2020
| 23rd December | Pyngottu et al., Treatment failure on integrase inhibitor |  |
Pyngottu et al. aimed to identify risk factors for treatment failure of integrase strand transfer inhibitor (InSTI-) based combined antiretroviral treatment (cART) in drug-naive individuals living with HIV from the Swiss HIV Cohort Study (SHCS) and to assess the impact of minor InSTI resistance-associated mutations (RAMs) on treatment outcome. The authors studied time-to-treatment failure and time to viral suppression among 1’419 drug-naive patients in the Swiss HIV Cohort Study. In 646 patients with a baseline genotypic resistance test of the integrase, they studied the impact of minor integrase resistance mutations. Virological failure was defined as follows: 2 consecutive RNA values >50 copies/mL after at least 180 days of continuous treatment, 1 value >50 copies/mL after 180 days of treatment followed by treatment change to another drug class, or no viral suppression <50 copies/mL after more than 180 days of treatment. They observed 121 virological failures during 18 447 person-years of follow-up. A baseline viral load ≥100 000 copies/mL (multivariable hazard ratio [mHR], 2.2; 95% confidence interval [CI], 1.3–3.6) and an AIDS-defining event (mHR, 1.8; 95% CI. 1.1–3.0) were associated with treatment failure. CD4 counts between 200 and 500 cells/μL (mHR, 0.5; 95% CI, .3–.8) and >500 cells/ μL (mHR, 0.4; 95% CI, .2–.7) were protective. Time to suppression was shorter in lower viral load strata (mHR, 0.7; 95% CI, .6–.8) and in dolutegravir-based therapy (mHR, 1.2; 95% CI, 1.0–1.4). Minor resistance mutations were found at baseline in 104 of 646 (16%) patients with no effect on treatment outcome. In conclusion, the study shows that response to InSTI-based first-line treatment of drug-naïve patients was excellent. Nevertheless, many of the risk factors commonly associated with therapeutic failure such as the severity of immunodeficiency and stage of the disease were still relevant despite the potency of InSTIs. The chance for virological failure was consistently associated with the baseline viral load and the CD4 count, even in patients on dolutegravir. Additional comment Dominique Braun and Huldrych Günthard | ||
| 18th December | Surial et al., TAF in HIV/HBV and renal dysfunction | |
Surial et al. aimed to evaluate the impact of replacing tenofovir disoproxil fumarate (TDF) with Tenofovir alafenamide (TAF) on estimated glomerular filtration rate (eGFR), urine protein-to-creatinine ratio, and alanine aminotransferase (ALT) levels in HIV/hepatitis B virus (HBV-) coinfected individuals with renal dysfunction using data from the Swiss HIV Cohort Study (SHCS). The authors included all participants from the SHCS with an HIV/HBV coinfection who switched from TDF to TAF and had an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 and a suppressed HIV viral load (<200 cp/mL). They assessed changes in eGFR, urine protein-to-creatinine ratio, and ALT after 1 year. Among 106 participants (15.1% women, median age 53 years), eGFR was 60–89 mL/min/1.73 m2 in 84 (79.2%) and <60 mL/min/1.73 m2 in 22 (20.8%) individuals at the time of switch. One year after the switch from TDF to TAF, individuals with an eGFR between 60 and 89 mL/min/1.73 m2 experienced increases in eGFR of 3.2 mL/min/1.73 m2 (95% confidence interval [CI] 1.2 to 5.2), whereas those with an eGFR <60 mL/min/1.73 m2 experienced improvements of 6.2 mL/min/1.73 m2 (95% CI 2.4 to 10.0). Urine protein-to-creatinine ratio decreased overall (26.3 mg/mmol, 95% CI 210.0 to 22.7), and ALT levels declined in patients with elevated baseline levels (211.8 IU/L, 95% CI 217.3 to 26.4) 1 year after replacing TDF with TAF. In conclusion, switching from TDF to TAF among HIV/HBV coinfected individuals with renal impairment led to improvements in eGFR, a decline in proteinuria, and to ALT normalization in those with elevated ALT levels. The use of TAF in those individuals seems to be safe and effective, and switching from TDF to TAF should be considered among coinfected individuals with renal impairment or with otherwise unexplained ALT elevations. | ||
| 17th December | AIDS day: talks against HIV-stigma |  |
In its 2016 political declaration, the United Nations has set the goal of eliminating HIV-related stigma and discrimination by 2030. Has this goal been achieved? What areas are affected by these issues? What are the implications for people living with HIV and for the global response to HIV? How are professionals, global organisations and associations, and people living with HIV themselves responding to this "stigma epidemic"? What are the directions that are emerging to improve the current situation? This series of conferences brings together the testimonies and expertise of many actors in the field: scientists, researchers, lawyers, representatives of global non-governmental organisations and associations, people living with HIV and health professionals. Presentations are given in English or French, with subtitles in the other language. www.chuv.ch/fr/vih-stigma-2020
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| 9th December | Wan et al., HIV-1 reservoir size and decay under long-term suppressive ART | |
