiating d4T.

In conclusion, there is still a low but persistent proportion of HIV positive patients in Eastern Europe receiving d4T. All HIV clinicians should be aware of the potential harmful effects associated with d4T treatment and avoid the drug as far as possible.

PubMed

13th October Vrancken et al., Estimating evolutionary history and repeated traits phylogenetic signal


Simultaneously estimating evolutionary history and repeated traits phylogenetic signal: applications to viral and host phenotypic evolution.Methods in Ecology and Evolution

Vrancken et al. developed a novel Bayesian inference method to estimate the evolutionary history and phylogenetic signal for setpoint viral load (spVL) and declining slope of CD4+ T-cell (dsCD4) from molecular sequence data from the SHCS to study virulence heritability in HIV. As a control trait they included the estimated probability that a treatment-naïve virus is resistant to zidovudine (prAZT) from the pol sequence. They found a relatively high phylogenetic signal for spVL in the men who have sex with men subset and a low phylogenetic signal for prAZT. For dsCD4 the phylogenetic signals were generally lower.

In conclusion, comparative phylogenetic approaches can be used for understanding HIV dynamics.

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8th October Bihl et al., HBV genotypes and response to tenofovir in HIV/HBV-coinfected persons


HBV genotypes and response to tenofovir disoproxil fumarate in HIV/HBV-coinfected persons. BMC Gastroenterology

Bihl et al. assessed the impact of hepatitis B virus (HBV) genotype on the efficacy of tenofovir (TDF) in the treatment of HIV/HBV-coinfected patients from the SHCS. The predominant HBV genotypes were A (57%) and D (24%) and 14% of patients were infected with multiple genotypes. Treatment with TDF resulted in a complete suppression of HBV DNA in 92% of patients within 6 months. In the 8% with a delayed decline in HBV DNA no HBV resistance mutation to TDF was found but all were infected with HBV genotype A and all had previously been exposed to lamivudine.

Prior lamivudine treatment with selected mutations, poor drug adherence or HBV genotype A infection may influence TDF response and warrants further investigation.

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7th October Aebi-Popp et al., Retention in care of HIV-infected women after delivery


Postnatal retention in HIV care: Insight from the Swiss HIV Cohort Study over a 15-year observational period. HIV Medicine

Aebi-Popp et al. aimed to quantify loss to follow-up (LTFU) in HIV care of HIV-infected women after delivery and to identify risk factors for LTFU. The mother to child transmission rate dropped from 3.6% in 1996–2004 to 0.9% in 2005–2011. Twelve percent of women were lost to follow-up in HIV care after delivery. A history of intravenous drug use and a failure to suppress viral replication by delivery were associated with an increased risk of dropping out of HIV care. Fifty-five percent of women returned to care after LTFU, half of them with a CD4 count <350 cells/μL. Effective strategies are warranted to retain women in care beyond pregnancy.

PubMed

1st October Ussher et al., MAIT cell quantitative PCR in HIV infection


Molecular analyses define Vα7.2-Jα33+ MAIT cell depletion in HIV infection. Medicine

Mucosal-associated invariant T (MAIT) cells are innate-like T-cells that may play a role in controlling systemic and mucosal bacterial infection in humans. Ussher et al. determined whether MAIT cells are truly depleted in HIV infection using molecular and cytometric approaches from blood of healthy controls and HIV-infected patients. They found a significant depletion of both messenger RNA and genomic DNA encoding the MAIT cell T cell receptor in HIV infection.

The study results indicate that MAIT cells are depleted from blood in HIV infection. Further studies to determine the role and the impact of MAIT cell depletion in HIV-induced immunodeficiency are warranted.

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30th September Kovari et al., Ribavirin concentration level and sustained virological response


Ribavirin concentrations do not predict sustained virological response in HIV/HCV-coinfected patients treated with ribavirin and pegylated interferon in the Swiss HIV Cohort Study. PLoS ONE

Kovari et al. assessed the impact of ribavirin (RBV) steady-state concentration on sustained virological response (SVR) in HIV/hepatitis C (HCV) coinfected patient groups treated with pegylated interferon/RBV in the SHCS. Median RBV plasma level was 2.0 mg/L in genotype (GT) 1/4 and 1.9 mg/L in GT 2/3 infections. In patients with SVR the RBV concentration was similar compared to patients without SVR. RBV levels ≥2.0 mg/L were not significantly associated with HCV cure, regardless of treatment phase, HCV genotype or IL28B.

