[Show abstract][Hide abstract] ABSTRACT: Objectives
Fat mass ratio (FMR) has been suggested as an objective indicator of abnormal body fat distribution in HIV infection. Although it could provide more comprehensive information on body fat changes than limb fat mass, FMR has scarcely been used in clinical trials examining body fat distribution in HIV-infected patients.MethodsA subanalysis of a controlled, randomized clinical trial in virologically suppressed HIV-1-infected men switching from zidovudine (ZDV)/lamivudine (3TC) to emtricitabine (FTC)/tenofovir (TDF) versus continuing on ZDV/3TC was carried out. FMR was assessed by dual X-ray absorptiometry (DEXA) for a period of 72 weeks. Lipoatrophy was defined as FMR ≥ 1.5. Multivariate linear regression models for the change in FMR from baseline were fitted.ResultsSixty-five men were randomized and treated (28 in the FTC/TDF arm and 37 in the ZDV/3TC arm), and 57 completed the study (25 and 32 in each arm, respectively). In the FTC/TDF arm, adjusted mean FMR decreased by 0.52 at week 72 (P = 0.014), and in the ZDV/3TC arm it increased by 0.13 (P = 0.491; P between arms = 0.023). Among subjects with lipoatrophy (baseline FMR ≥ 1.5), adjusted FMR decreased by 0.76 (P = 0.003) in the FTC/TDF arm and increased by 0.21 (P = 0.411; P between arms = 0.009) in the ZDV/3TC arm. Baseline FMR and treatment group were significant predictors (P < 0.05) of post-baseline changes in FMR.Conclusions
Switching from ZDV/3TC to FTC/TDF led to an improvement in FMR, compared with progressive worsening of FMR in subjects receiving ZDV/3TC, showing that fat mass not only increased but was also distributed in a healthier way after the switch.
[Show abstract][Hide abstract] ABSTRACT: Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice.
[Show abstract][Hide abstract] ABSTRACT: Background:
We compared the prognostic value of liver biopsy (LB) and FIB-4 index in patients with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection.
We studied patients from the Grupo de Estudio del SIDA 3603 study cohort, in whom fibrosis was evaluated at baseline using both LB (Metavir score) and FIB-4 index. We assessed overall death (OD) and liver-related events (LREs), defined as decompensation or hepatocellular carcinoma, whichever occurred first. We used receiver operating characteristic (ROC) curves to determine the ability of LB and FIB-4 to predict outcomes. We also assessed the association between advanced fibrosis-LB (F3 or greater) or FIB-4 (≥3.25)-and outcomes using multivariate Cox regression analysis.
The study sample comprised 903 patients (328 with sustained virologic response [SVR]). Baseline fibrosis by LB was as follows: F0, n = 71; F1, n = 242; F2, n = 236; F3, n = 236; F4, n = 118. Fibrosis by FIB-4 was as follows: ≤1, n = 148; >1 to <3.25, n = 597; ≥3.25, n = 158. After a median follow-up of 62 months, there were 46 deaths and 71 LREs. The area under the ROC curves for OD/LREs was 0.648 and 0.742 for LB and FIB-4, respectively (P = .006). Similar results were found for patients without SVR and for OD and LREs separately. The adjusted hazard ratios of OD or LRE were 1.740 (95% confidence interval [CI], 1.119-2.7.06; P = .014) for advanced fibrosis assessed by LB and 3.896 (95% CI, 2.463-6.160; P < .001) assessed by FIB-4.
FIB-4 outperformed LB as a predictor of OD and LRE. These findings are of relevance for clinical practice and research and call into question the role of LB as a gold standard for assessing prognosis in HIV/HCV coinfection.
Full-text · Article · Nov 2014 · Clinical Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Introduction
Emerging non-AIDS related causes of death have been observed in HIV-positive subjects in industrialized countries. We aimed to analyze overall and cause-specific excess of mortality of HIV-positive patients compared to the general population and to assess the effect of prognostic factors.
