Suchergebnisse

Purpose of the studyNNRTIs are commonly used to initiate HAART. Despite their demonstrated efficacy, tolerability and resistance issues could lead to a treatment change. The objective of the NEXT study was to evaluate the reasons for switching an initial non‐nucleoside based regimen in the clinical setting, and the alternative regimen selected.MethodsA retrospective multicentre study was undertaken between April and October 2009. Patients from 38 Spanish centres who had changed the initial EFV or NVP‐based regimen in the previous six‐month period were included. Social‐demographic and HIV‐related data was collected from medical records. Responsible physicians were interviewed about reasons for switching the non‐nucleoside and the alternative regimen of choice.Summary of resultsA total of 391 HIV‐1 infected patients had changed the initial EFV or NVP‐based regimen in the previous six months. Data were available for 316 (80.8%) of them. 245/316 patients received EFV as first line (77.5%). Median time to switch the NNRTI regimen was 16.9 months, shorter in case of EFV‐based regimen, 15.4 months, than NVP‐based regimen, 20.8 months. Most of changes were observed in the first month after initiation, representing 51.3% of the discontinuations, especially in case of EFV (57.1% EFV; 31% NVP). 9.2% of the patients switched due to chronic toxicity (after the first month of treatment). CNS toxicity was the most common reason for switching therapy in the acute term in 63% of the patients. Other tolerability issues that led to treatment discontinuation in the short term were lipid abnormalities due to EFV (4.1%) and liver enzyme elevations related to NVP (7%). Rash led to a similar rate discontinuation with both NNRTIs (12%). The second reason to discontinue the first‐generation NNRTI was virological/immunological failure in 40.5% of the patients (128/316). The new regimen selected was a boosted PI regimen in 52% of the cases, and was another NNRTI based regimen in 62.3%. Physicians marked safety/tolerability as the main reason for switching in 58.5% of cases (185/316).imageConclusionsIn the clinical setting, both acute and chronic intolerance/toxicity represents the main cause of the first line treatment change based on a first generation NNRTI, mainly EFV. CNS toxicity was the most common reason for switching therapy in the acute term. Therefore, the tolerability profile of the alternative regimen played a relevant role when switching regimens.

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

PurposeAmong traditional cardiovascular risk factors, dyslipidemia could be particularly prevalent since virus, treatment and host factors may be involved in its development. Our analysis aimed to describe the prevalence of different types of dyslipidemia in a population of HIV‐infected, treatment‐experienced patients in Spain.MethodsCross‐sectional analysis within 10 HIV units across Spain. We collected data on demographics and cardiovascular risk factors, including lipid profile as well as information on current use of lipid‐lowering drugs. This analysis describes subjects under first‐line ART as compared with others in more advanced lines of treatment.ResultsWe included 860 patients (76.3% male) with no history of CVD, with median age 45.6 years. Median time since HIV diagnosis was 3 and 14 years (p=0.000) and median time on ART was 22 and 136 months (p=0.000) respectively. Lipid profile is described in the table.









n (%)
First line regimens, n=219
Subsequent regimens, n=641
p‐value




Dyslipidemia


Total cholesterol >240 mg/dL
17 (7.9)
70 (11.1)
0.180


LDL‐cholesterol >160 mg/dL
19 (9.0)
49 (7.9)
0.636


HDL‐cholesterol <40 mg/dL
85 (39.9)
188 (30.0)
0.008


Total cholesterol/HDL ratio>5
60 (28.2)
160 (25.5)
0.447


Triglycerides≥200 mg/dL
43 (20.0)
136 (21.6)
0.616


Lipid‐lowering drugs


Statin use
10 (4.6)
101 (15.8)
0.000


Statin use AND Tcol/HDL>5
3 (33.3)
36 (36.0)
1.000


Fibrate use
7 (3.2)
12 (1.9)
0.286


Fibrate use AND TG≥200 mg/dL
3 (42.9)
9 (75.0)
0.326




ConclusionsDyslipidemia, especially low HDL and high TG, is highly prevalent in this population regardless being in their first or more advanced lines of treatment. The use of lipid‐lowering drugs in our population is low and furthermore the control of dyslipidemia is not always achieved. Additional research is needed to understand how to achieve lipid goals in this population.

