Just days into the rollout of fixed-dose combination (FDC) antiretrovirals (ARVs) by South Africa’s HIV treatment programme - the world's largest - activists are raising fears of drug shortages.
Patients on the triple-therapy regimen will be able to take just one pill daily to control the virus. This has the advantages of improving adherence, simplifying regimens so that prescribing errors are reduced, and enabling the introduction of community models of care.
Motsoaledi launched the phased rollout of FDCs on 8 April at a small community health centre north of the country's capital, Pretoria. New patients and HIV-positive women who are pregnant or breastfeeding will be the first to receive the new medication. They will initially receive a one-month supply of FDCs, while stable patients will be given a three-month supply.
"The central procurement unit in the national department of health has worked tirelessly with suppliers, provincial medical depots as well as facilities, to ensure that depots placed orders with suppliers, and health facilities placed orders with depots," Health Minister Dr Aaron Motsoaledi said. "We are confident that we have sufficient supplies of ARVs for all patients who are eligible for the FDCs."
But stock shortages have already been reported in Western Cape Province and more are thought to be occurring in other provinces, according to activists. In March, the Western Cape Department of Health told AIDS lobby group the Treatment Action Campaign (TAC) and Médecins Sans Frontières (MSF) / Doctors Without Borders that it had received significantly smaller stocks of the FDCs than had been ordered from suppliers.
Dr Lynne Wilkinson, the MSF project coordinator in Khayelitsha, a township on the outskirts of Cape Town, said this meant the depot could not maintain the usual two- or three-month buffer stock.
The ARV tender, worth about US$672 million, was awarded in November 2012. It logged the country's second consecutive drop in drug prices and also introduced a 3-in-1 pill combining tenofovir, emtricitabine and efevarinz.
Researcher Simonia Mashangoane said TAC continues to receive reports from health facilities in Mpumalanga and Gauteng provinces, with some saying they have received insufficient supplies of the FDCs. Recent shortages of the ARV, lamivudine, have also been reported. In a joint statement with the National Association of People Living with HIV and AIDS (NAPWA), TAC criticised the health department’s communications and called for clear timelines regarding the introduction of FDC drugs.
"Public announcements created the expectation that the pills will be widely available from 1 April, but non-priority groups might have to wait many more months before being switched to the FDCs," TAC and NAPWA said in their statement. "Patients have not been given any indication as to when the various phases will be initiated, and how long they will have to wait."
Wilkinson said there are also concerns that because new ARV patients have been prioritized to receive the FDC, they could be especially vulnerable if FDC stockouts force clinicians to switch them to the old regimen of three separate ARVs.
"Newly initiated patients are counselled about the treatment that they are about to receive," Wilkinson told IRIN. "The problem is if they are counselled on how to take one pill a day, and in a few months that stock runs out and they have to be put on three separate pills, the clinic has to re-counsel them. If that doesn't happen, then there's a chance patients won't take the treatment properly."
According to Western Cape Department of Health spokesperson Hélène Rossouw, the problem lies with the National Department of Health. “The problem is that the national government procures the medicines, so it’s all centralized at the national level in accordance with treasury regulations,” Rossouw told IRIN. “The awarding of the tenders… the signing of contracts… takes time.”
"What’s happening in the Western Cape is a domino effect of [those delays],” she added. “The Western Cape Minister of Health Theuns Botha is looking at the possibility of procuring our own stocks separately because we have had too many problems with national government delays, and our patients go without.”
Supply and demand
The inability of pharmaceutical companies to ramp up production to meet demand after winning a tender has at times been seen as contriuting to the threat of drug shortages.
Stavros Nicolaou, Senior Executive at Aspen Pharmacare, one of three companies to be given the FDC tender, said the latest award had sought to avoid stockouts at dispensing level by introducing a grace period for suppliers. Aspen is the largest supplier of generic medicines to the public and private health sectors in South Africa, he said, and is also the only local company producing the FDCs.
"Historically, what happened was that a tender was awarded on 15 December, and on 1 January… you'd be expected to supply," Nicolaou told IRIN. "If it was the first time you were going to supply, you had to have anticipated winning the tender to be ready to go out with product on the first of January."
Drug companies need about three months of lead-time to order, ship, receive and assure the quality of the active pharmaceutical ingredients needed for manufacturing drugs. In the case of FDCs, Aspen had also had to make structural alterations to its manufacturing facilities to accommodate the special technology required to manufacture a pill that combines three drugs.
Nicolaou said he did not believe that any possible FDC shortage was attributable to the inability of drug companies to supply. He noted that Aspen and other drug companies had met with the Department of Health in June 2012, before the tender was opened, to devise feasible timelines for ramped up production of the FDCs, develop plans for a phased rollout, and discuss the requirements of the tender, which hinged largely on projections of how many patients would make the switch to FDCs.
An estimated 70 to 80 percent of patients on the triple regimen are expected to make the switch by the end of the year. To combat stockouts, data is being collected on a weekly basis from provincial depots to identify weaknesses in the supply chain, and the department has also instituted monthly meetings with suppliers, at which three-month forecasts are presented.
Recent stockouts of regularly prescribed ARVs in Gauteng Province have been attributed to financial management problems, including corruption, in the provincial department of health, rather than to supply-chain issues. The Gauteng provincial treasury intervened in December 2012.
"We've been told that some of the drug shortages in Gauteng are due to poor budgeting and financial management," said TAC provincial coordinator Stephen Ngcobo. "We did our own research and found that... the budget was not covering the need, and that the [ARV] budget had been cut in half over the past two or three years, and this was having an effect… [now]."
Activists have begun a civil disobedience campaign in the province to draw attention to ARV and other drug stockouts, and civil society organizations will soon be launching a project to monitor supply problems.