Material and Methods
We used generalized linear models with Poisson error structure to estimate overall and cause-specific excess of mortality in HIV-positive patients from 2004 to 2012 in the cohort of the Spanish Network of HIV Research (CoRIS), compared to Spanish general population and to assess the impact of multiple risk factors. We investigated differences between short-term and long-term risk factors effects on excess of mortality. Multiple Imputation by Chained Equations was used to deal with missing data.
In 9162 patients there were 363 deaths, 16.0% were non-AIDS malignancies, 10.5% liver and 0.3% cardiovascular related. Excess mortality was 1.20 deaths per 100 person years (py) for all-cause mortality, 0.16 for liver, 0.10 for non-AIDS malignancies and 0.03 for cardiovascular. Short-term (first-year follow-up) excess Hazard Ratio (eHR) for global mortality for baseline AIDS was 4.27 (95% CI 3.06–6.01) and 1.47 (95% CI 0.95–2.27) for HCV coinfection; long-term (subsequent follow-up) eHR for baseline AIDS was 0.88 (95% CI 0.58–1.35) and 4.48 (95% CI 2.71–7.42) for HCV coinfection. Lower CD4 count and higher viral load at entry, lower education, being male and over 50 years were predictors for overall excess mortality. Excess of liver mortality was higher in patients with CD4 counts at entry below 200 cells compared to those above 350 (eHR: 6.49, 95% CI 1.21–34.84) and in HCV-coinfected patients (eHR: 3.85, 95% CI 0.85– 17.37), although it was borderline significant. Patients over 50 years old (eHR: 5.55, 95%CI 2.4–12.85) and HCV coinfected (eHR: 5.81, 95% CI 2.6–13) showed a higher risk of non-AIDS malignancies mortality excess. Excess of cardiovascular mortality was related with HCV coinfection (eHR: 6.68, 95% CI 1.25–35.73).
Our results show overall, liver, non-AIDS malignancies and cardiovascular excess of mortality associated with being HIV-positive, despite improvements in HIV disease management and antiretroviral therapies. Differential short-term and long-term effect of AIDS before entry and HCV coinfection was found for overall mortality.
Full-text · Article · Nov 2014 · Journal of the International AIDS Society
[Show abstract][Hide abstract] ABSTRACT: Introduction
Due to their low CNS penetrance, there are concerns about the capacity of non-conventional PI-based ART (monotherapy and dual therapies) to preserve neurocognitive performance (NP).
We evaluated the NP change of aviremic participants of the SALT clinical trial  switching therapy to dual therapy (DT: ATV/r+3TC) or triple therapy (TT: ATV/r+2NRTI) who agreed to perform an NP assessment (NPZ-5) at baseline and W48. Neurocognitive impairment and NP were assessed using AAN-2007 criteria  and global deficit scores (GDS) . Neurocognitive change (GDS change: W48 – baseline) and the effect of DT on NP evolution crude and adjusted by significant confounders were determined using ANCOVA.
A total of 158 patients were included (Table 1). They had shorter times because HIV diagnosis, ART initiation and HIV-suppression and their virologic outcome at W48 by snapshot was higher (79.1% vs 72.7%; p=0.04) compared to the 128 patients not included in the sub-study. By AAN-2007 criteria, 51 patients in each ART group (68% vs 63%) were neurocognitively impaired at baseline (p=0.61). Forty-seven patients were not reassessed at W48: 30 lost of follow-up (16 DT-14 TT) and 17 had non-evaluable data (6 DT-11 TT). Patients retested were more likely to be men (78.9% vs 61.4%) and had neurological cofounders (9.6% vs 0%) than patients non-retested. At W48, 3 out of 16 (5.7%) patients on DT and 6 out of 21 (10.5%) on TT who were non-impaired at baseline became impaired (p=0.49) while 10 out of 37 (18.9%) on DT and 7 out of 36 (12.3%) on TT who were neurocognitively impaired at baseline became non-impaired (p=0.44). Mean GDS changes (95% CI) were: Overall −0.2 (−0.3 to −0.04): DT −0.26 (−0.4 to −0.07) and TT −0.08 (−0.2 to 0.07). NP was similar between DT and TT (0.15). This absence of differences was also observed in all cognitive tests. Effect of DT: −0.16 [−0.38 to 0.06]) (r2=0.16) on NP evolution was similar to TT (reference), even after adjusting (DT: −0.11 [−0.33 to 0.1], TT: reference) by significant confounders (geographical origin, previous ATV use and CD4 cell count) (r2=0.25).
