The advent of pre-exposure prophylaxis (PrEP) has prevented countless individuals from getting infected with HIV, but it’s only effective when taken consistently. Adherence to PrEP can be hard to maintain
though, as previous research has shown.
To measure adherence, researchers have largely relied on subjective measures, such as self-reported information. The limitations of this method have been well-documented, and highlight a discrepancy between what patients report and what is actually happening. Therefore, researchers are now turning toward more objective measures to accurately access their patients' adherence to PrEP.
In an oral abstract session at the 25th Conference on Retroviruses and Opportunistic Infections (CROI)
, Monica Gandhi, MD, professor of medicine and associate division chief of the division of HIV, Infectious Diseases, and Global Medicine at the University of California, San Francisco (UCSF), shared the results of a study which assessed pharmacologic measures of adherence
using human hair.
Hair has advantages over other pharmacologic measures used to assess adherence, such as plasma and urine levels (which only measure short-term adherence), and dried blood spots (which require some degree of intracellular metabolism of phosphorylation (eg, tenofovir or TFV/ emtricitabine or FTC).
“Occiput hair grows steadily at about 1 cm per month, [and so] the hair shaft can become a marker of time,” Dr. Gandhi explained. “One can perform segmental hair analysis where you take hair levels closest to the scalp to indicate [recent] adherence, and farthest from the scalp for more distal adherence.” She pointed out that hair samples are not only easy to collect, but they are also cheap to store as the samples can be stored and shipped at room temperature.
A previous study from Dr. Gandhi and her team, the AIDS Clinical Trials Group (ACTG) A5257 3-arm study, compared atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), and raltegravir (RAL)-based regimens in treatment-naïve HIV-positive patients. Follow-up was at 96 weeks after randomization of the last subject and the team assessed virologic failure (VF) as well as tolerability failures.
The initial results of the study showed that the RAL-based regimen proved superior to the other regimens for combined tolerability and virologic efficacy. The investigators then took their work a step further by turning to hair, in order to assess the relationship between hair levels of the assigned antiretroviral (ARV) and virologic outcomes for those enrolled in the treatment trial, for the first time.
According to Dr. Gandhi, the Hair Analytical Laboratory at UCSF has created assays that were peer-reviewed by the Clinical Pharmacology and Quality Assurance Program (CPQAIP)—which receives supported by the National Institute of Health’s Division of AIDS (DAIDS)—for the analysis of multiple ARVs in hair.
For the new study, hair was collected at weeks 4, 8, 16, and then, on a quarterly basis. Using liquid chromatography-mass spectrometry, the investigators measured ATV, DRV, and RAL concentrations in the hair samples. “The primary endpoint of this study was that ACTG5257-defined VF endpoint. Proportional hazards regression models estimated the association of ARVs in hair with VF,” Dr. Gandhi explained. “Taking a log of the most recently measured hair level divided by the within-arm median enabled us to model a common hair level effect across arms. We also examined the relationship of hair levels with tolerability.”
Data on hair and viral load were available for 2192 person-visits among 599 participants in the trial. Of the 599 participants, 32% were female, median age was 38, and 33% were African American; 17% were Hispanic. The median follow-up was 124 weeks.
“The rates of VF for 2 years were much higher (26%) for those who had a hair level in the lowest tertile compared to those who had hair levels in the middle and the highest tertiles; 26% versus 6% and 3% respectively,” Dr. Gandhi reported. “The hazard of VF for those who had hair ARV level in the lowest tertile was 6.8 times that of VF seen in those who had hair levels in the highest tertile.” There were similar results seen in both men and women.
The best place to collect hair from? The back of the head. “Don’t get it from the back,” Dr. Gandhi joked. “Acceptability as far as we can tell was about 55%. In other studies, acceptability has been higher, and the general trend is that there’s more acceptability in women over men who have sex with men (MSM) and in the African and Asian setting over the US setting.”
“Hair levels were the strongest independent predictor of virologic success in this treatment trial. This has been shown in cohort studies, but never in a randomized clinical trial,” she concluded. “Higher baseline viral load, being African American, and having a lower educational level, [were] all associated with VF, as had been observed in the parent study. And, as seen in multiple PrEP clinical trials at this point, there was a poor correlation between self-reported adherence and hair concentrations of the drug.”
Although risk pertaining to VF was high following a low hair level in this study, further research is needed to explore if early monitoring of hair ARV levels with subsequent targeted adherence interventions in HIV treatment could potentially reduce succeeding VF or even the development of resistance.
Feature Picture Source: ErrorTribune / flickr / Creative Commons.
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