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Infection With Multidrug-Resistant HIV While Adherent to TDF/FTC PrEP
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HIV Research for Prevention (HIVR4P), October 17-19, 2016, Chicago
Mark Mascolini
A man adhering to preexposure prophylaxis (PrEP) with tenofovir/emtricitabine (TDF/FTC) became infected with multidrug-resistant (MDR) HIV, US researchers reported [1]. The current HIV testing algorithm did not detect a serologic response to HIV-1 in this TDF/FTC PrEP user.
PrEP has proved successful in preventing sexual and drug-injection transmission of HIV in people who adhere to a daily regimen of oral TDF/FTC. Poor adherence is the primary cause of HIV acquisition in TDF/FTC PrEP users. Earlier in 2016 researchers from Canada reported the first case of a man who used TDF/FTC PrEP successfully for 24 months then picked up MDR HIV despite clinical and pharmacokinetic data indicating continued good adherence [2].
That case was not unique, according to US researchers who reported similar findings [1].
The new case involves an initially HIV-negative man in his 20s in a relationship with an antiretroviral-treated man with an undetectable viral load. The initially negative man tested negative for HIV at least 5 times over the past few years. In January 2016 he started TDF/FTC PrEP. In May 2016 a fourth-generation HIV-1 test indicated HIV infection.
In the months before testing positive, the man reported both insertive and receptive condomless anal sex with his suppressed HIV-positive partner and condomless insertive anal sex with two other partners. A follow-up HIV test proved reactive 2 weeks after the first reactive test. A week later the man's clinician added the integrase inhibitor dolutegravir to the TDF/FTC. Two weeks after that another HIV test came back reactive. At the times of the second and third reactive tests, the man had (1) a viral load below 20 copies with a signal detected and (2) a viral load below 20 copies with no signal detected. At the second and third time points, western blot tests for HIV were reactive. The Multispot HIV1/2 test was nonreactive at all three testing points. The NAAT test was reactive at the first two points and nonreactive at the third point.
Phylogenetic analysis indicated that the man had not been infected by his suppressed positive partner: their two virus populations were not genetically related. The man claimed perfect adherence to daily TDF/FTC PrEP, an assertion confirmed by measuring tenofovir levels in a dried blood spot and hair.
Resistance testing on proviral DNA from the newly infected man indicated that his virus bore mutations conferring resistance to TDF (K65R), to FTC (M184V), and to nonnucleosides (K103S, K138Q, Y188L). Resistance analysis indicated high-level resistance to the nucleotide TDF, to the nucleosides FTC, lamivudine, abacavir, and didanosine, and to the nonnucleosides efavirenz, nevirapine, and rilpivirine.
The researchers concluded that this man became infected with MDR HIV-1 while maintaining good adherence to TDF/FTC PrEP, probably during insertive anal sex. Although the fourth-generation HIV-1 assay consistently detected infection, the investigators stressed that the "current testing algorithm failed to detect a serologic response to HIV-1 in the presence of TDF/FTC."
References
1. Grossman H, Anderson P, Grant R, Gandhi M, Mohri H, Markowitz M. Newly acquired HIV-1 infection with multi-drug resistant (MDR) HIV-1 in a patient on TDF/FTC-based PrEP. HIV Research for Prevention (HIVR4P 2016), October 17-19, 2016, Chicago. Abstract OA03.06LB.
2. Knox DC, Tan DH, Harrigan PR, Anderson PL. HIV-1 infection with multiclass resistance despite preexposure prophylaxis (PrEP). Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston. Abstract 169aLB.
http://www.croiconference.org/sessions/hiv-1-infection-multiclass-resistance-despite-preexposure-prophylaxis-prep and
http://www.natap.org/2016/CROI/croi_47.htm
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