The data do not support RBV therapeutic drug monitoring in HIV/HCV-coinfected patients treated with pegylated interferon/RBV to enhance HCV cure.

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24th September Bruyand et al., Cancer risk and antiretroviral therapy


Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: the D: A: D study. Journal of Acquired Immune Deficiency Syndromes

Bruyand et al. assessed the association between combination antiretroviral therapy (cART) and cancer risk. They found that longer exposure to both nonnucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitor (PI) based cART was associated with a lower risk of AIDS-defining cancers (ADC). In contrast, PI use was associated with a higher Non-AIDS-defining cancer (NADC) risk, which was mainly driven by an association with anal cancer. Each additional year of exposure to PI-based cART was associated with a 2% increase in NADC risk.

These study results suggest that a cumulative use of PIs could be associated with a higher risk of invasive anal cancer, and possibly other NADC.

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23rd September Braun et al., Silibinin for difficult-to-treat HIV/hepatitis C coinfected patients


A lead-in with silibinin prior to triple-therapy translates into favorable treatment outcomes in difficult-to-treat HIV/Hepatitis C coinfected patients. PLoS ONE

Braun et al. investigated the efficacy and safety of a lead-in therapy with intravenous silibinin followed by triple-therapy (i.e., telaprevir in combination with peginterferon-ribavirin) in HIV/HCV-coinfected patients with advanced liver fibrosis and non-response to previous peginterferon-ribavirin. Administration of silibinin was safe, well tolerated and highly effective and resulted in a pronounced HCV RNA decline during the lead-in phase. The subsequent initiation of triple-therapy led to a sustained virologic response 12 in ten of sixteen (63%) patients, which is 3-fold higher compared with reported treatment outcomes in similar patient groups. Due to its anti-viral and anti-inflammatory properties, silibinin may serve in the future as part of the cure for hepatitis C and other viral infections and liver diseases.

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16th September Kovari et al., Long-term epidemiological trends of HCV-coinfected persons in the SHCS


High hepatic and extrahepatic mortality and low treatment uptake in HCV-coinfected persons in the Swiss HIV cohort study between 2001 and 2013. Journal of Hepatology

Kovari et al. assessed treatment uptake and outcome parameters among HIV/HCV-coinfected people since the availability of HCV therapy in the SHCS. Seventeen percent of all SHCS participants harbored a replicating HCV infection. Of those, 30% were treated and 15% were cured during a follow-up period of thirteen years. Sixteen percent of participants with active HCV-infection died, 59% due to extrahepatic complications. By the end of 2013, 41% of patients with a replicating HCV infection remained to be treated.

The findings underscore the importance of efforts for optimizing care of comorbidities in HIV/HCV-coinfected patients, given that curing HCV alone is not sufficient to achieve mortality rates similar to HIV-monoinfected patient.

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10th September Glass et al., Impact of adherence to antiretroviral drugs


Self-reported nonadherence to antiretroviral therapy as a predictor of viral failure and mortality: Swiss HIV Cohort Study. AIDS

Glass et al. determined the effect of nonadherence to antiretroviral therapy (ART) on virological failure and mortality in naïve individuals starting ART. Missing of two or more ART doses in the previous 4 weeks increased the risk of both viral failure and mortality. The risk of viral failure increased with each missed dose. Simplification to once-daily regimens was associated with an increased risk of viral failure compared to twice-daily regimens in the presence of nonadherence.

The study-results underscore the importance of regular investigation of adherence at each clinical visit.

PubMed

9th September Hasse et al., Effect of HIV infection on multimorbidity


Strong impact of smoking on multimorbidity and cardiovascular risk among HIV infected individuals in comparison to the general population. Open Forum Infectious Diseases

Hasse et al. assessed the prevalence of comorbidities and multimorbidity in participants of the SHCS compared with the population-based CoLaus study and the primary-care based FIRE records. They identified associations of HIV with increased risks of hypertension and kidney and liver disease, unlike cardiovascular disease where the risk is associated with smoking. They did not find evidence for an increased prevalence or incidence of diabetes mellitus associated with HIV infection or smoking.

