Search

INTRODUCTION:Previous studies have reported that the rate of FEV1 decline over time is increased in HIV patients but the mechanisms underlying this observation are unclear. Since current HIV treatment with Highly Active Antiretroviral Therapy (HAART) results in very good immune-viral control, we hypothesized that HAART should normalize the elevated rate of FEV1 decline previously reported in HIV patients if it was somehow related to the immune alterations caused by HIV, particularly in never smokers or quitters, since smoking is a well established risk factor for accelerated FEV1 decline in the general population. METHODS:We explored this hypothesis in a prospectively recruited cohort of 188 HIV (smoker and non-smoker) patients treated with HAART in Palma de Mallorca (Spain) and followed-up for 6 years. The cross-sectional characteristics of this cohort have been published elsewhere. RESULTS:We found that: (1) HAART resulted in good immune-viral control; (2) the rate of FEV1 decline remained abnormally elevated, even in non-smokers and quitters; and, (3) alcohol abuse during follow-up was related to FEV1 decline in these patients. DISCUSSION:Despite adequate immune-viral control by HAART, lung function decline remains increased in most HIV patients, even in non-smokers and quitters. Alcohol abuse is a preventable risk factor to decrease the accelerated FEV1 decline in this population.

BACKGROUND:Interatrial blocks are considered a new important risk factor for atrial fibrillation and cerebrovascular events. Their prevalence and clinical implications have been reported in general population and several subgroups of patients but no data from HIV-infected populations, with a non-negligible prevalence of atrial fibrillation, has been previously reported. METHODS:We conducted a cross-sectional study in a previously enrolled cohort of randomly selected middle-aged HIV-infected patients who attended our hospital and were clinically stable. Patients underwent both a 12-lead rest electrocardiogram and clinical questionnaires while epidemiological, clinical and HIV-related variables were obtained from electronic medical records and interviews with the patients. Electrocardiograms were then analyzed and codified using a standardized form by two trained members of the research team who were blinded to clinical variables. RESULTS:We obtained electrocardiograms from 204 patients with a mean age of 55.22 years, 39 patients (19.12%) presented an interatrial block, 9 (4.41%) advanced and 30 (14.71%) partial. Patients with interatrial block had a lower nadir lymphocyte CD4 count (124 vs 198 cells, p = 0.02) while advanced interatrial blocks were associated to older age (62.16 vs. 54.95 years, p = 0.046) and hypertension (77.8% vs. 32.3%, p = 0.009). We did not find differences regarding baseline CD4 lymphocyte count or CD4/CD8 lymphocyte ratio. Clinical variables and functional capacity among patients with or without interatrial block were similar. CONCLUSIONS:In a cohort of clinically stable HIV infected patients the prevalence of interatrial blocks, specially advanced, is high and associated to previously known factors (age, hypertension) and novel ones (nadir CD4 lymphocyte count).

Previous studies have reported that the rate of FEV1 decline over time is increased in HIV patients but the mechanisms underlying this observation are unclear. Since current HIV treatment with Highly Active Antiretroviral Therapy (HAART) results in very good immune-viral control, we hypothesized that HAART should normalize the elevated rate of FEV1 decline previously reported in HIV patients if it was somehow related to the immune alterations caused by HIV, particularly in never smokers or quitters, since smoking is a well established risk factor for accelerated FEV1 decline in the general population. We explored this hypothesis in a prospectively recruited cohort of 188 HIV (smoker and non-smoker) patients treated with HAART in Palma de Mallorca (Spain) and followed-up for 6 years. The cross-sectional characteristics of this cohort have been published elsewhere. We found that: (1) HAART resulted in good immune-viral control; (2) the rate of FEV1 decline remained abnormally elevated, even in non-smokers and quitters; and, (3) alcohol abuse during follow-up was related to FEV1 decline in these patients. Despite adequate immune-viral control by HAART, lung function decline remains increased in most HIV patients, even in non-smokers and quitters. Alcohol abuse is a preventable risk factor to decrease the accelerated FEV1 decline in this population. [ABSTRACT FROM AUTHOR]

