2020

24th June Greiter et al., Impact of neonatal PEP with AZT on lymphocyte subsets in HIV-exposed uninfected infants


Lymphocyte subsets in HIV-exposed uninfected infants: The impact of neonatal postexposure prophylaxis with zidovudine.   Open Forum of Infectious Diseases

Greiter et al. on behalf of the Swiss HIV Cohort Study and the Swiss Mother and Child HIV Cohort Study aimed to analyze the impact of zidovudine (AZT-) based neo-natal postexposure prophylaxis (PEP) on lymphocyte subsets and hematological parameters in HIV-exposed, uninfected (HEU) children from birth to 24 months of age. Postnatal AZT exposure was defined as administration of neo-natal PEP with AZT for at least 2 weeks. Lymphocyte subsets and hematological parameters were evaluated at 1, 2, 6, and 24 months of age during routine visits-

Among 178 HEU infants included in the analysis, 25 (14%) did not receive any neonatal PEP after birth. Eighty-two (53.6%) neonatal PEP recipients and 1 (4%) of the infants without PEP were born to mothers with AZT-containing cART during pregnancy (P <.001). Overall, there were no statistically significant differences in either absolute CD4 and CD8 T-cell counts or absolute CD19 B-cell counts comparing adjusted means between HEU infants who received neonatal PEP and those who did not. Although not statistically significant, a consistent trend of lower adjusted means during the first 24 months of life in HEU infants receiving neonatal PEP compared with those not receiving PEP could be observed in the performed linear multivariate mixed models, especially for absolute CD4 T cells.

In conclusion, lymphocyte subsets in HEU infants receiving neonatal PEP did not differ from those of infants not receiving PEP but did show nonsignificant trends of lower adjusted means. Even though these observations are of questionable clinical significance, it remains unclear whether the effect of postnatal AZT exposure might have an impact on the overall health of HEU infants or might contribute to the previously observed higher incidence of infection in HEU infants within their first 2 years of life. As other high-income countries may soon follow the Swiss example to omit neonatal PEP with AZT if maternal HIV plasma viral load is fully suppressed in the last trimester of pregnancy, further studies to investigate the impact of postnatal AZT exposure in larger cohorts of HEU infants should be pursued.

pdf publication

10th June Courlet et al., DDIs between antiretrovirals and statins


Real-life management of drug-drug interactions between antiretrovirals and statins.    Journal of Antimicrobial Chemotherapy

Courlet et al. aimed to assess the management of drug–drug interactions (DDIs) between antiretrovirals (ARVs) and statins in people living with HIV (PLWH) of the Swiss HIV Cohort Study (SHCS) considering statin plasma concentrations, compliance with dosing recommendations and achievement of lipid targets. Individual non-HDL and triglyceride (TC) target values were set using the Framingham score and the 2018 European AIDS Clinical Society recommendations.

Data were analysed for rosuvastatin (n= 99), atorvastatin (n= 92), pravastatin (n= 46) and pitavastatin (n= 21). Rosuvastatin and atorvastatin underdosing frequently led to suboptimal pharmakodynamic response. Insufficient lipid control was observed with protease inhibitors (PIs) despite high atorvastatin concentrations, likely explained by inhibition of OATP1B1 resulting in less statin uptake in the liver. Target lipid values were more often achieved with unboosted integrase inhibitors due to both their favourable DDI profiles and neutral effect on lipids. Insufficient lipid control was common with pravastatin and pitavastatin regardless of co-administered ARVs and despite using maximal recommended statin doses. The latter suggests lower efficacy compared with rosuvastatin or atorvastatin.

In conclusion, suboptimal management of dyslipidaemia is common in PLWH due to statin underdosing or the use of low-intensity statins leading overall to 41% of statin prescriptions with suboptimal response. Management of dyslipidaemia in patients on PIs is challenging due to DDIs and their negative impact on lipidprofile, potentially impairing the therapeutic effect of statins. Unboosted integrase strand transfer inhibitors or rilpivirine-based regimens and/or treatment with rosuvastatin or atorvastatin should be favoured in patients with re-fractory dyslipidaemia.

