title: Accuracy of Self-Report and Pill-Count Measures of Adherence in the FEM-PrEP Clinical Trial: Implications for Future HIV-Prevention Trials.
abstract: Oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) has been evaluated as pre-exposure prophylaxis (PrEP). We describe the accuracy of self-reported adherence to FTC/TDF and pill counts when compared to drug concentrations in the FEM-PrEP trial. Using drug concentrations of plasma tenofovir (TFV) and intracellular tenofovir diphosphate (TFVdp) among a random sub-sample of 150 participants assigned to FTC/TDF, we estimated the positive predictive value (PPV) of four adherence measures. We also assessed factors associated with misreporting of adherence using multiple drug-concentration thresholds and explored pill use and misreporting using semi-structured interviews (SSIs). Reporting use of ≥1 pill in the previous 7 days had the highest PPV, while pill-count data consistent with missing ≤1 day had the lowest PPV. However, all four measures demonstrated poor PPV. Reported use of oral contraceptives (OR 2.26; p = 0.014) and weeks of time in the study (OR 1.02; p < 0.001) were significantly associated with misreporting adherence. Although most SSI participants said they did not misreport adherence, participant-dependent adherence measures were clearly unreliable in the FEM-PrEP trial. Pharmacokinetic monitoring remains the measure of choice until more reliable participant-dependent measures are developed.
authors.affiliation: Impact Research and Development Organization, P.O. Box 9171-40141, Kisumu, Kenya, mamagifto@yahoo.com.
authors.forename: Kawango
authors.initials: K
authors.lastname: Agot
authors.forename: Douglas
authors.initials: D
authors.lastname: Taylor
authors.forename: Amy L
authors.initials: AL
authors.lastname: Corneli
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Julie
authors.initials: J
authors.lastname: Ambia
authors.forename: Angela D M
authors.initials: AD
authors.lastname: Kashuba
authors.forename: Caleb
authors.initials: C
authors.lastname: Parker
authors.forename: Ansley
authors.initials: A
authors.lastname: Lemons
authors.forename: Mookho
authors.initials: M
authors.lastname: Malahleha
authors.forename: Johan
authors.initials: J
authors.lastname: Lombaard
authors.forename: Lut
authors.initials: L
authors.lastname: Van Damme
mesh_terms: D000225:Adenine / Q000097:blood / Q000627:therapeutic use*; D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D007407:Interviews as Topic; D007630:Kenya; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D065129:Pre-Exposure Prophylaxis; D011237:Predictive Value of Tests; D036301:Qualitative Research; D057566:Self Report; D000068698:Tenofovir / Q000097:blood* / Q000627:therapeutic use; D016896:Treatment Outcome; D016903:Drug Monitoring
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine
references.citation: PLoS Clin Trials. 2007 May 25;2(5):e27
references.pmid: 17525796
references.citation: PLoS Med. 2013;10(9):e1001511
references.pmid: 24058300
references.citation: J Acquir Immune Defic Syndr. 2013 Mar 1;62(3):260-6
references.pmid: 23111578
references.citation: Contemp Clin Trials. 2009 Nov;30(6):504-12
references.pmid: 19665587
references.citation: Lancet. 2013 Jun 15;381(9883):2083-90
references.pmid: 23769234
references.citation: AIDS Behav. 2013 Jul;17(6):2143-55
references.pmid: 23435697
references.citation: N Engl J Med. 2012 Aug 2;367(5):399-410
references.pmid: 22784037
references.citation: Lancet. 2008 Dec 6;372(9654):1977-87
references.pmid: 19059048
references.citation: N Engl J Med. 2012 Aug 2;367(5):423-34
references.pmid: 22784038
references.citation: AIDS Behav. 2013 Jan;17(1):284-97
references.pmid: 22407465
references.citation: N Engl J Med. 2012 Aug 2;367(5):411-22
references.pmid: 22784040
references.citation: N Engl J Med. 2010 Dec 30;363(27):2587-99
references.pmid: 21091279