Background
Injectable lenacapavir (LEN) has been shown to be 100% effective in protecting African women from HIV infection, but its acceptable price and cost-effectiveness is unknown. We estimated the impact of LEN compared to daily oral tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) and injectable cabotegravir (CAB) for HIV prevention in South Africa, and the threshold price at which LEN or CAB would be as cost-effective as further TDF/FTC scale up.
Methods
We used Thembisa, a deterministic HIV transmission model, to evaluate the impact and cost-effectiveness of PrEP provision to women (incl. female sex workers), heterosexual men, gay men and other men who have sex with men over current TDF/FTC use over 20 years (2024-2045) of a) LEN; b) CAB; and c) TDF/FTC scale up. We estimated the average cost of provision in 2024 USD using ingredients-based costing and current South African market prices for TDF/FTC and CAB drugs. For LEN we assumed a price of $40 or $100 per injection. We estimated the threshold price of LEN and CAB, with a credible interval informed by probabilistic sensitivity analysis sampling 50 parameter combinations (incl. PrEP effectiveness, duration on TDF/FTC, tail protection for LEN/CAB, and condom use reduction on PrEP). We assumed higher uptake and longer effective use duration of LEN or CAB compared to TDF/FTC throughout, with two scenarios each defined by average duration of use across populations (LEN: 6-12 or 12-24 months, CAB: 4-8 or 8-16 months).
Results
Despite similar effectiveness, LEN leads to higher impact throughout compared to CAB, due to higher uptake and longer effective use. LEN could avert 27-41% of new HIV infections and 4-6% of deaths, and CAB 21-35% and 3-5%, resp., compared to 8% and 1% averted by TDF/FTC scale-up, resp. (see Table). Under high uptake, LEN could reduce incidence to below 0.1% by 2032 instead of 2042, thus helping to eliminate HIV in South Africa 10 years earlier. Because of this higher impact, LEN can be accepted at a higher price than CAB, with a threshold price of $32-59/injection (range $19-115) or $117-225 per person year, pppy (range $74-469) for LEN, compared to $14-22/injection (range $9-30), and $88-$144pppy (range $45-343) for CAB.
Conclusions
Injectable lenacapavir could be more cost-effective than scaling up oral PrEP, and much more cost-effective than injectable cabotegravir, even at a drug price of $100 per injection. However, CAB should be rolled out now to cover the time to large-scale LEN manufacture (3-4 years).