Suchergebnisse

BackgroundIn previous studies of protease inhibitor (PI) monotherapy, patients with higher nadir CD4 counts, baseline HIV RNA<1 copy/mL and high adherence to treatment have been most likely to show sustained HIV RNA suppression<50 copies/mL.MethodsIn the MONET trial, 256 patients with HIV RNA <50 copies/mL at screening switched to DRV/r 800/100 mg once daily, either as monotherapy (n=127) or with 2 NRTIs (n=129). HIV RNA results were classified as either<5 (no detection), 5–49 (virus detected under quantification limit) or >50 copies/mL. Treatment failure was defined as two consecutive HIV RNA levels >50 copies/mL (TLOVR) by Week 144, or discontinuation of study drugs. Additional analyses were conducted (i) excluding discontinuations for adverse events or other reasons (ii) including patients who intensified with NRTIs. Multivariate logistic regression was used to identify factors predictive of treatment failure by Week 144.ResultsBy Week 144, the percentage of patients with HIV RNA <50 copies/mL (ITT, TLOVR, Switch=Failure) was 69% versus 75% in the DRV/r monotherapy and triple therapy arms respectively. In the Switch Included analysis, HIV RNA <50 copies/mL was 84.0% versus 83.5% in the DRV/r monotherapy and triple therapy arms respectively. In the multivariate analysis for the TLOVR endpoint, positive HCV serology correlated with treatment failure (odds ratio [OR]=2.44, 95% CI 1.20–5.00). In the analysis including only virological endpoints, both positive HCV serology (OR=2.77, 95% CI 1.18‐6.67) and baseline HIV RNA >5 copies/mL (OR=2.71, 95% CI 1.21‐6.08) predicted treatment failure. In the Switch Included analysis, only HIV RNA >5 copies/mL was predictive of treatment failure (OR=2.78, 95% CI 1.28–6.01). Nadir CD4 count and prior PI use were not predictive of treatment failure in any analysis. In the ITT TLOVR analysis, the response rates in the DRV/r monotherapy arm at Week 144 were 79% (66/84) for HCV‐ve patients with baseline HIV RNA <5 copies/mL, 63% (12/19) for HCV‐ve patients with baseline HIV RNA >5 copies/mL, 47% (9/19) for HCV+ve patients with baseline HIV RNA<5 copies/mL and 20% (1/5) for HCV+ve patients with baseline HIV RNA>5 copies/mL.ConclusionsIn the MONET trial, patients without HCV co‐infection (based on serology), and with baseline HIV RNA <5 copies/mL by the Roche Amplicor assay (i.e. no virus detected) were most likely to show sustained HIV RNA suppression<50 copies/mL on DRV/r monotherapy.

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

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)

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.

Purpose of the studyTo investigate if boosted protease inhibitor monotherapy is associated with a higher risk of neurocognitive impairment (NCI).MethodsHIV‐infected patients from two hospitals in Madrid (Spain) without concomitant major neurocognitive confounders, currently receiving for ≥1 year lopinavir/ritonavir (LPV) or darunavir/ritonavir (DRV) as monotherapy or with two N(t)RTIs were included if they had prolonged (≥1 year) plasma viral suppression (<50 c/mL, single blip allowed). Patients underwent full neurocognitive assessment (7 domains) by two psychologists blinded to the treatment group. NCI was defined as per 2007 Frascati criteria using demographically adjusted normative scores. Rates of NCI and the association between NCI and boosted protease inhibitor monotherapy, adjusted by significant confounders, were analyzed. Two categories of monotherapy duration were considered: short‐term (1–2 years) and long‐term (2–9 years). We evaluated as potential confounding variables: demographics, HIV risk factor, AIDS, CD4 (nadir/current), smoking, alcohol/illicit drug use, prior medical, neurological and psychiatric disease, HCV coinfection, years of ART, prior blips, time with HIV viral suppression, type of protease inhibitor, lipids and HOMA index.Summary of results191 patients (89.5% Caucasian) were included (Table 1).










