[Show abstract][Hide abstract] ABSTRACT: HIV-1 infection increases plasma levels of inflammatory markers. Combination antiretroviral therapy (cART) does not restore inflammatory markers to normal levels. Since intensification of cART with raltegravir reduced CD8 T-cell activation in the Discor-Ral and IntegRal studies, we have evaluated the effect of raltegravir intensification on several soluble inflammation markers in these studies.
Longitudinal plasma samples (0-48 weeks) from the IntegRal (n = 67, 22 control and 45 intensified individuals) and the Discor-Ral studies (44 individuals with CD4 T-cell counts<350 cells/µl, 14 control and 30 intensified) were assayed for 25 markers. Mann-Whitney, Wilcoxon, Spearman test and linear mixed models were used for analysis.
At baseline, different inflammatory markers were strongly associated with HCV co-infection, lower CD4 counts and with cART regimens (being higher in PI-treated individuals), but poorly correlated with detection of markers of residual viral replication. Although raltegravir intensification reduced inflammation in individuals with lower CD4 T-cell counts, no effect of intensification was observed on plasma markers of inflammation in a global analysis. An association was found, however, between reductions in immune activation and plasma levels of the coagulation marker D-dimer, which exclusively decreased in intensified patients on protease inhibitor (PI)-based cART regimens (P = 0.040).
The inflammatory profile in treated HIV-infected individuals showed a complex association with HCV co-infection, the levels of CD4 T cells and the cART regimen. Raltegravir intensification specifically reduced D-dimer levels in PI-treated patients, highlighting the link between cART composition and residual viral replication; however, raltegravir had little effect on other inflammatory markers.
PLoS ONE 12/2014; 9(12):e114142. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fixed-dose combination antiretroviral therapy administered as a single-tablet regimen (STR) may improve virologic suppression rates. The effect of STRs on development of resistance when virologic failure occurs on STRs is not known.
To compare the rate of emergent drug resistance mutations (DRMs) on first-line therapy with coformulated tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/efavirenz (EFV) as an STR versus TDF, lamivudine (3TC) or FTC, and EFV given as non-STR.
Patients from eight cohorts and four randomized clinical trials who received first-line antiretroviral therapy with Atripla (STR group) or with TDF + FTC/3TC + EFV (non-STR group) were eligible if a genotypic resistance test was available immediately after the first episode of viral failure. The DRM list from the 2013 version of IAS-USA was used.
One hundred and eighty-six patients were included in the final analysis, 122 (65.6%) from eight cohorts and 64 (34.1%) from four randomized clinical trials. The overall proportion of patients with at least one DRM at viral failure was 67.7%, including 53.4% (31 of 58) in the STR group vs. 74.2% (95 of 128) in the non-STR group (P = 0.005). Among patients exclusively from cohorts, at least one DRM was detected in 53.4% (31 of 58) in the STR group vs. 78.1% (50 of 64) in the non-STR group (P = 0.004). DRMs for individual drugs were: TDF, 15.5 vs. 16.4% (P = 0.87); 3TC/FTC, 31 vs. 35.2% (P = 0.58); and NNRTI, 51.7 vs. 65.6% (P = 0.07). The proportion of patients with an M184V/I among the 128 patients who received FTC was 32.8 vs. 36.2% among the 58 treated with 3TC (P = 0.65).
Compared to patients receiving the STR-Atripla, those receiving the same components individually in a non-STR regimen have a statistically significantly increased risk of selecting for DRMs associated with their drugs on failure.