The study-results suggest that in clinical practice emphasis should be given to smoking cessation and lifestyle interventions among HIV-infected patients.

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3rd September Weber et al., Drug use and course of HIV infection


Influence of noninjecting and injecting drug use on mortality, retention in the cohort, and antiretroviral therapy, in participants in the Swiss HIV Cohort Study. HIV Medicine

Weber et al. investigated how noninjecting and injecting drug use influenced different outcome parameters among participants in the SHCS. They found that injecting drug use, noninjecting drug use and smoking were significant risks for death. Mortality was mainly driven by non-HIV-associated causes. Drug use lowered adherence, and increased rates of ART change and ART interruptions.

The study results indicate that comprehensive HIV care needs to incorporate interdisciplinary strategies to integrate prevention and treatment of these modifiable risk factors.

PubMed

26th August Schaerer et al., Hepatitis C treatment in HIV-infected patients


Protease inhibitors to treat hepatitis C in the Swiss HIV Cohort Study: high efficacy but low treatment uptake. HIV Medicine

Schaerer et al. assessed treatment uptake and efficacy in routine clinical setting among HIV/hepatitis C virus (HCV) coinfected patients after the introduction of first generation direct-acting antiviral agents (DAAs). Fifty-seven (11%) out of 516 patients with chronic HCV genotype 1 infection started HCV-treatment with first-generation protease inhibitors (e.g. telaprevir, boceprevir, faldepravir) during the first 2 years after their approval. Sustained virological response was 78%, 86% and 40% in treatment-naïve patients, patients with relapse and nonresponders, respectively.

The study-results indicate that introduction of HCV protease inhibitors into clinical practice was beneficial at the individual level, but had only a modest effect on the burden of HCV infection at the population level.

PubMed

19th August Castillo et al., Prognostic Factors in HIV-Hodgkin Lymphoma


Prognostic factors for advanced-stage human immunodeficiency virus-associated classical hodgkin lymphoma treated with doxorubicin, bleomycin, vinblastine, and dacarbazine plus combined antiretroviral therapy. Cancer

Castillo et al. aimed at identifying predictive and prognostic factors in patients with HIV-associated classical Hodgkin Lymphoma (HL) receiving a combination of chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine; ABVD) and antiretroviral therapy. Patients experienced high overall response rates to therapy of 91% and high 5-year progression-free survival and overall survival rates of 69% and 78%, respectively. A CD4-positive count

The study supports the finding that HIV-infected patients with HL should receive standard doses of ABVD and underscores the prognostic value of the CD4-positive cell count at HL diagnosis. 

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11th August Cozzi-Lepri et al., Impact of minority variants on ART


Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case–control study using centralized ultrasensitive 454 pyrosequencing. Journal of Antimicrobial Chemotherapy

Cozzi-Lepri et al. investigated the impact of pre-existing minority drug-resistant HIV-1 variants (MV) on the virological outcomes of first-line NNRTI- (i.e. nevirapine or efavirenz) containing antiretroviral treatment. They found that detection of at least one MV conferring resistance to reverse transcriptase inhibitors (RTIs) was associated with a >2-fold increased risk of virological failure, regardless of the NRTI backbone started or whether nevirapine or efavirenz was commenced. There was a direct dose-effect relationship between the mutational load of MVs and risk of viral failure.

The study results suggests that ultrasensitive HIV-1 genotyping could have a role in improving the outcomes of ART including NNRTIs.

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6th August Schäfer et al., Predicting smoking cessation and relapse


Predicting smoking cessation and its relapse in HIV-infected patients: the Swiss HIV Cohort Study. HIV Medicine

Schäfer et al. assessed whether information routinely collected at 6-monthly follow-up visits within the SHCS could be used to predict (i) the smokers most likely to stop and (ii) among smokers who stop, those most likely to relapse. The authors built simple prediction models, including clinical and statistical models with patients classified into three motivational groups. Of 4’833 smokers, 1’261 (26%) stopped smoking. Among those who stopped, 48% started smoking again. More patients who stopped were in the highly motivated group. The predictive performance of the clinical and statistical models for smoking cessation and relapse was modest.

