Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide ...international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In a longitudinal study on 181 naïve patients who responded to therapy (mean follow-up 4 years), high baseline human immunodeficiency virus (HIV)-RNA values correlated with high levels of cellular ...HIV-DNA at all time points (p < 0.0001, p 0.045, p 0.0055, and p 0.0025, respectively) and negatively correlated with undetectable residual viremia (URV; <2.5 copies/mL) at T1, T2, and T3 (p 0.026, p 0.0149, and p 0.0002, respectively). Baseline high HIV-DNA levels predicted the persistence of high values (p 0.0001) and negatively correlated with URV (p 0.0254, p 0.0481, and p 0.0085). These results suggest that baseline viral load, cellular HIV-DNA, and URV were strongly correlated over long-term follow-up of antiretroviral therapy responders.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background. Chronic cytomegalovirus (CMV) infection has been associated with immunosenescence and immunoactivation in the general population. In human immunodeficiency virus type 1 (HIV-1)-infected ...people, CMV coinfection, in addition to residual HIV replication and microbial translocation, has been proposed as a key factor in sustaining immune activation, even in individuals with a controlled HIV load. Methods. Patients from the ICONA Study with at least 1 CMV immunoglobulin G (IgG) test available without active CMV disease were included in the analysis. AIDS-defining event or AIDS-related death and severe non-AIDS-defining event or non-AIDS-related death were taken as clinical progression end points. Independent predictors of CMV were identified by multivariable logistic regression. Probabilities of reaching the end points were estimated by survival analyses. Results. A total of 6111 subjects were included, of whom 5119 (83.3%) were CMV IgG positive at baseline. Patients with CMV IgG positivity at baseline were more likely to develop a severe non-AIDS-defining event/non-AIDS-related death (adjusted hazard ratio HR, 1.53 95% confidence interval {CI}, 1.08-2.16. In particular, CMV seropositivity was an independent risk factor for cardiovascular and cerebrovascular diseases (adjusted HR, 2.27 95% CI, .97-5.32). Conclusions. In our study population, CMV/HIV coinfection was associated with the risk of severe non-AIDS-defining events/non-AIDS-related death, especially with cardiovascular and cerebrovascular events, independently of other prognostic factors. This finding supports a potential independent role of CMV coinfection in vascular/degenerative organ disorders in HIV-infected subjects.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
In patients with HIV, immune reconstitution after antiretroviral therapy (ART) is often incomplete. We assessed the probability of patients reaching a CD4/CD8 ratio of 1 or more after the start of ...ART and its association with the onset of non-AIDS-defining events and death.
We did an analysis of the ICONA cohort, which recruited treatment-naive patients with HIV in Italy. We included participants in the cohort who started ART, reached an undetectable viral load (≤80 copies per mL), and had a CD4/CD8 ratio of less than 0·8 at the time of an undetectable viral load. We defined ratio normalisation in patients as two consecutive values of 1 or more. We used Kaplan-Meier curves to estimate the cumulative probability of ratio normalisation. We then used Poisson regression models to identify factors independently associated with normalisation and with progression to non-AIDS-defining events or death.
We included 3236 participants, enrolled between Jan 22, 1997, and Feb 25, 2013. At the start of ART, median CD4/CD8 ratio in our population was 0·39 (IQR 0·26-0·55). 458 (14%) patients reached a CD4/CD8 ratio of 1 or more; the estimated probability of normalisation was 4·4% (95% CI 3·7-5·2) by 1 year from baseline, 11·5% (10·2-13·0) by 2 years, and 29·4% (26·7-32·4) by 5 years. Factors associated with normalisation were high pre-ART CD4 cell counts, a high CD4/CD8 ratio at baseline, and negative cytomegalovirus serological findings. The incidence rate of non-AIDS-defining events for patients with a CD4/CD8 ratio of less than 0·30 (4·2 per 100 patient-years, 95% CI 3·4-5·3) was double that for those with a ratio of 0·30-0·45 (2·3, 2·1-2·5) or more than 0·45 (2·2, 1·7-2·9). A ratio of less than 0·30 was independently associated with an increased risk of non-AIDS-defining events or death compared with one of more than 0·45.
Few patients had normalised CD4/CD8 ratios, even though they had viral suppression. Low ratios were associated with increased risk of serious events and deaths. The CD4/CD8 ratio could be used by clinicians to identity patients at risk of non-AIDS-related events.
AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp & Dohme, ViiV Italy.
•Treating MDR-TB is complicated, long and expensive.•Bedaquiline (BQ) is a new active drug to treat MDR-TB.•No study evaluated safety and effectiveness of surgery in BQ-treated patients.•57 ...BQ-exposed cases resistant to 7 drugs (median) underwent surgery in 9 countries.•60% of cases initiated BQ after surgery, 36.4% before and completed it afterwards.•90% culture-converted and 69.1% achieved treatment success at the end of treatment.
