Oral Pre-Exposure Prophylaxis (PrEP) is highly effective for HIV prevention when adherence is optimal, with rare HIV breakthrough infections usually happening within 1-2 years since PrEP start. After 6 years of daily PrEP, routine HIV testing identified seroconversion in a 46-year-old Italian cisgender man. He reported high adherence, confirmed by pharmacy refill history and plasma tenofovir concentration. Genotypic resistance test identified a recombinant HIV-1 strain with M184V and K70E reverse transcriptase mutations. Immediate antiretroviral therapy with FTC/TAF/DRV/c+DTG was initiated, achieving rapid viral suppression. A hair sample was sent for therapeutic drug monitoring and results were consistent with correct daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) before the acquisition of HIV infection. This case represents a rare PrEP failure after the longest reported duration of daily TDF/FTC PrEP with confirmed optimal adherence. It highlights that breakthrough HIV infection can occur even after many years of successful PrEP use, underlying the importance of periodic HIV surveillance.

Half a century after smallpox eradication, this feat has not been repeated, although there is hope for the Guinea worm. This article examines whether two uncommon genital ulcerative diseases, donovanosis and chancroid, should be targeted for eradication. Many think that their decline has been such that they might be heading towards spontaneous eradication, following more effective treatments, integration of sexually transmitted infection management in primary healthcare, enhanced condom use by sex workers and promotion of male circumcision. However, examples of syphilis and mpox suggest spontaneous eradication may be a fallacy.Donovanosis occurs sporadically in several countries, especially India. In other formerly endemic nations (eg, Papua New Guinea and the Papua region of Indonesia), the current epidemiological situation is unclear. Worldwide incidence might be a few hundred cases annually, perhaps a thousand. The availability of effective interventions, relatively easy clinical diagnosis, adequate laboratory tests and the absence of animal reservoirs suggest that eradication could be achieved through enhanced surveillance and a stronger contact tracing system with presumptive treatment of all sexual contacts, including sex workers.Chancroid's current annual caseload is unknown but likely in the hundreds of thousands of cases globally. Prior to eradication activities, a first phase should document its status in all previously endemic countries using molecular tests on patients presenting with genital ulcers in sentinel clinics. Additional research should investigate whether Haemophilus ducreyi in skin ulcers can cause genital infections. Chancroid is strongly associated with sex work: this is the tap that must be turned off. Where it remains endemic, sex workers' services should be supported to treat symptomatic cases, enhance condom use and deliver periodic presumptive treatment with azithromycin.Given their overlapping geographic distribution and the preponderant role of sex workers in transmission dynamics, an eradication programme could address both diseases simultaneously, with the same personnel.