[Show abstract][Hide abstract] ABSTRACT: Purpose: Very scarce information has been published to date with the combination of ABC/3TC/NVP but it is currently being used in clinical practice in Spain and Portugal. Our aim was to present the clinical experience with this regimen in a cohort of adult HIV-infected antiretroviral (ARV)-naïve patients. Methods: Retrospective, multicentre, cohort study. Consecutive adult HIV-infected ARV-naïve HLA-B*5701-negative patients, who started ABC/3TC/NVP between 2005-2013, with at least one follow-up visit, were included. Demographic, clinical and laboratory variables were assessed at baseline, month 1, and every three-four months thereafter. The primary end point was HIV-1 viral load (VL)<40 c/mL at 48 weeks. Data were analyzed by intent-to-treat (ITT) (switch=failure, and missing=failure) and on treatment (OT) analyses. Results: 78 patients were included. Median follow up was 26 (0.1-84) months. 86% were male, median age 41 (23-69) years, 9% had AIDS, 8% were HCV+, baseline CD4 was 275 (10-724) cells/µL and median VL 4.58 (3.02-6.92) log. After 48 weeks, VL was<40 c/mL in 89.8% (OT), 79.7% (M=F) and 65.4% (S=F) and at 96 weeks in 88.5%, 78.9% and 61.6%, respectively. CD4 increased +246 (p<0.001) and +292 (p<0.001) cells/uL after 48 and 96 weeks, respectively. One or more drugs of the regimen were discontinued in 33 (42.3%) patients. In 15 (19.2%) patients (13 NVP, 2 ABC/3TC) therapy was stopped due to toxicity after a median of one month (in only two cases after six months of follow up): 80% of them had rash/liver toxicity. Six (7.7%) patients discontinued ART due to virologic failure, five (6.4%) because of other reasons and seven (9%) were lost to follow-up. ALT but not AST significantly increased (+0.07 ukat/L at 96 weeks, p=0.033). A significant increase of 25%, 26% and 42% in total cholesterol, LDLc and HDLc, respectively, and a significant decrease in TC/HDL ratio (6%, p=0.008) was observed after 96 weeks. Conclusions: Despite a considerable proportion of patients had to stop therapy due to toxicity (most associated with NVP), those initially tolerating this regimen presented a high virologic and immunologic response after 96 weeks, as well as a favourable lipid profile. ABC/3TC/NVP may be a suitable alternative first regimen, mainly in countries with economic constraints.
Journal of the International AIDS Society 11/2014; 17(4(Suppl 3)):19773. · 4.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The National AIDS Plan and the Spanish AIDS study group (GESIDA) panel of experts propose "preferred regimens" of antiretroviral treatment (ART) as initial therapy in HIV-infected patients for 2013 . All these regimens are triple therapy regimens. The Gardel Study assessed the efficacy and safety of a dual therapy (DT) combination of lopinavir/ritonavir (LPV/r) 400/100 mg BID+ lamivudine (3TC) 150 mg BID . The objective of this study is to evaluate the costs and efficiency of initiating treatment with the GESIDA "preferred regimens" and DT.
Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19603. · 4.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction: Monotherapy with protease-inhibitors (MPI) may be an alternative to cART for HIV treatment. We assessed the impact of this strategy on immune activation, bacterial translocation and inflammation. Methods: We performed a cross-sectional study comparing patients on successful MPI (n=40) with patients on cART (n=20). Activation, senescence, exhaustion and differentiation stage in CD4+ and CD8+ T lymphocyte subsets, markers of monocyte activation, microbial translocation, inflammation, coagulation and low-level viremia were assessed. Results: CD4+ or CD8+ T lymphocyte subset parameters were not significantly different between both groups. Conversely, as compared with triple cART, MPI patients showed a higher proportion of activated monocytes (CD14+ CD16-CD163+ cells, p=0.031), soluble markers of monocyte activation (sCD14 p=0.004, sCD163 p=0.002), microbial translocation (lipopolysaccharide (LPS)-binding protein; LBP p=0.07), inflammation (IL-6 p=0.04) and low-level viremia (p=0.035). In a multivariate model, a higher level of CD14+ CD16-CD163+ cells and sCD14, and presence of very low-level viremia were independently associated with MPI. Monocyte activation was independently associated with markers of inflammation (IL-6, p=0.006), microbial translocation (LBP, p=0.01) and low-level viremia (p=0.01). Conclusions: Patients on MPI showed a higher level of monocyte activation than patients on standard therapy. Microbial translocation and low-level viremia were associated with the high level of monocyte activation observed in patients on MPI. The long-term clinical consequences of these findings should be assessed.