The study results suggest that smoking cessation and its relapse cannot be accurately predicted from variables typically collected in observational cohorts of HIV-infected patients. Targeting those trying to stop or those who have just stopped are the best candidates for an intervention.

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29th July Marzolini et al., Efavirenz treatment response and weight


Impact of body weight on virological and immunological responses to efavirenz-containing regimens in HIV-infected, treatment-naive adults. AIDS

Marzolini et al. on behalf of COHERE assessed the virological and immunological responses to initial efavirenz (EFV)-containing regimens in heavy compared to normal-weight HIV-infected individuals. There was no statistical difference in the time to initial undetectable viral load between heavier and normal-weight groups. Overall, 81.1% patients attained an undetectable viral load, of which 34.1% subsequently experienced viral load rebound. After multiple adjustments, no statistical differences were observed among weight categories in time to undetectable viral load and time to viral rebound. The CD4+ recovery was comparable between heavier and normal-weight individuals.

The findings of this study suggest that the standard 600 mg dose of EFV is appropriate across a wide weight range. Since most cohorts did not measure levels of EFV, the observations could not be correlated with drug concentrations.

PubMed

29th July Martin Rickenbach is retiring at the end of July


Martin Rickenbach goes into retirement the 1st of August 2015. He has been the head of the Swiss HIV Cohort Study data centre for the last 20 years. In 1995, when the data centre was transferred from Zurich to the CHUV, he took over the leadership from Bruno Ledergerber. Together with all the data managers and Yannick Vallet, he contributed to the high quality of the data from the SHCS. He also implemented various quality controls that are of major importance for such a project. He was a quiet leader but highly appreciated by the data managers, the SHCS participants and the international collaborators for his endeavours to provide a top service for the researchers and laboratories. He also played an important role when integrating the Swiss Mother and Child Cohort into the SHCS in 2004. An endless problem he was confronted with was the constant change in HIV/AIDS data collection due to the ever changing face of the HIV-epidemic, in particular from the clinical side. Consequently, the database permanently had to be adapted, a never-ending challenge for a data centre and its leader.

The SHCS wants to express its gratitude to Martin Rickenbach for his dedication and the high quality of his work and wishes him all the best for the future!

 

28th July Rosin et al., HIV/AIDS and women


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

Rosin et al. compared treatment responses to combination antiretroviral therapy (cART) between genders in a setting of equal access to cART over a 14-year period. Men who have sex with men were excluded from the analysis. Women were less likely to achieve virological suppression at 1 and at 2 years. After adjustment for potential confounders, no major differences in virological suppression were observed between the sexes. In multivariate analysis, only non-white ethnicity was an independent risk factor for not achieving virological suppression. Overall, 48.2% of patients modified their initial cART regimen during the first year of treatment. Women were more likely to modify their treatment, even if pregnant women were excluded. Women showed a better immunological recovery at 1 year than men. The virological response and immunological recovery improved in both genders over time.

In conclusion, gender inequalities in the response to cART are mainly explained by the different prevalences of socio-economic characteristics in women compared with men.

PubMed

22nd July Perkins et al., Genetics of microbial translocation in HIV


The interplay between host genetic variation, viral replication, and microbial translocation in untreated HIV-infected individuals. Journal of Infectious Diseases

Perkins et al. searched in a genome-wide association study for human genetic variations associated with determinants of chronic immune activation such as markers of gut damage (e.g., fatty acid-binding protein; FABP) and microbial translocation (e.g., soluble CD14; sCD14) in untreated HIV-infected individuals. They did not identify any significant genetic association with the tested plasma markers and found that the human genetic variants known to be associated with control of HIV viremia are not associated with sCD14 or FABP levels. On the other hand, they observed strong associations between sCD14 and both HIV viral load and FABP.

This finding reinforces the role of microbial translocation in the pathogenesis of untreated HIV infection.

pdf publication

15th July Helleberg et al., Impact of smoking and HIV on life expectancy


Smoking and life expectancy among HIV-infected individuals on antiretroviral therapy in Europe and North America. AIDS

Helleberg et al. on behalf of the ART Cohort Collaboration estimated associations of smoking with all-cause and cause-specific mortality and loss of life years among HIV-infected individuals. They found that smoking was associated with a two-fold increase in mortality. Deaths from non-AIDS related malignancies and cardiovascular diseases accounted for most of the excess mortality among smokers. Previous smokers had similar mortality compared to never smokers. The life expectancy of smokers was on average 8 years less than that of nonsmokers. The loss of life years associated with smoking was markedly higher compared to that associated with HIV.