The impact of the viral genome on the HIV-1 reservoir, i.e. its heritability, remains unknown. To address this question, Wan et al. aimed to investigate the heritability of the HIV-1 reservoir size and long-term decay using viral sequences and total HIV-1 DNA measurements from Swiss HIV Cohort Study (SHCS) participants infected with HIV-1 subtype B. The authors investigated the heritability of the HIV-1 reservoir size and its long-term decay by analyzing the distribution of those traits on viral phylogenies from both partial-pol and viral near full-length genome sequences. They used a unique nationwide cohort of 610 well-characterized HIV-1 subtype-B infected individuals on suppressive ART for a median of 5.4 years. They found that a moderate but significant fraction of the HIV-1 reservoir size at ~1.5 years after the initiation of ART was explained by viral genetic factors (at least 10% of the variability of the reservoir size could be explained by heritability by each of the models used. Some models also showed higher effects). Additionally, a tentative signal was also found for the decay of the viral reservoir 1.5-5.4 years after the initiation of ART using full-genome sequences, indicating that it was heritable in the corresponding study population. While the mechanisms underlying this heritability remain to be defined, the study-results indicate that the infecting HIV strain should be taken into consideration in future efforts to cure HIV. | ||
| 3rd December | Kusejko et al., HIV long-term survivors among people who inject drugs | |
Kusejko et al. aimed to study social, clinical and mental factors of long-term survivors (LTS) in the Swiss HIV Cohort Study, with a particular focus on people who inject drugs (PWID). LTS were defined as individuals who survived at least 15 years after diagnosis of HIV. The authors quantified differences between PWID LTS, and men who have sex with men (MSM) and heterosexual (HET) LTS. The used phylogenetic methods to distinguish between heterosexual LTS who most likely shared a social network with PWID at the time of infection, termed clusteredHET, and those who did not, termed HET not clustered (HETnc). The analysis was performed using data collected at least 15 years post diagnosis. Overall, 1,663 of 5,686 (29.2%) PWID were LTS. The study found significant differences between PWID LTS and MSM/HETnc LTS regarding self-reported depression (59.4% versus 43.3%; odds ratio [OR]=1.8; P<0.001), incarceration (30.6% versus 7.0%; OR=6.9; P<0.001) and full work ability (25.4% versus 59.0%; OR=0.27; P<0.001). ClusteredHET were less vulnerable with respect to these variables than PWID LTS but more at risk compared with MSM/HETnc LTS, indicating that clusteredHET are closer to PWID with regard to social and mental aspects compared with all MSM/HETnc. In conclusion, even 15 years post HIV diagnosis, there are significant differences regarding social and mental well-being between PWID and other SHCS sub-populations. The results show that, although HIV transmission among PWID has virtually stopped in Switzerland, special care for HIV-positive PWID is still needed. | ||
| 19th November | Carlisle et al., HCV genetic diversity and time since infection | |
HIV-1 genetic diversity can be used to infer time since infection and infection recency. Carlisle et al. aimed to investigate whether the same next-generation sequencing (NGS-) derived-diversity method can be applied to HCV, and to identify the region of the genome over which it is most informative to measure diversity. The authors included 72 HCV/HIV-1 coinfected participants of the Swiss HIV Cohort Study, for whom reliable estimates of infection date and viral sequences were available. Average pairwise diversity (APD) was calculated over each codon position for the entire open reading frame of HCV. Utilizing cross validation, they evaluated the correlation of APD with time since infection and its ability to infer time since infection via a linear model. They additionally studied the ability of diversity to classify infections as recent (infected for <1 year) or chronic, using receiver-operator-characteristic area under the curve (ROC-AUC) in 50 patients whose infection could be unambiguously classified as either recent or chronic. Measuring HCV diversity over third or all codon positions gave similar performances, and notable improvement over first or second codon positions. APD calculated over the entire genome enabled classification of infection recency (ROC-AUC = 0.76). Additionally, APD correlated with time since infection (R2 = 0.33) and could predict time since infection (mean absolute error = 1.67 years). Restricting the region over which APD was calculated to E2-NS2 further improved accuracy (ROC-AUC = 0.85, R2 = 0.54, mean absolute error = 1.38 years). In conclusion, the study found a substantial correlation between time since infection and average pairwise diversity. Based on this, the authors could show that infection recency and time since infection can be accurately predicted by using average pairwise diversity. Thus, in the cases where samples from HCV-infected persons are sequenced, this method provides recency and date of infection information as free by-products of standard NGS sequencing, which can add to such monitoring studies. | ||
| 11th November | Sculier et al., DTG + FTC dual maintenance therapy in a nationwide study | |