PubMed

4th June Surial et al., Renal function after switching to TAF


Changes in renal function after switching from TDF to TAF in HIV-infected individuals: a prospective cohort study.   Journal of Infectious Disease

Surial et al. aimed to estimate the impact of replacing tenofovir disoproxil fumarate (TDF) by tenofovir alafenamide (TAF) on estimated glomerular filtration rate (eGFR) and proteinuria, and to assess whether differences exist among patients with renal dysfunction and other comorbidities.

In all participants from the Swiss HIV Cohort Study who switched from TDF to TAF-containing antiretroviral regimen or continued TDF, the authors estimated changes in eGFR and urine protein-to-creatinine ratio (UPCR) after 18 months.

Of 3’520 participants (26.6% women, median age 50 years), 2404 (68.5%) switched to TAF. Overall, 1664 (47.3%) had an eGFR <90 mL/min and 1087 (30.9%) an UPCR ≥15 mg/mmol. In patients with baseline eGFR ≥90 mL/min, eGFR decreased with the use of TDF and TAF (−1.7 mL/min). Switching to TAF was associated with increases in eGFR of 1.5 mL/min (95% confidence interval [CI], .5–2.5) if the baseline eGFR was 60–89 mL/min, and 4.1 mL/min (95% CI, 1.6–6.6) if <60 mL/min. In contrast, eGFR decreased by 5.8 mL/min (95% CI, 2.3–9.3) with continued use of TDF in individuals with baseline eGFR <60 mL/min. UPCR decreased after replacing TDF by TAF, independent of baseline eGFR.

In conclusion, these findings suggest that switching from TDF to TAF or to another TDF-free backbone should be considered in individuals with established renal dysfunction. In the absence of other risk factors for TDF-associated toxicity, continuing TDF in individuals with a normal renal function seems reasonable, and has the potential to reduce HIV-related costs due to the availability of generic formulations of TDF. Additionally, because TAF seems to be associated with other adverse events such as increases in cholesterol levels and weight gain, longer term follow-up from observational cohort studies is needed to confirm the safety and efficacy of TAF in individuals with comorbidities.

PubMed

28th May Roth et al., Repeated syphilis episodes among MSM from the SHCS


Repeated syphilis episodes in HIV-infected men who have sex with men: a multicentre prospective cohort study on risk factors and the potential role of syphilis immunity.   Open Forum Infectious Diseases

Roth et al. aimed to identify risk factors for incident syphilis and in particular for repeated syphilis episodes among men who have sex with men (MSM) from the Swiss HIV Cohort Study (SHCS).

Within a 14-year observation period, the authors included 2’513 HIV-infected MSM with an initially negative syphilis test. In the univariable and multivariable analysis, the number of prior syphilis episodes (adjusted hazard ratio [aHR] per 1-episode increase, 1.15; 95% confidence interval [CI], 1.01–1.31), having occasional sexual partners with or without condomless anal sex (aHR, 4.99; 95% CI, 4.08–6.11; and aHR, 2.54; 95% CI, 2.10–3.07), and being currently on antiretroviral therapy (aHR, 1.62; 95% CI, 1.21–2.16) were associated with incident syphilis.

In conclusion, in HIV-infected MSM, there was no indication of a decreased syphilis risk with repeated syphilis episodes. The extent of sexual risk behavior over time was the strongest risk factor for recurrent syphilis episodes. The observed association of ART with repeated syphilis episodes may not be causal and warrants further epidemiological and immunological investigation.

pdf publication

20th May Greenberg et al., Uptake and discontinuation of INSTIs


Uptake and discontinuation of integrase inhibitors (INSTIs) in a large cohort setting.    JAIDS

Greenberg et al. on behalf of the RESPOND Study Group aimed to describe the characteristics of patients initiating integrase strand transfer inhibitors (INSTIs) for the first time in heterogeneous real-world settings across Europe and Australia. In this analysis, RESPOND participants starting dolutegravir (DTG), elvitegravir (EVG), or raltegravir (RAL) after January 1, 2012 were included.

