Daily dosing key to the efficacy of tenofovir-based HIV PrEP

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.”

Tenofovir-based 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.

They therefore 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.

Three plasma 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.

People with 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 follow-up.

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.

For people 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 FTC/tenofovir.

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).

“Tenofovir 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.”