Hair concentrations of atazanavir are associated with the success of HIV treatment

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Hair concentrations of the HIV protease inhibitor atazanavir (Reyataz) are strongly associated with suppression of viral load, US investigators report in the May 15th edition of Clinical Infectious Diseases.

“We reveal that antiretroviral concentrations in hair are the strongest independent predictor of virologic suppression,” comment the authors, “because low hair antiretroviral concentrations can predict virologic failure prior to its development, this measurement may be useful in designing interventions aimed at prolonging the durability of cART [combination antiretroviral therapy].”

Thanks to antiretroviral therapy many patients with HIV now have a normal prognosis. The goal of treatment is an undetectable viral load in blood, and to achieve this outcome it is necessary to maintain therapeutic levels of anti-HIV drugs in the blood.

Glossary

therapeutic drug monitoring (TDM)

The measurement of plasma drug concentrations in an effort to provide the most effective dosage with the least possible side-effects; TDM can help guide decisions regarding changes in drug dosing.

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

systemic

Acting throughout the body rather than in just one part of the body.

 

prognosis

The prospect of survival and/or recovery from a disease as anticipated from the usual course of that disease or indicated by the characteristics of the patient.

odds ratio (OR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 

A snap-shot impression of drug concentrations can be obtained using therapeutic drug monitoring, and checking adherence is also a useful measure of drug exposure. However, neither of these methods is perfect, involving either expensive laboratory tests, or relying on patient recall, which can be inaccurate. 

Research conducted by investigators from the Women’s Interagency HIV Study (WIHS) has previously shown that antiretroviral drug concentrations can be accurately monitored by analysing hair samples.

Now the same team of investigators wished to see how well atazanavir levels in hair predicted treatment outcomes.

“Levels of medications in hair reflect drug uptake from the systemic circulation over periods of weeks to months and capture average, as well as individual pharmacokinetic information,” explain the investigators. “A level measured in hair synthesizes adherence and pharmacokinetic variability over time to provide a robust exposure measure in a single assay.”

Their study involved 424 HIV-positive women, all of whom were taking antiretroviral therapy that included atazanavir, with or without a ritonavir booster.

Small hair samples were cut from close to the scalp, just below the crown of the head.

Using 2 mg of human hair, atazanavir can be detected at levels as low as 0.05 ng/ml, and ritonavir can be detected at a level of just 0.01 ng/ml.

The patients’ records were studied to determine how many achieved virological suppression (defined as a blood viral load below 80 copies/ml). A series of statistical analyses were then performed to see if suppression of HIV was associated with atazanavir levels in hair.

Most of the women (51%) were African American and had previous experience of therapy with a protease inhibitor (76%).

The patients contributed 1443 person visits during the study. Adherence above the target 95% was reported at 77% of these visits, and HIV was suppressed to below 80 copies/ml at 64% of visits.

Atazanavir concentrations in hair were divided into quintiles. The investigators found a strong association between hair levels of the drug and self-reported adherence (above 95% vs. below 95%; p < 0.001).

Viral load was suppressed in only 25% of visits in which hair concentrations of atazanavir were in the lowest quintile (below 0.658 ng/ml). In contrast, viral load was below 80 copies/ml in 87% of visits when levels of the drug were in the highest quintile (above 5.19 ng/mg).

The odds of patient having an undetectable viral load improved as hair concentrations increased. For patients in the top quintile the odds ratio (OR) was 63.3 (95% CI, 30.8-130.0; p < 0.001).

Factors associated with viral suppression included a pre-treatment viral load below 100,000 copies/ml compared to a higher viral load (OR = 3.2; 95% CI, 1.5-6.9; p = 0.02) and self-reported adherence above 95% compared to adherence below 75% (OR = 4.0; 95% CI, 1.9-8.6; p < 0.001).

However, the strongest predictor of a virologic response to therapy was hair concentrations of atazanavir in the highest quintile (OR = 59.8; 95% CI, 29.0-123.2; p < 0.001).

Results were similar when analysis was restricted to the 1132 person visits during which ritonavir was used to boost atazanavir.

There was an even stronger association between hair concentrations of atazanavir and resuppression of viral load in the subgroups of patients who had had poor adherence (OR = 210.0; 95% CI, 46.0-961.1); previous low hair levels (OR = 132.8; 95% CI, 26.5-666.0); or detectable viral load (OR = 400.0; 95% CI, 52.3-3069.7).

“Our models show that antiretroviral exposure as measured in hair far surpasses commonly used covariates to predict HIV treatment outcomes,” comment the authors.

They believe that analysis of drug levels in hair samples could help identify patients who are at risk of virologic failure.

“Hair measures in the clinical setting could…trigger interventions to correct adherence or low pharmacokinetic levels.”

The researchers also believe that monitoring hair samples has a number of advantages for both patients and healthcare providers.

“Hair collection is noninvasive and does not require specific skills, sterile equipment, or specialized storage conditions…[it] merely requires a pair of scissors, and storage is at room temperature.”

They conclude, “the results of the analyses presented here argue for the possibility of hair antiretroviral concentrations serving as a method of HIV therapeutic drug monitoring that may increase the durability of current antiretroviral regimens in a variety of settings.”

References

Gandhi M et al. Atazanavir concentration in hair is the strongest predictor of outcomes on antiretroviral therapy. Clin Infect Dis 52: 1267-75, 2011 (click here for the free abstract).