icon-    folder.gif   Conference Reports for NATAP  
  Conference on Retroviruses
and Opportunistic Infections (CROI)
Boston, Massachusetts
March 4-7, 2018
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Seroconversion on PrEP [4th case]: A Protocol for Untangling Adherence vs. Resistance Failure
  Reported by Jules Levin
CROI 2018 March 4-7 Boston MA
Joshua T. Thaden1, Monica Gandhi2,Karen Kuncze2, Alexander Louie2, Hideaki Okochi2, Christopher B. Hurt3, MehriS. McKellar1
1Division of Infectious Diseases, Duke University, Durham, NC; 2Division of HIV, Infectious Diseases, and Global Medicine, University of California San Francisco, San Francisco, CA; 3Institute for Global Health & Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC



Program Abstract:
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.