Overall, 9’702 persons were included; 5’051 (52.1%) starting DTG, 1’933 (19.9%) EVG, and 2’718 (28.0%) RAL. The likelihood of starting RAL or EVG vs DTG decreased over time and was higher in Eastern and Southern Europe compared with Western Europe. At 6 months after initiation, 8.9% (95% confidence interval: 8.3% to 9.5%) had discontinued the INSTI (6.4% DTG, 7.4% EVG, and 14.0% RAL). The main reason for discontinuation was toxicity (44.2% DTG, 42.5% EVG, 17.3% RAL). Nervous system toxicity accounted for a higher proportion of toxicity discontinuations on DTG (31.8% DTG, 23.4% EVG, 6.6% RAL). Overall, treatment simplification was highest on RAL (2.7% DTG, 1.6% EVG, and 19.8% RAL). Factors associated with a higher discontinuation risk included increasing year of INSTI initiation, female gender, hepatitis C coinfection, and previous non–AIDS-defining malignancies. Individuals in Southern and Eastern Europe were less likely to discontinue. Similar results were seen for discontinuations after 6 months.

In conclusion, uptake of DTG compared with EVG/c or RAL has increased over calendar time, and more in Western Europe compared with other European regions. INSTI discontinuation was mainly due to toxicity in the first 6 months and patient/physician choice thereafter, but was low overall. Discontinuation was significantly higher for RAL, mainly due to treatment simplification, whereas discontinuation due to nervous system toxicities was highest on DTG. Our findings highlight the need for further research to better understand adverse events on INSTIs

PubMed

13th May Glass et al., Asymptomatic HIV and clinical outcomes


The role of HIV asymptomatic status when starting ART on adherence and treatment outcomes and implications for test and treat: the Swiss HIV Cohort Study.   Clinical Infectious Disease

Glass et al. aimed to assess trends in starting antiretroviral therapy (ART) over time and the potential impact of symptom status at ART initiation on adherence and treatment outcomes.

People living with human immunodeficiency virus (PLHIV) registered in the Swiss HIV Cohort Study (SHCS) between 2003 and 2018 were included. The authors defined asymptomatic as Centers for Disease Control and Prevention stage A within 30 days of starting ART, non-adherence as any self-reported missed doses and viral failure as two consecutive viral load>50 copies/mL after >24 weeks on ART.

Of 7’131 PLHIV, 76% started ART when asymptomatic and 1’478 (22%) experienced viral failure after a median of 1.9 years (interquartile range, 1.1–4.2). In multivariable models, asymptomatic PLHIV were more likely to be younger, men who have sex with men, better educated, have unprotected sex, have a HIV-positive partner, have a lower viral load, and have started ART more recently. Asymptomatic status was not associated with nonadherence (odds ratio, 1.03 [95% confidence interval {CI}, .93–1.15]). Asymptomatic PLHIV were at a decreased risk of viral failure (adjusted hazard ratio, 0.87 [95% CI, .76–1.00]) and less likely to develop resistance (14% vs 27%, P < .001) than symptomatic PLHIV.

In conclusion, this is the first study to report comprehensive clinical picture of asymptomatic PLHIV starting ART in a high-income setting. After adjusting for a comprehensive list of confounders, asymptomatic PLHIV did not report more nonadherence and remained less likely to experience viral failure at the threshold of RNA < 50 copies/mL. These results are particularly encouraging considering the already low rates of virologic failure and emergence of drug resistance in the cohort. With additional cost and resources required to treat PLHIV earlier, differentiated care models will be important for monitoring newly diagnosed PLHIV starting ART and providing targeted support for vulnerable groups—younger, less educated, and lacking social support.

Additional comment Dominique Braun and Huldrych Günthard
After a longer break due to the Corona crisis, we are back now and will continue to share interesting results from the SHCS on a weekly base. We hope that you and your families are doing well and we are looking forward to meeting you soon in person.

PubMed

1st April Congratulations!


It is with great pleasure that we can inform you on two projects that will be supported by the Swiss National Science Foundation for the coming years.

