Suchergebnisse

Atripla is a fixed‐dose drug combining FTC/TDF/EFV into a single pill and may increase adherence. To our knowledge, there is little data comparing the durability of Atripla vs. other regimens. Our first aim was to compare the durability of Truvada (TVD)/EFV or TVD/PIr or Atripla started when ART‐naïve, in terms of time to virological failure (VF first of 2 consecutive values>50 and>200 copies/mL), time to discontinuation of any drug in the regimens, or both. Then, we aimed to compare the incidence of virological rebound (VR)>200 copies/mL in patients (pts) currently receiving these same regimens after achieving a viral load (VL)≤80 copies/mL. Pts in the Icona Foundation Study who started for the first time a cART regimen with TVD/EFV or TVD/PIr or Atripla, either while ART‐naïve (analysis 1) or while with a VL≤80 (analysis 2) were included. In analysis 1, pts' follow‐up accrued from cART initiation to the date of the event (VF or discontinuation of any drug in the regimen) or to the date of last available visit/VL. In the TVD/EFV group a switch to Atripla was not counted as an event. Survival analysis employing KM curves and Cox regression model was used. In analysis 2, follow‐up accrued from the date of first VL≤80 (which could be achieved with any cART) to VR or last VL and only person years (PY) on the regimens of interest were considered. Rates were calculated as number of VR per 1000 PY and relative rates (RR) compared using a Poisson regression model. In analysis 1, 515 pts starting TVD/EFV, 1001 TVD/PIr and 160 Atripla when ART‐naïve on average in 2010 (IQR: 2008–2011) were included. PI/r were LPV (33%), ATV (38%) fos‐APV (4%) and DRV (24%). Median age was 38 years, 19% females, 40% heterosexuals. Pts starting Atripla were younger, less likely to be female, IDU, HCV co‐infected, to have AIDS and they had higher CD4 count (334 vs. 280). By 2 years, 48% (95% CI: 43–53) of those initiating TVD/PIr experienced the composite endpoint of VF or drug discontinuation vs. 20% in the other groups (p=0.0001). Median time to switch from TVD to Atripla in the EFV group was 17 months (95% CI: 12–23). The table shows the results of the Cox regression analysis. In analysis 2 (n=1,425), the rates of VR were 16.8 per 1000 PY for TVD/PIr, 11.17 for TVD/EFV and 5.3 for Atripla (adjusted RR vs. TVD/PIr=0.51, 95% CI: 0.19–1.34). Durability of Atripla was comparable to that of TVD/EFV and potentially longer than that of TVD/PIr. Unmeasured confounding cannot be ruled out.












Crude and adjusted relative hazards from fitting a Cox regression


Outcomes
No. with event (%)
Crude RH (95% CI)
p‐value
Adjusted* RH (95% CI)
p‐value




VL>50 copies/mL


Truvada+PI/r
131 (13%)
1.00

1.00



Truvada+EFV
54 (10%)
0.60 (0.43,0.83)
0.002
0.61 (0.42,0.89)
0.009


Atripla
8 (5%)
0.66 (0.32,1.37)
0.265
1.15 (0.54,2.48)
0.716


Stop of any drug







Truvada+PI/r
322 (32%)
1.00

1.00



Truvada+EFV
79 (15%)
0.37 (0.29, 0.47)
<.001
0.33 (0.25,0.44)
<.001


Atripla
23 (14%)
0.50 (0.32,0.77)
0.002
0.50 (0.31,0.80)
0.004


VL>200 copies / mL or stop of any drug


Truvada+PI/r
314 (31%)
1.00

1.00



Truvada+EFV
84 (16%)
0.39 (0.31,0.50)
<.001
0.37 (0.28,0.49)
<.001


Atripla
23 (14%)
0.52 (0.33,0.80)
0.003
0.57 (0.35,0.91)
0.017





*adjusted for age, gender, nation of birth, mode of HIV tranmission, hepatitis co‐infection status, AIDS diagnosis, baseline CD4 count and viral load an year of starting cART and stratified by clinical centre

Complexity of antiretroviral treatment (ART) is a reason for non‐adherence and may impact treatment outcome. The association between daily dosing and pill burden and chance of virological success (VS) of first ART has been rarely assessed. 3,674 naïve patients who started treatment after January 2000 were identified from the ICoNA cohort. Number of daily doses and pills were estimated on the basis of the drugs used to rank first ART complexity: 1–2 daily pills once a day (low‐pills QD [lpQD]); 3–6 daily pills QD (high‐pills QD [hpQD]); 2–5 daily pills BID (low‐pills BID [lpBID]); >6 daily pills BID (high‐pills BID [hpBID]). VS was the date of first HIV RNA <50 cp/ml. Follow‐up was censored at the date of VS or last available HIV RNA. Kaplan‐Meier curves estimated probability of achieving VS according to ART complexity. Univariable and multivariable Cox regression stratified by clinical site was used to identify variables associated with VS. ITT principle was applied, using competing risk approach for death. Population: male 75%; median age 37 y (IQR, 32–44); HIV transmission heterosexual 43%, homosexual 33%, drug use 16%; Italian origin 86%; CDC group C 17%; median pre‐ART CD4 and log HIV‐RNA were 271/mm3 (range, 0–1672) and 4.84 cp/ml (1.70–6.38), respectively. Regimens were started in '00–'02 24%,'03–'05 17%,'06–'08 17%,'09–'12 42% and based on NNRTI in 40%, PI/r 43%, PI 8%, other ART 10%. Frequencies in complexity ranks were: 19% lpQD, 23% hpQD, 32% lpBID, 26% hpBID. VS was achieved by 85% of patients with an overall median time to VS of 5.6 months (95% CI: 5.4–5.8). Median months to VS were shorter with decreasing complexity: hpBID 6.5; lpBID 6.0; hpQD 5.3, lpQD 4.5. Kaplan‐Meier curves are shown (Figure).imageAfter stratifying for clinical site and adjusting for age, gender, origin, transmission route, CDC group C, HCV/HBV infection, years of HIV, pre‐cART CD4 and HIV‐RNA, type of regimen a significantly reduced likelihood of achieving VS was found for ART complexity (hpQD: HR 0.76 95% CI 60–0.96; lpBID: 0.74, 0.59–0.94) when compared with lpQD. The chance of VS was higher in people starting ART more recently (RH 1.28 [95% CI 1.09–1.51] for '03–'05; RH 1.64 [1.27–2.10] for '09–'12; vs. '00–'02) and was lower in people with previous AIDS (RH 0.85 [0.73–0.98]). Once‐a‐day dosing of ART, especially when combined with low daily pill burden, seems to be one of main factors contributing to the higher rate of success of ART in recent years.