Sculier et al. aimed to assess the 48-week efficacy and safety of dolutegravir (DTG) + emtrictabine (FTC) dual maintenance therapy in virologically suppressed people living with HIV (PWHIV) compared with standard combination antiretroviral therapy (cART). Participants were enrolled between 12 May 2017 and 30 May 2018. Patients virologically suppressed for at least 24 weeks on standard cART were randomized 1:1 to switching to DTG + FTC or to continuing cART. The primary endpoint was the proportion of patients virologically suppressed with <100 copies/ml through 48 weeks; the secondary endpoints included virological suppression at 48 weeks according to the US Food and Drug Administration (FDA) snapshot analysis. Quality of life was evaluated using the PROQOL-HIV questionnaire. Median nadir CD4 count was 246 cells/mm3; median age was 48 years; 17% of participants were female. DTG + FTC was non-inferior to cART. The proportion of patients with viral suppression (<100 copies/ml) through 48 weeks was 93.5% in the DTG + FTC arm and 94.7% in the cART arm in the intention-to-treat population (risk difference -1.2%; 95% CI −7.8% to 5.6%). Per-protocol analysis showed similar results, with viral suppression in 96.5% of patients in both arms (risk difference 0.0%; 95% CI -5.6% to 5.5%). Using the FDA snapshot algorithm, 84/93 (90.3%) participants in the DTG + FTC arm had an HIV-1 RNA viral load of <50 copies/ml compared to 86/94 (91.5%) participants on standard cART (risk difference -1.1%; 95% CI -9.3% to 7.1%; p = 0.791). Quality of life improved more between baseline and week 48 in the DTG + FTC compared to the cART arm (adjusted difference +2.6; 95% CI +0.4 to +4.7). There was no occurrence of resistance, and thus no loss of future drug options, among patients who virologically failed according to the primary or secondary outcome. In conclusion, this study provides evidence that the combination of DTG + FTC expands the possibility of offering 2-drug simplification in maintenance treatment. The combination demonstrated non-inferiority in efficacy and safety, as well as a greater improvement in quality of life over time compared to standard regimens. An ongoing assessment of data from the SIMPL’HIV study regarding healthcare-related costs and patient choices and satisfaction will provide additional insights into potential advantages of dual therapy and patient-centered monitoring. comment Huldrych Günthard und Dominique Braun | ||
| 29th October | Kamal et al., Retention in care and cART adherence | |
Kamal et al. tested a theory-based cognitive behavioral intervention to increase HIV treatment engagement and retention. The study hypothesis was that the interprofessional medication adherence program (IMAP) has the ability to increase retention in care by reinforcing pharmaceutical care as well as coordination of care between pharmacists, physicians, and nurses. The authors retrospectively compared their intervention center (intervention group [IG]) with a standard of care center (control group [CG]) both participating in the Swiss HIV Cohort Study between 2004 and 2012. Endpoints were defined as >6-month and >12-month gaps in care for intervals of care longer than 6 and 12 months without any blood draw. Viral failure was defined as HIV-1 RNA ≥50 copies/ mL after 24+ weeks on antiretrovirals. In the IMAP, medication adherence is monitored via electronic monitors (EM’s), fitted with a digital display showing the number of openings day by day to the patient; EM is combined with manual pill count. During motivational interviews (MIs), electronic adherence data, in the form of a chronology plot, is shown to the patient as feedback every 30 to 90 days depending on patients’ needs, and a report is sent to the physician after each interview to ensure continuity in care. All adherence moderating factors are discussed during the MI in a comprehensive approach. Patients are referred to social or psychological aid if needed. The IG included 451 patients, CG 311. In the IG, 179 (40%) patients took part in the IMAP for a median of 27 months (interquartile range, 12–45). Gaps in care of ≥6 months were significantly more likely to happen in the CG versus IG (74.6% vs 57%, P < .001). The median time until the first treatment gap was longer in the IG vs CG (120 vs 84 weeks, P < .001). Gaps in care of ≥12 months evaluated in 709 (93%) patients were significantly more likely to occur in the CG compared with the IG (22.6% vs 12.5%, P < .001). The rate of viral failure was significantly lower in the IG (8.3% vs 15.1%, P = .003). In conclusion, there is an ongoing need for evidence-based interventions to increase retention in care. This study showed the potential of a theory-based medication adherence program for reducing gaps in follow up over 6- and 12-month periods among adult PWH. The authors suggest adapting and implementing this intervention in other settings to verify its effectiveness in increasing retention in care. | ||
| 13th October | Engel et al., Telomere length and coronary artery disease in persons living with HIV | |
Engel et al. aimed to evaluate any independent association of leukocyte telomere length (TL) with coronary artery disease (CAD) events in persons living with human immunodeficiency virus (PLWH), in the context of all relevant clinical risk factors, HIV-related factors, and adverse antiretroviral exposures. Of note, TL shortens with age and is associated with CAD events in the general population. The authors measured TL by quantitative polymerase chain reaction (PCR) in white Swiss HIV Cohort Study participants. Cases had a first CAD event during 1 January 2000 to 31 December 2017. They matched 1–3 PLWH controls without CAD events on sex, age, and observation time. They included 333 cases (median age 54 years; 14% women; 83% with suppressed HIV RNA) and 745 controls. Median time (interquartile range) of TL measurement was 9.4 (5.9–13.8) years prior to CAD event. Compared to the 1st (shortest) TL quintile, participants in the 5th (longest) TL quintile had univariable and multivariable CAD event OR = 0.56 (95% confidence interval [CI], .35–.91) and OR = 0.54 (95% CI, .31–.96). Multivariable OR for current smoking was 1.93 (95% CI, 1.27–2.92), dyslipidemia OR = 1.92 (95% CI, 1.41–2.63), and for recent abacavir, cumulative lopinavir, indinavir, and darunavir exposure was OR = 1.82 (95% CI, 1.27–2.59), OR = 2.02 (95% CI, 1.34–3.04), OR = 3.42 (95% CI, 2.14–5.45), and