Protease inhibitor levels in hair can predict success of HIV treatment

In a study published in the February 20^th edition of AIDS, US researchers report that levels of some antiretroviral drugs in head hair samples are a strong predictor of the success of HIV treatment.

The researchers suggest that hair samples could provide a cheap and acceptable method of monitoring the success of HIV treatment, particularly in resource-limited settings.

Antiretroviral therapy can mean a longer and healthier life for HIV-positive patients. However, for such treatment to work, it is essential that patients take their treatment correctly. It is difficult to accurately assess adherence, and blood tests to measure levels of antiretrovirals in the blood (therapeutic drug monitoring) have had inconsistent results.

Many drugs are incorporated into the hair as it grows and earlier research has suggested that it is possible to monitor levels of the now rarely used protease inhibitor indinavir (Crixivan) in this way.

Investigators from the US Women’s Interagency Health Study (WIHS) wished to establish the relationship between concentrations of the commonly used protease inhibitors lopinavir/ritonavir (Kaletra) and atazanavir (Reyataz) with ritonavir in hair and the outcome of HIV treatment.

All the women were starting a treatment with these drugs for the first time. The study population included 70 women who were receiving treatment with Kaletra and 154 women taking atazanavir/ritonavir. The racial/ethnic origins of the women were representative of the wider HIV epidemic amongst US women (60% African American, 23% Hispanic, 17% white).

Small samples of hair, cut from below the top layer so as not to cause a change in appearance, were obtained to measure drug levels.

For the purposes of the study, successful HIV treatment was defined as a viral load below 50 copies/ml (an undetectable viral load). A total of 74% of women taking Kaletra and 79% treated with atazanavir/ritonavir achieved this outcome.

Concentrations of Kaletra were significantly higher in the women experiencing successful treatment with this drug than women who had had a detectable viral load (median, 1.58 vs 0.290ng/mg, p = 0.0008). This was also the case as regards atazanavir/ritonavir levels (median 2.60 vs 0.669ng/mg, p < 0.0001).

Further analysis was then conducted by the investigators. They found that other factors associated with the success of Kaletra were a lower viral load before treatment was started (p = 0.042) and a CD4 cell count above 200 cells/mm³. However, the strongest single predictor of successful treatment with Kaletra was the level of the drug in the hair (p = 0.006).

Factors associated with successful atazanavir/ritonavir therapy included self-reported adherence of at least 95% (p = 0.042) and a pre-treatment CD4 cell count above 200 cells/mm³ (p = 0.036). But, once again, the strongest predictor was levels of the drug in hair (p = 0.003).

“In a cohort of HIV-infected women initiating new protease inhibitor-based combination regimens, the strongest independent predictor of virologic response…was hair concentrations of the anchor drug,” write the investigators.

They note that the taking of hair samples was highly acceptable to women in the study, adding that the test was “simple and inexpensive”.

The investigators believe “assessing hair exposure to antiretrovirals in resource-constrained settings may be cost-effective when HIV RNA quantification is too expensive for routine monitoring.”

Lead researcher, Dr Monica Gandhi commented, "This is a painless, bloodless, biohazard-free method of collecting a stable specimen from HIV patients that may allow for the monitoring of levels of antiretroviral drugs absorbed over time and the prediction of treatment success." She added that their next priority was to assess the method in resource-limited settings, "where blood collection and viral load monitoring may be expensive and difficult. Not only could this method help in measuring pill-taking, but its strong correlation with viral suppression could allow its use as an inexpensive, non-invasive method of monitoring treatment success in particularly challenging settings."

Dr Gandhi also told aidsmap.com that the test might also be used to measure levels of nevirapine, commenting "we are particularly interested in this application given the widespread use of nevirapine in the resource-poor setting, both for the prevention of mother-to-child transmission and for treatment, and are working on collaborations now to study the utility of hair levels of nevirapine in an African setting."