Virological failure and development of new resistance mutations according to CD 4 count at combination antiretroviral therapy initiation

Objectives No randomized controlled trials have yet reported an individual patient benefit of initiating combination antiretroviral therapy ( cART ) at CD 4 counts > 350 cells/μL. It is hypothesized that earlier initiation of cART in asymptomatic and otherwise healthy individuals may lead to poorer adherence and subsequently higher rates of resistance development. Methods In a large cohort of HIV ‐positive individuals, we investigated the emergence of new resistance mutations upon virological treatment failure according to the CD 4 count at the initiation of cART . Results Of 7918 included individuals, 6514 (82.3%), 996 (12.6%) and 408 (5.2%) started cART with a CD 4 count ≤ 350, 351–499 and ≥ 500 cells/μL, respectively. Virological rebound occurred while on cART in 488 (7.5%), 46 (4.6%) and 30 (7.4%) with a baseline CD 4 count ≤ 350, 351–499 and ≥ 500 cells/μL, respectively. Only four (13.0%) individuals with a baseline CD 4 count > 350 cells/μL in receipt of a resistance test at viral load rebound were found to have developed new resistance mutations. This compared to 107 (41.2%) of those with virological failure who had initiated cART with a CD 4 count < 350 cells/μL. Conclusions We found no evidence of increased rates of resistance development when cART was initiated at CD 4 counts above 350 cells/μL.