Long‐term effectiveness of initiating non‐nucleoside reverse transcriptase inhibitor‐ versus ritonavir‐boosted protease inhibitor‐based antiretroviral therapy: implications for first‐line therapy choice in resource‐limited settings

Abstract

Introduction In many resource‐limited settings, combination antiretroviral therapy (cART) failure is diagnosed clinically or immunologically. As such, there is a high likelihood that patients may stay on a virologically failing regimen for a substantial period of time. Here, we compared the long‐term impact of initiating non‐nucleoside reverse transcriptase inhibitor (NNRTI)‐ versus boosted protease inhibitor (bPI)‐based cART in British Columbia (BC), Canada. Methods We followed prospectively 3925 ART‐naïve patients who started NNRTIs (N=1963, 50%) or bPIs (N=1962; 50%) from 1 January 2000 until 30 June 2013 in BC. At six months, we assessed whether patients virologically failed therapy (a plasma viral load (pVL) >50 copies/mL), and we stratified them based on the pVL at the time of failure ≤500 versus >500 copies/mL. We then followed these patients for another six months and calculated their probability of achieving subsequent viral suppression (pVL 500 copies/mL, they had a 20% lower probability of suppressing at 12 months than pVL‐matched bPI initiators (0.37 (0.29–0.45) vs. 0.46 (0.38–0.54)). In terms of evolving HIV drug resistance, those who failed on NNRTI performed worse than bPI in all scenarios, especially if they failed with a viral load >500 copies/mL. Conclusions Our results show that patients who virologically failed at six months on NNRTI and continued on the same regimen had a lower probability of subsequently achieving viral suppression and a higher chance of evolving HIV drug resistance. These results suggest that improving access to regular virologic monitoring is critically important, especially if NNRTI‐based cART is to remain a preferred choice for first‐line therapy in resource‐limited settings.

Keywords

• antiretroviral therapy
• viral suppression
• viral failure
• resistance
• NNRTI boosted PI
• cohort study