NP stability was observed after 48 weeks of follow up in the majority of patients whether DT or TT was used to maintain HIV-suppression. Incidence rates of NP impairment or NP impairment recovery were also similar between DT and TT.
Full-text · Article · Nov 2014 · Journal of the International AIDS Society
[Show abstract][Hide abstract] ABSTRACT: To evaluate the results of the treatment with pegylated interferon and ribavirin for recurrence of hepatitis C after liver transplantation in HCV/HIV-coinfected patients.
No preview · Article · Aug 2014 · Journal of Hepatology
[Show abstract][Hide abstract] ABSTRACT: In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation varies with clinical circumstances, number of CD4 cells, comorbid conditions and prevention of transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load. Initial ART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors and a third drug from a different family (non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase inhibitor). This update presents the causes and criteria for switching ART in patients with undetectable plasma viral load and in cases of virological failure. An update is also provided for the specific criteria for ART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid conditions (tuberculosis or other opportunistic infections, kidney disease, liver disease, and cancer).
Full-text · Article · Aug 2014 · Enfermedades Infecciosas y Microbiología Clínica
[Show abstract][Hide abstract] ABSTRACT: Objectives
We compared reasons for the choice of regimen, time to and reasons for third drug modification, virological response and change in CD4 T-cell counts in patients started on atazanavir/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line regimens.Methods
We included patients from the Cohort of the Spanish HIV Research Network (CoRIS), a multicentre cohort of HIV-positive treatment-naïve subjects, in the study. We used logistic regression to assess factors associated with choosing ATV/r vs. EFV, proportional hazards models on the subdistribution hazard to estimate subdistribution hazard ratios (sHRs) for third drug modification, logistic regression to estimate odds ratios (ORs) for virological response and linear regression to assess mean differences in CD4 T-cell count increase from baseline.ResultsOf 2167 patients, 10.7% started on ATV/r. ATV/r was more likely than EFV to be prescribed in injecting drug users [adjusted OR 1.85; 95% confidence interval (CI) 1.03–3.33], in 2009–2010 (adjusted OR 1.63; 95% CI 1.08–2.47) and combined with abacavir plus lamivudine (adjusted OR 1.53; 95% CI 0.98–2.43). Multivariate analyses showed no differences, comparing ATV/r vs. EFV, in the risk of third drug modification (sHR 1.04; 95% CI 0.74–1.46) or in virological response (OR 0.81; 95% CI 0.46–1.41); differences in mean CD4 T-cell count increase from baseline were at the limit of statistical significance (mean difference 29.8 cells/μL; 95% CI −4.1 to 63.6 cells/μL). In patients changing from EFV, 48% of changes were attributable to toxicity/adverse events, 16% to treatment failure/resistance, 3% to simplification, and 8 and 12%, respectively, to patients' and physicians' decisions; these percentages were 24, 6, 12, 14 and 24%, respectively, in those changing from ATV/r.ConclusionsATV/r- and EFV-based regimens meet the requirements of both efficacy and safety for initial combination antiretroviral regimen, which relate to better durability.