Journal of the International AIDS Society 09/2014; 17(1):19246. · 4.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since recent data suggest that nanoparticles and modified vaccinia ankara (MVA) vectors could play a pivotal role in HIV-1 therapeutics and vaccine design, in an ex vivo model of human monocyte-derived dendritic cells (MDDCs), we compared two different loading strategies with HIV-1 vaccine vehicles, either viral or synthetic derived. We used polylactic acid (PLA) colloidal biodegradable particles, coated with HIV Gag antigens (p24), and MVA expressing Gag (rMVA-gag and rMVA-gag/trans membrane) or Tat, Nef and Rev genes (rMVA tat+rev and rMVA nef). PLA-p24 captured by MDDCs from HIV-1 individuals induced a slight degree of MDDC maturation, cytokine and chemokine secretion and migration towards a gradient of CCL19 chemokine and highly increased HIV-specific CD8+ T-cell proliferation compared with p24 alone. After complete maturation induction of PLA-p24-pulsed MDDCs, maximal migration towards a gradient of CCL19 chemokine and induction of HIV-specific T-cell proliferation (two-fold higher for CD4+ than CD8+) and cytokine secretion (IFN-γ and IL-2) in the co-culture were observed. Upon exposure to MVA-gag, MDDCs produced cytokines and chemokines and maintained their capacity to migrate to a gradient of CCL19. MDDCs infected with MVA-gag and MVA-gag trans-membrane were able to induce HIV-specific CD8+ proliferation and secretion of IFN-γ, IL-2, IL-6 and TNF-α. We conclude that both HIV antigens loading strategies (PLA-p24 nanoparticles or MVA expressing HIV genes) induce HIV-1-specific T-cell responses, which are able to kill autologous gag-expressing cells. Thus, they are plausible candidates for the development of anti-HIV vaccines.
[Show abstract][Hide abstract] ABSTRACT: Objetivo
Describir la incidencia, la etiología y el pronóstico de la infección de las vías respiratorias bajas (IVRB) en los pacientes VIH, que acudieron a un Servicio de Urgencias (SU), durante el período del 2000–2010.
Diseño del estudio
Estudio prospectivo de 10 años de evolución.
Se recogió únicamente el primer episodio del paciente que acude al SU por IRVB (definida según la European Respiratory Society). Se analizaron una serie de variables epidemiológicas y de laboratorio, así como la necesidad de ingreso en una unidad de cuidados intensivos (UCI). Se estudió la etiología de la IRVB y la incidencia. Finalmente se analizaron la influencia de las variables con la mortalidad a 30 días.
Se incluyeron un total de 131 pacientes. La edad media fue de 39 ± 9 años. El 72% de los pacientes eran varones y el 18% de los pacientes requirieron ingreso en la UCI. La IRVB más frecuente fue la neumonía por P. jirovecci, seguida de la neumonía bacteriana en 27 y la tuberculosis pulmonar en 20. La incidencia de IRVB se ha ido reduciendo gradualmente de forma significativa, 6,13 × 1.000 pacientes/año en 2000 a 0,23 × 1.000 pacientes/año en 2010 (p < 0,05). El análisis de regresión logística mostró que la única variable que predijo mortalidad fue el ingreso en UCI (p < 0,05; OR: 73,01).
La IRVB es una enfermedad cuya incidencia y etiología han ido disminuyendo y cambiando respectivamente, probablemente en relación con la utilización generalizada del TAR. Sin embargo, todavía presenta una mortalidad nada despreciable, que es mayor cuando el paciente requiere ingreso en la UCI.
