We read with interest the recent article published in AIDS by Streeck et al. , highlighting a case of HIV pre-exposure prophylaxis (PrEP) failure in a gay man who was seemingly adherent to tenofovir-diphosphate (TDF) therapy for suppression of hepatitis B but who still acquired HIV.
Although we acknowledge and fully agree with the importance of presenting such cases, we would like to highlight the possibility that this man developed drug resistant HIV whilst receiving TDF monotherapy, as opposed to acquiring a transmitted drug-resistant strain as the letter suggested. The individual in this case received TDF monotherapy for up to 3 months after HIV acquisition, before treatment was intensified to a three-drug regime, and this is sufficient time for drug-resistant mutations to develop . An alternative explanation for this case of PrEP failure could be that TDF monotherapy was not effective for anal sex or that adherence at the time of exposure was suboptimal.
The absence of TDF drug levels (either dried blood spot or peripheral blood mononuclear cells) at the time of HIV acquisition limits evidence of adherence to TDF. Long-term virological suppression of hepatitis B viral load may not be a good surrogate for adherence requirements for HIV prevention. The drug level and indeed adherence requirements for TDF monotherapy in HIV prevention are not known and evidence suggests that drug requirements for hepatitis B viral suppression may be less than for HIV suppression: first, daily lamivudine (3TC) dosing for hepatitis B is 150 mg compared with 300 mg for HIV and, second, low-dose TDF (75 mg/day) is effective maintenance therapy in chronic hepatitis B envelope antigen negative . Therefore, in theory, low adherence to tenofovir could suppress hepatitis B, but fail to prevent HIV infection.
Although PrEP is highly effective at preventing HIV infection, the WHO guidelines recommend TDF and emtricitabine as a preferred treatment for all individuals at high HIV risk . There is limited data for single-agent TDF PrEP in gay men, which limits its use .
We previously reported two cases of HIV seroconversion in gay men taking TDF monotherapy for hepatitis B with good adherence evidence by patient self-report, tenofovir diphosphate drug levels at acute HIV diagnosis and long-standing undetectable HBV DNA viral load . Both infections were with wild-type virus, and antiretroviral therapy was intensified within 3 weeks of the presumed date of HIV acquisition. In the case reported by Streek et al. , HIV was not diagnosed rapidly after HIV acquisition and ART intensification was not immediate, leading to a period of HIV infection treated with TDF monotherapy. This provides a window of opportunity for acquired drug resistance to develop. The possibility of PrEP failure with a wild-type virus is important to acknowledge as TDF PrEP efficacy in gay men is still not known.
Conflicts of interest
There are no conflicts of interest.
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