[Show abstract][Hide abstract] ABSTRACT: The presence of transmitted HIV drug resistance (TDR) threatens the efficacy of antiretroviral treatment. We aimed to assess the changes in TDR prevalence over the last decade in Madrid, Spain, to verify the role of the patients' risk groups in these changes. We analysed the trends of TDR between 2000 and 2011 in a cohort of 1,022 naïve HIV-infected patients in Madrid, Spain, whose pol sequences were available. They included, among others, 369 heterosexuals, 340 men who have sex with men (MSM), and 90 injection drug users (IDUs). TDR was reported following the WHO mutation list. The TDR rate in the whole cohort was 8.3 %, being the highest in MSM (9.1 %) and the lowest in IDUs (4.4 %). Over time, this rate decreased significantly (to 5.4 % in 2009-2011) since the period 2004-2006, when it peaked (10.7 %). Heterosexuals and IDUs showed similar trends, but in the 2009-2011 period, the TDR rate among MSM rebounded to 9.0 % (being absent among IDUs). TDR stabilized in the last years (2007-2011) for nucleoside reverse transcriptase inhibitors. The risk group also determined differences in the mutational profile, sex distribution, proportion of immigrants, and viral variants. In conclusion, the risk group caused different HIV sub-epidemics, determined by the patients' profiles. Despite the general decreasing trend in TDR, we observed a non-significant increase in TDR rate among MSM, a tendency that needs confirmation. Periodic TDR surveillance is important to prevent the widespread distribution of resistance, especially in MSM, given the growing HIV/AIDS epidemic in this high-risk population.
Full-text · Article · Dec 2013 · Archives of Virology
[Show abstract][Hide abstract] ABSTRACT: Background
Atazanavir (ATV) boosted with ritonavir (ATV/r) is a potent, well-tolerated, once-daily protease
inhibitor (PI). Few data are available on this agent as a treatment simpliﬁcation option for patients
taking other PIs.
The aim of the study was to determine the effectiveness and safety of ATV-containing regimens in
patients who have simpliﬁed their antiretroviral treatment.
SIMPATAZ was a multicentre, prospective, noninterventional study in patients who had
undetectable HIV RNA on their current PI-containing therapy and who were switched to an ATV/
r-based regimen. Patients underwent a routine physical examination, and data were collected on
HIV RNA levels, CD4 cell counts, liver function, lipid parameters, adverse reactions, adherence to
treatment and patient satisfaction.
A total of 183 patients were enrolled in the study and included in the analysis (80% were male, 29%
had AIDS, and 52% were coinfected with HIV and hepatitis B virus or hepatitis C virus). The median
baseline CD4 count was 514 cells/mL. Median exposure to previous HIV therapy was 8 years, and 32%
of patients had a history of PI failures. Lopinavir boosted with ritonavir was the most frequent PI
replaced (62%) and tenofovir1lamivudine /emtricitabine the backbone most used during the study
(29%). The study drug was discontinued early by 25 patients (14%), two of whom discontinued as a
result of adverse events (Hodgkin lymphoma and vomiting). Two patients died (lung cancer and
myocardial infarction). At month 12, 93% of the study population had an undetectable HIV RNA viral
load. Hyperbilirubinaemia 43 mg/dL and increased alanine aminotransferase levels4200 IU/L were
observed in 38.5% and 4.4% of patients, respectively. Median changes from baseline to month 12 in
total cholesterol, triglycerides and low-density lipoprotein cholesterol were �13 mg/dL (�7%;
Po0.0001), �19 mg/dL (�13%; Po0.0001) and �7 mg/dL (�6%; P50.021), respectively.
In a real-world setting, switching from other PIs to ATV/r is a well-tolerated and safe option for
improving the lipid proﬁle and for retaining virological resp
[Show abstract][Hide abstract] ABSTRACT: Background
Day care units have become an usual way of medical care for AIDS patients. However,their influence on the incidence of hospital admissions has not been evaluated.
Observational and longitudinal study of a cohort of 308 patients with aids diagnosedbetween 1990 and 1994 and followed-up to June 1996. The incidence of hospital admissionsaccording to the hospital of follow-up (with or without day care unit) was analyzed. A multivariateanalysis of the number of hospital admissions was performed using regression model adjustedto a distribution of Poisson.
After AIDS diagnosis, the incidence of hospital admissions was 108 per 100 patientyearsof follow up (21 days as inpatient per patient-year). Those patients controlled in the hospitalwith day care unit have less hospital admissions (relative risk after adjusting by CD4+cells count and type of diagnostic disease: 0.64; CI95% 0.55-0.76), and less days as inpatientthrough their follow-up (11 to 31 days less). There was no difference in survival among patientsfollowed in both hospitals.
