CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Methods: We developed a semi-quantitative urine assay using liquid chromatography mass spectrometry with high sensitivity/specificity for TFV. This assay allowed us to determine TFV concentrations in log categories between <10 ng/ml to > 10,000 ng/ml. To clinically validate the assay we conducted 3 cohort studies: 1) A cross sectional study of 10 HIV positive subjects with undetectable HIV viral loads on a TFV-based regimen to evaluate the qualitative relationship of urine TFV levels to plasma levels, 2) A single dose study of TDF/FTC in 10 healthy subjects to evaluate TFV clearance in plasma and urine over 7 days, 3) A 16 week study of 10 HIV negative subjects receiving daily PrEP to evaluate concordance between plasma and urine over time. Results: Cohort 1 demonstrated 100% concordance between presence of TFV in plasma and urine (PPV 100%, 95% CI, 0.63-1.0; NPV 100%, 95%CI, 0.05-1.0). TFV concentration was 3-4 logs higher in urine than plasma. In cohort 2, TFV was detected for >7 days in urine and 2-4 days in plasma after a single dose of TDF/FTC. Urine TFV was cleared in a log-linear fashion, with a direct correlation of urine levels to time since last dose. The urine assay was 2 logs more sensitive than serum over 7 days. In cohort 3, TFV was detected in 93% of urine samples (concentration range: >10 to >10,000 ng/mL) and 74% of plasma samples (concentration range: >10 ng/ml to >100 ng/ml). Urine TFV concentration > 1000 ng/ml was highly predictive of presence of TFV in plasma (>10 ng/ml) (PPV 0.88, 95%CI, 0.69-0.97; NPV 0.88, 95%CI, 0.47-0.99), suggesting that the urine assay could be used to distinguish between recent adherence as defined by a dose of TFV within 48 hours (>1000 ng/ml), low adherence (>10 to >100 ng/ml), and non-adherence as defined by last dose more than one week prior (<10 ng/ml).

Conclusions: We provide proof-of-concept that a semi-quantitative urine assay measuring levels of TFV could be further developed into a point of care test to monitor adherence to PrEP. 976 Comparison of Adherence Measures in a Clinical Trial of Preexposure Prophylaxis Davis C. Muganzi 1 ; Jessica Haberer 2 ;Yap Boum 1 ; Nicholas Musinguzi 1 ; Allan Ronald 4 ; Connie Celum 3 ; Jared Baeten 3 ; David R. Bangsberg 4 1 Mbarara University of Science and Technology, Kampala, Uganda; 2 Massachusetts General Hospital, Harvard Medical School, Boston, MA, US; 3 University of Washington, Seattle, WA, US; 4 University of Manitoba, Winnipeg, Canada Background: No gold standard exists for adherence measurement. Self-report is commonly used but it is subjective. Objective measures are more costly and difficult to implement. Research is limited on the performance of these measures for pre-exposure prophylaxis (PrEP) against HIV infection. Methods: The Partners PrEP Ancillary Adherence Study collected the following adherence measures in 1,147 HIV-uninfected partners in serodiscordant couples from 3 Ugandan sites in the Partners PrEP Study (a randomized placebo-controlled trial of tenofovir-based PrEP collected).: Monthly self-report Rating- “How well have you taken your study tablets?” Frequency- “How often do you take your study tablets?” Percent- “What percent of the time were you able to take your study tablets?” Objective measures Electronic monitoring (MEMS, downloaded monthly) Unannounced pill counts (UPC, performed monthly at home) Plasma tenofovir level (month 6 in a randomly selected subset of 228 participants on active drug) Rating and frequency responses were recorded on a 6-point Likert scale and converted to percents (e.g., most of the time=80%). Monthly adherence over 6 months was compared by Spearman correlation and to tenofovir level (detectable >0.32ng/ml) by regression analysis with the Huber White sandwich variance estimator. Results: A total of 1,143 individuals were included in the analysis; median age 34 (IQR: 30-40), 606 (53%) were male. Median (IQR) adherence by each measure was as follows: rating 90% (83-93), frequency 93% (90-97), percent 97% (93-98), MEMS 97% (91-99), and UPC 98% (96-99). Correlations among self-report measures ranged from 0.61-0.67 (p<0.001). Correlations of self-report measures ranged from 0.31-0.36 with UPC (p<0.001) and 0.23-0.25 with MEMS (p<0.001). Comparisons of adherence levels with detection of tenofovir are shown in Figure 1.

Poster Abstracts

578

CROI 2015