PurposeHIV‐infected patients present an increased cardiovascular risk (CVR) of multifactorial origin, usually lower in women than in men. Information by gender about prevalence of modifiable risk factors is scarce.MethodsCoronator is a cross‐sectional survey of a representative sample of HIV‐infected patients on ART within 10 hospitals across Spain in 2011. Variables include sociodemographics, CVR factors and 10‐year CV disease risk estimation (Regicor: Framingham score adapted to the Spanish population).ResultsWe included 860 patients (76.3% male) with no history of CVD. Median age 45.6 years; 84.1% were Spaniards; 29.9% women were IDUs. Median time since HIV diagnosis for men and women was 10 and 13 years (p=0.001), 28% had an AIDS diagnosis. Median CD4 cell count was 596 cells/mm3, 88% had undetectable viral load. Median time on ART was 91 and 108 months (p=0.017). There was a family history of early CVD in 113 men (17.9%) and 41 women (20.6%). Classical CVR factors are described in the table. Median (IQR) Regicor Score was 3% (2‐5) for men and 2% (1–3) for women (p=0.000), and the proportion of subjects with mid‐high risk (>5%) was 26.1% for men and 9.4% for women (p=0.000).ConclusionsIn this population of HIV‐infected patients, women have lower cardiovascular risk than men, partly due to higher levels of HDL cholesterol. Of note is the high frequency of smoking, abdominal obesity and sedentary lifestyle in our population.










Men n=656
Women n=204
P value




Age (men >55 y, women >65 y) n (%)
72 (11.0)
8 (3.9)
0.002


Smoking, n (%)
358 (54.9)
110 (53.9)
0.805


Waist >102 cm (men), >88 cm (women), n (%)
84 (12.9)
55 (27.4)
0.000


Hypertension, n (%)
208 (31.8)
45 (22.2)
0.009


Diabetes, n (%)
50 (7.8)
11 (5.4)
0.262


Total cholesterol>240 mg/dL, n (%)
63 (9.8)
24 (11.9)
0.399


HDL‐cholesterol <40 mg/dL, n (%)
239 (37.5)
34 (16.8)
0.000


Total cholesterol/HDL >5, n (%)
197 (30.9)
23 (11.4)
0.000


Physical inactivity, n (%)
324 (56.7)
108 (69.2)
0.005

PurposeDue to the relative low age of HIV‐infected patients, Framingham risk score (FRS) usually estimates a low CVD risk. Lifetime risk estimations use the risk of developing CVD over the course of an individual's remaining lifetime and may be useful in communicating the risk of CVD to young patients. Our aim is to estimate the lifetime risk of CVD in a representative sample of HIV patients under antiretroviral therapy in Spain.MethodsCross‐sectional analysis in 10 HIV units across Spain, including information on demographics, HIV disease status, treatment history and cardiovascular risk factors of subject under ART. Lifetime CVD risk was calculated with the method of Berry et al, which classifies the lifetime risk in five mutually exclusive categories: 1. All risk factors are optimal; 2. At least one risk factor is not optimal; 3. At least one risk factor is elevated; 4. One major risk factor is present; and 5. Two or more major risk factors are present. Risk factors included are cholesterol level, blood pressure, diabetes and tobacco smoking. We grouped these five categories in two major groups, low‐risk (groups 1+2+3) and high‐risk category (groups 4+5). We calculated the prevalence of having a high lifetime risk, and its crude and aOR (adjusted by age, sex, place of origin, education level, transmission category, time since HIV diagnosis, CDC stage, current and nadir CD4 count, HCV coinfection, time on current and total ART, being on the first ART regimen, and PI vs. NNRTI regimen).ResultsWe included 839 subjects free of previous CVD disease: 72% men, median age 45.6y, median CD4 count 598 cells, median time since HIV diagnosis 11y, median time on ART 6.3y, 87% had undetectable VL. Estimated 10‐year CVD risk was low (<5%) in 78% of the patients, and intermediate (5–10%) in 20%. Lifetime risk estimation shows a high risk profile for 71.4% of the population studied (≥1 major risk factors). Factors significantly and independently associated with an increased lifetime risk were older age, non‐Spanish origin and longer time on ART. Adjusted OR for patients on ART longer than 10 years (vs<5 years) was 2.2 [95% CI 1.13–4.34]. No relationship was found with current or nadir CD4 lymphocyte counts, CDC stage C, HCV confection or type of ART.ConclusionsThere are significant disparities between the low 10y CVD risk estimated with FRS and the elevated lifetime risk in HIV patients on ART. Prolonged ART is associated with an increased CVD lifetime risk.