  • NAMACO: step 2
    principal investigator: Matthias Cavassini
    awarded amount: CHF 459'520.-
    partners: Laurent Decosterd, Roger Kouyos, Catia Marzolini, Cristina Granziera, Katie Darling, Renaud Du Pasquier, Bruno Ledergerber and the SHCS data centre

    funding period: April 2020 - March 2024
  • Novel long acting injectable antiretrovirals: Real-life monitoring in the Swiss HIV Cohort Study
    principal investigator: Laurent Decosterd
    partners: Matthias Cavassini, Thierry Buclin, Monia Guidi, Pascal André, Chantal Csajka, Eva Choong
    awarded amount: CHF 643’365.-
    funding period: November 2020 - October 2023

We wish Matthias Cavassini, Laurent Decosterd and their teams all the best for these projects!

17th March COVID-19 und HIV

Die SHCS bekommt mehr und mehr Anfragen wegen COVID-19 von Menschen mit HIV.

Zurzeit gibt es keine Evidenz, dass Menschen mit HIV ein höheres Risiko haben, an SARS-CoV-2 schwerer zu erkranken als andere. Es gelten deshalb die gleichen Risikofaktoren wie für die Gesamtbevölkerung.

Die hauptsächlichen Risikofaktoren schwerer zu erkranken sind,

  • Höheres Alter (> 65 Jahre)

  • Begleiterkrankungen wie, Herz-Kreislauf-Erkrankungen, Diabetes, chronische Lungenerkrankungen (z.B. COPD), Nierenerkrankungen, erhöhter Blutdruck

  • Immunsuppression/Krebs (z.B. durch Chemotherapien, Immunsuppressiva, immunmodulatorische Medikamente etc.)

Wichtig ist, dass Menschen mit HIV sich jährlich gegen Grippe impfen lassen und auch gegen Pneumokokken geimpft sind.

Bei Menschen mit HIV und obgenannten Risikofaktoren, einer unbehandelten HIV-Infektion oder bei Unsicherheiten rufen Sie doch bitte Ihren behandelnden Arzt an.

Wir beobachten die Situation ständig und werden entsprechende Anpassungen vornehmen.

Am wichtigsten ist es, dass sie den Empfehlungen vom Bundesamt für Gesundheit folgen und insbesondere, die Händehygiene und das Abstandhalten einhalten.

12th March Pantazis et al., Determining the likely place of HIV acquisition for migrants in Europe


Determining the likely place of HIV acquisition for migrants in Europe combining subject-specific information and biomarkers data.    Statistical Methods in Medical Research

Pantazis et al. aimed to propose a method to derive subject-specific estimates of unknown HIV infection times among migrants in Europe using information from HIV biomarkers’ measurements, demographic, clinical, and behavioral data. For example, the method could determine if HIV-positive migrants participating in the Advancing Migrant Access to Health Services in Europe (aMASE) study, diagnosed in Europe, were infected pre- or post-migration.

The authors assumed that CD4 cell count (CD4) and HIV-RNA viral load trends after HIV infection follow a bivariate linear mixed model. Using post-diagnosis CD4 and viral load measurements and applying the Bayes’ rule, they derived the posterior distribution of the HIV infection time, whereas the prior distribution was informed by AIDS status at diagnosis and behavioral data. Parameters of the CD4–viral load and time-to-AIDS models were estimated using data from a large study of individuals with known HIV infection times (CASCADE).

Simulations showed substantial predictive ability (e.g. 84% of the infections were correctly classified as pre- or post-migration). Application to the aMASE study (n=2009) showed that 47% of African migrants and 67% to 72% of migrants from other regions were most likely infected post-migration.

In conclusion, applying a Bayesian method based on bivariate modeling of CD4 and viral load, and subject-specific information, the authors found that the majority of HIV-positive migrants in aMASE were most likely infected after their migration to Europe.

PubMed

4th March Ryom et al., CKD disease burden in HIV-positive persons


Serious clinical events in HIV-positive persons with chronic kidney disease (CKD).    AIDS

Ryom et al. on behalf of the D:A:D study group aimed to investigate the disease spectrum and the prognosis after a diagnosis of chronic kidney disease (CKD) stage G3+ in people living with HIV (PLWH) with focus on the incidence of serious clinical events (SCE) and the role of modifiable risk factors.

D:A:D participants developing CKD (confirmed, >3 months apart, eGFR <= 60 ml/min per 1.73 m2 or 25% eGFR decrease when eGFR <= 60 ml/min per 1.73 m2) were followed to incident SCE; end stage renal and liver disease (ESRL and ESLD), cardiovascular disease (CVD), AIDS-defining and non-AIDS-defining malignancies (NADM), other AIDS or death, 6 months after last visit or 1 February 2016.

