A growing number of case reports have described tenofovir (TDF)-related proximal renal tubulopathy and impaired calculated glomerular filtration rates (cGFR). We assessed TDF-associated changes in ...cGFR in a large observational HIV cohort.
We compared treatment-naive patients or patients with treatment interruptions > or = 12 months starting either a TDF-based combination antiretroviral therapy (cART) (n = 363) or a TDF-sparing regime (n = 715). The predefined primary endpoint was the time to a 10 ml/min reduction in cGFR, based on the Cockcroft-Gault equation, confirmed by a follow-up measurement at least 1 month later. In sensitivity analyses, secondary endpoints including calculations based on the modified diet in renal disease (MDRD) formula were considered. Endpoints were modelled using pre-specified covariates in a multiple Cox proportional hazards model.
Two-year event-free probabilities were 0.65 (95% confidence interval CI 0.58-0.72) and 0.80 (95% CI 0.76-0.83) for patients starting TDF-containing or TDF-sparing cART, respectively. In the multiple Cox model, diabetes mellitus (hazard ratio HR = 2.34 95% CI 1.24-4.42), higher baseline cGFR (HR = 1.03 95% CI 1.02-1.04 by 10 ml/min), TDF use (HR = 1.84 95% CI 1.35-2.51) and boosted protease inhibitor use (HR = 1.71 95% CI 1.30-2.24) significantly increased the risk for reaching the primary endpoint. Sensitivity analyses showed high consistency.
There is consistent evidence for a significant reduction in cGFR associated with TDF use in HIV-infected patients. Our findings call for a strict monitoring of renal function in long-term TDF users with tests that distinguish between glomerular dysfunction and proximal renal tubulopathy, a known adverse effect of TDF.
Objectives
The aim of this study was to quantify loss to follow‐up (LTFU) in HIV care after delivery and to identify risk factors for LTFU, and implications for HIV disease progression and subsequent ...pregnancies.
Methods
We used data on pregnancies within the Swiss HIV Cohort Study from 1996 to 2011. A delayed clinical visit was defined as > 180 days and LTFU as no visit for > 365 days after delivery. Logistic regression analysis was used to identify risk factors for LTFU.
Results
A total of 695 pregnancies in 580 women were included in the study, of which 115 (17%) were subsequent pregnancies. Median maternal age was 32 years (IQR 28–36 years) and 104 (15%) women reported any history of injecting drug use (IDU). Overall, 233 of 695 (34%) women had a delayed visit in the year after delivery and 84 (12%) women were lost to follow‐up. Being lost to follow‐up was significantly associated with a history of IDU adjusted odds ratio (aOR) 2.79; 95% confidence interval (CI) 1.32–5.88; P = 0.007 and not achieving an undetectable HIV viral load (VL) at delivery (aOR 2.42; 95% CI 1.21–4.85; P = 0.017) after adjusting for maternal age, ethnicity and being on antiretroviral therapy (ART) at conception. Forty‐three of 84 (55%) women returned to care after LTFU. Half of them (20 of 41) with available CD4 had a CD4 count < 350 cells/μL and 15% (six of 41) a CD4 count < 200 cells/μL at their return.
Conclusions
A history of IDU and detectable HIV VL at delivery were associated with LTFU. Effective strategies are warranted to retain women in care beyond pregnancy and to avoid CD4 cell count decline. ART continuation should be advised especially if a subsequent pregnancy is planned.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
The number of HIV‐infected individuals from developed countries travelling to tropical and subtropical areas has increased as a result of the clinical and survival benefits of combination ...antiretroviral therapy. The aim of our study was to describe the traveler population in the SHCS and to determine the frequency of viral rebound in virologically suppressed individuals after a travel episode to the tropics compared to non‐travelers.
Methods
Swiss HIV Cohort Study participants with at least one follow‐up visit between 1 January 1989 and 28 February 2015 were eligible for inclusion in the study. The primary outcome was the occurrence of viral rebound (viral load > 200 HIV‐1 RNA copies/mL) after a travel episode compared with a nontravel episode in previously suppressed individuals (≤ 200 copies/mL). All virologically suppressed patients contributed multiple travel or nontravel episodes to the analysis. Logistic regression was performed including factors associated with viral rebound.
