Tenofovir used as a single agent for pre-exposure prophylaxis (PrEP) may be as effective as the Truvada (tenofovir/emtricitabine) coformulation for preventing HIV infection, which, if confirmed, could have implications for cost and access worldwide.
PrEP, or HIV negative people taking antiretroviral medications on a regular basis to prevent the virus from taking hold in the body, has been one of the major recent breakthroughs in the HIV/AIDS field.
The iPrEx trial of mostly gay and bisexual men found that taking tenofovir plus emtricitabine once-daily reduced the risk of HIV infection by 42% overall, rising to 92% among participants with blood drug levels indicating regular use.
Similarly, the Partners PrEP trial, which looked at heterosexual couples in Africa, found that PrEP using Truvada or tenofovir alone reduced the risk of HIV acquisition by 75% and 67%, respectively — a difference between the interventions that was not statistically significant. TheBangkok Tenofovir Study showed that daily tenofovir alone reduced HIV acquisition among people who inject drugs by about 50%.
Emtricitabine and the related agent lamivudine (3TC, Epivir) are very well-tolerated, but each additional drug in a regimen increases complexity and cost. The branded Truvada coformulation is considerably more expensive than tenofovir alone — and will be even more so when the patent on tenofovir expires in 2017. If tenofovir could be used alone, the lower cost might allow more people at risk to have access to PrEP.
Jared Baeten from the University of Washington and colleagues further analyzed data from Partners PrEP to learn more about the comparative effectiveness of tenofovir versus Truvada.
Partners PrEP included 4747 serodiscordant (1 HIV positive, 1 HIV negative) heterosexual couples in Kenya and Uganda; in about 62% of couples the man had HIV.
The trial started by comparing tenofovir alone, tenofovir/emtricitabine, or placebo. The placebo arm was halted in July 2011 after early data showed more new HIV infections in that group. The other 2 arms continued to be followed, with treatment assignments remaining blinded, and those in the placebo arm were re-randomized to one of the active arms. Data collection was completed in December 2012.
- A total of 30 new HIV infections occurred after randomization and before July 2011: 17 among participants taking tenofovir alone and 13 among those taking Truvada
- 22 new occurred after the placebo arm was stopped: 14 in the tenofovir arm and 8 in the Truvada arm.
- Taken together, there were 31 new infections among tenofovir recipients and 21 among those taking Truvada.
- Combined incidence rates were 0.70 vs 0.48 per 100 person-years, respectively; for comparison, HIV incidence in the placebo arm prior to July 2011 was considerably higher, at 2.0 per 100 person-years.
- The preventive efficacy of Truvada was 33% greater than that of tenofovir alone (hazard ratio 0.67), but this difference was not statistically significantly (p=0.16).
- Subgroup analyses stratified by sex, age, country, sexual behavior, male partners' circumcision status, and HIV viral load and CD4 count also did not show any significant differences in protection between tenofovir alone and Truvada.
- Detection of tenofovir in blood plasma samples was associated with a relative reduction in the risk of HIV acquisition of 85% in the tenofovir-only arm and 90% in the Truvada arm.
- Viral sequences revealed no cases of drug resistance related to tenofovir or emtricitabine among seroconverters after July 2011.
"These updated results demonstrate that the HIV-1 protective efficacy and safety for once-daily oral [tenofovir] and [tenofovir/emtricitabine] appear to be comparable, with no statistically significant difference in direct comparison and high estimated protection when drug was detectable in plasma," the researchers concluded.
"Our findings suggest a single highly effective PrEP agent may provide substantial prophylaxis benefit," they added. "This paradigm contrast with HIV-1 treatment, where a combination of antiretroviral agents is essential."
While these data suggest tenofovir and Truvada may be similarly effective in preventing HIV infection, Centers for Disease Control and Prevention (CDC) and World Heath Organization PrEP guidelines recommend only tenofovir/emtricitabine — not tenofovir alone — for pre-exposure prevention.
J Baeten, D Donnell, P Ndase, et al. Single-Agent TDF Versus Combination FTC/TDF PrEP Among Heterosexual Men and Women . 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014). Boston, March 3-6. Abstract 4