pre-exposure prophylaxis (PrEP) does not involve a significant risk of HIV drug
resistance should seroconversion occur, results from the iPrEx study published
in the online edition of the Journal of
Infectious Diseases demonstrate.
The only cases of
drug resistance among people who had taken PrEP involved individuals with
unrecognised acute HIV infection when they started therapy.
PrEP-selected DR [drug resistance] mutations was infrequent,” comment the
PrEP is a
promising HIV prevention technology. Results of the iPrEx study showed that PrEP
with FTC/tenofovir (Truvada) reduced
the risk of infection with HIV by 44% for men/transgender women who have sex
with men. The risk was reduced by 99% for those with blood levels of Truvada that were sufficient to suggest
they took the treatment as instructed.
Poor adherence to
antiretroviral drugs can lead to the emergence of drug-resistant strains of
HIV. Therefore, infection with HIV when adherence to PrEP is inadequate could mean
resistance to FTC and/or tenofovir develops. This is a major concern, given
that both of these agents are key first-line drugs in HIV therapy.
the iPrEX study therefore used phenotypic and genotypic resistance assays to
test for drug-resistant HIV in people who seroconverted during the study.
Samples of virus with minor FTC/tenofovir resistance mutations were analysed using deep
sequencing and an allele-specific PCR-based assay.
The total iPrEx
study population comprised 2451 individuals who were equally randomised into
treatment and placebo arms.
There were 141 HIV
infections. These included ten patients with unrecognised acute HIV infection
at the time of randomisation. Two of these patients were in the treatment arm. Both
developed resistance to FTC.
There were 131
post-randomisation seroconversions, 48 of which involved patients taking
None of the
patients infected post randomisation had FTC- or tenofovir-selected resistance
mutations or reduced phenotypic susceptibility to these drugs.
showed minor variant FTC-associated resistance, but in both cases this was at
a very low level (<1.0%).
“Minor variant DR
mutations were rare, and when detected, were measured at very low frequencies,”
emphasise the authors.
adherence explain the rarity of drug resistance and minor variant drug
resistance in the treated patients who seroconverted? To test this
hypothesis, the investigators examined plasma and PBMC (peripheral blood mononuclear cells) levels of FTC/tenofovir
in all patients with an incident infection who had at least one measurement
that was detectable within 90 days of their seroconversion.
Only one patient
with low-level minor variant drug resistance had low but detectable PBMC
concentrations of FTC/tenofovir prior to seroconversion.
“Periods of low
drug exposure were not sufficient for selection of drug resistance,” write the
They conclude, “clinically
significant DR selected by PrEP was limited to those who initiated drug after
established infection, and was associated with FTC exposure.” Resistance was
absent in people who seroconverted after randomisation. The authors believe
this was due to insufficient drug levels and the short duration of
therapy. “Continued surveillance of PrEP
exposure and DR in seroconverters from ongoing PrEP demonstration projects will
extend these findings from randomized controlled trials.”