Determinants of Virological Failure after Successful Viral Load Suppression in First-Line Highly Active Antiretroviral Therapy

Abstract

Background

We aimed to investigate the long-term virological outcomes of a cohort initially showing good responses to first-line highly active antiretroviral therapy (HAART) with no evidence of virological failure during the first year after achieving viral load (VL) undetectability (<50 copies/ml).

Methods

Virological failure was defined as a confirmed VL>400 copies/ml or a single VL>400 copies/ml followed by a treatment change or end of follow-up. Risk factors for low-level VL rebound (50–400 copies/ml) in the first year after achieving undetectability and for virological failure during subsequent follow-up were investigated by logistic and Poisson regression.

Results

In the first year after achieving VL undetectability, 354/1,386 (25.5%) patients experienced low-level VL rebound, the remaining patients maintained consistent undetectability. Low-level rebound occurred less commonly with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART than with other regimens (P=0.01). Over median 2.2 (range 0.0–7.4) years of subsequent follow-up, 86 (6.2%) patients experienced virological failure, corresponding to 2.30 failures per 100 person-years (95% confidence interval [CI] 1.82–2.79). Independent predictors of virological failure included low-level rebound during the first year after achieving undetectability relative to consistent undetectability (rate ratio [RR] 2.18, 95% CI 1.15–4.10), female gender (RR 1.79, 95% CI 1.12–2.85) and receiving a ritonavir-boosted protease inhibitor (PI/r) relative to NNRTI-based HAART (RR 1.88, 95% CI 1.02–3.46).

Conclusions

Patients on first-line HAART who maintain consistent VL undetectability for 1 year have a low risk of subsequent virological failure. A subset might benefit from targeted interventions, including women and patients on PI/r-based HAART.