A novel immunoassay that measures urine tenofovir levels has high predictive utility and may adequately determine pre-exposure prophylaxis (PrEP) adherence and predict HIV protection, according to a study published in Clinical Infectious Diseases.

PrEP adherence among many populations has been proven to be challenging and self-reported adherence has limited accuracy. New tools and innovative approaches, especially those that enable real-time feedback, are needed to support PrEP adherence for individuals at risk for HIV. Researchers utilized a randomly-sampled, nested cohort of patients from the Partners PrEP Study (ClinicalTrials.gov identifier NCT00557245) to examine the efficacy of a novel urine assay in predicting HIV protection.

Partners PrEP Study is a randomized, placebo-controlled PrEP efficacy trial conducted among HIV serodiscordant couples in Kenya and Uganda. In total, 4432 participants assigned to receive either tenofovir disoproxil fumarate (TDF) or TDF/emtricitabine (FTC). Of these, 292 participants were included in the nested cohort. 

Participants contributed 722 paired urine and plasma samples. Urine samples were archived at visits that occurred at 3, 12, 24, and 36 months follow-up. These urine samples were measured for tenofovir concentrations using a quantitative enzyme-linked immunosorbent assay (ELISA) with the novel TFV antibody. Correlation between paired urine and plasma concentrations was assessed, and the sensitivity and specificity of detectable tenofovir in urine for determining detectable tenofovir concentrations in plasma was calculated. A nested case-control analysis was conducted to assess the association between urine tenofovir concentrations ³1500 ng/mL and protection from HIV acquisition.


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Results demonstrated that the urine immunoassay had many advantages to other available methods used to appraise PrEP adherence. Median tenofovir concentration was 37,500 ng/mL in the urine via ELISA and 65.4 ng/mL in plasmas via standard liquid chromatography/tandem mass spectrometry. Of the 558 plasma samples with detectable tenofovir, 486 had a paired urine sample with detectable tenofovir for a sensitivity of 87%. Of the 164 plasma samples with undetectable tenofovir, 119 had a paired urine sample with undetectable tenofovir for a specificity of 73%. Of the 468 individuals with plasma tenofovir >40 ng/mL, 420 had a paired urine sample with tenofovir ³1500 ng/mL for a sensitivity of 90%. Of the 254 samples that had tenofovir levels £40 ng/mL, 146 had a paired urine sample with tenofovir <1500 ng/mL for a specificity of 57%.

In the case-control study, 770 control samples from 280 individuals were matched to 22 case samples. Urine concentrations of tenofovir ³1500 ng/mL were associated with a 71% (95% CI, 30%-88%) reduction in HIV risk. Conversely, plasma concentrations of tenofovir >40 ng/mL were associated with an 87% (95% CI, 54%-96%) reduction in HIV risk.

“The urine immunoassay has been developed into a lateral flow assay, which is low-cost, easy to perform, can be administered at the [point of care], and provides results in minutes,” the researchers concluded. “This assay should be evaluated in a variety of populations for adherence monitoring and feedback.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Stalter RM, Baeten JM, Donnell D, et al; for the Partners PrEP Study Team. Urine tenofovir levels measured by a novel immunoassay predict HIV protection [published online June 22, 2020]. Clin Infect Dis. doi:10.1093/cid/ciaa785/5860911