Two HIV combination medicines delisted from the PBS

• From 1 March 2020, two fixed-dose combination (FDC) medicines for HIV will be delisted from the PBS
  Tenofovir disoproxil fumarate (TDF) with emtricitabine (FTC) and rilpivirine FDC (Eviplera), and TDF with FTC, elvitegravir and cobicistat FDC (Stribild), will be removed from the PBS.
• PBS-listed brands of TDF and FTC were subject to legislated price reductions on 1 April 2019
  The sponsor for these two medicines did not agree for them to remain listed at the new prices.
• Tenofovir alafenamide (TAF) with emtricitabine has largely replaced TDF + FTC combinations in this population
  At the March 2019 PBAC meeting, the PBAC advised there was no clinical reason for these two medicines to remain PBS-listed.
  
• The two medicines will remain listed on the PBS for 6 months from initial notification
  The notice about delisting was first published on 1 September 2019, providing a transitional period for people to switch to alternative treatment options. 

From 1 March 2020, two combination antiretroviral medicines for HIV will be delisted from the PBS Highly Specialised Drugs Program. The two medicines, which both contain tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC), are:^1,2

• TDF (300 mg) + FTC (200 mg) + rilpivirine (25 mg) FDC (Eviplera)
• TDF (300 mg) + FTC (200 mg) + elvitegravir (150 mg) + cobicistat (150 mg) FDC (Stribild).

The abbreviations used in this article are from the Australasian Society for HIV Viral Hepatitis and Sexual Health Medicine (ASHM) antiretroviral guidelines.²

See the PBS website for complete details for each item.

On 1 April 2019, TDF + FTC containing regimens listed on the PBS were subject to legislated price reductions. However, the sponsor for TDF + FTC + rilpivirine FDC (Eviplera) and TDF + FTC + elvitegravir + cobicistat FDC (Stribild) did not agree for them to remain listed on the PBS at the new prices.³

At the March 2019 PBAC meeting, the delisting of these medicines was considered. The PBAC advised there was no reason to retain these medicines on the PBS.³

The PBAC considered that tenofovir alafenamide (TAF) + emtricitabine has largely replaced TDF and FTC in combination medicines used to treat people living with HIV.³ Switching patients to TAF-containing regimens is consistent with current Australian guidelines.³

This was confirmed by PBS data that showed declines in TDF + FTC + rilpivirine FDC and TDF + FTC + elvitegravir + cobicistat FDC dispensing after listing of newer TAF-containing FDCs, such as TAF + emtricitabine (Descovy) which was listed on 1 December 2016.³

The committee also considered that people living with HIV usually follow up with their prescribers every 6 months and that transitional arrangements would allow sufficient time for people to switch to alternative treatments.³

As a result, advanced notice regarding the delisting of TDF + FTC + rilpivirine FDC and TDF + FTC + elvitegravir + cobicistat FDC on 1 March 2020 was published in the PBS schedule on 1 September 2019.^1,4

The public summary of the PBAC’s consideration is available on the PBS website.

TDF + FTC + efavirenz FDC

At the March 2019 PBAC meeting, TDF 300 mg + emtricitabine 200 mg + efavirenz 600 mg FDC (Atripla) was also considered for delisting from the PBS.³ However, on 1 August 2019, price reductions were agreed for this FDC, meaning it can remain subsidised through the PBS.⁵

Additionally, on 1 August 2019, an FDC containing tenofovir disoproxil maleate 300 mg + emtricitabine 200 mg + efavirenz 600 mg was PBS-listed as a generic equivalent to Atripla.⁶

There is no surcharge (brand premium) for Atripla.⁷ See Table 1. 

Table 1: Medicine active ingredients and brand names with abbreviations

With the upcoming delisting of TDF + FTC + rilpivirine (Eviplera) and TDF + FTC + elvitegravir + cobicistat (Stribild) from the PBS,¹ prescribers will need to ensure that people living with HIV who are taking either one of these medicines are managed safely and effectively through this transition period and going forward.³

Transition period until 1 March 2020

As most people living with HIV are reviewed by their doctors on a 6-monthly basis, prescribers should counsel patients that the two medicines will be delisted on 1 March 2020 as they come in for appointments.³