During 2.7 (IQR 1.1-5.1) years median follow-up, 595 persons with CKD (24.1%) developed a SCE [incidence rate 68.9/1000 PYFU (95% confidence interval 63.4-74.4)] with 8.3% (6.9-9.0) estimated to experience any SCE at 1 year. The most common SCE was death (12.7), followed by NADM (5.8%), CVD (5.6%), other AIDS (5.0%) and ESRD (2.9%). Crude SCE ratios were significantly higher in those with vs. without CKD, strongest for ESRD [65.9 (43.8-100.9)] and death [4.8 (4.3-5.3)]. Smoking was consistently associated with all CKD-related SCE. Diabetes predicted CVD, NADM and death, whereas dyslipidaemia was only significantly associated with CVD. Poor HIV-status predicted other AIDS and death, eGFR less than 30 ml/min per 1.73 m2 predicted CVD and death and low BMI predicted other AIDS and death.

In conclusion, this study shows that in an era where many PLWH require less monitoring because of effective and well tolerated ART, those living with even moderate levels of CKD have a high morbidity and mortality burden with almost one in three developing a SCE within just 5 years. Our data further suggest the modifiable risk factors smoking, dyslipidaemia, poor HIV-status, diabetes and low BMI in addition to eGFR less than 30 ml/min per 1.73 m2 play a central role for CKD-related morbidity, and highlight the need of increased monitoring, targeted interventions and focus on preventive measures for those living with both HIV and CKD.

PubMed

27th February Courlet et al., Drug-drug interactions in people living with HIV


Polypharmacy, drug-drug interactions, and inappropriate drugs: New challenges in the aging population with HIV.    Open Forum Infectious Disease

Courlet et al. aimed to compare prescribed medications, polypharmacy, and potential drug–drug interactions (DDIs) between young and elderly people with HIV (PWH) included in 2 centers of the Swiss HIV Cohort Study (SHCS). PWH from 2 centers within the Swiss HIV Cohort Study were asked to fill in a form with all their current medications. Polypharmacy was defined as being on ≥5 non-HIV drugs.

Among the 996 PWH included, 122 were ≥65 years old. Polypharmacy was more frequent in the elderly group (44% vs 12%). Medications and potential DDIs differed according to the age group: cardiovascular drugs and related potential DDIs were more common in the elderly group (73% of forms included ≥1 cardiovascular drug; 11% of cardiovascular drugs involved potential DDIs), whereas central nervous system drugs were more prescribed and involved in potential DDIs in younger PWH (26%, 11%). Potential DDIs were mostly managed through dosage adjustments. Potentially inappropriate medications were found in 31% of the elderly group.

In conclusion, high rates of polypharmacy and the consequent DDI potential suggest that particular attention is needed when prescribing treatments to elderly PWH. Although the use of unboosted INSTIs is growing, one-fourth of elderly PWH had complex antiretroviral treatments acting as perpetrator of DDIs. The acknowledgment that some medications may be inappropriate for aged patients constitutes an additional burden in health care provision to elderly PWH. Thus with the aging HIV population, education on geriatric medicine principles and periodic review of medicines is warranted to limit the risk of inappropriate prescribing in this vulnerable population. Clinicians should maintain a proactive approach for the recognition and management of potential DDIs, as well as for other prescribing issues traditionally encountered in geriatric medicine.

pdf publication

19th February Ryom et al., Use of contemporary protease inhibitors and risk of incident chronic Kidney disease in persons with HIV


Use of contemporary protease inhibitors and risk of incident chronic Kidney disease in persons with human immunodeficiency virus: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study.   Journal of Infectious Diseases

Ryom et al. on behalf of the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study aimed to assess whether cumulative use of more contemporary protease inhibitors (PIs), including ritonavir-boosted darunavir (DRV/r) and ritonavir-boosted atazanavir (ATV/r), are associated with an increased incidence of chronic kidney disease (CKD) to a similar extent as some of the older PIs.

