Question and Answers: The fixed – dose combination drug
South African Health Minister, Dr Aaron Motsoaledi, rolled out a fixed-dose combination (FDC) antiretroviral pill throughout South Africa on 01 April 2013. There is much excitement on this FDC pill that contains 300mg tenofovir, 200mg emtricitabine, and 600mg efavirenz (Davies, N. E. C. G, 2013). He also highlighted that since 2010, South Africa has moved from buying the most expensive ARVs in the world, to being the country where ARVs are the cheapest in the world (Huffington, 2013). This new FDC pill has been shown to increase adherence, reduces mother-to-child-transmission, promising to be more economical in the long run (Davies, N. E. C. G, 2013).
Below are a few questions that clinicians, nurses and community health workers would find valuable in understanding government’s goal in changing from single component drugs to the FDC regimen. This information would be beneficial for them, their colleagues and patients.
Question: What are the economic benefits of using the fixed-dose combination?
- Dispensing and stock management is simplified because there is now only one tablet to administer and is therefore easier to roll out and to monitor stock (Davies, N. E. C. G.2013). Currently many countries all over Africa experience stock-outs of ARVs. According to the South African Government News Agency (SANEWS) (2013), the main reason these stock-outs occur is due to ineffective communication between the healthcare facilities and the National Department of Health (NDoH). The intention of the NDoH is that health district managers, facility managers, healthcare providers and pharmacy staff should work closely together to manage drug supply (Davies, N. E. C. G, 2013). Effective communication will ensure timely ordering of ARVs before a stock-out occurs. It is also imperative to boost healthcare workers’ (HCWs) adherence to the new ARV guidelines by ensuring that they do not strain resources. FDC’s will eventually lead to easier procurement and supply-chain management (SANEWS, 2013).
- Data have been collected on a weekly basis from provincial depots in order to identify weaknesses in the supply chain process to be addressed by either the province, or the supplier (SouthAfrica.info, 2013).
- The NDoH are working with three suppliers to ensure ARVs are available without disruption of supply, resulting in patients not receiving their ARVs and therefore placing them at risk of viral resistance (SouthAfrica.info, 2013). Up to now, 389 857 units of FDCs have been supplied throughout the country, and another 915 000 units will be delivered during April 2013 (SouthAfrica.info, 2013).
- Previously, the cost of ARV therapy varied between R120 – R130 per person per month, whereas the three contractors charged R89.38, R94.80, and R95.50 respectively. With these savings, more HIV patients will have access to antiretroviral therapy (ART) (Buthelezi, 2013).
Question: What are the main advantages of fixed-dose combination?
The combination of intense adherence counselling and reducing the pill burden from between three and five pills to one pill per day has been reported to increase adherence levels (NDOH SA, 2013) which will help to prevent the risk of drug resistance (Buthelezi, 2013). During pregnancy, optimal adherence would lead to minimal risk of mother-to-child HIV-transmission, which will decrease the risk of infant mortality (Marinda et al, 2007).
The efficacy of the FDC pill has been proven in several randomised controlled trials (Davies, N. E. C. G, 2013). For instance, Pozniak et al (2006) proved the effectiveness of the fixed dosage, as it maintained an HIV RNA level <400 copies/mL with an increase in CD4 cells.
Question: How does it affect my job as a healthcare worker?
- The new FDC regimen will be easier to order, store and manage as the logistics around supply chain have been simplified. Relationships between patients and HCWs would benefit, as the treatment plan is easier to explain and manage (NDOH SA, 2013). This will also save time, and HCWs will be able to see more patients.
- Currently more than 7000 HCWs and at least one healthcare professional per facility have been trained on the new guidelines. Another 200 master trainers have been trained to train HCWs, and facilitate the implementation of the FDC (SouthAfrica.info, 2013).
Question: What are the side effects?
