Provisional observations

1. WHO has developed a public health approach to ART that has identified four first-line therapies using five specific medicines. These guidelines considered a range of factors including: demonstrated efficacy, adherence potential, side-effects, co-existing conditions such as TB or pregnancy, availability of FDCs, concomitant medications, presence of resistant viral strains, cost and availability, and infrastructure needs including possibilities of rural delivery.

2. WHO guidelinesⁱ indicate a preference for FDCs (or CBCs as interim) of proven quality and bioequivalence for first-line ART. This is an experience-based recommendation taking into account the total health-care delivery system in developing countries.

3. Management of toxicities, resistance and other treatment challenges will require alternative 3-drug FDCs, 2-drug FDCs and single product formulations.

4. FDCs, co-blistering and loose combinations will co-exist and can be transitional.

5. Paediatric preparations for HIV/AIDS are sorely lacking. While more clinical evidence is desirable, there is sufficient evidence to make operational paediatric treatment guidelines. The greater problem is that of convenient paediatric dosing. Issues around the treatment of mothers who have received ARVs to prevent MTCT remain unclear.

6. Recent developments for uncomplicated malaria have focused on combination therapies and there are at least seven new FDC therapies recently developed or under development.

ⁱ Scaling up antiretroviral therapy in resource-limited settings: Treatment guidelines for a public health approach 2003. Revision http://www.who.int/3by5/publications/guidelines/en/arv_guidelines.pdf.

Some ways forward

1. WHO treatment guidelines provide indications of desirable FDCs and CBCs. Guidelines, based on the best available clinical and public health evidence, should be widely communicated to national disease control programmes, procurement agencies and the pharmaceutical industry.

2. It is essential to continue to build the evidence base within the health-care system regarding procurement, distribution, use and outcomes of FDCs and CBCs, moving from initial successful pilot projects, to the practical, to the proven.

3. Research is needed to develop and modify policy - e.g., malaria/ACT. This will include operational research.

4. From the client perspective there is a preference for simplicity in the choice of delivery system.

5. There is an urgent need for the development of paediatric formulations and specifically paediatric FDCs.

6. Special attention must be given to the packaging and dispensing of the “combination of combinations” needed for simultaneous treatment of HIV/AIDS and TB - perhaps through co-blistering of TB 4-FDCs and HIV/AIDS 3-FDCs.

7. Tiered guidelines providing practical information to health workers operating at different levels of the health system on how to use the available medicines need to be developed within each country and within each health system.

8. There are multiple modalities to promote adherence which includes but is not limited to FDCs.

9. Operational research is needed to clarify options, particularly for the treatment of mothers who have received ARVs to prevent MTCT and the issue of women of childbearing ages or women who are pregnant and coinfected with HIV and TB. The interactions between contraception and therapies for TB and HIV need to be investigated.

10. Pharmacovigilance is required for new products and formulation releases.