Safety concerns delay new HIV drug
• Low numbers using cheaper pill lead to scrapping of consent forms
The department of health’s plans to switch HIV patients to a cheaper pill containing dolutegravir have hit yet another stumbling block after measures instituted by the medicines regulator to warn women of its potential risks have unexpectedly scared them off. More than six months after the government awarded supply contracts to pharmaceutical manufacturers, a mere 35,000 patients are on the new pills.
The health department’s plans to switch HIV patients to a cheaper pill containing dolutegravir have hit another stumbling block after measures instituted by the medicines regulator to warn women of its potential risks have unexpectedly scared them off.
More than six months after the government awarded supply contracts to pharmaceutical manufacturers, a mere 35,000 patients are on the new pills.
The extremely low numbers have prompted the health department to ask the SA Health Products Regulatory Authority (Sahpra) to review its requirements, which are to be relaxed from this week.
“There has been a reluctance by prescribers and female patients to have to sign a form to access TLD [the new pill, which contains tenofovir, lamivudine and dolutegravir],” said the health department’s acting director-general, Anban Pillay. “Currently no other HIV treatment has this restriction.”
SA had the world’s biggest HIV burden, with 7.1-million people afflicted, and had the world’s biggest treatment programme reaching about 5million patients, Pillay said.
The government aimed to have 6.1-million patients on treatment by year’s end.
Projections in the supply contracts awarded to pharmaceutical manufacturers in July 2019 for TLD forecast the provision of 147-million packs over three years, equivalent to about 4-million patients a month.
PROGRESS
Successful implementation of the new treatment regimen is crucial for the health department, not only because it will save money, but also because it needs to assure key donors such as the US Presidential Plan for Aids Relief (Pepfar) that it is making progress in bringing the HIV epidemic under control.
Delays are bad news for pharmaceutical manufacturers such as Adcock Ingram, which has said it needs to increase volumes in its loss-making Wadeville facility. The government’s decision to switch first-line therapy from a pill called TEE (which combines tenofovir, emtricitabine and efavirenz) to TLD was driven by economic and clinical considerations.
“Dolutegravir-containing treatments are better tolerated, have an incredibly high resistance barrier, and are cheaper,” said Francois Venter, deputy director of the Wits Reproductive Health and HIV Institute. “It’s not often we simultaneously get a better and cheaper drug. The weight gain side effect, which we are still teasing out, and teratogenicity issues are real headaches, though,”
TLD has been on the health department’s radar since September 2017, when the Clinton Health Access Initiative and the Bill and Melinda Gates Foundation brokered a deal to cut its price in 90 low- and middleincome countries, including SA.
At that stage, then health minister Aaron Motsoaledi said the switch was expected to save SA $900m over the next six years, enabling the government to put more people on treatment for the same resources.
REPEATED DELAYS
But the rollout has been dogged by repeated delays, first on safety worries that held up the registration of generic TLD pills with Sahpra, and more recently by the regulator’s requirement that women of childbearing age be counselled about the risks and benefits of dolutegravir, and sign an informed consent form.
Research in Botswana found dolutegravir increased the risk of neural tube defects in women who took it in early pregnancy.
Sahpra spokesperson Yuven Gounden said the latest data from the Botswana study suggested the risk of neural tube defects might be lower than initially indicated, falling from 0.9% to 0.3% “This is still a higher risk compared to women not exposed to dolutegravir (0.1%). Women need to be made aware of this risk and time in pregnancy when the risk is highest — from the time of conception and during the first six weeks of pregnancy,” he said.
Sahpra has relaxed its requirements and scrapped the requirement for consent forms. Clinicians will now only have to record that they have provided information on the risks to patients, and suppliers will be required to provide patient information leaflets to clinics.
TLD was launched by health minister Zweli Mkhize in November, but five provinces waited until this year to begin providing the drug as many patients had already received a two-month supply of medication to tide them over the Christmas holiday period, according to Pillay.