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SEROCONVERSION ON PrEP: A PROTOCOL FOR UNTANGLING ADHERENCE VS RESISTANCE FAILURE
Joshua T. Thaden1, Monica Gandhi2, Karen Kuncze2, Alexander Louie2, Hideaki Okochi2, Christopher B. Hurt3, Mehri McKellar1
1Duke University, Durham, NC, USA,2University of California San Francisco, San Francisco, CA, USA,3University of North Carolina Chapel Hill, Chapel Hill, NC, USA
PrEP with emtricitabine (FTC)/tenofovir (TFV) disoproxil fumarate (TDF) reduces risk of HIV acquisition with adequate adherence. Here, we describe a case of seroconversion with multidrug resistant (MDR) HIV despite good adherence, complicated by inappropriate prescribing practices and follow-up.
History was obtained from patient and records. PrEP adherence was assessed via self-report, pharmacy records, and measuring TFV/FTC levels with LC-MS/MS in plasma and hair. Segmental hair analysis was performed to assess PrEP adherence over prior months. Genotypic resistance was evaluated.
A 34 year-old white MSM started daily FTC 200 mg/TDF 300 mg in 2/2016 after a non-reactive antigen/antibody test in 12/2015; he had no interim sexual activity. He reported full adherence to FTC/TDF from February to May 2016. He self-discontinued PrEP from May-July due to perceived lack of risk, and restarted 7/2016-4/2017. At PrEP initiation, he was prescribed 30 days of FTC/TDF with 11 refills by an ID specialist. He was told to return in 1 month and 6 months for HIV and renal testing, but no visits occurred. In 3/2017, he developed fevers, chills, myalgias and had a negative rapid influenza A/B test at an urgent care site. No HIV test was performed. In 4/2017, an antigen/antibody HIV test was reactive at an evaluation for anal condylomata (day 0). He was seen in an HIV clinic on day 2. FTC/TDF was stopped; no additional therapy was yet started. HIV-1 RNA was 27,316 copies/mL and genotyping revealed M184V, K65R, and K103N mutations. Day 2 plasma revealed TFV and FTC levels of 75 ng/mL and 281 ng/mL, respectively, consistent with recent dosing. To evaluate adherence over preceding months, a hair sample was collected at day 27 and segmental analysis of TFV/FTC levels performed in 1 centimeter segments from the scalp. Hair drug levels were commensurate with consistently high PrEP adherence over the last 3 months (Figure).
Acquisition of MDR HIV despite excellent PrEP adherence has been described in 3 prior reports. Though exact time of acquisition is unknown, our case acquired a virus with at least K103N; subsequent development of K65R and M184V from consistent FTC/TDF use is epidemiologically most likely. This study employs segmental analysis of PrEP drug levels for the first time to assess adherence over preceding months. Proper PrEP prescribing and follow-up would have allowed for quicker identification of HIV and possible prevention of further drug resistance in this individual.