No study evaluated the contribution of adjunctive surgery in bedaquiline-treated patients. This study describes treatment outcomes and complications in a cohort of drug-resistant pulmonary tuberculosis (TB) cases treated with bedaquiline-containing regimens undergoing surgery.
This retrospective observational study recruited patients treated for TB in 12 centres in 9 countries between January 2007 and March 2015.
Patients who had surgical indications in a bedaquiline-treated programme-based cohort were selected and surgery-related information was collected. Patient characteristics and surgical indications were described together with type of operation, surgical complications, bacteriological conversion rates, and treatment outcomes. Treatment outcomes were evaluated according to the time of surgery.
57 bedaquiline-exposed cases resistant to a median of 7 drugs had indication for surgery (52 retreatments; 50 extensively drug-resistant (XDR) or pre XDR-TB). Sixty percent of cases initiated bedaquiline treatment following surgery, while 36.4% underwent the bedaquiline regimen before surgery and completed it after the operation. At treatment completion 90% culture-converted with 69.1% achieving treatment success; 21.8% had unfavourable outcomes (20.0% treatment failure, 1.8% lost to follow-up), and 9.1% were still undergoing treatment.
The study results suggest that bedaquiline and surgery can be safely and effectively combined in selected cases with a specific indication.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Objectives
To compare the long-term risk of treatment failure of dolutegravir-based ART in men and women in a real-life setting.
Patients and methods
Persons living with HIV (PLWH) from the ...ICONA cohort were included if they had started dolutegravir in a two- or three-drug regimen as ART-naive or as virologically controlled ART-experienced. The primary endpoint was time to treatment failure (virological/clinical failure or dolutegravir discontinuation). Secondary endpoints were: time to dolutegravir discontinuation due to toxicity and to neuropsychiatric adverse events; and time to virological failure. Cox regression analyses focused on differences in outcomes by sex.
Results
A total of 2304 PLWH (15% women) initiated dolutegravir-based therapy from ART-naive, and 1916 (19.8% women) while experienced. After a median follow-up of 2.2 (IQR: 0.9–3.9) years in ART-naive and 2.4 (IQR: 1.1–4.3) years in experienced, the 4-year cumulative probability of treatment failure was 33% (95% CI 30.5–35.1) and 20% (95% CI 17.8–22.3), respectively. In the multivariable analyses, in ART-naive the risk of treatment failure was higher for women, but not different after excluding women discontinuing dolutegravir for pregnancy concerns. We also observed a higher risk of discontinuation for toxicity in women (ART-naives: Adjusted Hazard Ratio (AHR): 1.56%; 95% CI: 1.03–2.37; ART-experienced: AHR: 1.53%; 95% CI: 1.01–2.32), although the absolute 4-year probability was low: 7.7% (95% CI 6.5–9.2) in ART-naive and 8.3% (95% CI 6.9–9.9) in experienced.
Conclusions
In our cohort of PLWH treated with dolutegravir-based regimens and followed up for up to 4 years, we observed a low risk of treatment failure and no evidence for a difference by sex, after excluding discontinuation due to pregnancy concerns. However, we observed a higher risk of dolutegravir discontinuation for toxicity in women.
To evaluate the durability of three integrase strand transfer inhibitors (INSTIs) and two NRTIs in ART-naive individuals.
The study design was observational. Patients were HIV-positive, ART-naive ...subjects starting raltegravir, elvitegravir/cobicistat or dolutegravir with two NRTIs. The primary endpoint was time to treatment failure, i.e. occurrence of virological failure (first of two consecutive plasma HIV RNAs ≥200 copies/mL after 24 weeks) or INSTI discontinuation for any reason apart from simplification. Secondary endpoints were INSTI discontinuation due to toxicity/intolerance and CD4 count response. Survival analysis was done using Kaplan-Meier and Cox regression.
Two thousand and sixteen patients were included: 310 (15.4%) started raltegravir-based regimens, 994 (49.3%) started dolutegravir-based regimens and 712 (35.3%) started elvitegravir/cobicistat-based regimens. Over a median of 11 months, 167 patients experienced treatment failure; the 1 year probability of treatment failure was 6.5% for raltegravir, 5.4% for dolutegravir and 6.7% for elvitegravir/cobicistat (P = 0.001). Sixty-eight patients (3.4%) discontinued INSTIs owing to toxicity/intolerance. By multivariable analysis, patients starting raltegravir had a 2.03-fold (95% CI = 1.2-3.2) higher risk and patients on elvitegravir/cobicistat a 1.88-fold (95% CI = 1.2-2.9) higher risk of treatment failure versus dolutegravir; there was no difference in risk of discontinuation due to toxicity/intolerance when comparing dolutegravir and raltegravir and marginal evidence for a difference when comparing elvitegravir/cobicistat and dolutegravir (adjusted relative hazard = 1.94 for elvitegravir/cobicistat versus dolutegravir, 95% CI = 1.00-3.76, P = 0.05).
In our real-life setting, INSTI-based regimens showed high potency and durability. Among regimens currently recommended in Europe, those including dolutegravir are associated with a lower risk of treatment failure.
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