Interatrial blocks are considered a new important risk factor for atrial fibrillation and cerebrovascular events. Their prevalence and clinical implications have been reported in general population and several subgroups of patients but no data from HIV-infected populations, with a non-negligible prevalence of atrial fibrillation, has been previously reported. We conducted a cross-sectional study in a previously enrolled cohort of randomly selected middle-aged HIV-infected patients who attended our hospital and were clinically stable. Patients underwent both a 12-lead rest electrocardiogram and clinical questionnaires while epidemiological, clinical and HIV-related variables were obtained from electronic medical records and interviews with the patients. Electrocardiograms were then analyzed and codified using a standardized form by two trained members of the research team who were blinded to clinical variables. We obtained electrocardiograms from 204 patients with a mean age of 55.22 years, 39 patients (19.12%) presented an interatrial block, 9 (4.41%) advanced and 30 (14.71%) partial. Patients with interatrial block had a lower nadir lymphocyte CD4 count (124 vs 198 cells, p = 0.02) while advanced interatrial blocks were associated to older age (62.16 vs. 54.95 years, p = 0.046) and hypertension (77.8% vs. 32.3%, p = 0.009). We did not find differences regarding baseline CD4 lymphocyte count or CD4/CD8 lymphocyte ratio. Clinical variables and functional capacity among patients with or without interatrial block were similar. In a cohort of clinically stable HIV infected patients the prevalence of interatrial blocks, specially advanced, is high and associated to previously known factors (age, hypertension) and novel ones (nadir CD4 lymphocyte count). [ABSTRACT FROM AUTHOR]

Background Our aim was to determine whether α-chain of the IL-7 receptor ( IL7 RA) polymorphisms (rs10491434, rs6897932 and rs987106) are associated with the clinical pattern of AIDS progression in ART-naïve HIV-infected patients. Materials and methods We carried out a cross-sectional study in 673 HIV-infected patients who were classified into three groups according to the clinical pattern of AIDS progression (188 long-term nonprogressors ( LTNPs), 334 moderate progressors ( MPs) and 151 rapid progressors ( RPs)). Additionally, 134 healthy blood donors participated as a Control-group. We selected three IL7 RA polymorphisms located at three regulatory regions [rs6897932 (exon 6), rs987106 (intronic region) and rs10491434 (3′ UTR)]. DNA genotyping was performed using Sequenom's Mass ARRAY platform. Results The Control-group and all HIV-infected patients had similar age and percentage of males. LTNP-group was older at HIV diagnosis and at the inclusion in the study and had higher percentage of intravenous drug users ( IDU) ( P < 0·001). Besides, LTNP-group had lower proportion of male patients and homosexual HIV transmission than MP and RP groups ( P < 0·001). Moreover, similar values of allelic, genotypic and haplotype frequencies for IL7 RA polymorphisms were found between healthy controls and HIV-infected patients ( P > 0·05), and among different subgroups of HIV patients according to AIDS progression ( LTNPs, MPs and RPs) ( P > 0·05). The adjusted logistic regression did not show any significant association between IL7 RA polymorphisms and AIDS progression. Conclusions IL7 RA polymorphisms (rs6897932, rs987106 and rs10491434) were not associated with AIDS progression in Spanish population. Therefore, IL7 RA polymorphisms do not seem to help us to understand HIV pathogenesis in untreated HIV-infected patients with different clinical evolution. [ABSTRACT FROM AUTHOR]

While hepatitis C virus ( HCV) infection seems to be expanding among HIV-infected men who have sex with men ( MSM), the rate of coinfection in intravenous drug users ( IDU) is assumed to remain constant. We evaluated the serial prevalence of HIV/ HCV coinfection across all risk groups for HIV infection in Spain. We used data from 7045 subjects included in the multicentre, prospective Spanish Cohort of Adult HIV-infected Patients (Co RIS) between 2004 and 2011. We analysed risk factors for HIV/ HCV coinfection by logistic regression analyses. The prevalence of HIV/ HCV coinfection decreased from 25.3% (95% CI, 23.1-27.5) in 2004-2005 to 8.2% (95% CI, 6.9-9.5) in 2010-2011. This trend was consistently observed from 2004 to 2011 among all risk groups: IDU, 92.4% to 81.4%; MSM, 4.7% to 2.6%; heterosexual men, 13.0-8.9%; and heterosexual women, 14.5-4.0% (all P < 0.05). Strongest risk factors for HIV/ HCV coinfection were IDU ( OR, 54.9; 95% CI, 39.4-76.4), birth decade 1961-1970 ( OR, 2.1; 95% CI, 1.1-3.7) and low educational level ( OR, 2.4; 95% CI, 1.6-3.5). Hence, the prevalence of HIV/ HCV coinfection decreased in Spain between 2004 and 2011. This decline was observed across all risk groups and is likely to be explained by a declining burden of HCV in the general population. [ABSTRACT FROM AUTHOR]

Introduction: Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone. Methods and analysis: A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1 ) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, β: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis. Ethics and dissemination: The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study. [ABSTRACT FROM AUTHOR]

