Background. We investigated whether CD4:CD8 ratio and CD8 count were prognostic for all-cause, AIDS, and non-AIDS mortality in virologically suppressed patients with high CD4 count. Methods. We used ...data from 13 European and North American cohorts of human immunodeficiency virus–infected, antiretroviral therapy (ART)–naive adults who started ART during 1996–2010, who were followed from the date they had CD4 count ≥350 cells/μL and were virologically suppressed (baseline). We used stratified Cox models to estimate unadjusted and adjusted (for sex, people who inject drugs, ART initiation year, and baseline age, CD4 count, AIDS, duration of ART) all-cause and cause-specific mortality hazard ratios for tertiles of CD4:CD8 ratio (0–0.40, 0.41–0.64 reference, >0.64) and CD8 count (0–760, 761–1138 reference, >1138 cells/μL) and examined the shape of associations using cubic splines. Results. During 276 526 person-years, 1834 of 49 865 patients died (249 AIDS-related; 1076 non-AIDS-defining; 509 unknown/unclassifiable deaths). There was little evidence that CD4:CD8 ratio was prognostic for all-cause mortality after adjustment for other factors: the adjusted hazard ratio (aHR) for lower vs middle tertile was 1.11 (95% confidence interval CI, 1.00–1.25). The association of CD8 count with all-cause mortality was U-shaped: aHR for higher vs middle tertile was 1.13 (95% CI, 1.01–1.26). AIDS-related mortality declined with increasing CD4:CD8 ratio and decreasing CD8 count. There was little evidence that CD4:CD8 ratio or CD8 count was prognostic for non-AIDS mortality. Conclusions. In this large cohort collaboration, the magnitude of adjusted associations of CD4:CD8 ratio or CD8 count with mortality was too small for them to be useful as independent prognostic markers in virally suppressed patients on ART.
Background. The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a "90-90-90" target to curb the human immunodeficiency virus (HIV) epidemic by 2020, but methods used to assess whether ...countries have reached this target are not standardized, hindering comparisons. Methods. Through a collaboration formed by the European Centre for Disease Prevention and Control (ECDC) with European HIV cohorts and surveillance agencies, we constructed a standardized, 4-stage continuum of HIV care for 11 European Union countries for 2013. Stages were defined as (1) number of people living with HIV in the country by end of 2013; (2) proportion of stage 1 ever diagnosed; (3) proportion of stage 2 that ever initiated ART; and (4) proportion of stage 3 who became virally suppressed (≤200 copies/mL). Case surveillance data were used primarily to derive stages 1 (using back-calculation models) and 2, and cohort data for stages 3 and 4. Results. In 2013, 674 500 people in the 11 countries were estimated to be living with HIV, ranging from 5500 to 153 400 in each country. Overall HIV prevalence was 0.22% (range, 0.09%–0.36%). Overall proportions of each previous stage were 84% diagnosed, 84% on ART, and 85% virally suppressed (60% of people living with HIV). Two countries achieved ≥90% for all stages, and more than half had reached ≥90% for at least 1 stage. Conclusions. European Union countries are nearing the 90-90-90 target. Reducing the proportion undiagnosed remains the greatest barrier to achieving this target, suggesting that further efforts are needed to improve HIV testing rates. Standardizing methods to derive comparable continuums of care remains a challenge.
Background
The European AIDS Clinical Society (EACS) Guidelines cover key aspects of HIV management with major updates every two years.
Guideline highlights
The 2019 Guidelines were extended with a ...new section focusing on drug–drug interactions and other prescribing issues in people living with HIV (PLWH). The recommendations for treatment‐naïve PLWH were updated with four preferred regimens favouring unboosted integrase inhibitors. A two‐drug regimen with dolutegravir and lamivudine, and a three‐drug regimen including doravirine were also added to the recommended initial regimens. Lower thresholds for hypertension were expanded to all PLWH and for cardiovascular disease prevention, the 10‐year predicted risk threshold for consideration of antiretroviral therapy (ART) modification was lowered from 20% to 10%. Frailty and obesity were added as new topics. It was specified to use urine albumin to creatinine ratio to screen for glomerular disease and urine protein to creatinine ratio for tubular diseases, and thresholds were streamlined with the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations. Hepatitis C virus (HCV) treatment recommendations were split into preferred and alternative treatment options. The algorithm for management of recently acquired HCV infection was updated and includes recommendations for early chronic infection management. Treatment of resistant tuberculosis (TB) was streamlined with the World Health Organization (WHO) recommendations, and new tables on immune reconstitution inflammatory syndrome, on when to start ART in the presence of opportunistic infections and on TB drug dosing were included.