Triple therapy (n=95)
Monotherapy (n=96)
p value




Male. n (%)
70 (73.7)
70 (72.9)
0.91


Former IVDU. n (%)
30 (31.6)
34 (35.4)
0.85


MSM. n (%)
29 (30.5)
30 (31.3)
0.85


Age. Median (IQR)
44.7 (40.6–48.4)
47.4 (44.8–51.4)
<0.01


Years of education. Mean (SD)
11.3 (4.1)
10.4 (4.4)
0.13


Prior neurologic disease. N (%)
12 (12.6)
10 (10.4)
0.63


Prior psychiatric disease. n (%)
19 (20.0)
24 (25.0)
0.44


Current or past use of illicit drugs. n (%)
49 (53.6)
46 (47.9)
0.66


HCV coinfection (past or active)
43 (47.3)
43 (45.3)
0.54


Years of ART. Median (IQR)
10.7 (4.8–15.7)
14.1 (10.7–15.9)
0.01


Years of monotherapy. Median (IQR)
Not applicable
2.3 (1.7–3.2)
Not applicable


Years suppressed (<50 c/mL). Median (IQR)
4.8 (2.9–8.9)
7.5 (4.5–10.0)
<0.01


No prior blip
63 (66.3)
61 (63.5)
0.17


Currently on LPV. n (%)
70 (73.7)
53 (55.2)
<0.01


Currently on DRV. n (%)
25 (26.3)
43 (44.8)
<0.01


CPE score (2010). Median (IQR)
7 (7–7)
3 (3–3)
Not applicable


CD4 cell nadir. Median (IQR)
153 (49–255)
182 (76–288)
0.11


CD4 cell current. Median (IQR)
560 (440–754)
629.5 (476–845.5)
<0.05




Proportion (95% CI) with NCI: Overall: 27.2% (20.9–33.6, all asymptomatic or mild). Triple therapy: 31.6 (22.1–41.0). 1–2 years of monotherapy (n=40): 25.0 (11.3–38.7). 2–9 years of monotherapy (n=56): 21.4 (10.5–32.3) No differences in rates of NCI were found by treatment group (p=0.38). In our regression model confounding variables for NCI were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by those variables the odds ratio (95% CI) for NCI of patients receiving boosted protease inhibitor monotherapy monotherapy during 1–2 years was 0.85 (0.29–2.50) and for 2–9 years was 0.40 (0.14–1.15).ConclusionsBoosted protease inhibitor monotherapy, regardless of duration, was not associated with a higher rate of neurocognitive impairment than triple drug ART. These results call into question the ability of neuropenetrance scores to predict the neuroefficacy of antiretroviral regimens in HIV‐infected patients with adequate blood viral suppression.

Increasing scientific evidences indicate that agroforestry is a land use that can support economic, social and environmental sustainability, thus promoting resistance and resilience towards ongoing climate changes. The implementation and management of agroforestry systems still face social, economic and political barriers. Mediterranean agroecosystems suffer from increasingly negative climate change effects and urgent measures are needed to improve their rural economy while protecting soils and the environment. In this context, the LIFE Project Desert-Adapt: "Preparing desertification areas for increased climate change" (http://www.desert-adapt.it), aims to demonstrate the feasibility of innovative climate adaptation strategies and measures, based on the agroforestry concept, over 1000 hectares at risk of desertification in Italy, Spain and Portugal. The core of the project is the Desert Adaptation Model (DAM), an integrative development model fitted to the specific requirements of each farm which guide the implementation of sustainable agroforestry systems (e.g. montado, dehesa). The results will be evaluated through an array of multidisciplinary social, economic and environmental indicators. The project will deal with the most common conceptual, technical, and legal constraints encountered along the implementation and management of agroforestry systems in marginal lands and its results will fill the gap between farmers' needs and policy makers at local and global level.

