Objectives To compare the potential impact of rectal (RMB), vaginal (VMB) and bi-compartment (RVMB) (applied vaginally and protective during vaginal and anal intercourse) microbicides to prevent HIV in various heterosexual populations. To understand when a RMB is as useful than a VMB for women practicing anal intercourse (AI).

Methods Mathematical model was used to assess the population-level impact (cumulative fraction of new HIV infections prevented (CFP)) of the three different microbicides in various intervention scenarios and prevalence settings. We derived the break-even RMB efficacy required to reduce a female's cumulative risk of HIV infection by the same amount than a VMB.

Results Under optimistic coverage (fast roll-out, 100% uptake), a 50% efficacious VMB used in 75% of sex acts in population without AI may prevent ∼33% (27, 42%) new total (men and women combined) HIV infections over 25 years. The 25-year CFP reduces to ∼25% (20, 32%) and 17% (13, 23%) if uptake decreases to 75% and 50%, respectively. Similar loss of impact (by 25%–50%) is observed if the same VMB is introduced in populations with 5%–10% AI and for RR_RAI=4–20. A RMB is as useful as a VMB (ie, break-even) in populations with 5% AI if RR_RAI=20 and in populations with 15%–20% AI if RR_RAI=4, independently of adherence as long as it is the same with both products. The 10-year CFP with a RVMB is twofold larger than for a VMB or RMB when AI=10% and RR_RAI=10.

Conclusions Even low AI frequency can compromise the impact of VMB interventions. RMB and RVMB will be important prevention tools for heterosexual populations.