The incidence of CKD (10.0/1000 person-years of follow-up; 95% confidence interval, 9.5–10.4/1000 person-years of follow-up) increased gradually with increasing exposure to ATV/r, but the relation was less clear for DRV/r. After adjustment, only exposure to ATV/r (adjusted incidence rate ratio, 1.4; 95% confidence interval, 1.2–1.6), but not exposure to DRV/r (1.0; .8–1.3), remained significantly associated with CKD.

In conclusion, in this large heterogeneous cohort of people living with HIV, more extended use of DRV/r was not significantly associated with a gradually increasing incidence of CKD, even after a median follow-up of >6 years. Discontinuation of DRV/r use was, in contrast to discontinuation of ATV/r, unrelated to declining eGFRs. A gradually increasing CKD risk with longer use of ATV/r was confirmed, with a 40% increased CKD incidence after 4 years of use, when compared with those never exposed to ATV/r.

pdf publication

11th February Rodger et al., HIV transmission through condomless sex in serodifferent gay couples


Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study.   Lancet

The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. In the first phase of the PARTNER study, some evidence on transmission risk in gay men was provided but follow-up in these studies was not sufficient to exclude a significant upper limit of risk around the study estimates of zero transmissions in gay men. In PARTNER2, Rodger et al. on behalf of the PARTNER study group aimed to fill this gap and to produce a similar level of evidence for transmission risk through condomless anal sex between men with suppressive ART (defined as HIV-1 RNA viral load <200 copies per mL) to that generated for heterosexual couples in PARTNER1.

Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1’593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1–3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33–46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4–2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76’088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up).

In conclusion, the results from the PARTNER studies support wider dissemination of the message of the U=U campaign (undetectable equals untransmittable) that risk of transmission of HIV in the context of virally suppressive ART is zero. This dissemination is necessary to promote the benefits of early testing and treatment and to tackle stigma, discrimination, and criminalization laws that continue to affect HIV-positive people. However, U=U is only easy to apply when HIV-positive people have access to testing, effective treatment, viral load monitoring to levels of less than 200 copies per mL, and support to reach and maintain viral suppression.

pdf publication

4th February Neesgaard et al., Uptake and effectiveness of 2DR versus 3DR


Uptake and effectiveness of two-drug compared with three-drug antiretroviral regimens among HIV-positive individuals in Europe.    AIDS

Neesgaard et al. on behalf of the EuroSIDA study analysed the uptake of two-drug antiretroviral regimens (2DRs), factors associated with starting or switching to a 2DR in the European-based EuroSIDA cohort, and virologic and immunologic outcomes of using 2DRs compared with three-drug regimens (3DRs) in this large, heterogeneous, population of people living with HIV (PLWHIV) seen in routine clinical care.

Virologic outcomes were assessed on-treatment as the proportion of individuals with controlled viral load (<400 copies/ml), or with a composite modified FDA snapshot endpoint (mFDA), with mFDA success defined as controlled viral load at 6 months or 12 months for individuals with a known viral load, no regimen changes, AIDS or death. Immunologic response was defined as a 100 cells/[mu]l or a 25% increase in CD4+ cell counts from baseline.

Between 1 July 2010 and 31 December 2016, 423 individuals started or switched to a 2DR (eight antiretroviral-naive) and 4’347 started a 3DR (566 naive). Individuals on 2DR tended to have suppressed viral load, higher CD4+ cell counts and more comorbidities at baseline compared with those on 3DR. There were no differences in the proportions of individuals who obtained on-treatment or mFDA success, and no significant differences in the adjusted odds ratios for mFDA success or immunologic responses between the 2DR and 3DR groups at 6 months or 12 months.

In conclusion, the study found that the 2DRs in this analysis were largely used according to the current clinical guidelines. The study-results show that 2DRs in the period were mainly prescribed to antiretroviral-experienced individuals who switched from their previous regimen with virologic suppression, high CD4+ cell counts and preexisting or higher risk of comorbidities. Although the study observed favourable outcomes for antiretroviral-naive individuals starting a 2DR, the numbers were too low to allow meaningful conclusions. Overall, virologic and immunologic outcomes in individuals on 2DRs were similar to individuals on 3DRs in this selected population, in line with results from randomized clinical trials, although confounding by indication cannot be fully excluded.