Objectives We aimed to characterize depression in newly diagnosed HIV-infected patients, to determine the effect of antiretroviral therapy ( ART) on its incidence, and to investigate whether efavirenz use was associated with a higher risk, compared with non-efavirenz-containing regimens, in the Spanish CoRIS cohort. Methods CoRIS is a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naïve at entry, launched in 2004. Poisson regression models were used to investigate demographic, clinical and treatment-related factors associated with a higher incidence of clinically significant depression to October 2010. Results In total, 5185 patients (13 089 person-years) participated in the study, of whom 3379 (65.2%) started ART during follow-up. The incidence rates of depression before and after starting ART were 11.68 [95% confidence interval ( CI) 9.01-15.15] and 7.06 (95% CI 5.45-9.13) cases per 1000 person-years, respectively. After adjustment, there was an inverse association between the occurrence of depression and the initiation of ART [incidence rate ratio ( IRR) 0.53; 95% CI 0.28-0.99], while the likelihood of depression increased in patients of age > 50 years ( IRR 1.94; 95% CI 1.21-3.12). Longer exposure to ART was associated with a decreased IRR of depression in unadjusted and adjusted analyses. The IRR for patients receiving < 2, 2-4 and > 4 years of ART was 0.72 (95% CI 0.36-1.44), 0.10 (95% CI 0.04-0.25) and 0.05 (95% CI 0.01-0.17), respectively, compared with ART-naïve patients. This protective effect was also observed when durations of exposure to nonnucleoside reverse transcriptase inhibitor-based regimens and efavirenz-containing regimens were analysed separately. Conclusions The incidence of clinically significant depression was lower among HIV-infected patients on ART. The protective effect of ART was also observed with efavirenz-containing regimens. [ABSTRACT FROM AUTHOR]

Background: The aim was to analyse trends in clinically relevant resistance to first-line antiretroviral drugs in Spain, applying the Stanford algorithm, and to compare these results with reported Transmitted Drug Resistance (TDR) defined by the 2009 update of the WHO SDRM list. Methods: We analysed 2781 sequences from ARV naive patients of the CoRIS cohort (Spain) between 2007–2011. Using the Stanford algorithm “Low-level resistance”, “Intermediate resistance” and “High-level resistance” categories were considered as “Resistant”. Results: 70% of the TDR found using the WHO list were relevant for first-line treatment according to the Stanford algorithm. A total of 188 patients showed clinically relevant resistance to first-line ARVs [6.8% (95%Confidence Interval: 5.8–7.7)], and 221 harbored TDR using the WHO list [7.9% (6.9–9.0)]. Differences were due to a lower prevalence in clinically relevant resistance for NRTIs [2.3% (1.8–2.9) vs. 3.6% (2.9–4.3) by the WHO list] and PIs [0.8% (0.4–1.1) vs. 1.7% (1.2–2.2)], while it was higher for NNRTIs [4.6% (3.8–5.3) vs. 3.7% (3.0–4.7)]. While TDR remained stable throughout the study period, clinically relevant resistance to first line drugs showed a significant trend to a decline (p = 0.02). Conclusions: Prevalence of clinically relevant resistance to first line ARVs in Spain is decreasing, and lower than the one expected looking at TDR using the WHO list. Resistance to first-line PIs falls below 1%, so the recommendation of screening for TDR in the protease gene should be questioned in our setting. Cost-effectiveness studies need to be carried out to inform evidence-based recommendations. [ABSTRACT FROM AUTHOR]

Objectives The aim of the study was to assess the adequacy of initial antiretroviral therapy ( ART), in terms of its timing and the choice of regimens, according to the Spanish national treatment guidelines [ Spanish AIDS Study Group− National Plan for AIDS ( GeSIDA- PNS) Guidelines] for treatment-naïve HIV-infected patients. Methods A prospective cohort study of HIV-positive ART-naïve subjects attending 27 centres in Spain from 2004 to 2010 was carried out. Regimens were classified as recommended, alternative or nonrecommended according to the guidelines. Delayed start of treatment was defined as starting treatment later than 12 months after the patient had fulfilled the treatment criteria. Multivariate logistic and Cox regression analyses were performed. Results A total of 6225 ART-naïve patients were included in the study. Of 4516 patients who started treatment, 91.5% started with a recommended or alternative treatment. The use of a nonrecommended treatment was associated with a CD4 count > 500 cells/μL [odds ratio ( OR) 2.03; 95% confidence interval ( CI) 1.14-3.59], hepatitis B ( OR 2.23; 95% CI 1.50-3.33), treatment in a hospital with < 500 beds, and starting treatment in the years 2004-2006. Fourteen per cent of the patients had a delayed initiation of treatment. Delayed initiation of treatment was more likely in injecting drug users, patients with hepatitis C, patients with higher CD4 counts and during the years 2004-2006, and it was less likely in patients with viral loads > 5 log HIV-1 RNA copies/ml. The use of a nonrecommended regimen was significantly associated with mortality [hazard ratio ( HR) 1.61; 95% CI 1.03-2.52; P = 0.035] and lack of virological response. Conclusions Compliance with the recommendations of Spanish national guidelines was high with respect to the timing and choice of initial ART. The use of nonrecommended regimens was associated with a lack of virological response and higher mortality. [ABSTRACT FROM AUTHOR]