OR = 1.66 (95% CI, 1.00–2.74), respectively. The TL-CAD association remained significant when adjusting only for Framingham risk score, when excluding TL outliers, and when adjusting for CMV-seropositivity, HCV-seropositivity, time spent with detectable HIV viremia, and injection drug use. In conclusion, the study shows that TL was independently associated with CAD events in PLWH. The exact mechanisms of shorter TL in PLWH compared to the general population and the potential for accelerated TL shortening in PLWH remain incompletely understood. The study results suggest that short TL in PLWH matters, by documenting a relevant TL-CAD link in PLWH, and by putting the TL association into perspective with other relevant traditional and HIV-related risk factors. TL might therefore provide CAD risk information that current knowledge on CAD risk stratification in PLWH does not yet capture. As a clinical consequence, documenting short TL in a given patient might further emphasize the need to optimize management of CAD risk factors, including dyslipidemia, diabetes, and selection of appropriate ART. The clinical value of TL testing, however, will rely on demonstration of improved CAD risk stratification in other populations of PLWH and in prospective studies. | ||
| 7th October | Deutschmann et al., Drug–drug interactions in the era of integrase inhibitors | |
Deutschmann et al. aimed to assess the prevalence of and risk factors for potential drug–drug interactions (PDDIs) between antiretroviral drugs (ARVs) and co-medications in the SHCS for 2018 and to compare the prevalence with a previous analysis performed in 2008. The University of Liverpool HIV drug interaction database was used to detect PDDIs between ARVs and co-medications and linked with the SHCS database. PDDIs were categorized as harmful (red flagged), of potential clinical relevance (amber flagged), or of weak clinical significance (yellow flagged). In 9’298 included individuals, median age was 51 years (IQR, 43–58), and 72% were males. Individuals received unboosted integrase inhibitors (INIs) (40%), boosted ARVs (30%), and nonnucleoside reverse transcriptase inhibitor (NNRTIs) (32%)–based regimens. In the entire cohort, 68% received ≥1 co-medication, 14% had polypharmacy (≥5 co-medications) and 29% had ≥1 PDDI. Among individuals with co-medication, the prevalence of combined amber and yellow PDDIs was 43% (33% amber—mostly with cardiovascular drugs—and 20% yellow-flagged PDDIs) compared to 59% in 2008. Two percent had red-flagged PDDIs (mostly with corticosteroids), the same as in the 2008 survey. Compared with 2008, fewer individuals received boosted ARVs (-24%) and NNRTIs (-13%) but the use of co-medications was higher. In conclusion, the prevalence of PDDIs in the SHCS has decreased in the past decade, although a lower extent than anticipated. This is explained by the fact that half of the population were on unboosted regimens characterized by a favorable interaction profile and by a currently higher co-medication use. Co-medications are unavoidable in the context of an aging population and are often prescribed by non-HIV physicians who may not be aware of the drug interaction risk, notably with boosted regimens. PDDIs may be further reduced by the use of unboosted INIs or noninteracting NNRTIs (i.e., rilpivirine, doravirine), in particular in people living with HIV (PLWH) with multimorbidity and polypharmacy, with regular medication reconciliation and review, and with the systematic use of comprehensive drug interaction search tools for drug prescribing in PLWH. | ||
| 1st October | Braun et al., HCV micro-elimination among HIV+ MSM | |
Braun et al. aimed to test whether the world health organization (WHO) hepatitis C virus (HCV) elimination targets are achievable in clinical practice among men who have sex with men (MSM) living with HIV in the Swiss HIV Cohort Study (SHCS). During phase A (10/2015–06/2016), they performed a population-based and systematic screening for HCV-RNA among MSM from the SHCS. During phase B (06/2016–02/2017) they offered treatment with HCV direct-acting antiviral (DAA) agents to MSM identified with a replicating HCV infection. During phase C (03/2017–11/2017), they offered rescreening to all MSM for HCV-RNA and initiated DAA treatment in MSM with replicating infections. Incident genotype 1a HCV infections identified during phase C were sequenced to build phylogenetic trees. During phase A, they screened 3715/4640 (80%) MSM and identified 177 with replicating HCV infections (4.8%); 150 (85%) of whom started DAA treatment and 149 (99.3%) were cured. During phase B, they rescreened 2930/3538 (83%) MSM with a prior negative HCV-RNA and identified 13 (0.4%) with a new HCV infection, reflecting a 57% decrease in incident HCV infections. At the end of the micro-elimination program, 176/190 MSM (93%) were cured, and the HCV incidence rate declined from .53 per 100 patient-years (95% CI, .35–.83) prior to the intervention to .12 (95% CI, .03–.49) by the end of 2019. Out of the six sequenced genotype 1a strains, 4 sequences were classified as corresponding to international transmissions. In conclusion, the study-results demonstrate the feasibility of a comprehensive systematic test, treat, and cure HCV micro-elimination program among MSM living with HIV. This approach could be proposed as a model to reach the WHO targets towards HCV micro-elimination in a setting with necessary resources. The fact that a substantial part of incident HCV infections occurred within international transmission networks shows that phylogenetic analysis is key to understanding the epidemic. Likewise, it emphasizes the need for cross-international efforts to reach the WHO elimination goals. Finally, HCV-RNA–based screening with timely diagnosis and treatment initiation is crucial among high-risk MSM to reduce onward transmission and to contain the HCV epidemic in the long run. | ||