Enfermedades Infecciosas y Microbiología Clínica 09/2014; · 1.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gene expression studies of subcutaneous adipose tissue may help to better understand the mechanisms underneath body fat changes in HIV-infected patients who initiate antiretroviral therapy (ART). Here we evaluated early changes in adipose tissue gene expression and their relationship with fat changes in ART-naïve HIV-infected patients randomly assigned to initiate therapy with emtricitabine/tenofovir plus efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r). This was a substudy of a randomized clinical trial (LIPOTAR-NCT00759070). Patients had abdominal subcutaneous adipose tissue biopsies at baseline and week 16 and dual-energy-X-ray absorptiometry at baseline, week 16 and 48. mRNA changes of eleven genes involved in adipogenesis, lipid and glucose metabolism, mitochondrial energy and inflammation were assessed through RT-qPCR. Additionally, correlations between gene expression changes and fat changes were evaluated. Fat increased preferentially in the trunk with EFV and in the limbs with LPV/r (p<0.05). After 16 weeks of exposure to the drug regimen, transcripts of CEBP/A, ADIPOQ, GLUT4, LPL and COXIV were significantly down-expressed in EFV arm compared to LPV/r (p<0.05). Significant correlations were observed between LPL expression change and trunk fat change at week 16 in both arms, and CEBP/A or COXIV changes and trunk fat change at the same time-point only in EFV arm and not in LPV/r. When combined with emtricitabine/tenofovir as standard backbone therapy, EFV or LPV/r induced differential early expression of genes involved in adipogenesis and energy metabolism. Moreover, these mRNA expression changes correlated with trunk fat change in the EFV arm.
Antimicrobial Agents and Chemotherapy 08/2014; · 4.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introducción
El panel de expertos de GESIDA/Plan Nacional del Sida ha recomendado pautas preferentes (PP) y alternativas (PA) de tratamiento antirretroviral (TARV) como terapia de inicio en pacientes infectados por VIH para 2014. El objetivo de este estudio es evaluar los costes y la eficiencia de iniciar tratamiento con estas pautas.
Evaluación económica de costes y eficiencia (coste/eficacia) mediante construcción de árboles de decisión. Se definió eficacia como la probabilidad de tener carga viral <50 copias/mL en la semana 48 en análisis por intención de tratar. Se definió coste de iniciar tratamiento con una pauta como los costes del TARV y de todas sus consecuencias (efectos adversos, cambios de pauta y estudio de resistencias) que se producen en las siguientes 48 semanas. Se utilizó la perspectiva del Sistema Nacional de Salud, considerando sólo costes directos diferenciales: fármacos (a precio oficial), manejo de efectos adversos, estudios de resistencias y determinación de HLA B*5701. El ámbito es España, con costes de 2014. Se realizó análisis de sensibilidad determinista construyendo tres escenarios para cada pauta: basal, más favorable y más desfavorable.
En el escenario basal, los costes de iniciar tratamiento oscilaron entre 5.133 euros para ABC/3TC + EFV y 11.949 euros para TDF/FTC + RAL. La eficacia osciló entre 0,66 para ABC/3TC + LPV/r y ABC/3TC + ATV/r, y 0,89 para TDF/FTC/EVG/COBI. La eficiencia, en términos de coste/eficacia, osciló entre 7.546 y 13.802 euros por respondedor a las 48 semanas, para ABC/3TC + EFV y TDF/FTC + RAL, respectivamente.
Considerando el precio oficial del TARV, la pauta más eficiente fue ABC/3TC + EFV (PA), seguida de las PP que contienen no nucleósidos (TDF/FTC/RPV y TDF/FTC/EFV). El análisis de sensibilidad confirmó la robustez de estos hallazgos.
Enfermedades Infecciosas y Microbiología Clínica 08/2014; · 1.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the association of host genetics with changes in limb or trunk fat in a group of antiretroviral therapy (ART)-naive HIV-infected patients prospectively followed up according to the initiation and the type of ART.