The findings of this study underscore the importance of smoking cessation interventions in HIV-infected individuals.

pdf publication

9th July Fitzmaurice et al., Effects of HLA alleles and innate immune genes on viral outcome in HCV infection


Additive effects of HLA alleles and innate immune genes determine viral outcome in HCV infection. GUT

Fitzmaurice et al. assessed the collective influence of HLA- and innate immune genes on viral outcome in HCV infection in a cohort of women who had been infected from a single source as well as the more heterogeneous Swiss HIV Cohort Study. They found that HLA class I and II genes are significantly associated with viral outcomes even when the profound impact of immune genes (e.g., IL28B) are considered. There is no evidence of a genetic interaction effect between HLA I and II alleles and IL28B, however, there is a clear additive effect.

These data support a critical role for the adaptive immune response alongside the innate immune response in the control of HCV.

pdf publication

6th July Boillat-Blanco et al., Persistent low-level viraemia and virological outcome and management


Virological outcome and management of persistent low-level viraemia in HIV-1-infected patients: 11 years of the Swiss HIV Cohort Study. Antiviral Therapy

Boillat-Blanco et al. examined virological outcome and management in HIV-infected patients under combination antiretroviral therapy (cART) with persistent low-level viraemia (pLLV), defined as viral load (VL) of 21-400 cp/ml on ≥3 consecutive undetectable plasma samples. At week 48, 19/155 pLLV patients (12%) developed viral failure (VF), defined as VL >400 cp/ml. There was a strong correlation between pLLV of 201-400 cp/ml and VF. Compared to the control group, patients with pLLV were more often on unboosted protease inhibitor (PI) based and NRTI-only combination. No VF occurred in patients with persistent very LLV (21-49 c/ml). Most patients who changed ART had undetectable VLs thereafter.

These findings support cART modification for pLLV >200 cp/m.

pdf publication

1st July Mansfeld et al., Health care for HIV/TB patients in Europe


Major differences in organisation and availability of health care and medicines for HIV/TB coinfected patients across Europe. HIV Medicine

Mansfeld et al. on behalf of EuroCoord investigated the organization of and access to HIV/tuberculosis (TB) health care between treatment centres in Eastern (EE) and Western Europe (WE). Compared with WE, treatment of HIV and TB in EE are significantly less often located at the same site and less often provided by the same doctors, whereas regular screening of HIV-infected patients for TB and directly observed treatment were more common in EE. The reported availability of rifabutin and second- and third-line TB drugs was lower, and opioid substitution therapy was available at fewer centres in EE compared with WE.

The findings from this study emphasize the need for an increased focus on patient-centred care and integration across specialities. Linking regional differences of HIV/TB health care to treatment outcomes is crucial for future care.

pdf publication

24th June Ciaffi et al., Switch to etravirine for HIV-positive patients receiving statin treatment


Switch to etravirine for HIV-positive patients receiving statin treatment: a prospective study. European Journal of Clinical Investigation

Ciaffi et al. tested one of the proposed strategies to manage patients with cardiovascular risk and hyperlipidemia. In this multicenter, one-arm, open label 12-week study, 31 HIV undetectable patients on statin were included. Statin treatment was stopped and 8 weeks later the antiretroviral drug possibly causing lipid increase (EFV or bPI) was replaced with etravirine (400 mg, 8 weeks) in 27 participants. At the end of the study not only patients had a significantly lower concentration of total and LDL cholesterol and triglycerides, but 56% of them did not qualify for statin treatment anymore according to EACS guidelines.

In addition, changes in pro-inflammatory cardiovascular biomarkers showed as well a favorable trend, suggesting possible future research focus.

PubMed

17th June Kouyos et al., Increases in condom-less sex in the Swiss HIV Cohort Study


Increases in condom-less sex in the Swiss HIV Cohort Study.
Open Forum Infectious Diseases

Kouyos et al. assessed the long-term changes of the occurrence of condom-less sex in HIV-infected individuals enrolled in the SHCS. The frequencies of reported condom-less sex were stable for 2000-2008 and increased significantly from 2008-2013 for stable relationships among heterosexuals and men who have sex with men (MSM) and for occasional relationships among MSM. The changes may be partially explained by the “Swiss statement” that has been endorsed in 2008, advocating that individuals on effective antiretroviral therapy are non-infectious and thus do not need to use condoms.