PubMed

30th January Metral et al., Screening questions for neurocognitive impairment


How helpful are the European AIDS Clinical Society cognitive screening questions in predicting cognitive impairment in an aging, well-treated HIV-positive population?    HIV Medicine

Metral et al. for the Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study group from the Swiss HIV Cohort Study aimed to determine the positive and negative predictive values (PPVs and NPVs, respectively) of the three European AIDS Clinical Society (EACS) screening questions in identifying neurocognitive impairment (NCI).

Patients aged ≥45 years were enrolled between 1 May 2013 and 30 November 2016. NAMACO participants (1) answered EACS screening questions, (2) underwent standardized neuropsychological assessment and (3) completed self-report forms [Center for Epidemiologic Studies Depression Scale (CES-D)] rating mood. NCI categories were defined using Frascati criteria.

Of 974 NAMACO participants with complete EACS screening question data, 244 (25.1%) expressed cognitive complaints in answer to at least one EACS screening question, of whom 51.3% had NCI (26.1% HIV-associated and 25.2% related to confounding factors). The PPV and NPV of the EACS screening questions in identifying HIV-associated NCI were 0.35 and 0.7, respectively. Restricting analysis to NCI with functional impairment or related to confounding factors, notably depression, the NPV was 0.90. Expressing cognitive complaints for all three EACS screening questions was significantly associated with depression (P < 0.001).

In conclusion, in this large cohort of patients with well-controlled HIV infection, one quarter had cognitive complaints, most frequently related to memory loss. The EACS screening questions had an NPV of 0.7 for excluding HIV-associated NCI in NAMACO study participants using Frascati criteria. However, it remains to be seen whether the PPV and NPV of these questions improve if patients are classified according to other, yet to be defined, NCI severity criteria. Currently, these questions lack sensitivity and specificity as a tool to guide clinicians as to which patients should be referred for formal neuropsychological testing.

pdf publication

23rd January Borges et al., SMART and START combined analysis


The effect of interrupted/deferred antiretroviral therapy on disease risk: A SMART and START combined analysis.    Journal of Infectious Disease

Borges et al. on behalf of the Strategies for Management of Antiretroviral Therapy (SMART) and Strategic Timing of AntiRetroviral Treatment (START) studies aimed to quantify the relative difference between deferred/intermittent antiretroviral therapy (ART) and immediate/continuous ART on risk of AIDS- and non-AIDS–defining events. Endpoints assessed were AIDS, serious non-AIDS (SNA), cardiovascular disease (CVD), cancer, and death.

Among 10’156 participants, there were 124 AIDS, 247 SNA, 117 cancers, 103 CVD, and 120 deaths. Interventions in each trial led to similar differences in CD4 count and viral suppression. Pooled HRs (95% confidence interval) of deferred/intermittent ART versus immediate/continuous ART were for AIDS 3.63 (2.37–5.56); SNA 1.62 (1.25–2.09); CVD 1.59 (1.07–2.37); cancer 1.93 (1.32– 2.83); and death 1.80 (1.24–2.61). Underlying risk was greater in SMART than START. Given the similar HRs for each trial, absolute risk differences between treatment groups were greater in SMART than START. Pooled HRs were similar across subgroups.

In conclusion, compared to a strategy of immediate/continuous ART, a strategy of deferred/intermittent ART, increased the risk of AIDS and SNA events among HIV-positive persons consistently in SMART and START. Interventions in SMART and START led to similar absolute differences in mean CD4+ cell count and percentage with viral suppression, which in turn led to similar relative risk estimates for AIDS and SNA in each study. Pooled treatment differences for the composite outcome of AIDS, SNA, or death were similar across a number of subgroups.

pdf publication

16th January Hampel et al., Chemsex drugs in the Swiss HIV Cohort Study


Chemsex drugs on the rise: a longitudinal analysis of the Swiss HIV Cohort Study from 2007 to 2017.    HIV Medicine

Hampel et al. aimed to analyse the trend in the consumption of all recreational drugs over the last 11 years among all participants in the Swiss HIV Cohort Study (SHCS), with a particular focus on the use of chemsex drugs and other potentially sex-enhancing drugs among men who have sex with men (MSM).