Journal of Antimicrobial Chemotherapy 07/2014; · 5.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The virologic efficacy of switching from a boosted protease inhibitor (PI/r) to raltegravir (RAL) containing regimens remains controversial according to the results of SWITCHMRK and SPIRAL studies. The aim of this analysis is to assess the impact of prior resistance mutations to nucleos(t)ides and other potential factors on the virologic outcome.
[Show abstract][Hide abstract] ABSTRACT: 0501/14 www.nature.com/mtm INTRODUCTION Recombinant BCG (rBCG) has been developed as a candidate neo-natal vaccine vector against pertussis, measles, respiratory syncytial virus, and breast milk HIV transmission.
Molecular Therapy Methods and Clinical Development. 05/2014; Molecular Therapy — Methods & Clinical Development 1, Article number: 14017 doi:10.1038/mtm.2014.17.
[Show abstract][Hide abstract] ABSTRACT: Abstract
A relationship between obesity and intestinal bacterial translocation has been reported. Very little information is available with respect to the involvement of the bacterial translocation mechanistic pathway in HIV-1/highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS). We determined whether lipopolysaccharide (LPS)-binding protein (LBP), cluster of differentiation 14 (CD14), myeloid differentiation protein 2 (MD2) and toll-like receptor 4 (TLR4) single-nucleotide polymorphisms and LPS, LBP and soluble CD14 (sCD14) plasma levels are involved in HALS.
PATIENTS AND METHODS:
This cross-sectional multicentre study involved 558 treated HIV-1-infected patients, 240 with overt HALS and 318 without HALS. Anthropometric, clinical, immunovirological and metabolic variables were determined. Polymorphisms were assessed by genotyping. Plasma levels were determined by ELISA in 163 patients (81 with HALS and 82 without HALS) whose stored plasma samples were available. Student's t-test, one-way ANOVA, two-way repeated measures ANOVA, the χ2 test and Pearson and Spearman correlation analyses were carried out for statistical analysis.
LBP rs2232582 T→C polymorphism was significantly associated with HALS (P = 0.01 and P = 0.048 for genotype and allele analyses, respectively). Plasma levels of LPS (P = 0.009) and LBP (P < 0.001) were significantly higher and sCD14 significantly lower (P < 0.001) in patients with HALS compared with subjects without HALS. LPS levels were independently predicted by triglycerides (P < 0.001) and hepatitis C virus (P = 0.038), LBP levels by HALS (P < 0.001) and sCD14 levels by age (P = 0.008), current HIV-1 viral load (P = 0.001) and protease inhibitor use (P = 0.018).
HALS is associated with LBP polymorphism and with higher bacterial translocation.
Journal of Antimicrobial Chemotherapy 02/2014; · 5.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND:: Latent HIV-1-infected cells generated early in the infection are responsible for viral persistence, and we hypothesized that addition of maraviroc to triple therapy in patients recently infected with HIV-1 could accelerate decay of the viral reservoir.METHODS:: Patients recently infected (<24 weeks) by chemokine receptor 5 (CCR5)-using HIV-1 were randomized to a raltegravir + tenofovir/emtricitabine regimen (control arm, n = 15) or the same regimen intensified with maraviroc (+MVC arm, n = 15). Plasma viral load, cell-associated HIV-1 DNA (total, integrated, and episomal), and activation/inflammation markers were measured longitudinally.RESULTS:: Plasma viral load decayed in both groups, reaching similar residual levels at week 48. Total cell-associated HIV-1 DNA also decreased in both groups during the first month, although subsequently at a slightly faster rate in the +MVC arm. The transient increase in two long terminal repeat (2-LTR) circles observed in both groups early after initiation of treatment decreased earlier in MVC-treated individuals. Early (week 12) increase of CD4 T-cell counts was higher in the +MVC arm. Conversely, CD8 T-cell counts and CD4 T-cell activation decreased slower in the +MVC arm. Absolute CD4 T-cell and CD8 T-cell counts, immune activation, CD4/CD8 T-cell ratio, and soluble inflammation markers were similar in both arms at the end of the study.CONCLUSION:: Addition of maraviroc in early integrase inhibitor-based treatment of HIV-1 infection results in faster reduction of 2-LTR newly infected cells and recovery of CD4 T-cell counts, and a modest reduction in total reservoir size after 48 weeks of treatment. Paradoxically, CCR5 blockade also induced a slower decrease in plasma viremia and immune activation
[Show abstract][Hide abstract] ABSTRACT: Introduction
The GESIDA and National AIDS Plan panel of experts have proposed “preferred regimens” of antiretroviral treatment (ART) as initial therapy in HIV infected patients for 2013. The objective of this study is to evaluate the costs and effectiveness of initiating treatment with these “preferred regimens”.