While only tertiary consultants and accredited general practitioners may prescribe antiretroviral therapy,⁸ other health professionals also play an important role in HIV care. Patient counselling (eg, by a pharmacist supplying antiretroviral therapy) may help to avoid the risk of people first finding out about the change when trying to fill a prescription.³

Selecting an alternative treatment

Safety, cost and access may need to be considered when selecting an alternative treatment regimen to prescribe.² The US DHHS guidelines have recommended several different first-line treatment options.²

TDF-containing regimens in other combinations such as TDF 300 mg + emtricitabine 200 mg (Truvada and generic equivalent brands) are still PBS-listed.⁹ At the time of writing, there have not been any other tenofovir-containing regimens marked for deletion from the PBS.¹

Additionally, the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) has provided some guidance on alternative treatment options for certain patient groups for whom these medications are the preferred treatment.¹⁰

For people currently treated with TDF + FTC + rilpivirine FDC without adverse effects and who are adequately virologically suppressed, prescribers may wish to consider switching to TAF-containing regimens or alternatives such as dolutegravir + rilpivirine, where appropriate, to maintain a single-tablet FDC regimen.¹⁰

For people currently treated with TDF + FTC + elvitegravir + cobicistat FDC who have reached virological suppression, other FDC treatments may be considered such as TAF + FTC + elvitegravir + cobicistat.¹⁰

Treatment options for pregnant women

The sponsor indicated that TDF + FTC + rilpivirine FDC (Eviplera) has a role in HIV treatment for pregnant women.³ Women taking antiretroviral therapy for HIV infection should continue their treatment regimen during pregnancy, provided it is well tolerated, safe, and effective in suppressing viral replication.^2,10

However, guidelines from the US Department of Health and Human Services (DHHS) state that abacavir + lamivudine or TDF + FTC or lamivudine are also suitable HIV treatment options for pregnant women (for initial or continuing therapy, or to switch to if their current antiretroviral therapy is not well tolerated or is not resulting in virologic suppression).¹¹ The PBAC also noted the PBS-listed medicines lamivudine or abacavir are preferred for HIV treatment of pregnant women.³

A third medicine may be added to these combinations, such as raltegravir, darunavir/ritonavir, atazanavir/ritonavir or rilpivirine.² 

Find more information in the US DHHS guidelines on use of antiretroviral drugs during pregnancy.

Compassionate access

People who require treatment with TDF + FTC + rilpivirine FDC or TDF + FTC + elvitegravir + cobicistat FDC for medical reasons, who prefer taking an FDC and who cannot receive an alternative PBS-listed treatment, can ask their health professionals to apply to the sponsor for access on compassionate grounds.²

TAF has fewer bone and kidney toxicities compared to TDF, while TDF is associated with lower lipid levels.²

The US DHHS guidelines state that TDF may be associated with proximal tubulopathy, acute or chronic renal failure and reduced bone mineral density scores, particularly in the presence of pharmacologic boosters (cobicistat or ritonavir). Proximal tubulopathy has been associated with resultant osteomalacia.²

Health professionals should check for drug interactions when changing antiretroviral therapy. Some medicines may reduce the effect of TAF (eg, carbamazepine) and concurrent use is not recommended.²

Combinations including cobicistat, a pharmacological booster which inhibits cytochrome P450 (CYP) 3A4, increase the potential for drug interactions.²

An HIV medicine interaction checker is available from the University of Liverpool website.

It is important that people living with HIV who are currently being treated with TDF + FTC + rilpivirine, or TDF + FTC + elvitegravir + cobicistat, visit their treating prescriber before 1 March 2020 to start the transition to an alternative treatment option.¹²

Changes to the available treatment options may confuse some people living with HIV who are currently treated with FDCs. In some cases, people may need to be switched to multi-tablet regimens.²

People living with HIV should be aware that they need regular monitoring, particularly when changing treatment.¹³ This is important, as measurements of viral load (amount of HIV virus in the blood) indicate how a person is responding to treatment and can also be used to confirm treatment failure.^13,14 After changing treatment, this should be checked after 4–8 weeks.²

Viral load is also useful to help people understand the importance of adherence to treatment.¹⁴

Health professionals need to tell patients that any extra monitoring requirements and potential side effects will depend on the type of treatment they are taking.¹³

For more information about HIV, visit the ASHM website, including Australian-specific commentary on the US DHHS guidelines.