Results
We included 16 635 patients in the study, of whom 6084 (36.5%) had ever travelled to the tropics. Travel frequency increased over time, with travellers showing better HIV parameters than nontravellers less advanced Centers for Disease Control and Prevention (CDC) stage and higher CD4 count nadir. Viral rebound was seen in 477 (3.9%) of 12 265 travel episodes and in 5121 (4.5%) of 114 884 nontravel episodes unadjusted odds ratio (OR) 0.87; 95% confidence interval (CI) 0.78–0.97. Among these 477 post‐travel viral rebounds, 115 had a resistance test performed and 51 (44%) of these showed new resistance mutations. Compared with European and North American patients, the odds for viral rebound were significantly lower in Southeast Asian (OR 0.67; 95% CI 0.51–0.88) and higher in sub‐Saharan African (SSA) patients (OR 1.41; 95% CI 1.22–1.62). Travel further increased the odds of viral rebound in SSA patients (OR 2.00; 95% CI 1.53–2.61).
Conclusions
Region of origin is the main risk factor for viral rebound rather than travel per se. Pre‐travel adherence counselling should focus on patients of SSA origin.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
Metabolic changes caused by antiretroviral therapy (ART) may increase the risk of coronary heart disease (CHD). We evaluated changes in the prevalence of cardiovascular risk factors (CVRFs) ...and 10‐year risk of CHD in a large cohort of HIV‐infected individuals.
Methods
All individuals from the Swiss HIV Cohort Study (SHCS) who completed at least one CVRF questionnaire and for whom laboratory data were available for the period February 2000 to February 2006 were included in the analysis. The presence of a risk factor was determined using cut‐offs based on the guidelines of the National Cholesterol Education Program (NCEP ATP III), the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), the American Diabetes Association, and the Swiss Society for Cardiology.
Results
Overall, 8033 individuals completed at least one CVRF questionnaire. The most common CVRFs in the first completed questionnaire were smoking (57.0%), low high‐density lipoprotein (HDL) cholesterol (37.2%), high triglycerides (35.7%), and high blood pressure (26.1%). In total, 2.7 and 13.8% of patients were categorized as being at high (>20%) and moderate (10–20%) 10‐year risk for CHD, respectively. Over 6 years the percentage of smokers decreased from 61.4 to 47.6% and the percentage of individuals with total cholesterol >6.2 mmol/L decreased from 21.1 to 12.3%. The prevalence of CVRFs and CHD risk was higher in patients currently on ART than in either pretreated or ART‐naive patients.
Conclusion
During the 6‐year observation period, the prevalence of CVRFs remains high in the SHCS. Time trends indicate a decrease in the percentage of smokers and individuals with high cholesterol.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
This randomized study evaluated the efficacy and tolerability of continued treatment with protease inhibitor plus nucleoside-analogue combination regimens (n = 79) or a change to the simplified ...regimen of abacavir-lamivudine-zidovudine (n = 84) in patients with suppressed human immunodeficiency virus type 1 (HIV-1) RNA for ⩾6 months who did not have the reverse transcriptase 215 mutation. After a median follow-up of 84 weeks, virologic failure was 6% in the continuation and 15% in the simplified group (P = .081). Previous zidovudine monotherapy or dual therapy and archived reverse transcriptase resistance mutations in HIV-1 DNA at baseline were significant predictors of failure. Study treatment was discontinued because of adverse events in 20% of the continuation and 7% of the simplified group (P = .021). Simplification to abacavir-lamivudine-zidovudine significantly decreased nonfasting cholesterol and triglyceride levels; however, this switch strategy carries a risk of virologic failure when treatment history or resistance testing suggest the presence of archived resistance mutations to the simplified regimen.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Summary
Background
Food allergy in developed countries represents a growing concern as reflected by epidemiological studies, indicating that up to 4% of the overall population is affected. Reduction ...of symptoms takes place following eviction or processing of some allergens. However, it cannot be predicted which structural changes will be associated with significant effects on the allergenicity.
Objective
To determine how various treatments of bovine β‐lactoglobulin (BLG) used as a model antigen alters its immunoreactivity and transepithelial transport, and whether this correlates with reduced allergenicity using an in vitro basophil activation assay.
Methods
BLG was subjected to reduction/alkylation, trypsin digestion or exposed to Lactococcus lactis. The remaining immunoreactivity toward IgG raised against native BLG was assessed by ELISA. Transepithelial transport of BLG and derivatives was examined using polarized Caco‐2 cell monolayers mimicking the intestinal epithelium. Selective passage of tryptic peptides was determined using colchicine and cytochalasin D. Basophil activation was measured following stimulation with BLG and derivatives.
