Good adherence is
key to the efficacy of tenofovir-based HIV pre-exposure prophylaxis (PrEP),
according to research published in the online edition of the Journal of Acquired Immune Deficiency
Syndromes. Plasma-concentrations of tenofovir that were consistent with daily
dosing reduced the risk of infection with HIV by between 88 and 91%. There was also
evidence that people who established good pill-taking habits at the start of
the study tended to maintain high levels of adherence in the longer term.
“Our results might
imply that persons who decide to initiate PrEP for HIV prevention, will likely
return for their PrEP drugs and use consistently,” comment the authors. “These
patterns of consistent use support the cost-effectiveness of targeted PrEP to
those who are motivated to use PrEP.”
PrEP is a highly promising HIV prevention technology. The Partners PrEP study
involving HIV serodiscordant heterosexual couples in Kenya and Uganda showed
that tenofovir PrEP reduced the risk of infection with HIV by 67%, with treatment
with FTC/tenofovir (the drugs combined in the pill marketed as Truvada) reducing the risk by 75%.
The efficacy of
PrEP has been linked to adherence. Investigators from the Partners PrEP study
wished to see if this was the case in their study.
analysed plasma concentrations of tenofovir for the 29 people who acquired HIV despite taking PrEP and 196 randomly selected controls who
received the treatment and remained HIV negative.
tenofovir threshold levels were used to categorise the participants’ adherence: above
0.31 ng/ml, consistent with dosing in the last week; above 10ng/ml, consistent
with dosing the previous two to three days; above 40 ng/ml, consistent with the recommended daily dosing schedule (or with having taken a dose just before the study visit).
Study participants who
acquired HIV contributed a median of five plasma samples for analysis;
the HIV-negative controls providing a median of four.
Drug concentrations above 40ng/ml were detected in 71% of samples provided by the HIV-negative controls and in 48% of samples provided by the cases before they acquired HIV.
plasma levels above 40ng/ml at the month-one follow-up visit (81%) had
consistently high levels of adherence. Three-quarters still had plasma levels
of tenofovir above 40ng/ml at the twelve-month visit and 72% at month 18 of
Only 32% of individuals
who seroconverted had plasma tenofovir levels above 40ng/ml at the time their
HIV infection was detected. Just 5 of the 29 people who acquired HIV had plasma drug concentrations that suggested consistent adherence.
Pill counts supported
the hypothesis that high levels of adherence were associated with the efficacy
of PrEP. Approximately two-thirds of people who acquired HIV and 96% of
controls had pill counts suggesting they took at least 80% of their doses.
taking tenofovir monotherapy, a plasma concentration of the drug above 40ng/dl
reduced the risk of infection with HIV by 88%. A plasma concentration above
40ng/dl reduced the risk of infection by 91% for individuals treated with
Older age was
associated with tenofovir levels above 40ng/ml (aOR = 1.3; 95% CI, 1.0-1.8 for
each ten year increase, p = 0.04).
concentrations in plasma which were consistent with daily dosing were highly
predictive of protection from HIV,” conclude the authors. “Participants had
consistent patterns of adherence over multiple time points, with the majority
able to achieve and sustain PrEP adherence. These data strongly support the use
of PrEP for the prevention of HIV infection in heterosexual men and women.”