Suchergebnisse

Purpose of the studyEfficacy, toxicity and complexity of antiretroviral (ARV) regimens may impact the quality of life (QoL). Since over the past years the simplification approach of lopinavir/ritonavir (LPV/r) as monotherapy (MT) has been shown to be non‐inferior to triple therapy (TT) in virological and immunological efficacy, the objective of this study was to compare several health‐ and treatment‐related outcomes between both ARV strategies with LPV/r.MethodsA phase IV national, multicenter, controlled, randomized (2:1), open label, parallel‐group clinical trial to compare the QoL in patients on ARV TT containing any boosted protease inhibitor (PI), undetectable viral load (VL< 50 cop/mL) in the past 6 months and a CD4 nadir > 100 cells/µL, versus those who were simplified to LPV/r MT, for 24 weeks. QoL and health outcomes were evaluated by the Medical Outcomes Study HIV Health Survey (MOS‐HIV) and the five‐dimensional EuroQol questionnaire (EQ‐5D). Treatment satisfaction was assessed by the Spanish Questionnaire of Satisfaction with ARV Treatment (CESTA). Treatment adherence was assessed by the Spanish Multifactorial Adherence questionnaire (GEEMA) and a visual analog scale (VAS). Tolerability, safety and virological and immunological efficacy at week 24 were also analyzed.Summary of results225 patients from 29 sites were enrolled (MT: 146, 64.5%; TT: 79, 35.1%). Mean age (years) was 44.5 in MT and 45.2 in TT (p=0.745); mean duration (years) from HIV infection was 13.4 in MT and 12.8 in TT (p=0.587) and 71% were male in both arms. 87.6% of patients completed correctly the study (MT: 88.4%; TT: 86.1%; p=0.674). Health and treatment outcomes evaluated at final study visit are shown in figure 1 1. At study end, 84.1% in MT and 89.6% in TT had undetectable VL (p=0.313) and mean CD4 count were 742.8 cells/µL in MT and 646.5 cells/µL in TT (p=0.060). There were no significant differences in the percentage of patients with virological failure at week 24 as VL >50 cop/mL (MT: 8.2%; TT: 3.9%; p=0.271) and as VL >200 cop/mL (MT: 3.4%; TT: 0%; p=0.167).'Quality of life' impact: monotherapy vs triple therapy.imageConclusionsThe MT simplification strategy with LPV/r maintains comparable virological and immunological efficacy, as well as the tolerability profile, than the TT. The saving resulting from NRTIs withdrawal from the ARV regimen and the good results on QoL and patients treatment satisfaction make MT strategy with LPV/r be taken into account in clinical practice.

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.

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