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ACUTE INFECTION WITH A WILD-TYPE HIV-1 VIRUS IN PREP USER WITH HIGH TDF LEVELS
Elske Hoornenborg1, Godelieve J. de Bree2
1Pub Hlth Service Amsterdam, Amsterdam, Netherlands,2Academic Med Cntr, Amsterdam, Netherlands
Clinical trials show that pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine is highly effective against acquisition of HIV-infection. World-wide, only one case of PrEP failure was reported in an individual infected with a multi-class resistant virus under adequate tenofovir-diphosphate (TFV-DP) levels. We report a case with potentially very high HIV-1 exposure who was infected with wild-type HIV-1 while adhering well to a daily PrEP regimen.
A 50-year-old men who has sex with men (MSM) started daily PrEP via the Amsterdam PrEP (AMPrEP) study. At enrollment, he tested HIV negative (4th generation HIV Ag/Ab test and HIV RNA test). Pill counts and daily diary information indicated adequate adherence of 7 pills per week. This was confirmed by a TDF-DP level in DBS of 2234 and 2258 fmol/punch at respectively 6 and 8 months after start of PrEP. HIV Ag/Ab tests during follow-up were repeatedly negative at 1, 3 and 6 months after starting PrEP. The number of episodes of condomless anal sex (CAS) was remarkably high (table 1).
Eight months after PrEP start, HIV seroconversion was observed with an indeterminate HIV Ag/Ab test (Ab positive, Ag negative). At the same day, the patient had a negative serum HIV RNA test (LOD 50 copies/mL) and western blot showed an atypical pattern characterized by a single p160 band. We were not able to detect HIV by nested pol PCR (DNA and RNA) on bulk peripheral blood mononuclear cells and sigmoid biopsies. Based on these findings and fear of inducing drug resistance, PrEP was stopped and the patient was monitored at weekly intervals. Three weeks after Ab seroconversion, HIV RNA was detected in his plasma (40,000 cop/ml) without detectable resistance mutations using routine clinical sequencing. Combination antiretroviral therapy was started resulting in an undetectable viral load after one month.
Wild-type HIV-1 infection, despite confirmed adherence to PrEP, occurred in a MSM with potentially high HIV-1 exposure. It remains speculative why the patient seroconverted. The presence of an aberrant immune response under appropriate serum TDF levels raises the possibility that a very high HIV exposure, possibly in combination with inadequate TDF levels in gut mucosa may have led to infection. This case underscores the importance of counseling and monitoring PrEP users, including frequent HIV testing. Furthermore, we should be alert for atypical seroconversion resulting in indeterminate HIV Ag/Ab test in individuals on PrEP.