Suchergebnisse

Purpose of the studyGood penetration of antiretroviral drugs to the seminal plasma may be associated with a decrease in viral replication and play an important role in the prevention of sexual transmission of HIV. We present data from a series of HIV‐infected ARV‐experienced patients receiving etravirine‐containing regimens, in whom etravirine concentrations and viral loads were determined in blood plasma and seminal plasma. The objective was to determine etravirine concentrations and HIV‐1 viral load (VL) in blood plasma (BP) and seminal plasma (SP) of HIV‐infected patients.MethodsTen HIV‐1 adult antiretroviral‐experienced patients receiving an etravirine‐containing regimen for at least 1 month were enrolled. Semen and blood samples were both collected around 12–24 h after the last etravirine dose, depending on once‐daily or twice‐daily dosing, respectively. HPLC/MS/MS was used to determine etravirine concentrations, and HIV‐1 VL was determined by real‐time PCR (limit of detection, VL 40 copies/mL).ResultsTen blood and twenty semen samples were collected. Median (range) CD4 count was 502 cells/mm3 (252–817) and median (range) BP VL was<40 copies/mL (40–362). Median (range) time on etravirine was 52 weeks (12–124). Median (range) BP etravirine concentration was 452.5 ng/mL (258–751). Median (range) SP etravirine concentration was 62.9 ng/mL (31.2–166), and values were above the protein‐free IC50 range (0.39–2.4 ng/mL) in all cases. Median (range) etravirine SP:BP ratio was 0.16 (0.07–0.26). SP VL was<40 copies/mL in all patients, whereas BP VL was detectable in one patient with poor adherence to treatment.












Patient
SP (ng/ml)
BP (ng/ml)
SP VL (copies/ml)
BP VL (copies/ml)
SP:BP
Concomitant ARV




1
31.2
375
<40
<40
0.08
DRVr/TDF


2*
57.1
307
<40
<40
0.18
3TC/ABC


3*
36.9
506
<40
<40
0.07
TDF/FTC


4*
60.6
399
<40
<40
0.15
3TC/ABC


5
68.1
258
<40
<40
0.26
LPVr/TDF


6*
104
414
<40
<40
0.25
3TC/ABC


7
107
491
<40
362
0.21
DRVr/TDF/FTC


8*
65.3
592
<40
<40
0.11
TDF/FTC


9
52.2
518
<40
<40
0.1
DRVr


10
166
751
<40
<40
0.22
TDF/FTC


Median
62.9
452.5
<40
<40
0.16






Patients taking ETR once a day.

ConclusionsTotal etravirine concentrations in male genital secretion are modest, reaching only 16% of the BP concentration, but nevertheless, more than 10 times above the wild type IC50 range.

Purpose of the studyFew clinical trials have compared non‐nucleoside reverse transcriptase inhibitors (NNRTI) and ritonavir‐boosted protease inhibitors (PI/r) as initial combined antiretroviral therapy (cART) for HIV‐1‐infected patients with high plasma viral load (pVL), and non‐conclusive results have been reported. We compared the effectiveness between NNRTI and PI/r as first‐line cART for HIV‐1‐infected patients with high pVL.MethodsObservational retrospective study of 664 consecutive treatment‐naïve HIV‐1‐infected patients with pVL (HIV‐1 RNA) >100,000 copies/mL who initiated NNRTI or PI/r‐based cART between 2000–2010 in three University hospitals. Only currently preferred or alternative regimens in clinical guidelines were included. Primary endpoint: percentage of therapeutic failures at week 48. Virologic failure was defined as: a) lack of virologic response (<1 log RNA HIV‐1 decrease in first 3 months); b) RNA HIV‐1 >50 c/mL at week 48; c) confirmed rebound >50 c/ml after a previous value <50 c/mL. Intent‐to‐treat (ITT noncompleter=failure) and on‐treatment (OT) analyses were performed.Results62% of patients initiated NNRTI‐regimens (83% efavirenz) and 38% PI/r‐regimens (62% lopinavir/). Baseline characteristics: male 83%; median age 39 yrs; median CD4 count: 212/µL (NNRTI 232 vs PI/r 177, p=0.028); pVL 5.83 log10 c/mL (NNRTI 5.43 vs PI/r 5.55, p=0.007); AIDS 24% (NNRTI 21% vs PI/r 29%, p=0.015). NRTI backbones were tenofovir plus 3TC or FTC in 72%. The percentage of therapeutic failure was higher in the PI/r group (ITT NC=F 26% vs 18%, p=0.012) with no differences in virologic failures (PI/r 5%, NNRTI 6%, p=0.688). The rate of treatment changes due to toxicity and/or voluntary discontinuations was higher in the PI/r group (15% vs 8%, p=0.008). A multivariate analysis adjusted for age, gender, CD4 count, VL and AIDS showed NNRTI vs PI/r as the only variable associated with treatment response (OR 0.61, 95% CI 0.41–0.88). Median pVL and rate of resistance at virologic failure were higher in patients receiving NNRTI (3.97 vs 2.49 log copies/mL, p<0.001 and 62% vs 12%, p=0.004, respectively).ConclusionsInitial NNRTI‐regimens showed higher effectiveness compared with PI/r‐regimens in HIV‐1‐infected patients with high pVL, although virologic failure rates were low and comparable. Resistance emergence was more frequent and pVL higher in patients failing NNRTI. However, more patients initiating PI/r‐based regimens changed or discontinued therapy.