Abstract
ObjectivesNo randomized controlled trials have yet reported an individual patient benefit of initiating combination antiretroviral therapy (cART) at CD4 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.MethodsIn a large cohort of HIV‐positive individuals, we investigated the emergence of new resistance mutations upon virological treatment failure according to the CD4 count at the initiation of cART.ResultsOf 7918 included individuals, 6514 (82.3%), 996 (12.6%) and 408 (5.2%) started cART with a CD4 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 CD4 count ≤ 350, 351–499 and ≥ 500 cells/μL, respectively. Only four (13.0%) individuals with a baseline CD4 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 CD4 count < 350 cells/μL.ConclusionsWe found no evidence of increased rates of resistance development when cART was initiated at CD4 counts above 350 cells/μL.
Highlights
It is hypothesized that earlier initiation of combination antiretroviral therapy (cART) in asymptomatic and otherwise healthy individuals may lead to poorer adherence and subsequently higher rates of resistance development
In a large cohort of HIV-positive individuals, we investigated the emergence of new resistance mutations upon virological treatment failure according to the CD4 count at the initiation of cART
We found no evidence of increased rates of resistance development when cART was initiated at CD4 counts above 350 cells/lL
Summary
Morbidity and mortality benefits of starting combination antiretroviral therapy (cART) at CD4 counts > 350 cells/lL have been reported in cohort studies [1,2], there is little randomized evidence on the individual risk–benefit ratio of initiating combination antiretroviral therapy (cART) at higher CD4 counts [3]. Randomized controlled Strategic Timing of AntiRetroviral Treatment (START) trial has recently investigated the optimal timing of cART initiation in order to improve morbidity and mortality outcomes in HIV-positive individuals [4]. As adherence to cART has been associated with perceived “need” for treatment [8], there is concern that a recommendation to start cART at higher CD4 counts may be met with patients’ ambivalence to cART, leading to suboptimal adherence and antiretroviral resistance. The START trial will investigate antiretroviral resistance development as a secondary endpoint, and will report these findings after 2016
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