Transitioning Long-Acting Products to a Generic Marketplace: What's Missing?

Development of and increased access to generic oral medications to treat high-burden diseases including human immunodeficiency virus (HIV), tuberculosis, viral hepatitis, and malaria have had a major impact on reducing global morbidity and mortality. However, access and adherence to these life-saving treatments remains limited for some of the most vulnerable and underserved populations, for whom stigma, control, and discretion are critical to decisions around care. Current efforts to develop long-acting formulations to treat and prevent these conditions could overcome many of these barriers. However, generic manufacturing of these innovative products will be required to ensure affordable access to the communities and patients in greatest need. Strategic investments in new infrastructure will be required even before markets and manufacturing costs are clear, to ensure that access to these new products is not delayed, particularly for patients in low- and middle-income countries. Unlike conventional oral medications, long-acting products require greater investment for formulation, packaging, and delivery. The requirement for long-term bioequivalence studies will introduce additional delays in regulatory approval of generic long-acting products, and expedited approval pathways must be developed. Lessons learned from the development of long-acting hormonal contraceptives and long-acting antiretroviral products may provide a way forward.

Treatment optimization: an outline for future success.

PURPOSE OF REVIEW: In this issue of Current Opinion, the Guest Editors and their colleagues provide a comprehensive overview of current activities aimed at optimizing global HIV treatment. In this introduction, we outline current goals and approaches that will be described in more detail elsewhere in this issue. RECENT FINDINGS: Two recent conferences, the first and second Conference on Antiretroviral Drug Optimization (CADO), brought together experts from academia, governments, foundations, the pharmaceutical industry, and community activists to develop a global HIV-treatment research agenda for the coming decade focused on better therapies and how to make them accessible to a broader population of people living with HIV. Important recommendations included a focus on more efficient process chemistry for antiretroviral drugs, investigation of antiretroviral dose reduction as a possible optimization strategy, recognition of the increasing importance of concurrent infections and comorbidities especially tuberculosis and aging-related diseases, and identifying a highly effective and affordable nontoxic, once-daily fixed-dose combination regimen for first-line treatment. SUMMARY: HIV treatment optimization is a process intended to enhance the long-term efficacy, adherence, tolerability, safety, convenience, and affordability of combination ART. The ultimate goal of this process is to expand access to well tolerated and effective lifetime treatment to all those in need.

Optimizing antiretroviral product selection: a sample approach to improving patient outcomes, saving money, and scaling-up health services in developing countries.

Over the last decade, increased funding to support HIV treatment programs has enabled millions of new patients in developing countries to access the medications they need. Today, although demand for antiretrovirals continues to grow, the financial crisis has severely constrained funding leaving countries with difficult choices on program prioritization. Product optimization is one solution countries can pursue to continue to improve patient care while also uncovering savings that can be used for further scale up or other health system needs. Program managers can make procurement decisions that actually reduce program costs by considering additional factors beyond World Health Organization guidelines when making procurement decisions. These include in-country product availability, convenience, price, and logistics such as supply chain implications and laboratory testing requirements. Three immediate product selection opportunities in the HIV space include using boosted atazanavir in place of lopinovir for second-line therapy, lamivudine instead of emtricitabine in both first-line and second-line therapy, and tenofovir + lamivudine over abacavir + didanosine in second-line therapy. If these 3 opportunities were broadly implemented in sub-Saharan Africa and India today, approximately $300 million of savings would be realized over the next 5 years, enabling hundreds of thousands of additional patients to be treated. Although the discussion herein is specific to antriretrovirals, the principles of product selection are generalizable to diseases with multiple treatment options and fungible commodity procurement. Identifying and implementing approaches to overcome health system inefficiencies will help sustain and may expand quality care in resource-limited settings.