| 24th September | Atkinson et al., PcP prophylaxis stop using HIV-RNA | |
Atkinson et al. for the Opportunistic Infections Project Working Group of the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord investigated whether primary prophylaxis for pneumocystis pneumonia (PcP) might be withheld in all patients on antiretroviral therapy (ART) with suppressed plasma human immunodeficiency virus (HIV) RNA (≤400 copies/mL), irrespective of CD4 count. The author group implemented an established causal inference approach whereby observational data were used to emulate a randomized trial. Patients taking PcP prophylaxis were eligible for the emulated trial if their CD4 count was ≤200 cells/μL in line with existing recommendations. They compared the following 2 strategies for stopping prophylaxis: (1) when CD4 count was >200 cells/ μL for >3 months or (2) when the patient was virologically suppressed (2 consecutive HIV RNA ≤400 copies/mL). A total of 4’813 patients (10’324 person-years) complied with eligibility conditions for the emulated trial. With primary PcP diagnosis as an endpoint, the adjusted HR (aHR) indicated a slightly lower, but not statistically significant, different risk for the strategy based on viral suppression alone compared with the existing guidelines (aHR, .8; 95% confidence interval, .6–1.1; P = .2). In conclusion, this study indicated that HIV replication measured as plasma HIV RNA is a major contributor to the risk of developing primary PcP. In virologically suppressed patients on ART, irrespective of CD4 levels, the risk of PcP is marginally lower using viral suppression alone, compared with when prophylaxis is taken based on the CD4 count threshold according to current guidelines. The study suggests that primary PcP prophylaxis might be safely withheld in patients on ART with confirmed plasma viral suppression, regardless of their CD4 count. | ||
| 3rd September | Trickey et al., Survival after diagnosis of cancer among HIV-positive patients | |
Trickey et al. on behalf of COHERE in EuroCoord aimed to investigate causes of death within 5 years of cancer diagnosis in people living with HIV (PLHIV) enrolled in European and North American HIV cohorts starting antiretroviral therapy (ART) 1996–2015, aged ≥16 years, and subsequently diagnosed with cancer. Cancers were grouped in AIDS-defining malignancies (ADMs), viral non-ADMs (NADMs) and nonviral NADMs. Of 603 deaths after ADM diagnosis, 292 (48%) were due to an ADM. There were 467/847 (55%) and 74/189 (39%) deaths that were due to an NADM after nonviral and viral NADM diagnoses, respectively. Cause-specific mortality rates (MR) were higher for diagnoses between 1996 and 2005 versus 2006–2015: ADMs 102 (95%CI92–113) per 1,000 years versus 88 (78–100), viral NADMs 134 (106–169) versus 111 (93–133) and nonviral NADMs 264 (232–300) versus 226 (206–248). Estimated 5-year survival for PLHIV diagnosed with liver (29% [19–39%]), lung (18% [13–23%]) and cervical (75% [63–84%]) cancer was similar to general populations. Survival after Hodgkin’s lymphoma diagnosis was lower in PLHIV (75% [67–81%]). Among ART-treated PLHIV diagnosed with cancer, MR and causes of death varied by cancer type, with mortality highest for liver and lung cancers. Deaths within 5 years of NADM diagnoses were more likely to be from cancer than AIDS. In conclusion, among PLHIV diagnosed with cancer, deaths due to an ADM were the leading cause of death after an ADM diagnosis while deaths due to an NADM were the leading cause of death after diagnosis of nonviral NADMs. Deaths after diagnosis with viral NADMs were most likely to be due to a NADM or due to other causes, many of which were classified as due to viral hepatitis. As the cohort of PLHIV ages, they will be at increased risk of cancers not considered related to HIV and many of these cancers are linked to lifestyle factors and comorbidities such as smoking and hepatitis C virus, Hence, emphasis should be placed on targeting such behaviours and treating co-morbidities such as chronic viral hepatitis in order to prevent cancer. | ||
| 20th August | Combes et al., Antibodies against HPV16E6 oncoprotein to predict anal cancer risk | |
Combes et al. aimed to describe human papilloma virus (HPV-) 16E6 antibody kinetics prior to anal cancer in people living with HIV/AIDS (PLWHA) and evaluate the possible contribution of HPV16E6 serology to anal cancer risk prediction. For 91 persons diagnosed with anal cancer in the Swiss HIV Cohort Study (1989–2017), serial serum/plasma samples were tested for HPV16E6 antibodies using multiplex serology, supplemented with samples from 1,356 participants without anal cancer. Anal cancer incidence was estimated for PLWHA from 40 years-old in the cART era, stratified by HPV16E6 serostatus. HPV16E6 seroprevalence was 23.3% in samples <2 years prior to anal cancer diagnosis and decreased with increasing time prior to cancer: 16.7% at 2–4 years, 4.4% at 5–9, and 7.0% at ≥10 years. Of 25 individuals with anal cancer who were HPV16E6-seropositive at any time during follow-up, the majority (n = 18) remained seropositive in all samples after seroconversion, whereas for seven cases, seropositivity was transitory. Among individuals with anal cancer, HPV16E6 seroprevalence was marginally higher in women vs. men who have sex with men (adjusted OR = 4.3, 95%CI:1.1,17.2) and in older participants (adjusted OR = 6.2, 95%CI:1.1, 34.8 for cases diagnosed at ≥55 vs.