A day care unit decrease the incidence of hospital admissions in aids patients.This positive impact is more evident in patients with lesser CD4+ cell counts.
No preview · Article · Jul 2013 · Medicina Clínica
[Show abstract][Hide abstract] ABSTRACT: In patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease inhibitor monotherapy is associated to a higher rate of neurocognitive impairment.
In this observational, cross-sectional study we included patients with plasma virological suppression (≥1 year) without concomitant major neurocognitive confounders, currently receiving for ≥1 year boosted lopinavir or darunavir as monotherapy or as triple ART. Neurocognitive impairment was defined as per the 2007 consensus of the American Association of Neurology. The association between neurocognitive impairment and protease inhibitor monotherapy, adjusted by significant confounders, was analysed.
Of the 191 included patients - triple therapy: 96, 1-2 years of monotherapy: 40 and >2 years of monotherapy: 55 - proportions (95% CI) with neurocognitive impairment were: overall, 27.2% (20.9-33.6); triple therapy, 31.6% (22.1-41.0); short-term monotherapy, 25.0% (11.3-38.7); long-term monotherapy: 21.4% (10.5-32.3); p = 0.38. In all groups, neurocognitive impairment was mildly symptomatic or asymptomatic by self-report. There were not significant differences in Global Deficit Score by group. In the regression model confounding variables for neurocognitive impairment were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by these variables the Odds Ratio (95% CI) for neurocognitive impairment of patients receiving short-term monotherapy was 0.85 (0.29-2.50) and for long-term monotherapy 0.40 (0.14-1.15).
Compared to triple drug antiretroviral therapy, monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with adequate plasma suppression was not associated with a higher rate of asymptomatic neurocognitive impairment than triple drug ART.
[Show abstract][Hide abstract] ABSTRACT: Background & aims:
Sustained viral response (SVR) after therapy with interferon-ribavirin (IF-RB) reduces liver-related (LR) complications and mortality in HIV/HCV-co-infected patients. Here, we assess the impact of end-of-treatment response with subsequent relapse (REL) on LR events (LR death, liver decompensation, hepatocellular carcinoma, or liver transplantation), and liver stiffness (LS) by transient elastography.
We analyzed the GESIDA 3603 Cohort (HIV/HCV-co-infected patients treated with IF-RB in 19 centers in Spain). Response to IF-RB was categorized as SVR, REL, and no response (NR). The study started when IF-RB was stopped and ended at death or the last follow-up visit. Multivariate regression analyses were adjusted for age, sex, HIV category of transmission, CDC clinical category, nadir CD4+ cell count, HCV genotype, HCV-RNA viral load, and liver fibrosis.
Of 1599 patients included, response was categorized as NR in 765, REL in 250 and SVR in 584. Median follow-up was more than 4 years in each group. Taking the group of patients with NR as reference, we found that the adjusted hazard ratios (95% confidence interval) of liver-related events (liver-related death, liver decompensation, hepatocellular carcinoma, liver transplantation) for patients with REL and for patients with SVR were 0.17 (0.05; 0.50) and 0.03 (0; 0.20), respectively. We also found that SVR was followed by less liver stiffness than both REL and NR. However, REL was associated with less liver stiffness than NR.
Best outcomes were achieved with an SVR. However, REL was associated with less LR mortality, decompensation, and liver stiffness than NR.
No preview · Article · Feb 2013 · Journal of Hepatology
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Lipoatrophy is a long-term adverse effect of some antiretrovirals that affects quality of life, compromises adherence and may limit the clinical impact of HIV treatments. This paper explores the effect of tenofovir/emtricitabine (TDF/FTC) on the amount of limb fat in patients with virological suppression.
A randomized, prospective clinical trial was performed to compare continuation on a zidovudine/lamivudine (ZDV/3TC)-based regimen with switching to a TDF/FTC-based regimen in terms of the effect on limb fat mass as assessed by DEXA over a 72-week period.
