Bone Changes in young men ages 18-22 enrolled in a PrEP safety and demonstration study using TDF/FTC

Day 1 of EACS always features a comorbidity workshop and this year all 5 of the presentations in the workshop were about bone loss.

The background to this of course is that in 2010 the metabolic sub-study of ACTG 5052 showed a 2-4% bone loss as measured by BMD over 96 weeks when naive patients commenced ART. Since then more studies have echoed this, we continue to worry about it and the pendulum has swung between how much of this is ART and how much is immune activation-reconstitution bone loss.

The current evidence base suggests it is mostly TDF, particularly when it is boosted and the robust evidence for this comes from studies such at TROP, PROGRESS and the newer naive and switch studies for TAF

The first presentation was a retrospective analysis of markers of bone turnover from 52 patients in the MACS cohort who initiated ART during seroconversion. Seroconversion is indeed a state of heightened immune activation and disturbances of bone markers having a net negative effect on bone formation were seen in both the seroconversion and ART initiation stages.

The other compelling argument for bone loss being driven by ART as opposed to immune activation is PrEP because these are men without either viraemia or immune activation. This brings us to the best presentation in the workshop which is the title above 

ATN 110 is an open label PrEP safety and demonstration study that enrolled 200 at risk young men who have sex with men (YMSM) in panamerican sites. 54% are black. DXA scans of the spine, hip and whole body (WB) were performed at baseline, 24 and 48weeks and adherence is assessed objectively using RBC TFV-DF levels in dried blood spots.

Interestingly baseline median BMD Z scores were below zero (spine -0.50, hip -0.45, WB -0.40). At week 24 there was a modest but significant decrease in BMD by WB (-0.61%, p<0.001). The iPrEx study also reported a similar bone loss.

What is good about this study however is, unlike iPrEx, it included stratification of the BMD analysis according to objective adherence. At week 48, a comparison was made between YMSM who had TFV-DP levels indicative of dosing 4 or more days a week and the subset that had levels below the level of quantification. Respective changes in BMD from baseline to week 48 in these subgroups were: spine -1.33% vs +1.54% (p<0.001); hip -1.68% vs 0.00% (p<0.001); WB -1.01% vs 0.34% (P=0.33)

So in conclusion there is a statistically significant TDF driven signal

In terms of clinical applicability however I think overall it is reassuring that there was no substantial bone loss from PrEP here. One could argue that 48 weeks is only a snapshot and what will accumulate with time but you have to remember that PrEP is not for life and does not share the same concerns as treating established HIV infection with TDF. Even in the case of naive HIV patents starting ART there seems to be some stabilization of the loss after 96 weeks and the fracture studies we have in HIV patients are based on population data which is subject to confounding such that we can't really say that any of this is tipping over into fractures.

Don't forget that bone is a very dynamic tissue as well with changes likely to be reversible with therapy change, not to mention lifestyle modification.

Additionally for our HIV patients the greatly reduced signals for bone of TAF over TDF in the naive and switch trials are really quite promising.

Putting my GP hat back on, the other interesting finding from this study is the baseline low BMD. Avoiding osteoporosis is still mostly about encouraging young people to reach their peak bone mass through adequate nutrition, tension loaded exercise and not smoking.

There is not much else to report back on today, it is opening ceremony day

There will be much more to report tomoz, here from sunny Barthththththththelona

CLINICAL APPLICABILITY OF THIS DATA: