APRETUDE (cabotegravir) - PrEP / HIV

The Committee deems that the clinical benefit of APRETUDE (cabotegravir), in combination with safer sex practices, is high in pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in high-risk adults and adolescents, weighing at least 35 kg.

Considering:

• the partially met medical need in pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in high-risk adults and adolescents, weighing at least 35 kg;
• evidence of the superiority of cabotegravir (APRETUDE) in terms of reduction in the incidence of documented new HIV-1 infections compared to the emtricitabine / tenofovir disoproxil (TRUVADA) combination as continuous administration:
  • in the HPTN 083 study (HIV-uninfected cisgender men who have sex with men and HIV-uninfected transgender women who have sex with men) with a relative risk reduction of 66%,
  • in the HPTN 084 study (HIV-uninfected cisgender women who have sex with men) with a relative risk reduction of 89%;
• pharmacokinetic data (“Pop PK-adults” model and HPTN 083-01 and HPTN 084-01 study extensions) demonstrating similar exposure to cabotegravir in the adolescent population
  (12 years and over and weighing at least 35 kg) and in adults, without demonstrating any clinically relevant difference between these two populations;
• a satisfactory safety profile, although marked by injection site reactions, and the fact that no new safety signals have been identified. The important identified risks (risk management plan) include hepatotoxicity, HIV-1 seroconversion and development of resistance;

but:

• a limited transposability of the available data (HPTN 083 and HPTN 084 studies) to the population liable to receive PrEP with APRETUDE (cabotegravir) in France, i.e.:
  • risky behaviours or practices of the subjects included in the studies not very or not transposable to those in the French population liable to receive HIV PrEP,
  • non-inclusion of pregnant or breastfeeding women and IV drug users in the clinical studies,
  • uncertainties with respect to long-term compliance for a long acting treatment, particularly since adherence was already lower in both groups in the HPTN-083 study after the first year,
  • the absence of data on cabotegravir enabling its role to be assessed compared to the other method of administration of the emtricitabine / tenofovir disoproxil combination (TRUVADA), a regimen that is off-label but validated by the WHO and national recommendations;
• a risk of selection of INI-resistant virus strains in individuals not complying with the injection schedule and of transmission of these viruses, whereas INIs are the pillars of first-lineantiretroviral (ARV) therapy;

the Committee deems that APRETUDE (cabotegravir) provides a minor clinical added value (CAV IV) compared to the emtricitabine / tenofovir disoproxil (TRUVADA) fixed-dose combination as a continuous administration regimen, when APRETUDE (cabotegravir) is combined with safer sex practices, in pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in high-risk adults and adolescents, weighing at least 35 kg.