Drugs referred to as chemsex drugs included N-methylamphetamine (methamphetamine), 4-methylmethcathinone (mephedrone), c-hydroxybutyric acid/c-butyrolactone (GHB/GBL) and ketamine. Drugs referred to as sex-enhancing drugs included cocaine, 3,4-methylenedioxymethamphetamine (XTC/MDMA), amyl nitrite and amphetamine.

The study analysed 166’167 follow-up entries for 12’527 SHCS participants, including 7’101 free text field entries containing information about recreational drugs other than cannabis, cocaine and heroin. Overall, there was a stable percentage (9.0%) of recreational drug use (excluding cannabis, amyl nitrite and prescription drugs). For MSM, however, there was an increase in overall drug use from 8.8% in 2007 to 13.8% in 2017, with particularly large increases for methamphetamine (from 0.2 to 2.4%; P <0.001) and GHB/GBL (from 1.0 to 3.4%; P <0.001). The use of each of the potentially sex-enhancing drugs methamphetamine, GHB/GBL, cocaine, XTC/MDMA and amphetamine was significantly associated with condomless sex with non-steady partners, and higher prevalences of depression, syphilis and hepatitis C.

In conclusion, the study identified a significant increase in the use of chemsex drugs, in particular methamphetamine and GHB/GBL, among MSM diagnosed with HIV infection in Switzerland and a strong association of this use with coinfections and depression. In light of these findings, more studies in this field are needed to better understand the relationship between sexual behaviour, drug consumption and depression in order to inform successful harm reduction strategies. This further understanding will not only help the patients and potentially decrease numbers of other sexually transmitted infections, including viral hepatitis C, but will also be crucial to the understanding of the current drivers in the ongoing HIV epidemic.

pdf publication

9th January Christe et al., Imaging PJP in HIV-pos and renal transplant patients


Imaging patterns of Pneumocystis jirovecii pneumonia in HIV-positive and renal transplant patients - a multicentre study.    Swiss Medical Weekly

Christe et al. aimed to explore the computed tomography (CT) and chest X-ray (CXRs) imaging features of Pneumocystis jirovecii pneumonia (PJP) in immunocompromised patients from two well-defined cohorts, the Swiss HIV Cohort Study (SHCS) and renal transplant recipients (RTRs) included in the Swiss Transplant Cohort Study (STCS).

From 2005 to 2012, 84 patients with PJP (RTR n = 24; HIV n = 60) were included in this retrospective multicentre study. CT scans and CXRs were recorded within 2 weeks after the onset of symptoms. PJP diagnosis was confirmed either by cytology/histology or successful empirical treatment. Two blinded radiologists analysed the conventional chest films and CT images.

Consolidations and solid nodules prevailed on CT in RTRs (91.7 ± 5.6% vs 58.3 ± 6.4% with HIV, p = 0.019 and 91.7 ± 5.6% vs 51.6 ± 6.5% with HIV, p = 0.005). HIV-positive patients with PJP showed more atelectasis (41.7 ± 6.4% vs 4.2 ± 4.1% in RTRs, p = 0.017) and hilar lymph node enlargement (23.3 ± 5.5% vs 0.0 ± 0.0% in RTRs, p = 0.088). Ground glass opacification was found in all cases. Pneumothorax was a rare complication, occurring in 3% of the HIV-positive patients; no pneumothorax was found in the RTRs. On CXR, the basal lungs were more affected in HIV-positive patients as compared with RTRs (p = 0.024).

In conclusion, the PJP radiological CT findings in renal transplant patients were dominated by multifocal consolidation and solid nodularities, whereas in the HIV population more classic subpleural sparing was present. A common feature in both groups was ground glass opacification. Of note, pulmonary cysts, previously described as a hallmark feature in PJP, were present in only 4% of the HIV-positive patients and in none of the RTRs. With the advance of prophylaxis in high-risk groups, this classic complication is now an infrequent finding. Based on the differing imaging manifestations of PJP in transplant recipients and HIV-positive patients, it is of utmost importance for radiologists to be aware of the spectrum of patterns in the context of different underlying diseases and to show high awareness in high-risk groups.

pdf publication