Background: Combination antiretroviral therapy (cART) has produced significant changes in mortality of HIVinfected persons. Our objective was to estimate mortality rates, standardized mortality ratios and excess mortality rates of cohorts of the AIDS Research Network (RIS) (CoRIS-MD and CoRIS) compared to the general population. Methods: We analysed data of CoRIS-MD and CoRIS cohorts from 1997 to 2010. We calculated: (i) all-cause mortality rates, (ii) standardized mortality ratio (SMR) and (iii) excess mortality rates for both cohort for 100 personyears (py) of follow-up, comparing all-cause mortality with that of the general population of similar age and gender. Results: Between 1997 and 2010, 8,214 HIV positive subjects were included, 2,453 (29.9%) in CoRIS-MD and 5,761 (70.1%) in CoRIS and 294 deaths were registered. All-cause mortality rate was 1.02 (95% CI 0.91-1.15) per 100 py, SMR was 6.8 (95% CI 5.9-7.9) and excess mortality rate was 0.8 (95% CI 0.7-0.9) per 100 py. Mortality was higher in patients with AIDS, hepatitis C virus (HCV) co-infection, and those from CoRIS-MD cohort (1997-2003). Conclusion: Mortality among HIV-positive persons remains higher than that of the general population of similar age and sex, with significant differences depending on the history of AIDS or HCV coinfection. [ABSTRACT FROM AUTHOR]

We show in human immunodeficiency virus–positive persons that the coronary artery disease effect of an unfavorable genetic background is comparable to previous studies in the general population, and comparable in size to traditional risk factors and antiretroviral regimens known to increase cardiovascular risk.Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection.Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort.Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10−4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05–2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06–1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16–1.96), diabetes (OR = 1.66; 95% CI, 1.10–2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06–1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17–2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD.Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD. [ABSTRACT FROM AUTHOR]

Objectives The objective of the study was to analyse key HIV-related outcomes in migrants originating from Latin America and the Spanish-speaking Caribbean ( LAC) or sub- Saharan Africa ( SSA) living in Spain compared with native Spaniards ( NSP). Methods The Cohort of the Spanish AIDS Research Network ( CoRIS) is an open, prospective, multicentre cohort of antiretroviral-naïve patients representing 13 of the 17 Spanish regions. The study period was 2004-2010. Multivariate logistic or Fine and Gray regression models were fitted as appropriate to estimate the adjusted effect of region of origin on the different outcomes. Results Of the 6811 subjects in CoRIS, 6278 were NSP (74.2%), LAC (19.4%) or SSA (6.4%). For these patients, the follow-up time was 15870 person-years. Compared with NSP, SSA and LAC under 35 years of age had a higher risk of delayed diagnosis [odds ratio ( OR) 2.0 (95% confidence interval ( CI) 1.5-2.8) and OR 1.7 (95% CI 1.4-2.1), respectively], as did LAC aged 35-50 years [ OR 1.3 (95% CI 1.0-1.6)]. There were no major differences in time to antiretroviral therapy ( ART) requirement or initiation. SSA exhibited a poorer immunological and virological response [ OR 0.8 (95% CI 0.7-1.0) and OR 0.7 (95% CI 0.6-0.9), respectively], while no difference was found for LAC. SSA and LAC showed an increased risk of AIDS for ages between 35 and 50 years [ OR 2.0 (95% CI 1.1-3.7) and OR 1.6 (95% CI 1.1-2.4), respectively], which was attributable to a higher incidence of tuberculosis. However, no statistically significant differences were observed in mortality. Conclusions Migrants experience a disproportionate diagnostic delay, but no meaningful inequalities were identified regarding initiation of treatment after diagnosis. A poorer virological and immunological response was observed in SSA. Migrants had an increased risk of AIDS, which was mainly attributable to tuberculosis. [ABSTRACT FROM AUTHOR]

The table of contents for the July 2013 issue of "Clinical Infectious Diseases" is presented.