<45 years). Anal cancer incidence was 402/100,000 person-years in HPV16E6-positive vs. 82/100,000 in HPV16E6-negative PLWHA (incidence rate ratio = 4.9, 95%CI:1.3, 13.1). In conclusion, in this first study of HPV16E6 antibodies in serial blood samples collected in PLWHA prior to anal cancer, HPV16E6 was shown to be a strong and specific determinant of future anal cancer risk and may have a place in secondary prevention algorithms in high-risk groups such as PLWHA. One out of every 30 HPV16E6-seropositive PLWHA (n = 4/114) developed anal cancer during their subsequent follow-up, highlighting the positive predictive value of this marker. Conversely, however, the vast majority of anal cancers diagnosed in PLWHA were HPV16E6-negative at study baseline and less than a quarter of PLWHA had seroconverted to HPV16E6 prior to anal cancer diagnosis, meaning that the negative predictive value of a single HPV16E6 test was poor. | ||
| 13th August | Hersberger et al., SNPs of SOCS-1 associated with HIV progression rate | |
Hersberger et al. aimed to investigate the role of 9 single-nucleotide polymorphisms (SNPs) within suppressor of cytokine signaling (SOCS) genes for their association with an HIV progression rate in a cohort of 318 rapid vs 376 slow progressors from the Swiss HIV Cohort Study. Of note, SOCS 1 and 3 are negative feedback regulators of the IFN-a and IFN-g axis. The authors analyzed 9 SNPs, which were identified in Swiss blood donors, in a cohort of HIV-infected patients (n = 1144), which were categorized according to the decline in CD4+ T-cell counts. In all the conducted analyses, they focused on the comparison between rapid and slow progressors with regard to SNPs in SOCS-1 and SOCS-3 and with regard to haplotypes using multivariate logistic regression models. Three SOCS-1 SNPs (rs193779, rs33989964, and rs4780355) were associated with a risk reduction for rapid progression. Two of these SNPs, rs33989964 and rs4780355, were in strong linkage disequilibrium, forming a frequent haplotype. Homozygous carriers of this haplotype were also associated with a risk reduction for rapid progression. By contrast, the minor TT genotype of rs33977706 was associated with twice the risk for rapid progression. No associations were observed for the 4 SOCS-3 SNPs or the major SOCS-3 haplotypes. In summary, SNPs in SOCS-1 are associated with HIV disease progression rate, speaking in favor that immune activation is causal for the progressive immunodeficiency. In addition, allelic variants of SOCS-1, with either decreased or increased transcriptional activity of SOCS-1, go along with slow and rapid progressor status, respectively. The latter findings imply that attenuating this specific pathway favors the HIV progression rate. Notwithstanding, we lack clinical studies, which specifically interfere with the IFN axis for ultimate proof of its pathogenic significance. | ||
| 12th August | European guidelines for the treatment of HIV and COVID-19 | |
EACS Society COVID and HIV 2020 Zusammenfassend wird auf folgende Punkte hingewiesen:
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| 5th August | Barcelo et al., BMI and WHR change after ART initiation | |
Barcelo et al. aimed to investigate the impact of genetic and nongenetic factors on body mass index (BMI) and waist-hip ratio (WHR) change in HIV-infected individuals initiating antiretroviral therapy. The authors used mixed-effects models characterizing BMI and WHR change over time in 1’090 SHCS participants initiating antiretroviral therapy (ART) between 2005 and 2015 to quantify the influence of demographics, clinical factors, and genetic background. Individuals with CD4 nadir <100 cells/μL gained 6.4 times more BMI than individuals with ≥200, and 2.8 times more WHR than individuals with ≥100 (P < .001) during the first 1.5 and 2.5 years after ART initiation, respectively. The risk of being over-weight or obese after 1.5 years increased with CD4 nadir <100 cells/μL compared to 100–199 (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.63–2.74) and ≥200 (OR, 1.69; 95% CI, 1.26–2.32), persisting after 10 years of ART. The risk of abdominal obesity after 2.5 years increased with CD4 nadir <100 compared to ≥100 (OR, 1.35; 95% CI, 1.17–1.54 [in men]; OR, 1.36; 95% CI, 1.18–1.57 [in women]), persisting after 10 years of ART. No significant differences were found across antiretroviral drug classes or genetic scores. In conclusion, the present models identified the critical period of 1.5 and 2.5 years after ART initiation where HIV-infected individuals are more prone to increase their BMI and WHR, respectively. These findings support the need to inform individuals starting ART about the likely early-on body composition changes despite the benefits of starting ART that vastly outweigh this risk. Regular monitoring and implementation of early weight management interventions to address body weight and fat gain are to be encouraged, especially in individuals initiating ART with a low nadir CD4 cell count. The present BMI and WHR models also can be applied to test the efficacy of such interventions, either pharmacological or lifestyle modifications, at different time points after ART initiation and further developed into joint models to predict incidence of CV events in the HIV-infected population. | ||
| 30th July | Bachmann et al., Identifying drivers of HIV transmission | |
