Background:  Little is known about the response to second line combined ART (cART), despite the fact that newly emerging therapies are likely to be initially aimed at this patient group. This study aims to describe the incidence and predictors of virological failure to second line cART in EuroSIDA. 

Methods:  All patients of EuroSIDA who started cART (≥3-drug-containing regimen) from ART-naïve, experienced confirmed virologic failure to this first regimen and subsequently started a second cART regimen were included. The time of starting ≥1 new drug as part of cART after a confirmed virologic failure of the first regimen was defined as baseline; CVF was defined as the time of the first of 2 consecutive viral loads >400 copies/mL ≥6 months after starting the first cART. Patient follow-up ended with the confirmed virologic failure of the second regimen or at the date of last available viral load. Kaplan-Meier curves were used to estimate the time to confirmed virologic failure and proportional hazards Cox regression (stratified by centre) to assess predictors of confirmed virologic failure.

Results:  Of 695 patients, 77% were male and 84% Caucasian with a median age of 38 years at baseline. The median baseline CD4 count was 275 cells/mm³ (IQR 165 to 417) and median baseline viral load was 4.24 log copies/mL (IQR 3.54 to 4.89). The median time from initiation of first cART to baseline was 26 months (IQR 16 to 42). The percentage of patients who had experienced virologic failure to 1, 2, and 3 classes before baseline were 2%, 79%, and 19%, respectively. Patients started their second regimen on average in 2001 with 2 nucleosides plus:  a NNRTI (n = 205, 29%), a single protease inhibitor (PI) (164, 24%), a PI/ritonavir (r) (196, 28%), abacavir (20, 3%), or other regimens containing >3 drugs (110, 16%); 31% started a single new drug class, 1% started 2 classes, and the remaining started ≥1 new drug within the same class. Overall, 310 patients (45%) experienced confirmed virologic failure on their second regimen and the Kaplan-Meier median time to failure was 39 months (95%CI:25 to 48). Factors independently associated with the risk of confirmed virologic failure to second cART are shown in the table.

Conclusions:  This study identified a high viral load at initiation, low predicted virological activity of the new drugs started, not achieving a viral load ≤400 on first cART and shorter time between initiating the first and second regimen as the main predictors of confirmed virologic failure to second cART. The latter 2 factors may reflect the fact that non-adherent patients failed quickly both regimens, though the role of adherence and drug resistance warrants further investigation.