Conclusions
The EACS Guidelines underwent major revisions of all sections in 2019. They are available in four different formats including a new interactive web‐based version and are translated into Chinese, French, German, Japanese, Portuguese, Russian and Spanish.
Prevalence of anxiety or depression was investigated in 105 coronavirus disease 2019 (COVID‐19) patients at 1 to 3 months from virological clearance by hospital anxiety and depression scale ...(HADS‐A/D). 30% of patients displayed pathological HADS‐A/D, 52.4% showed persistent symptoms. Pathological patients with HADS‐A/D more commonly reported symptom persistence, even after adjustment for age, gender, and disease severity. Psychological assessments should be encouraged in COVID‐19 patients' follow‐up.
Highlights
1‐3 months after clinical and virological recovery from symptomatic COVID‐19 disease, 30% and 52.4% of patients still presented psychological and physical symptoms, respectively
Persistence of anxiety and depression was independently associated with ongoing physical symptoms
Psychological evaluations should be included in the follow‐up of COVID‐19 patients.
Despite increased integrase strand transfer inhibitor (INSTI) use, limited large-scale, real-life data exists on INSTI uptake and discontinuation.
International multicohort collaboration.
RESPOND ...participants starting dolutegravir (DTG), elvitegravir (EVG), or raltegravir (RAL) after January 1, 2012 were included. Predictors of INSTI used were assessed using multinomial logistic regression. Kaplan-Meier and Cox proportional hazards models describe time to and factors associated with discontinuation.
Overall, 9702 persons were included; 5051 (52.1%) starting DTG, 1933 (19.9%) EVG, and 2718 (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.
Uptake of DTG vs EVG or RAL increased over time. Discontinuation within 6 months was mainly due to toxicity; nervous system toxicity was highest on DTG. Discontinuation was highest on RAL, mainly because of treatment simplification.
Model trajectories of CD4+ and CD8+ cell counts after starting combination antiretroviral therapy (ART) and use the model to predict trends in these counts and the CD4+ : CD8+ ratio.
Cohort study of ...antiretroviral-naïve HIV-positive adults who started ART after 1997 (ART Cohort Collaboration) with more than 6 months of follow-up data.
We jointly estimated CD4+ and CD8+ cell count trends and their correlation using a bivariate random effects model, with linear splines describing their population trends, and predicted the CD4+ : CD8+ ratio trend from this model. We assessed whether CD4+ and CD8+ cell count trends and the CD4+ : CD8+ ratio trend varied according to CD4+ cell count at start of ART (baseline), and, whether these trends differed in patients with and without virological failure more than 6 months after starting ART.
A total of 39 979 patients were included (median follow-up was 53 months). Among patients with baseline CD4+ cell count at least 50 cells/μl, predicted mean CD8+ cell counts continued to decrease between 3 and 15 years post-ART, partly driving increases in the predicted mean CD4+ : CD8+ ratio. During 15 years of follow-up, normalization of the predicted mean CD4+ : CD8+ ratio (to >1) was only observed among patients with baseline CD4+ cell count at least 200 cells/μl. A higher baseline CD4+ cell count predicted a shorter time to normalization.
Declines in CD8+ cell count and increases in CD4+ : CD8+ ratio occurred up to 15 years after starting ART. The likelihood of normalization of the CD4+ : CD8+ ratio is strongly related to baseline CD4+ cell count.
Hepatitis delta virus (HDV) infection results in the most aggressive form of chronic viral hepatitis. There is scarce information about the prevalence, epidemiology, virological profile and natural ...history of hepatitis delta in HIV patients.
From 16,597 HIV patients enrolled in EuroSIDA, 1319 (7.9%) have ever reported serum hepatitis B virus (HBV) surface antigen (HBsAg)-positive. At last follow-up, 1084 (6.5%) patients were HBsAg-positive. The HDV substudy was carried out in 422 individuals for whom stored sera were available at the time they were HBsAg-positive. Anti-HDV immunoglobulin G was assessed using a commercial enzyme immunoassay (EIA) and serum HDV-RNA was quantified using a real-time PCR method.