HCWs should inform their patients that the expected side effects would be similar to the regimen comprising the three separate drugs; however, new or different side effects may be experienced. This may occur due to the change of drugs, as different brands of the drug may contain different excipients, or due to the psychological effect caused by changing drugs. It is suggested that HCWs should adhere to existing guidelines when managing any adverse effects of FDC (Davies, N. E. C. G, 2013).
Question: Is FDC for all HIV-positive individuals?
The new FDC pill is suitable for the majority of adult patients, except those patients with kidney complications, severe psychiatric conditions or those who failed their first ARV regimen. However, as reported by SANEWS (2013), for the period 2013/2014, manufacturers can only supply 30 million units in phases, and there are currently 1.9 million patients on ARVs. Therefore, to avoid stock-outs, the FDC pill is being introduced in phases by prioritising new patients, pregnant and breastfeeding women, where a great impact would be made. There are currently seven priorities groups, and as more of the FDC pills become available, more priority groups will be phased into the new treatment plan (SANEWS, 2013).
The NDOH’s (2013) seven priority groups are as follows:
- All patients (adults, adolescents older than 18 years, and pregnant women) who are starting ART for the first time
- All pregnant women needing triple therapy and breastfeeding women
- Virally suppressed patients (currently on first-line therapy), needing a switch due to toxicity
- Patients who are stable on a tenofovir containing regimen but with TB co-morbidity
- Patients who are stable on a tenofovir containing regimen but with other co-morbidities, such as hypertension, diabetes
- Patients who are stable on a tenofovir containing regimen who requested the change to the fixed-dose combination pill
- Patients who are stable on a tenofovir containing regimen but after counselling agree to switch to the new fixed-dose combination pill.
Davies’ (2013) advice document on the fixed-dose combination for adults accessing antiretroviral therapy is extremely helpful, especially in understanding the FDC pill and will benefit other healthcare workers who may not have undergone training yet.
- Buthelezi, L. (2013) State’s new single dose ARV to save money, lives. Business Report [Online] Accessed on the 15th April 2013.
- Davies, N. E. C. G. (2013) Fixed –dose combination for adults accessing antiretroviral therapy. Southern African HIV Clinicians Society, 14 (1).
- Huffingtonpost. (2013) AIDS pill: South Africa announces $10 antiretroviral drug [Online] Accessed on the 15th April 2013
- National Department of Health South Africa (NDOH SA) (2013) Changes in the antiretroviral; therapy regimen in South Africa: What to tell new patents about fixed-dose combination ARVs [Online] Accessed on the 12th April 2013.
- Marinda, M. E., Humphrey, J. H., Lliff, P. J., Mutasa, K., Nathoo, K.J., Piwoz, E. G., Moulton, L. H., Salama, P., Ward, B, J., ZVITAMBO Study Group. (2007) Child mortality according to maternal and infant HIV status in Zimabbwe. Pediatric Infectious Diseases Journal, 26 (6), p. 519-526.
- Pozniak, A. L., Gallant, J. E., DeJesus, E., Arribas, J. R., Gazzard, B., Campo, R. E., Chen, S. S., McColl, D., Enejosa, J., Cheng, A. K. (2006) Tenofovir disoproxil fumarate, emtrictibine, and efavirenz versus fixed-dose zidovudine/lamivudine and efavirenz in antiretroviral-naive patients: virologic, immunologic, and morphologic change - -a 96-week analysis. Journal of Acquired Immune Deficiency Syndrome, 14(43) p. 535-540.
- SANEWS. (2013) Fixed-dose combination ARVs: Everything you need to know [Online] Accessed on the 12th April 2013.
- SouthAfrica.info. (2013) SA begins single-dose HIV drug roll-out [Online] Accessed on the 12th April 2013.
Author: Jodilee Erasmus (B.Soc Sci)
Reviewed by: Hendra van Zyl (MPH) and Michelle Moorhouse (MBBCh, DA)
Date: May 2013
Erasmus, J. (2013) Question and Answers: The fixed – dose combination drug, AfroAIDSinfo. Issue 13 no. 5, Health Profession (Open access).
2 May, 2013