Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylaxis: a case report

Abstract

Background: Pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir (TFV) disoproxil fumarate (FTC/TDF) is highly protective against HIV infection. We report a case of TDFsusceptible, FTC-resistant HIV acquisition despite high adherence to PrEP, confirmed by PrEP drug level testing. Methods: Adherence to FTC/TDF was assessed by measuring FTC/TFV levels or their metabolites in plasma, dried blood spots (DBS), and hair. Genotypic and phenotypic resistance of the acquired virus was evaluated by standard clinical tests and by single-genome sequencing (SGS) of > 50 proviruses obtained from peripheral blood mononuclear cells (PBMC). HIV partner services (PS) identified the likely transmission partner. Findings: A 21 year-old Latino man tested positive for HIV (negative HIV antibody, HIV RNA 559 copies per mL) 13 months after PrEP initiation. He reported excellent adherence to daily PrEP. He was linked to care and immediately started antiretroviral treatment (ART), at which point his RNA was 1544 copies per mL and his HIV Ab test was positive. The HIV genotype revealed M184V, L74V, L100I and K103N mutations in reverse transcriptase (RT); the phenotype showed susceptibility to TDF and resistance to FTC. FTC/TFV levels by liquid chromatography/tandemmass-spectrometry (LC-MS/MS) measured in 1 centimeter (cm) segments of hair from the scalp indicated consistently high PrEP adherence in each of the preceding six months. TFV-diphosphate and FTC-triphosphate levels in DBS indicated high adherence over the preceding six weeks. TFV and FTC levels measured in plasma ten weeks prior to HIV seroconversion confirmed adherence in the days preceding that visit. The likely transmission partner, named during PS, was not engaged in HIV primary care and the viral genotype was similar. Interpretation: Acquisition of TDF-susceptible, FTC-resistant HIV infection can occur despite high PrEP adherence. Quarterly HIV and STD screening of patients on PrEP, combined with prompt linkage to care and PS for those diagnosed with HIV, facilitates early diagnosis and prevents further transmission of HIV. Cohen et al.

Failure of pre-exposure prophylaxis with daily tenofovir/emtricitabine and the scenario of delayed HIV seroconversion

“…Standard guidelines are in place to ensure effective implementation of PrEP (Centers for Disease Control and Prevention: US Public Health Service, 2020), and failure is uncommon if adherence is upheld and maintained (Marcus et al, 2017). Only a handful of cases have failed to be protected from HIV infection despite confirmed adherence to the daily regimen (Knox et al, 2017;Hoornenborg et al, 2017;Cohen et al, 2019). We report a failure case and discuss the challenges of differentiating between true failure and defective protection due to suboptimal adherence.…”

Combination of Pre-Exposure and Postexposure Prophylaxes Used for an Occupational Exposure to HIV: A Case Report

“…Here we describe for the rst time the use of PrEP before occupational exposure. After the occurrence of occupational exposure, given the possibility of blocking failure of PrEP, which was reported by other researches 11 , PEP was still conducted timely. And the combination of PEP and PrEP ultimately ensured that Surgeon X was not infected with HIV after his occupational exposure.…”

Importance of early identification of PrEP breakthrough infections in a generalized HIV epidemic: a case report from a PrEP demonstration project in South Africa

“…However, the risk of potential PrEP-related resistance needs to be weighed against the number of HIV infections averted. The few documented cases of true PrEP-selected resistance could suggest that resistance is likely to be rare as PrEP is scaled up [16,[24][25][26][27][28]. Another trend seen on drug level testing is that the majority of seroconverters in PrEP studies were nonadherent to their oral PrEP at the time of seroconversion, resulting in low risk of resistance because of the lack of drug pressure [18].…”