Results
Reduction/alkylation, trypsin digestion or incubation with L. lactis was associated with decreased BLG recognition by IgG antibodies raised against the native protein. All treatments also resulted in a more efficient transepithelial transport of BLG. BLG crossed the Caco‐2 monolayer through passage across the cell, whereas tryptic peptides followed both the para‐ and transcellular routes. With the exception of denaturation by reduction/alkylation, cross‐linking of IgE antibodies by BLG derivatives led to lower basophil degranulation.
Conclusion
In vitro dissection of antigenicity and allergenicity may be a valid and convenient alternative to evaluate the effects of biotechnological processing on dietary proteins. In addition, it can help to define the molecular and cellular mechanisms that will provide improved means of diagnosis and possibly therapy of food‐allergic disorders.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
49.
Clinical relevance of cytomegalovirus viraemia El Amari, E Boffi; Combescure, C; Yerly, S ...
HIV medicine,
August 2011, 2011-Aug, 2011-08-00, 20110801, Volume:
12, Issue:
7
Journal Article
Peer reviewed
Open access
Background
Using new sensitive quantitative polymerase chain reaction (PCR) assays, cytomegalovirus (CMV) DNA is often detectable in the plasma of immunosuppressed patients. We investigated the ...prognostic value of a positive CMV DNA test for the development of CMV end‐organ disease, other AIDS‐defining events and mortality.
Methods
A survival analysis was performed, using the Kaplan–Meier method and Cox proportional hazards models, for patients prospectively followed in the Swiss HIV Cohort Study, from January 1996 to December 2007, who were CMV‐seropositive, had a CD4 count of ≤100 cells/μL, and had a plasma sample available for the measurement of baseline CMV DNA with an ultrasensitive PCR. The outcome analysed was an AIDS‐defining event, including CMV end‐organ disease, or death. Variables analysed at the time of CMV measurement were demographic variables, CD4 cell counts, HIV‐1 RNA loads, and use and type of highly active antiretroviral therapy (HAART).
Results
Of 1128 patients, 208 (18%) presented an AIDS‐defining event and 246 (22%) died. A total of 368 patients (34% of samples) had detectable CMV DNA at baseline, with DNA concentrations of up to 38 800 copies/mL. In the multivariate analysis, CMV DNA predicted evolution not only towards CMV end‐organ disease hazard ratio (HR) 12.6; 95% confidence interval (CI) 4.27–37.41, but also towards other AIDS‐defining events (HR 2.6; 95% CI 1.60–4.33) and death (HR 1.9; 95% CI 1.10–3.34).
Conclusion
Quantitative CMV DNA detected in the plasma of HIV‐infected patients with CD4 counts ≤100 cells/μL is a predictor for HIV disease progression, CMV disease and death. A single low value of 80 copies/mL identifies patients at low but significantly increased risk during the following months, after the measurement.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
The aim of the study was to investigate the influence of continued injecting drug use, enrolment in an opiate substitution treatment programme (OSTP), or cessation of injecting drug use on ...the uptake and course of antiretroviral therapy (ART).
Design
A prospective observational study of all participants in the Swiss HIV Cohort Study followed between 1997 and 2006 was carried out.
Methods
We distinguished four groups of former or current injecting drug users (IDUs): (i) abstinent former IDUs; (ii) persons in OSTPs without concomitant injecting drug use; (iii) persons in OSTPs with concomitant injecting drug use; (vi) current IDUs. These groups were compared with a group of patients who had never been IDUs. Factors related to ART uptake and virological endpoints were analysed using logistic generalized estimating equations.
Results
We followed 8660 participants for 48 477 person‐years; 29.7% were in the IDU HIV transmission group. The likelihood of being on ART at biannual visits was lower among individuals in OSTPs with concomitant injecting drug use odds ratio (OR) 0.79; 95% confidence interval (CI) 0.71–0.89 and current IDUs (OR 0.80; 95% CI 0.67–0.96), compared with those who had never been IDUs (reference), abstinent former IDUs (OR 1.13; 95% CI 1.02–1.25) and individuals in OSTPs without injecting drug use (OR 1.18; 95% CI 1.06–1.31). The likelihood of suppressed viral replication on ART was similar among those who had never been IDUs, abstinent former IDUs and individuals in an OSTP without injecting drug use, and lower among those in OSTPs with concomitant drug use (OR 0.82; 95% CI 0.72–0.93) and current IDUs (OR 0.81; 0.65–1.00). Adherence to ART was decreased among persons with continued injecting drug use, and correlated with virological outcome.
Conclusions
Uptake of and virological response to ART were improved among abstinent former IDUs and persons in OSTPs without concomitant injecting drug use, compared with persons with continued injecting drug use.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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