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Multidrug-Resistant HIV-1 Infection despite Preexposure Prophylaxis
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Download the PDF here
This new publication from David Knox in Canada was the case presented at CROI of transmitted HIV despite PrEP from person with HIV drug resistance
HIV-1 Infection With Multiclass Resistance Despite Preexposure Prophylaxis (PrEP) - (02/26/16)
And this was a different case presented at HIV4RP in NY presented by Howard Grossman also contain links to CROI webcast & abstract
Newly Acquired HIV-1 Infection with Multi-Drug Resistant HIV-1 in a Patient on TDF/FTC-based PrEP - (10/19/16)
Infection With Multidrug-Resistant HIV While Adherent to TDF/FTC PrEP - Mark Mascolini - (10/19/16)
N Engl J Med Feb 2 2017
"Genotypic and phenotypic testing of a plasma sample obtained on day 7 revealed multidrug resistance (Table 1). The M184V mutation, which compromises FTC activity, in addition to several thymidine analogue mutations, revertant substitutions, or both, which slightly decrease TDF susceptibility, probably explain this failure of preexposure prophylaxis. Genotypic and phenotypic testing of a plasma sample obtained on day 7 revealed multidrug resistance (Table 1). The M184V mutation, which compromises FTC activity, in addition to several thymidine analogue mutations, revertant substitutions, or both, which slightly decrease TDF susceptibility, probably explain this failure of preexposure prophylaxis.
Incident HIV is possible despite adherence to preexposure prophylaxis when persons are exposed to FTC-resistant virus, TDF-resistant virus, or both. We recommend that patients be counseled regarding the use of preexposure prophylaxis as part of a combination approach to HIV prevention.
Although data from Toronto are not available, in British Columbia, the proportion of patients with a plasma sample containing circulating virus that was resistant to FTC, TDF, or both was 1.7%, 0.004%, and 0.001%, respectively, in 2014-2015. Continued surveillance of mutations that may affect the efficacy of preexposure prophylaxis is needed."
To the Editor:
Preexposure prophylaxis with emtricitabine (FTC)-tenofovir disoproxil fumarate (TDF) has been shown to be efficacious in preventing human immunodeficiency virus type 1 (HIV-1) infection in men who have sex with men and in whom adherence to treatment is high, as measured by levels of tenofovir diphosphate (TFV-DP) in dried blood spots.1 We describe a case of HIV-1 infection despite FTC-TDF-based preexposure prophylaxis.2
A 43-year-old man in Toronto who reported having sex with men began to receive oral daily FTC-TDF in April 2013 and had seven nonreactive fourth-generation HIV screening tests over the next 21 months. Pharmacy dispensation records provided support for his report of "perfect" adherence to preexposure prophylaxis over 24 months.
On day 0, the initial result of a combination assay to detect antibodies to HIV types 1 and 2 was antigen/antibody-reactive, p24 antigen-reactive, and negative on Western blot testing. This test was followed by screen-positive, p24 antigen-negative, Western blot-negative results 7 days later. Since the level of p24 antigen peaks 3 to 4 weeks after infection and becomes nonreactive at 5 to 6 weeks, this change provided support for the clinical suspicion of HIV acquisition during the patient's reported receptive anal sex with multiple partners without the use of condoms 2 to 6 weeks before day 0.3 In addition, the infection date estimated by means of viral deep-sequencing analysis (BEAST software, version v1.8.3) was within the exposure period. Details are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.
Liquid chromatographic-tandem mass spectrometric analysis of a plasma sample obtained on day 0 revealed a tenofovir concentration of 152 ng per milliliter; this finding was consistent with recent administration of the drug. Dried blood spots were obtained on day 24 to assess long-term adherence, at which time the expected TFV-DP concentration (±SD) would have been 722±217 fmol or more per dried blood-spot punch had the patient not been receiving FTC-TDF before learning of his infection status on day 4. Steady-state TFV-DP concentrations after 8 weeks of daily FTC-TDF administration are usually 1560±468 fmol per punch.4 The observed TFV-DP concentration, 2297 fmol per punch, was consistent with long-term adherence.
Genotypic and phenotypic testing of a plasma sample obtained on day 7 revealed multidrug resistance (Table 1). The M184V mutation, which compromises FTC activity, in addition to several thymidine analogue mutations, revertant substitutions, or both, which slightly decrease TDF susceptibility, probably explain this failure of preexposure prophylaxis. The multiple thymidine analogue mutations detected are unlikely to have been selected in the short duration of drug exposure; this suggests that resistance was transmitted rather than acquired after drug exposure.5
Although data from Toronto are not available, in British Columbia, the proportion of patients with a plasma sample containing circulating virus that was resistant to FTC, TDF, or both was 1.7%, 0.004%, and 0.001%, respectively, in 2014-2015. Continued surveillance of mutations that may affect the efficacy of preexposure prophylaxis is needed.
Incident HIV is possible despite adherence to preexposure prophylaxis when persons are exposed to FTC-resistant virus, TDF-resistant virus, or both. We recommend that patients be counseled regarding the use of preexposure prophylaxis as part of a combination approach to HIV prevention.
David C. Knox, M.D.
Maple Leaf Medical Clinic, Toronto, ON, Canada
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