Bachmann et al. aimed to investigate the impacts of treatment as prevention (TasP) and the potentially increased risk behavior on HIV transmission in men who have sex with men (MSM) at both the individual and population levels. Using the comprehensive Swiss HIV Cohort Study and its drug-resistance database, the authors reconstructed phylogenetic trees for each year between 2007 and 2017. They identified HIV transmission clusters dominated by MSM and determined their annual growth. Both infectivity and behavioral risk scores were significantly higher in growing MSM transmission clusters compared to nongrowing clusters (P≤ .01). The fraction of transmission clusters without infectious members acquiring new infections increased significantly over the study period. The infectivity score was significantly associated with per-capita incidence of MSM transmission clusters in 8 years, while the behavioral risk score was significantly associated with per-capita incidence of MSM transmission clusters in 3 years. In conclusion, this study demonstrates a new method to track the epidemiology of HIV, hereby identifying hotspots of ongoing transmission among MSM. The identified high-risk clusters could be used to target social networks harboring undiagnosed individuals spreading HIV. In these social networks, intensification of prevention is likely to have the largest impact. The significantly increasing number of new infections within transmission clusters without infectious members indicates a relative shift of epidemiological importance from diagnosed to undiagnosed individuals as drivers of the epidemic. Furthermore, this highlights the need for additional efforts to identify infectious individuals as early as possible and to link them into care. This method combining phylogenetics, clinical data, and behavioral data sheds light on high-risk social networks, where prevention and HIV testing should be intensified, and may thus inform the optimal allocation of resources for ending HIV transmission. | ||
| 24th July | Metral et al., Neurocognitive assessment in the Metabolic and Aging Cohort (NAMACO) | |
Metral et al. for the NAMACO study group aimed to examine baseline neurocognitive impairment (NCI) prevalence and factors associated with NCI among patients enrolled in the Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study. In brief, the NAMACO study is an ongoing, prospective, longitudinal, multicentre and multilingual study within the Swiss HIV Cohort Study. Between 1 May 2013 and 30 November 2016, 981 patients ≥ 45 years old were enrolled in the study. All underwent standardized neuropsychological (NP) assessment by neuropsychologists. NCI was diagnosed using Frascati criteria and classified as HIV-associated or as related to other factors. Most patients (942; 96.2%) had viral loads < 50 HIV-1 RNA copies/mL. NCI was identified in 390 patients (39.8%): 263 patients (26.8%) had HIV-associated NCI [249 patients (25.4%) had asymptomatic neurocognitive impairment (ANI)] and 127 patients (13%) had NCI attributable to other factors, mainly psychiatric disorders. There was good correlation between dichotomized and continuous analyses, with NCI associated with older age, non-Caucasian ethnicity, shorter duration of education, unemployment and longer antiretroviral therapy duration. In conclusion, in this representative nation-wide study over a quarter of aging patients (≥ 45 years old) enrolled in the NAMACO study had HIV-associated NCI, a proportion that may increase as the patient cohort ages, despite optimal viral suppression. Among patients with non-HIV-associated NCI, psychiatric disorders, particularly depression, were prevalent. The longitudinal analysis of NAMACO study participants at 2 and 4 years from baseline will shed light on how NCI develops and may be modified in this cohort. | ||
| 15th July | Patel et al., Outcomes of second-line ART among children with HIV | |
Patel et al. on behalf of the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration aimed to analyze data on outcomes among children living with HIV after initiation of second-line antiretroviral therapy (ART) in the context of routine care within a large global cohort collaboration. Patient-level data from 1993 through 2015 from 11 paediatric HIV cohorts were pooled. Characteristics at switch and through two years of follow-up were summarized for children who switched to second-line ART after starting a standard first-line regimen in North America, Latin America, Europe, Asia, Southern Africa (South Africa & Botswana) and the rest of sub-Saharan Africa (SSA). Of the 85,389 children on first-line ART, 3,555 (4%) switched to second-line after a median of 2.8 years on ART (IQR: 1.6, 4.7); 69% were from Southern Africa or SSA and 86% of second-line regimens were protease inhibitor-based. At switch, median age was 8.4 years and 50% had a prior AIDS diagnosis. Median follow-up after switch to second-line ranged from 1.8 years in SSA to 5.3 years in North America. Median CD4 counts at switch to second-line ranged from 235 cells/mm3 in SSA to 828 cells/mm3 in North America. Improvements in CD4 counts were observed over two years of follow-up, particularly in regions with lower CD4 counts at second-line switch. Improvements in weight-for-age z-scores were not observed during follow-up. Cumulative incidence of loss to follow-up (LTFU) at two years was <5% in all regions except SSA (7.1%) and Southern Africa (7.4%). Risk of mortality was <3% at two years of follow-up in all regions, except Latin America (4.9%) and SSA (5.5%). In conclusion, children living with perinatal HIV who switched to second-line ART in large global cohorts have responded well, with increases in CD4 counts and low to moderate rates of LTFU and mortality within two years after switch. The large proportion of children with severe immune deficiency at time of switch in some settings emphasizes the need for improved recognition and management of treatment failure in children. The early age at switch among children and adolescents on second-line ART, also emphasizes the importance of providing access to more durable regimens to preserve their long-term treatment options and health through adulthood. | ||
