Plugging Hair ARV Levels as Adherence Biomarkers into HIV Prevention Trials

Investigator: Monica Gandhi, MD, MPH
Sponsor: NIH National Institute of Allergy and Infectious Disease

Location(s): Uganda


Our group has pioneered the use of small hair samples to monitor adherence to antiretroviral (ARV) therapy in HIV infection. We have demonstrated that hair concentrations of ARVs, which monitor long-term exposure, are stronger predictors of treatment success than self-reported adherence or plasma ARV levels in large cohorts of HIV-infected patients. Moreover, we have shown high sensitivity and specificity for tenofovir (TFV) detection in hair in a PrEP trial and have demonstrated a strong correlation between TFV dosing and TFV concentrations in hair. Recent data from HIV pre-exposure prophylaxis (PrEP) trials and prevention of mother to child transmission (PMTCT) settings indicate that adherence to prophylactic ARVs when assessed by more objective biomarkers of adherence (e.g. drug levels in plasma, peripheral blood mononuclear cells (PBMCs), breast milk, cord blood) is not always concordant with self report or other more traditional adherence measures, such as pill counts. Hair specimens are easy to collect, store and analyze, providing substantial feasibility, safety and accuracy advantages over other objective methods to monitor adherence, especially in resource-limited settings. This proposal seeks to extend our approach of using hair ARV levels to monitor adherence from the HIV treatment to the prevention setting, partnering with two large, ongoing NIH-funded global HIV prevention trials to further test our methodology in a cost-effective manner. Aim 1 adds hair measures for TFV and emtricitabine (FTC) adherence monitoring into the active oral arms of VOICE (Vaginal and Oral Interventions to Control the Epidemic), an ongoing MTN-sponsored PrEP trial in African women to assess the effectiveness and safety of oral TFV-based products or vaginal TFV gel in preventing HIV acquisition. Aim 2 adds hair measures for nevirapine (NVP) monitoring into the daily infant NVP prophylaxis arm of PROMISE BF (Promoting Maternal and Infant Survival Everywhere), a recently- launched IMPAACT-sponsored PMTCT trial in breastfeeding (BF) infants. We will analyze the relevant prophylactic ARV level(s) in hair in each trial once outcomes are available and analyze these hair levels as predictors for HIV seroconversion (aims 1A, 2A) and ARV toxicity (aims 1B, 2B) in multivariate models, comparing hair levels to self-report, pill counts and plasma ARV levels. We will also monitor hair TFV levels in women receiving vaginal TFV gel product to assess for systemic absorption (aim 1C) in VOICE and assess correlations between hair and breast milk ARV levels in the pharmacology sub-study of PROMISE BF (aim 2C). Finally, for Aim 3, we will develop a low-cost point-of care testing method to analyze ARV levels in hair and compare this assay to our validated and sensitive method using liquid chromatography/tandem mass spectrometry. At study completion, we expect to have validated hair levels of ARVs as a novel and practical biomarker of adherence which can easily be implemented into public health programs geared towards HIV prevention and prevention of maternal to child transmission.

HIV medications (antiretrovirals) taken by HIV-negative people can reduce the risk of getting HIV through sex in adults and through breastfeeding in infants. However, HIV-uninfected individuals may not be motivated to take medications every day. Recent clinical trials in HIV prevention have shown that HIV-negative people don't always tell investigators when they don't take the medications as prescribed, so ongoing prevention trials need more "objective" ways to measure adherence, such as measuring drug levels. We have proven that measuring antiretroviral levels in small cut pieces of scalp hair are excellent measures of drug adherence. Hair samples are easy to collect, store and analyze. Cutting small hair samples is painless and avoids drawing blood, a particular advantage in babies. This project will "plug" our hair measures into two ongoing large HIV prevention trials in Africa and India (one in women and one in infants) to more accurately measure adherence in these trials and in real-world HIV prevention programs. Our innovative way of monitoring medication levels in hair has public health relevance not only for HIV, but for many chronic disease states.