A total of 61 of 422 HBsAg-positive carriers were anti-HDV-positive (prevalence: 14.5%). Hepatitis delta predominated in intravenous drug users and for this reason in south and/or east Europe. Serum HDV-RNA was detectable in 87% of tested anti-HDV-positive patients, with a median titer of 1.76×10(7) copies/ml. Overall, delta hepatitis patients showed lower serum HBV-DNA than the rest of HBsAg-positive carriers, although the inhibitory effect of HDV on HBV replication was not recognized in HBV genotype D patients. Whereas HDV was not associated with progression to AIDS, it significantly influenced the risk of death.
The prevalence of anti-HDV in chronic HBsAg-positive/HIV carriers in EuroSIDA is 14.5%. Most of these patients exhibit detectable HDV viraemia. Viral interference between HBV and HDV is manifested in all but HBV genotype D carriers in whom overt coreplication of both viruses occurs which might result in enhanced liver damage. Overall, delta hepatitis increases the risk of liver-related deaths and overall mortality in HIV patients.
Early initiation of combination antiretroviral therapy (cART), at higher CD4 cell counts, prevents disease progression and reduces sexual transmission of human immunodeficiency virus (HIV). We ...describe the temporal trends in CD4 cell counts at the start of cART in adults from low-income, lower-middle-income, upper-middle-income, and high-income countries (LICs, LMICs, UMICs, and HICs, respectively).
We included HIV-infected individuals aged ≥16 years who started cART between 2002 and 2015 in a clinic participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) or the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). Missing CD4 cell counts at the start of cART were estimated through multiple imputation. Weighted mixed-effect models were used to smooth trends in median CD4 cell counts.
A total of 951855 adults from 16 LICs, 11 LMICs, 9 UMICs, and 19 HICs were included. Overall, the modeled median CD4 cell count at the start of cART increased from 2002 to 2015, from 78/µL (95% confidence interval, 58-104/µL) to 287/µL (250-328/µL) in LICs, from 99/µL (71-140/µL) to 234/µL (192-285/µL) in LMICs, from 71/µL (49-104/µL) to 311/µL (255-379/µL) in UMICs, and from 161/µL (143-181/µL) to 327/µL (286-372/µL) in HICs. In LICs, LMICs, and UMICs, the increase was more pronounced in women; in HICs, the opposite was observed.
Median CD4 cell counts at the start of cART increased in all income groups, but generally remained below 350/μL in 2015. Substantial additional efforts and resources are required to achieve earlier diagnosis, linkage to care, and initiation of cART.
Study aim was to estimate the rate and identify predictors of discontinuation of first combination antiretroviral therapy (cART) in recent years.
Patients who initiated first cART between January ...2008 and October 2014 were included. Discontinuation was defined as stop of at least 1 drug of the regimen, regardless of the reason. All causes of discontinuation were evaluated and 3 main endpoints were considered: toxicity, intolerance, and simplification. Predictors of discontinuation were examined separately for all 3 endpoints. Kaplan-Meier analysis was used for the outcome discontinuation of ≥ 1 drug regardless of the reason. Cox regression analysis was used to identify factors associated with treatment discontinuation because of the 3 reasons considered.
A total of 4052 patients were included. Main reason for stopping at least 1 drug were simplification (29%), intolerance (21%), toxicity (19%), other causes (18%), failure (8%), planned discontinuation (4%), and nonadherence (2%). In a multivariable Cox model, predictors of discontinuation for simplification were heterosexual transmission (P = 0.007), being immigrant (P = 0.017), higher nadir lymphocyte T CD4 cell (P = 0.011), and higher lymphocyte T CD8 cell count (P = 0.025); for discontinuation due to intolerance: the use of statins (P = 0.029), higher blood glucose levels (P = 0.050). About toxicity: higher blood glucose levels (P = 0.010) and the use of zidovudine/lamivudine as backbone (P = 0.044).
In the late cART era, the main reason for stopping the initial regimen is simplification. This scenario reflects the changes in recommendations aimed to enhance adherence and quality of life, and minimize drug toxicity.
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