Compared with START trial participants who deferred antiretroviral therapy, those who started immediately at a CD4 count above 500 reported better quality of life (QOL) by four measures during follow-up. QOL advantages with immediate treatment held true across demographic and clinical subgroups analyzed in this 35-country trial.
The START study randomized healthy antiretroviral-naive people with a CD4 count above 500 to two groups: those who received immediate treatment, and those who deferred antiretrovirals until their CD4 count fell below 350 or AIDS developed. After an average three years of follow-up, the immediate-treatment group had a 57% lower rate of serious events or death. Because QOL has emerged as "an important holistic measure assessing health" in the current antiretroviral therapy era, START investigators compared several QOL measures in the two study arms.
At regular intervals START participants completed standard questionnaires from which researchers derived four scores: visual analog scale (VAS) for perceived current health, general health perceptions, physical component summary (PCS), and mental component summary (MCS). The investigators used longitudinal mixed models adjusted for visit and baseline QOL to compare the immediate- and deferred-groups by intention to treat for changes in QOL through follow-up.
The analysis included 4,561 participants (97% of the START population) who had a baseline QOL assessment and at least one QOL follow-up measure. Median age was 36 years, 27% of participants were women, 48% white or other, 30% black, 14% Hispanic, and 8% Asian. More than half of participants (54%) lived in low/middle-income countries, and 46% lived in high-income countries. During a median follow-up of three years, the immediate-group used antiretrovirals 95% of the time, compared with 25% for the deferred group. Participants on treatment almost always reached a viral load below 200 copies/mL.
The four QOL measures did not differ significantly between study groups at the baseline measure. During follow-up, differences in all four measures significantly favored the immediate-group. Estimated differences were 1.9 for VAS, 3.6 for general health perception, 0.8 for PCS, and 0.9 for MCS. Modest but significant differences in QOL measures became apparent at the first follow-up visit, four months after baseline. VAS and general health perception improved in the immediate-treatment group and remained close to baseline in the deferred group. PCS scores remained stable in the immediate group through follow-up while falling in the deferred group. MCS improved in both groups.
When the START team analyzed QOL changes by subgroup (age, sex, race, geographic region, baseline CD4 count, baseline viral load, efavirenz or no efavirenz, Framingham cardiovascular risk, and baseline VAS), all QOL outcomes still favored the immediate-treatment group. Further analysis determined that improvements in CD4 count, even if statistically significant, had a minimal impact on QOL changes. Excluding people in whom a primary clinical event developed left between-group differences virtually unchanged.
The authors suggest a possible explanation for their findings may be that "deferred participants had a greater number of clinical symptoms and minor illnesses not meeting the criteria for clinical events, but reflected in poorer self-assessed physical QOL." Another possibility is that starting antiretrovirals "may have led to improvements in self-perceived emotional status in the immediate group." The START investigators believe their study "adds to the growing body of evidence that supports recommendations to start [antiretroviral therapy] as soon as possible after HIV diagnosis, irrespective of CD4+ cell count."