Antiretroviral drug
levels in a sample of hair were the strongest predictor of response to HIV
treatment, and this method also holds promise for monitoring adherence to
pre-exposure prophylaxis (PrEP), according to research presented at the 25th
Conference on Retroviruses and Opportunistic Infections (CROI 2018) this week
in Boston.
It is well know that medication
adherence is key to achieving the benefits of antiretroviral therapy (ART) or
PrEP. But taking medications as directed can be challenging, and PrEP trials
have shown that patient-reported adherence does not always correspond to
measured drug levels.
Dr Monica Gandhi of the University of California at San Francisco and colleagues looked at the
association between drug levels in hair and virological treatment outcomes in
the ACTG A5257 trial. This study compared ART regimens containing atazanavir/ritonavir
(Reyataz), darunavir/ritonavir (Prezista) or raltegravir (Isentress), all with tenofovir
DF/emtricitabine (the drugs in Truvada),
in people receiving HIV treatment for the first time.
Antiretroviral drug levels in hair
samples are a reflection of adherence over time, Gandhi explained. Drug levels can be measured in blood and in some cases in urine, but this
only gives information about levels shortly before testing. Measuring drug
levels within cells – where antiretrovirals must reach to be effective – is more complex.
Hair testing avoids the
"white coat" effect, in which an individual could take their
medication inconsistently but do so before a medical appointment, Gandhi said.
In addition, hair is easy and cheap to collect and samples can be stored and
shipped at room temperature without biohazard precautions. However, hair
testing currently must be performed in a lab and cannot be done in "real
time" while a patient waits.
This analysis used liquid
chromatography to measure atazanavir, darunavir or raltegravir levels in a single
hair sample, which reflects average adherence over time. She noted that segmental
analysis, as used in forensics, can assess drug exposure at different points in
time by comparing levels in hair segments near the scalp and those further
away, but that was not done in this study.
Viral load and hair data were
available for 599 study participants, obtained at 2192 visits over a median
follow-up period of 217 weeks. About two-thirds were men, a third were black,
17% were Latino and the median age was 38 years.
Hair samples were collected at
weeks 4, 8, 16 and then quarterly during the study. Participants were asked to
provide a sample of hair cut from the scalp; the hair root is not needed for
testing, so plucking an entire strand is not necessary. Over half of
participants (55%) agreed to give a hair sample. Gandhi noted that gay men were
more likely to decline because they didn't want to disrupt their
hairstyle.
Across all three drug regimens,
the rate of virological failure at two years – meaning a detectable viral load – was
3% for people with hair drug levels in the highest third, or tertile, and 6%
for those in the middle tertile, but rose to 26% for those in the lowest
tertile. Even a short period of non-adherence, reflected in a single low hair drug
level, could affect adherence, Gandhi said.
In fact, having a low hair drug
level was the strongest independent predictor of treatment failure. People with
the lowest levels were 6.8 times more likely to have detectable HIV than those
with the highest levels. For every twofold decrease in hair drug levels, the
risk of virological failure more than doubled.
This pattern was similar across
the three drugs and held after adjusting for self-reported adherence and other
factors. The correlation between self-reported adherence and measurable drug
levels in hair samples was weak, Gandhi said, underscoring the limitations of
self-reporting.
The analysis included people
with processed, coloured, permed, straightened and bleached hair. Hair procedures generally didn't
interfere much with drug level measurement, but bleaching had the greatest
effect, Gandhi noted. The relationship between hair drug levels and viral
suppression did not differ by race or ethnicity.
This testing method can be used
even on very short scalp hair, but if a person is bald, eyebrow or pubic hair
that doesn't grow over time is not recommended, Gandhi said at a CROI press
briefing.
The researchers concluded that further
study is warranted to see whether early monitoring of hair drug levels,
followed by targeted adherence interventions for those with low levels, could
help reduce virological failure.
Segmental hair testing that
looks at drug level changes over time holds promise for analysing HIV
seroconversion among people taking PrEP, as done in another study presented at
the conference.