Evidence for the effectiveness of the alternative formulation of oral PrEP in women was presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2025) in San Francisco last week.
The data come from the PURPOSE 1 study, conducted with 5338 cisgender women in South Africa and Uganda. The study compared HIV prevention efficacy of injectable lenacapavir and two types of oral PrEP: the oldest, cheapest and still most-used option of tenofovir disoproxil and emtricitabine (TDF/FTC), and the alternative formulation, tenofovir alafenamide and emtricitabine (TAF/FTC). As no studies have previously tested TAF/FTC in cisgender women, drug regulators have not approved the formulation for this population.
The alafenamide formulation is much more rapidly absorbed by cells, meaning fewer kidney and bone-related side effects and, in theory at least, more ‘forgiveness’ of partial adherence.
As has already been widely reported, there were no HIV diagnoses in PURPOSE 1 in the women receiving lenacapavir, compared with 39 in the women taking TAF/FTC and 16 in women on TDF/FTC (because half as many women took TDF, this is equivalent to 32 cases).
This means there were 16% fewer diagnoses on TAF and 30% fewer on TDF than there were in women with ‘background HIV incidence’ – a comparable group who did not join the study because they already had HIV and whose incidence during the previous year was calculated. These reductions in incidence were not statistically significant and could have been due to chance.
Incidence in women taking TDF was also 16% lower than in women on TAF – again, not a statistically significant difference.
However, Dr Flavia Kiweewa of Makerere University in Uganda, looking solely at the infections acquired in women allocated to TAF, said that all but two seroconversions were in women taking fewer than three pills a week, and of those two, one acquired HIV that had significant resistance to both tenofovir and emtricitabine. This leaves only one unexplained infection in a woman with better adherence, allowing Dr Kiweewa to calculate that even in women taking two or more TAF/FTC pills a week, the chance of acquiring HIV was reduced by 89%.
This is a higher efficacy than the efficacy of 87% given for four or more doses of TDF/FTC in an analysis by Professor Jeanne Marrazzo, and may possibly be due to the higher levels in cells achieved by TAF.
A similar calculation was made in respect of the DISCOVER study, in 2019. This compared the efficacy of the two types of oral PrEP in gay and bisexual men and transgender women. A post-hoc analysis of the study found that while no-one taking TAF/FTC who acquired HIV was taking the equivalent of more than two pills a week, some of the TDF/FTC users who seroconverted were taking two to four pills a week.
Dr Christoph Spinner, of the Technical University of Munich, who presented the analysis, stated at the time: “The more rapid onset and longer duration of protection may be the most probable explanation for the higher prevention efficacy of F/TAF.”
DISCOVER did, indeed, find that TAF/FTC was 45% more effective at preventing HIV than TDF/FTC – a very nearly statistically significant finding.
The problem is that in PURPOSE 1, the effectiveness went the other way, with TDF/FTC 16% more effective than TAF/FTC. Although this is not a significant difference, without presentation of the adherence patterns in the women who acquired HIV on TDF/FTC, it is impossible to say if more of them acquired it despite good adherence.
Kiweewa FM et al. Adherence to F/TAF in cisgender women prevents HIV with low risk of resistance or diagnostic delay. Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 194, 2025.