Background. Due to the unintended potential misclassifications of the World Health Organization (WHO) immunological failure criteria in predicting virological failure, limited availability of treatment options, poor laboratory infrastructure and health care providers confidence in making switches, physicians delay switching patients to second-line antiretroviral therapy (ART). Evaluating whether timely switching and delayed switching is associated with the risk of opportunistic infections among patients with unrecognized treatment failure is critical to improve patient outcomes.

Methods. A retrospective review of 637 adolescents and adults meeting WHO immunological failure criteria was conducted. Timely and delayed switching to second-line ART were defined when switching happens at<3 and≥3 months respectively after failure diagnosis is made. Cox proportional hazard marginal structural models were used to assess the effect of switching to second-line ART on the risk of developing opportunistic infections.

Results. Of 637 patients meeting WHO immunological failure criteria, 396 (62.2%) switched to second-line ART. Of those switched, 230 (58.1%) were delayed. Switching to second-line ART reduced the risk of opportunistic infections (adjusted hazards ratio [AHR] 0.4, 95% CI 0.2 – 0.6). Compared to patients who received timely switch after failure diagnosis is made, those who delayed switching were more likely to develop opportunistic infections (AHR 2.2, 95% CI 1.1 – 4.3).

Conclusion. Delayed switching to second-line ART after failure diagnosis may increase the risk of opportunistic infections. Serial immunological assessment for switching patients to second-line ART is critical to improve their outcomes.