Aim We describe the effectiveness and safety of the interferon-free regimen ombitasvir/paritaprevir/ritonavir plus dasabuvir with or without ribavirin (OBV/PTV/r ± DSV ± RBV) in a nationwide representative sample of the hepatitis C virus (HCV) monoinfected and human immunodeficiency virus-1/hepatitis C virus (HIV/HCV) coinfected population in Spain. Material and methods Data were collected from patients infected with HCV genotypes 1 or 4, with or without HIV-1 coinfection, treated with OBV/PTV/r ± DSV ± RBV at 61 Spanish sites within the initial implementation year of the first government-driven "National HCV plan." Effectiveness was assessed by sustained virologic response at post-treatment week 12 (SVR12) and compared between monoinfected and coinfected patients using a non-inferiority margin of 5% and a 90% confidence interval (CI). Sociodemographic and clinical characteristics or patients and adverse events (AEs) were also recorded. Results Overall, 2, 408 patients were included in the intention-to-treat analysis: 386 (16%) were patients with HIV/HCV. Patient selection reflected the real distribution of patients treated in each participating region in Spain. From the total population, 96.6% (95% CI, 95.8–97.3%) achieved SVR12. Noninferiority of SVR12 in coinfected patients was met, with a difference between monoinfected and coinfected patients of -2.2% (90% CI, -4.5% - 0.2%). Only genotype 4 was associated with non-response to OBV/PTV/r ± DSV ± RBV treatment (p<0.001) in the multivariate analysis. Overall, 286 patients (11.9%) presented AEs potentially related to OBV/PTV/r ± DSV, whereas 347 (29.0%) presented AEs potentially related to ribavirin and 61 (5.1%) interrupted ribavirin. Conclusions Our results confirm that OBV/PTV/r ± DSV ± RBV is effective and generally well tolerated in a representative sample of the HCV monoinfected and HCV/HIV coinfected population in Spain within the experience of a national strategic plan to tackle HCV.

The design, study conduct, and financial support for the study were provided by AbbVie (https://www.abbvie.com/). AbbVie participated in the interpretation of data, review, and approval of the manuscript. Medical writing and editing services were provided by Medical Statistics Consulting (MSC) and funded by AbbVie. ; Aim We describe the effectiveness and safety of the interferon-free regimen ombitasvir/paritaprevir/ritonavir plus dasabuvir with or without ribavirin (OBV/PTV/r ± DSV ± RBV) in a nationwide representative sample of the hepatitis C virus (HCV) monoinfected and human immunodeficiency virus-1/hepatitis C virus (HIV/HCV) coinfected population in Spain. Material and methods Data were collected from patients infected with HCV genotypes 1 or 4, with or without HIV-1 coinfection, treated with OBV/PTV/r ± DSV ± RBV at 61 Spanish sites within the initial implementation year of the first government-driven "National HCV plan." Effectiveness was assessed by sustained virologic response at post-treatment week 12 (SVR12) and compared between monoinfected and coinfected patients using a non-inferiority margin of 5% and a 90% confidence interval (CI). Sociodemographic and clinical characteristics or patients and adverse events (AEs) were also recorded. Results Overall, 2,408 patients were included in the intention-to-treat analysis: 386 (16%) were patients with HIV/HCV. Patient selection reflected the real distribution of patients treated in each participating region in Spain. From the total population, 96.6% (95% CI, 95.8-97.3%) achieved SVR12. Noninferiority of SVR12 in coinfected patients was met, with a difference between monoinfected and coinfected patients of −2.2% (90% CI, −4.5% - 0.2%). Only genotype 4 was associated with non-response to OBV/PTV/r ± DSV ± RBV treatment (p<0.001) in the multivariate analysis. Overall, 286 patients (11.9%) presented AEs potentially related to OBV/PTV/r ± DSV, whereas 347 (29.0%) presented AEs potentially related to ribavirin and 61 (5.1%) interrupted ribavirin. Conclusions ...