| 9th July | Stader et al., Ageing and drug–drug interaction magnitudes with antiretrovirals | |
Stader et al. aimed to investigate the impact of ageing on drug–drug interactions (DDI) magnitudes between comedications (amlodipine, atorvastatin, rosuvastatin) and boosted darunavir. This was a prospective clinical study including people living with HIV (PLWH) aged at least 55 years in Lausanne and Basel enrolled in the Swiss HIV Cohort Study receiving amlodipine, atorvastatin and/or rosuvastatin with a dolutegravir or a boosted darunavir-containing regimen. A total of 21 white PLWH (four women) aged 56–80 years were included in the study. The mean and standard deviation (SD) of the area under the curve (AUC) were calculated for the comedications received with either dolutegravir or boosted darunavir. The obtained AUC ratios in ageing PLWH were in the same range as DDI magnitudes reported in young individuals aged 20–50 years, thus, demonstrating that ageing has a marginal impact on DDI magnitudes. In conclusion, the clinically observed data demonstrate that DDI magnitudes between ARVs and comedications appear to be similar in ageing PLWH compared with young individuals and thus, the clinical management of DDIs can be similar. Further research is warranted in the future to investigate more DDI scenarios with a larger study population including more women to further support the clinical management of DDIs in ageing PLWH. | ||
| 8th July | Roth et al., Machine learning in HIV | |
Roth et al. aimed to evaluate different machine learning algorithms and modeling strategies for individual chronic kidney disease (CKD) prediction to exemplify whether machine learning models can be readily trained in a high-dimensional cohort setting. The authors included people living with HIV in the prospective Swiss HIV Cohort Study with a first estimated glomerular filtration rate (eGFR) >60 mL/minute/1.73 m2 after 1 January 2002. The primary outcome was chronic kidney disease (CKD)—defined as confirmed decrease in eGFR ≤60 mL/minute/1.73 m2 over 3 months apart. They split the cohort data into a training set (80%), validation set (10%), and test set (10%), stratified for CKD status and follow-up length. Of 2'761 eligible individuals (median baseline eGFR, 103 mL/minute/1.73 m2), 1'192 (9%) developed a CKD after a median of 8 years. The authors used 64 static and 502 time-changing variables: Across prediction horizons and algorithms and in contrast to expert-based standard models, most machine learning models achieved state-of-the-art predictive performances with areas under the receiver operating characteristic curve and precision recall curve ranging from 0.926 to 0.996 and from 0.631 to 0.956, respectively. In summary, in people living with HIV, there were state-of-the-art performances in forecasting individual CKD onsets with different machine learning algorithms. The underlying machine learning methods may help to advance personalized predictions of comorbidities in various populations. | ||
| 24th June | Greiter et al., Impact of neonatal PEP with AZT on lymphocyte subsets in HIV-exposed uninfected infants | |
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. | ||
| 10th June | Courlet et al., DDIs between antiretrovirals and statins | |
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. | ||
| 4th June | Surial et al., Renal function after switching to TAF | |
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. | ||
| 28th May | Roth et al., Repeated syphilis episodes among MSM from the SHCS | |
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. | ||
| 20th May | Greenberg et al., Uptake and discontinuation of INSTIs | |
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 | ||
| 13th May | Glass et al., Asymptomatic HIV and clinical outcomes | |
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 | ||
| 1st April | Congratulations! | |
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,
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 | |
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. | ||
| 4th March | Ryom et al., CKD disease burden in HIV-positive persons | |
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. | ||
| 27th February | Courlet et al., Drug-drug interactions in people living with HIV | |
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. | ||
| 19th February | Ryom et al., Use of contemporary protease inhibitors and risk of incident chronic Kidney disease in persons with HIV | |
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. | ||
| 11th February | Rodger et al., HIV transmission through condomless sex in serodifferent gay couples | |
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 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. | ||
| 4th February | Neesgaard et al., Uptake and effectiveness of 2DR versus 3DR | |
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. | ||
| 30th January | Metral et al., Screening questions for neurocognitive impairment | |
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. | ||
| 23rd January | Borges et al., SMART and START combined analysis | |
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. | ||
| 16th January | Hampel et al., Chemsex drugs in the Swiss HIV Cohort Study | |
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. | ||
| 9th January | Christe et al., Imaging PJP in HIV-pos and renal transplant patients | |
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. | ||