The study shows that indeed HIV-infected people in stable partnerships have taken up this message but not only as evidenced by less frequent condom usage also in MSM with occasional relationships. The observed patterns of condom-less sex in occasional partnerships may have driven the recent rise in sexually transmitted infections and the emergence of a sex-associated transmission-route for hepatitis C virus.

 

pdf publication
press release University Zurich

4th June 1st Swiss HIV Cohort Study Metabolic and Aging workshop

pdf

27th May Vingerhoets et al., Efficacy of etravirine plus a boosted protease inhibitor other than darunavir


Efficacy of etravirine combined with darunavir or other ritonavir-boosted protease inhibitors in HIV-1-infected patients: an observational study using pooled European cohort data. HIV Medicine

Vingerhoets et al.: A European observational study in antiretroviral treatment-experienced HIV-1 infected patients explored the efficacy of etravirine (ETR) plus darunavir/ritonavir (DRV/r) versus ETR plus an alternative boosted protease inhibitor (PI) together with an optimized background regimen. Overall, there was no difference in virological response rates between the two groups, for a given set of measured confounding factors. These data suggest that ETR exhibits similar efficacy together with a PI other than DRV/r, combined with an optimized background regimen. However, the results must be interpreted with caution given the small sample size.

PubMed

14th May Montazeri et al., Estimating the dynamics and dependencies of accumulating mutations


Estimating the dynamics and dependencies of accumulating mutations with applications to HIV drug resistance. Biostatistics

Montazeri et al. introduced a new model called “observed time conjunctive Bayesian network” (OT-CBN) to estimate the dynamics and dependencies of accumulating mutations with application to HIV drug resistance. The authors used their algorithm for estimation of the evolutionary rates for a given data set based on observed genotypes and corresponding sampling times and found that OT-CBN was superior compared to alternative models in term of likelihood and sampling time estimation.

Providing an analytical expression for the expected sampling time of a genotype, the authors assume that the expected sampling time of the genotype could serve clinicians as an informative predictor for HIV therapy outcome.

PubMed

30th April Jörg Schüpbach is retiring at the end of May


pdf

31st March Change in the management of the SHCS data centre


Martin Rickenbach will retire at the end of July 2015, after 20 years as head of the SHCS data centre!

Franziska Schöni-Affolter is the designated head of the SHCS data centre. To allow a smooth transfer of the activities, Franziska has been the acting chief of the SHCS data centre since the beginning of this year. This way, she gets acquainted with the many tasks that come with leading the data centre while Martin is still around.

For this reason, we ask you to primarily approach Franziska for questions related to the data centre. Of course, Martin is still around and will help if needed, respectively, he will support Franziska during the transition phase.

31st March Mocroft et al., Risk score for chronic kidney disease in HIV


Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study. PLoS Medicine

Mocroft et al. developed and externally validated a risk score for predicting chronic kidney disease (CKD) at 5 years in HIV-positive individuals from the D:A:D study. Incidence of CKD was 6.2/1’000 person-years of follow-up. The authors included 9 factors which were identified to predict CKD in their risk score model and defined three risk groups (i.e., low, medium and high risk of CKD development). The chance to develop CKD increased significantly by higher risk group as the number needed to harm (NNH) when starting potentially nephrotoxic antiretroviral drugs decreased (739 in the low risk, 88 in the medium risk, and 9 in the high risk group).