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

The major antiretroviral guidelines recommend starting ART in patients>50 y of age, regardless of CD4 cell count. However, no references to the preferred cART for these patients have been described. The combination FTC/TDF is one of the cornerstones of combined antiretroviral therapy (cART) in naïve patients. We studied the persistence of coformulated FTC/TDF in this scenario. National, retrospective cohort analysis of HIV‐infected patients>50 y at the time they began the first cART regimen (January 1, 2006 – December 31, 2009). Patients were selected in a proportion 2:1 to FTC/TDF vs. other NRTI regimens (no‐TDF). We compared the persistence of treatment in FTC/TDF users vs. no‐TDF (main groups). Among TDF users, we compared the persistence in PI vs. NNRTI users and in lopinavir/r vs. efavirenz users. Persistence was defined as the duration of the initial treatment; we analyzed time to any change or discontinuation according to initial regimen. We included 161 patients: median age: 54.6 y, 83% males, median CD4 count 191 cells/μl, median viral load 4.7 log, follow up: median 19 months, max 48 months. Of them, 112 started with FTC/TDF (53 with PIs, 57 with NNRTIs); and 49 with other NRTIs (no‐TDF) (22 with PI, 23 NNRTI). During the follow‐up period 79 patients (49%) modified their treatment, with statistically significant differences among groups, as shown in Table 1.*Adjusted by age, sex, transmission category and baseline CD4 count and viral load.In our study (antiretroviral‐naïve patients>50 y), the persistence of FTC/TDF regimens was significantly higher than other NRTI regimens. According to the third agent, there was a trend to a higher persistence with NNRTI vs. PI. This reaches statistical significance when we compare EFV vs. LPV/r. In the absence of randomized clinical trials, our data may contribute to a better understanding on how cART works in this ageing population, which is progressively increasing.

Proportion and hazard ratio of non‐persistence (any change or discontinuation of any component of initial cART), aOR adjusted by age, sex, transmission category and baseline CD4 count and viral load









Initial cART
Non‐persistence, N (%)
Log rank
Crude HR (95% CI)
Adjusted HR* (95% CI)




No‐TDF vs. TDF
35/49 (71.4) vs. 44/112 (38.6)
0.001
2.04 (1.31, 3.18)
2.10 (1.34, 3.29)


Among TDF users:






PI vs. NNRTI
26/53 (49.1) vs. 18/57 (31.6)
0.108
1.63 (0.89, 2.97)
1.63 (0.87, 3.06)


Lopinavir/r vs. efavirenz
19/35 (54.3) vs. 16/52 (30.8)
0.033
2.03 (1.04, 3.96)
2.05 (1.05, 3.99)

BackgroundSimplification of antiretroviral therapy (ART) may be an option for virologically suppressed patients for a variety of reasons. Etravirine (ETV) 400 mg qd has a good safety profile and retains activity against viruses resistant to nevirapine or efavirenz. Our objective was to evaluate the efficacy of ETV plus two nucleoside reverse transcriptase inhibitors (NRTIs) as a simplification strategy in treatment‐experienced virologically suppressed individuals with prior episodes of virological failure (VF) and presence of genotypic resistance mutations (GRM).MethodsEligible subjects were followed for ≥6 mo. Primary endpoint was proportion of patients remaining virologically suppressed using an ITT analysis. Genotypic sensitivity score (GSS) to new regimen was calculated according to Stanford resistance database.ResultsFourteen (10%) of 145 subjects switching to ETV+2NRTIs while virologically suppressed had a documented prior VF and presence of GRM and were included in the analysis. Median (range) number of previous episodes of VF to ART, NRTI‐containing regimen, to a NNRTI‐containing regimen and to a PI‐containing regimen were 4 (1–6), 2 (1–5), 1 (0–2) and 1 (0–2) respectively. Median duration of virological suppression before switching therapy was 22.5 months (1‐65). All patients switched from an effective PI‐containing regimen (8 LPV/r, 5 ATV/r and 1 DRV/r) to a qd regimen with ETV 400 mg plus Truvada® (n=12) or Kivexa® (2). 11/14 patients (79%) remained virologically suppressed at ≥6 mo. All of them had a GSS >1.5 to the new regimen and none had resistance to etravirine. Conversely 3/14 (21%) developed a VF at 1, 3 and 6 months respectively. All these 3 patients had a GSS ≤1.5 to the new regimen and 2 of them intermediate resistance to ETV (Y181C). No side effects were reported.ConclusionsOur results suggest that ETV plus 2NRTI could be a good strategy for simplification in virologically suppressed patients despite previous episodes of VF if the GSS to the new regimen is ≥1.5 and ETV remains active.

