START trial - Bone density and Lung function sub-studies

Two sub-studies, which formed part of START trial, were presented this morning.

The first study looked at lung-function decline in the immediate versus deferred arms of the START trial. The authors acknowledge the emergence of COPD as a co-morbidity in HIV, with prior studies showing mixed results on the the effects of ART on COPD risk.

This sub-study involved approximately 1000 patients divided between immediate and deferred treatment arms. The median follow-up time was relatively short - just 2 years. No difference of FEV1 slope was detected between the study arms, in both smokers and non-smokers.

This study suggests immediate vs deferred ART has no impact on lung function decline in HIV with CD4 >500. Further longitudinal data continues to be collected on this study population.

The second START sub-study presented looked at the effects of immediate versus deferred ART on bone density (abstract not available at time of writing this post). 424 naive patients with CD4 counts over 500 were enrolled (206 in the immediate group, 218 in the deferred arm).

Bone mineral density (BMD) was assessed by DEXA at the hip and lumbar spine at baseline and annually. The median age was young, 32 years old, with 26% female patients. Osteoporosis and low BMD were lower than in other cohorts (3.3% and 38%, respectively).

Over the course of the follow-up, 37% of patients in the deferred arm ended up on treatment. In the immediate treatment arm, 79% were on tenofovir containing regimens. Controlling for variables, significantly greater BMD loss was seen at both the hip and spine in those randomised to immediate ART. This effect was most pronounced in the first year, after which point it stabilised. No difference in the development of osteoporosis was seen between groups (or fractures - as presented in the results from the full START study population).

Both of these studies were extremely well presented, as one would expect from such a large multi-centre, multi-national trial. The presenter of the lung function sub-study acknowledges that they do not anticipate significant differences between the two study arms at the 3 year mark.

Clearly smoking status remains the most significant risk factor for lung function decline in HIV-infected individuals, and our focus should remain on supporting smoking cessation in this group. As for the bone sub-study, with the advent of TAF, I suspect the relevance of this study and associated concerns, certainly in Australia, will be further diminished.