Clinical experience for HIV treatment and prevention has demonstrated that adherence to a drug regimen schedule is a significant factor in the success of the HIV treatment regime and/or prevention strategies. Effective treatment of HIV-infected individuals requires strict adherence to a multi-component regimen of antiretroviral agents taken at least daily for the remainder of a patient’s life. Non-adherence can lead to emergence of drug-resistance and loss of therapeutic effectiveness. Among people living with HIV, morbidity and mortality is increasingly driven by co-infections, such as tuberculosis (TB) and hepatitis B, where the compliance and completion of prolonged multidrug regimens are significant factors in treatment success.
Effective prevention requires that the inhibitor be present at the right time, place, and concentration to stop HIV transmission and acquisition. Although many factors (social, behavioral, and individual preference) can influence adherence, the use of drug delivery systems to provide for a longer therapeutic exposure or window of protection and/or less frequent administration may improve their consistent use, reduce dosing intervals, and potentially improve adherence to the drug regimens.
Development of safe, effective, and well-tolerated sustained release (SR)/long acting (LA) products and strategies that maintain consistent and effective drug levels in plasma and target tissues for longer periods of time is critical for successful treatment and prevention of HIV and HIV-associated co-infections.
The purpose of this Notice is to encourage new applications to support further development of a diverse and comprehensive portfolio of SR/LA products for prevention and treatment of HIV. SR/LA antiretroviral products will have a minimum window of protection of three (3) months from either a single dosing (injection, oral administration) or continuous dosing regimen (implant, transdermal patch, etc.) to reflect current state of SR/LA drug market for HIV treatment or prevention.
This Notice also encourages applications to develop once-a-month SR/LA strategies for treatment of latent TB and hepatitis B. It is highly likely that in populations with a high burden of TB and/or hepatitis B, HIV patients receiving LA antiretrovirals often require treatments for these infections. Thus, the development of SR/LA drug products for latent TB and hepatitis B that are compatible with SR/LA antiretrovirals are sorely needed. Preferably, these new SR/LA treatments for latent TB and hepatitis B will have suitable pharmacological and safety profiles to enable co-administration with SR/LA antiretrovirals with similar dosing requirements.
Well-conceived milestone driven applications that consider optimal and minimally acceptable properties and targets for proposed technically feasible SR/LA products are encouraged. End-user assessments of the product attributes (route, dosing frequency, volume, location of application sites, etc.) and factors that might influence product implementation and dissemination, such as availability of drug substance, cost of goods, cold chain requirements, intellectual property (IP), and regulatory needs should be considered.