Eighty patients were included (39 in the TDF/FTC arm and 41 in the ZDV/3TC arm) and 73 completed the study (37 and 36, respectively). In the switch arm, limb fat increased by a median of 540 g from baseline (P = 0.022), while in the ZDV/3TC arm it decreased by a median of 379 g (P = 0.112; p between groups = 0.007). Subjects with baseline limb fat ≤ 7200 g, previous time on ZDV > 5 years or a body mass index > 25 kg/m(2) experienced higher limb fat gains than other subjects, and these differences were statistically significant. Haemoglobin increased by a median of 1.0 g/dL in the TDF/FTC arm (P < 0.001) and remained unchanged in the ZDV/3TC arm (p between groups = 0.0002). There were no significant differences between groups in other secondary endpoints (body weight, total body and trunk fat content, total body bone mineral density, laboratory parameters, CD4 cell count and viral load).
Switching from a ZDV/3TC-based to a TDF/FTC-based regimen led to a statistically significant improvement in limb fat, in contrast to the progressive loss of limb fat in subjects continuing ZDV/3TC.
[Show abstract][Hide abstract] ABSTRACT: Abstract A systematic screening for measles, mumps, rubella (MMR) and varicella zoster virus (VZV) in HIV-positive adult immigrants in Spain was evaluated, and factors associated with MMR and VZV vaccines' indication were studied. Every HIV-positive immigrant was tested for VZV and MMR-IgG. MMR vaccine was indicated to patients with lymphocytes CD4+ >200 cells/mm(3) and a negative measles-IgG, a negative mumps-IgG and/or a negative rubella-IgG. VZV vaccine was indicated to every VZV-IgG negative patient with CD4+ >400 cells/mm(3). In total, 289 patients were screened; seroprevalence was 95.2%, 92.2%, 70.3% and 89.3% for VZV, measles, mumps and rubella IgG, respectively. Having a negative VZV-IgG was statistically associated with coming from sub-Saharan Africa (prevalence ratio [PR]: 6.52; 95% CI: 1.71-24.84; p=0.006), while having secondary education was a protective factor (PR: 0.25; 95% CI: 0.07-0.97; p=0.045). Fourteen patients (4.8%) had indication of VZV vaccine; vaccination was feasible in 21.4% of them at first visit. Eighty-one patients (29.7%) had indication of MMR vaccine, most of them due to mumps-IgG negative (53.1%) or rubella-IgG negative (24.7%). Age < 30 years at first visit was the only factor statistically associated with MMR vaccine indication (PR: 1.47; 95% CI: 1.02-2.11; p=0.04). According to CD4+ cell counts, vaccination was feasible in 71.6% of patients at first visit. In conclusion, more than a third of HIV-infected immigrant patients are susceptible to at least one easily preventable infectious disease. Especial attention should be given to immigrant women of childbearing age.
[Show abstract][Hide abstract] ABSTRACT: The objective was to evaluate the implementation of a systematic Strongyloides stercoralis screening programme in HIV infected immigrants attending an HIV Unit in Spain. An enzyme-linked immunosorbent assay (ELISA) was performed to assess the presence of Strongyloides IgG. Patients with a positive serology were treated with ivermectin; serologic follow-up testing was performed. 237 patients were screened (65.4 % men). Origin: 64.1 % came from Latin America, 16.5 % from Sub-Saharan Africa, 9.7 % from the Caribbean, 9.7 % from other areas. Strongyloides stercolaris IgG was positive in 13 cases (5.5 %). In the multivariate analysis, factors associated with a positive Strongyloides serology were illiteracy (OR: 23.31; p = 0.009) and eosinophilia (OR: 15.44; p < 0.0001). Nine of the 13 patients positive for S. stercoralis IgG and treated with ivermectin had a follow up serologic test: 77.8 % achieved a serologic response (55.5 % seroreversion). Screening of HIV-positive immigrants may be desirable, at least in those with higher risk of hyperinfection syndrome. Serologic testing seems a useful tool in both diagnosis and follow-up of these patients.
No preview · Article · Dec 2012 · Journal of Immigrant and Minority Health