An economic assessment of costs and effectiveness (cost/effectiveness) was performed using decision tree analysis models. Effectiveness was defined as the probability of having viral load < 50 copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regime was defined as the costs of ART and its consequences (adverse effects, changes of ART regime and drug resistance analyses) during the first 48 weeks. The perspective of the analysis is that of the National Health System was applied, only taking into account differential direct costs: ART (official prices), management of adverse effects, resistance studies, and determination of HLA B*5701. The setting is Spain and the costs are those of 2013. A sensitivity deterministic analysis was performed, constructing three scenarios for each regimen: baseline, most favourable, and most unfavourable cases.
In the baseline case scenario, the cost of initiating treatment ranges from 6,747 euros for TDF/FTC + NVP to 12,059 euros for TDF/FTC + RAL. The effectiveness ranges between 0.66 for ABC/3TC + LPV/r and ABC/3TC + ATV/r, and 0.87 for TDF/FTC + RAL and ABC/3TC + RAL. Effectiveness, in terms of cost/effectiveness, varies between 8,396 euros and 13,930 euros per responder at 48 weeks, for TDF/FTC/RPV and TDF/FTC + RAL, respectively.
Taking ART at official prices, the most effective regimen was TDF/FTC/RPV, followed by the rest of non-nucleoside containing regimens. The sensitivity analysis confirms the robustness of these findings.
[Show abstract][Hide abstract] ABSTRACT: Whether critically ill human immunodeficiency virus (HIV)-infected patients are at risk of acquiring nosocomial infections and resistant or potentially resistant microorganisms (RPRMs) remains to be clarified. The aim was to compare the acquisition of RPRMs, infections and mortality in critically ill HIV-infected and non-infected patients. An observational, prospective cohort study of patients admitted to a medical intensive care unit (ICU) was undertaken. Swabbing of nares, pharynx and rectum, and culture of respiratory secretions were obtained within 48 h of admission and thrice weekly thereafter. Clinical samples were obtained as deemed necessary by the attending physician. Clinical variables, severity scores on admission and exposures during ICU stay were collected. Logistic regression was used to evaluate ICU mortality. Out of the 969 included patients, 64 (6.6 %) were HIV-infected. These patients had a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score on admission (19.5 ± 6.6 vs. 21.1 ± 5.4, p = 0.02), stayed longer in the care unit and were more exposed to several invasive devices and antibiotics. There were no differences in the rate of acquisition of RPRMs and the only difference in ICU-acquired infections was a significantly higher incidence of catheter-related bacteraemia (3 % vs. 9 %, p = 0.03). The ICU-related mortality was similar in both groups (14 % vs. 16 %, p = 0.70) and in HIV-infected patients, it tended to be associated with a lower CD4 cell count (p = 0.06). Despite a longer ICU stay, critically ill HIV-infected patients did not show a higher rate of RPRMs acquisition. The rate of ICU-acquired infection was similar between HIV-infected and non-infected patients, except for catheter-related bacteraemia, which was higher in the HIV-infected population. Mortality was similar in both groups.