These findings highlight the need for monitoring, screening and chronic disease prevention to minimize the risk of HIV-positive individuals developing CKD associated diseases.

pdf publication

25th March Wandeler et al., Acute HCV in the Swiss HIV Cohort Study


Incident hepatitis C virus infections in the Swiss HIV Cohort Study: Changes in treatment uptake and outcomes between 1991 and 2013. Open Forum Infectious Diseases

Wandeler et al. report changes in treatment uptake and treatment outcome of incident hepatitis C virus (HCV) infections within the SHCS before and after 2006. Treatment uptake and sustained virological response rates increased significantly after 2006, reflecting earlier treatment initiation and lower barriers to treatment in acute HCV infections affecting men who have sex with men.

pdf publication

23rd March Yang et al., Transmitted HIV-1 drug resistance mutations and fitness costs

Persistence of transmitted HIV-1 drug resistance mutations associated with fitness costs and viral genetic backgrounds. PLoS Pathogens

Yang et al. assessed the role of fitness cost and the genetic background for resistance in vivo by studying the persistence behavior of transmitted antiretroviral resistance mutations of HIV in 857 sequential samples from the SHCS. They found that the reversion rate of individual mutations varied substantially and were positively associated with the fitness costs these mutations had in their genetic background.

pdf publication

16th February Symposium in honour of Jörg Schüpbach, 23rd April 2015


pdf

28th January Yang WL et al., Persistent adaptability


Assessing the paradox between transmitted and acquired HIV type 1 drug resistance mutations in the Swiss HIV Cohort Study From 1998 to 2012. Journal of Infectious Diseases

Yang WL et al.

link to press release SNSF
pdf publication

28th January Vandenhende et al., Impact of low-level viremia in HIV


Impact of low-level viremia on clinical and virological outcomes in treated HIV-1-infected patients.
AIDS

The Antiretrovira Therapy Cohort Collaboration et al. assessed the prognostic impact of low-level viremia (LVV) among patients receiving antiretroviral therapy. They found that LVV between 200 and 400 copies/ml was significantly associated with virological failure, but not with AIDS event or death. In contrast, LVV between 50-199 copies/ml did not influence the outcome.

This study supports current guidelines defining virological failure as viral load above 200 copies/ml.

PubMed

14th January Gueler et al., Neighbourhoods and outcomes of HIV-Infection


Neighbourhood socio-economic position, late presentation and outcomes in people living with HIV in Switzerland. AIDS

Gueler et al. assessed the influence of neighbourhood socio-economic position (SEP) on outcomes in HIV-positive individuals in Switzerland. They found that virologic response to antiretroviral therapy was more likely in patients living in neighbourhoods of higher SEP, and presentation with advanced HIV disease more common in neighbourhoods of low SEP. However, in contrast to the general population, late presentation to care did not translate into increased mortality.

PubMed

12th January Funding by a SNSF Starting Grant


Dr. Roger Kouyos from the Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, was awarded a SNSF Starting Grant for the project "Using transmission networks for assessing and guiding prevention efforts in HIV".

12th January Funding by the State Secretariat for Education, Research and Innovation (SERI)


The SERI granted Prof. Alexandra Trkola from the Institute of Medical Virology of the University Zurich a financial support of CHF 1'000'000.- for the research project "Defining determinants of broadly neutralizing antibody evolution in viral infection to guide vaccine development". This project is partially based on the SHCS.

12th January Funding by SystemsX.ch


SystemsX.ch, The Swiss Initiative in Systems Biology, granted Prof. Huldrych Günthard from the Division of Infectious Diseases and Hospital Epidemiology of the University Hospital Zurich/UZH, and colleagues (Prof. Niko Beerenwinkel, ETHZ/BSSE, Dr. Jasmina Bogojeska, IBM, Prof. Sebastian Bonhoeffer, ETHZ, Prof. Jacques Fellay, EPFL, Dr. Roger Kouyos, USZ, Prof. Karin Metzner, USZ, and Prof. Volker Roth, UNIBAS) a financial support of CHF 2'182'086.- for the research project "The interplay of host and viral factors in the hurdle to cure HIV-1". The project builds on the SHCS.

1st January WebMED: First step into the future


The successful and longstanding existence of the SHCS is dependent on a modern database system and, increasingly important, an easy way to gather the huge amount of data. Unfortunately, the current infrastructure is old and reaching its limits. With todays established IT facilities including security issues it is possible to achieve the important steps for a sustained modernization of the outdated infrastructure. The data collection must be improved towards a modern and well-accepted user-centered tool. The first step is already done: the most complex but increasingly important table of antiretroviral and non-antiretroviral medication including vaccinations and adherence could be remodeled. Further steps are to come. The paper questionnaires will ultimately be available in a decentralized online tool. This step will fulfill the requirement of a modern and flexible tool for the collection of the increasing amount of data in the future.