PurposeIn the last decade the prevalence of HIV‐infected patients≥50 years of age has increased. FTC/TDF is nowadays one of the cornerstones of cART in naïve patients, generally considered safe and well tolerated; nevertheless there is a continuous debate about the renal safety of TDF, due to the report of cases linking this treatment with renal failure and tubular dysfunction. In addition, there is a well‐recognized age‐related decline in renal function. Our aim was to describe the impact of cART regimen (FTC/TDF vs. others) on renal function of subjects who start cART at≥50 years old.MethodsNational, retrospective cohort analysis of HIV‐infected patients>50 y at the time they began the first cART (Jan 1, 2006 – Dec 31, 2009). Patients were selected in a proportion 2:1 to FTC/TDF versus other NRTI regimens (no TDF). For this analysis we excluded subjects taking potentially nephrotoxic drugs at baseline. We compared the impact of FTC/TDF vs. no‐TDF regimens (main groups) on renal function by means of the changes, during the first 12 months of treatment, in glomerular filtration rate estimated by the CKD‐EPI formula, and by the analysis of time to renal deterioration during the complete follow up (defined as progression to an EPI‐CKD value<60 mL/min/1.73 m2 in subjects with baseline values>60). We also compared these outcomes among FTC/TDF users, according to the third agent: PI vs. NNRTI, and lopinavir/r vs. efavirenz.ResultsWe included 125 patients, median age: 54.8 y, 82% males, median CD4 count 235 cells/µl, median viral load 4.7 log, follow up: median 19 months, max: 66 months. Of them, 82 started with FTC/TDF and 43 with other NRTIs (no TDF). During the follow‐up 13/125 patients taking FTC/TDF (11%) presented with renal deterioration. The Cox regression model including age, sex, transmission category, baseline CD4 count and viral load, FTC/TDF use, PI/NNRTI use, and LPVr/EFV use showed a hazard ratio for renal deterioration of 4.13 (95% CI 0.92, 18.5) for LPV/r users. The table shows the evolution of glomerular filtration rate, and proportion and risk of renal deterioration.ConclusionIn subjects starting cART after 50 years of age, we have not found significant changes in glomerular filtration rate associated with the use of FTC/TDF‐based regimens. Overall, the risk of renal deterioration was 4.1 times higher for LPV/r users (almost statistically significant). Among FTC/TDF users, this risk was 8 times higher for LPV/r as compared to EFV.










Overall
Among TDF users



No TDF vs. TDF/FTC
PI vs. NNRTI
LPV vs. EFV




Glomerular filtration rate by CKD‐EPI (mL/min/1.73 m2)


Baseline (median)*
91.6 vs. 93.7
90.7 vs. 95.7
93.7 vs. 95.8


Month 12 (median)*
98.0 vs. 95.1
89.2 vs. 96.7
71.2 vs. 97.8 (p < 0.05)


Renal deterioration:





Cases (n, %)
4/38 (10.5%) vs. 9/79 (11.4%)
5/33 (15.1) vs. 4/45 (8.9)
4/21 (19.0) vs. 3/40 (7.5)


Log rank (time to event)
0.883
0.278
0.055


Crude HR (95% CI)
1.09 (0.34, 3.55)
2.06 (0.54, 7.86)
3.96 (0.87, 17.93)


Adjusted HR** (95% CI)
0.60 (0.15, 2.35)
3.37 (0.76, 14.87)
8.20 (1.30, 51.75)





All comparisons between arms, and between baseline and month 24 were not statistically significant unless otherwise indicated.
Adjusted by age, sex, transmission category and baseline CD4 count and viral load.