European Journal of Clinical Microbiology 10/2013; · 3.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine whether the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)- or Cockcroft-Gault (CG)-based estimated glomerular filtration rates (eGFRs) performs better in the cohort setting for predicting moderate/advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD).
A total of 9521 persons in the EuroSIDA study contributed 133 873 eGFRs. Poisson regression was used to model the incidence of moderate and advanced CKD (confirmed eGFR < 60 and < 30 mL/min/1.73 m(2) , respectively) or ESRD (fatal/nonfatal) using CG and CKD-EPI eGFRs.
Of 133 873 eGFR values, the ratio of CG to CKD-EPI was ≥ 1.1 in 22 092 (16.5%) and the difference between them (CG minus CKD-EPI) was ≥ 10 mL/min/1.73 m(2) in 20 867 (15.6%). Differences between CKD-EPI and CG were much greater when CG was not standardized for body surface area (BSA). A total of 403 persons developed moderate CKD using CG [incidence 8.9/1000 person-years of follow-up (PYFU); 95% confidence interval (CI) 8.0-9.8] and 364 using CKD-EPI (incidence 7.3/1000 PYFU; 95% CI 6.5-8.0). CG-derived eGFRs were equal to CKD-EPI-derived eGFRs at predicting ESRD (n = 36) and death (n = 565), as measured by the Akaike information criterion. CG-based moderate and advanced CKDs were associated with ESRD [adjusted incidence rate ratio (aIRR) 7.17; 95% CI 2.65-19.36 and aIRR 23.46; 95% CI 8.54-64.48, respectively], as were CKD-EPI-based moderate and advanced CKDs (aIRR 12.41; 95% CI 4.74-32.51 and aIRR 12.44; 95% CI 4.83-32.03, respectively).
Differences between eGFRs using CG adjusted for BSA or CKD-EPI were modest. In the absence of a gold standard, the two formulae predicted clinical outcomes with equal precision and can be used to estimate GFR in HIV-positive persons.
[Show abstract][Hide abstract] ABSTRACT: The GESIDA and National AIDS Plan panel of experts have proposed "preferred regimens" of antiretroviral treatment (ART) as initial therapy in HIV infected patients for 2013. The objective of this study is to evaluate the costs and effectiveness of initiating treatment with these "preferred regimens".
An economic assessment of costs and effectiveness (cost/effectiveness) was performed using decision tree analysis models. Effectiveness was defined as the probability of having viral load <50copies/mL at week48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regime was defined as the costs of ART and its consequences (adverse effects, changes of ART regime and drug resistance analyses) during the first 48weeks. The perspective of the analysis is that of the National Health System was applied, only taking into account differential direct costs: ART (official prices), management of adverse effects, resistance studies, and determination of HLA B*5701. The setting is Spain and the costs are those of 2013. A sensitivity deterministic analysis was performed, constructing three scenarios for each regimen: baseline, most favourable, and most unfavourable cases.
In the baseline case scenario, the cost of initiating treatment ranges from 6,747euros for TDF/FTC+NVP to 12,059euros for TDF/FTC+RAL. The effectiveness ranges between 0.66 for ABC/3TC+LPV/r and ABC/3TC+ATV/r, and 0.87 for TDF/FTC+RAL and ABC/3TC+RAL. Effectiveness, in terms of cost/effectiveness, varies between 8,396euros and 13,930euros per responder at 48weeks, for TDF/FTC/RPV and TDF/FTC+RAL, respectively.
Taking ART at official prices, the most effective regimen was TDF/FTC/RPV, followed by the rest of non-nucleoside containing regimens. The sensitivity analysis confirms the robustness of these findings.
Enfermedades Infecciosas y Microbiología Clínica 08/2013; · 1.48 Impact Factor