Abstract
The transition of clinical trial data to changes in routine clinical practice is often a slow process. We describe a rapid transition of patients from one form of antiviral therapy to a modified and potentially safer version that can occur quickly when there are no financial or organisational restrictions on the prescribers.
The majority of patients with human immunodeficiency virus (HIV) have been treated with a nucleotide reverse transcriptase inhibitor backbone containing tenofovir disoproxil fumarate (TDF) for many years. 1 A number of medications are currently available with a TDF backbone: Viread® (TDF 300 mg), Truvada® (TDF 300 mg/emtricitabine 200 mg), Atripla® (TDF 300 mg/emtricitabine 200 mg/efavirenz 600 mg), Eviplera® (TDF 300 mg/emtricitabine 200 mg/rilpivirine 25 mg) and Stribild® (TDF 300 mg/emtricitabine 200 mg/cobicistat 150 mg/elvitegravir 150 mg). While TDF-based regimens have been effective at controlling viraemia, there are concerns about cumulative proximal renal tubulopathy and a reduction in bone mineral density with long-term use. 2 Randomised clinical trials have shown that tenofovir alafenamide (TAF)-based regimens have achieved similar antiretroviral activity without these renal and bone concerns.3,4 As patients with HIV infection require lifelong therapies, the clinical consequence of these toxicities are likely to have an adverse impact on people aging with HIV infection. At the end of 2016, an estimated 43% of Australians living with diagnosed HIV were aged 50 and older. 5 TAF-based combination therapies: Genvoya®, Descovy® and Odefsey® are all now licensed and fully reimbursed in Australia. We therefore looked at the transition from TDF to TAF-based therapies within our clinic population. The Albion Centre is a large inner city ambulatory clinic specialising in providing no-cost HIV and sexual health services to a predominately men who have sex with men client base.
Prescription dispensing data encompassing a representative three-month period in 2015 (before the approval of any TAF-based regimens) was extracted from the Albion Centre pharmacy dispensing database. Most HIV+ patients collect their prescription refills either every two or four months, so a three-month audit period was selected as a representative timeframe. A similar dispensing interval was selected in 2017, once Genvoya®, Descovy® and Odefsey® had been all been approved and reimbursed. The Pharmaceutical Benefits Scheme (PBS) reimbursement of these drugs occurred in April 2016 for Genvoya®, December 2016 for Descovy® and May 2017 for Odefsey®. The PBS reimburses pharmacies at a national level, removing the cost of medications from the local health service or patient expenses. We excluded subjects receiving antiretrovirals through randomised clinical trials or compassionate access programmes.
During the months of August–October 2015, TDF-based regimens accounted for 63% (501 of 795) of all internal prescriptions: Truvada® 221, Eviplera® 140, Stribild® 73, Atripla® 46 and Viread® 21.
In 2017, only 3% of patients remained on TDF-based therapy. Conversely, Descovy®, Genvoya® and Odefsey® accounted for 22%, 31%, and 13% of prescriptions, respectively (Table 1).
HIV+ client prescriptions by clinic specialists who presented to clinic pharmacy in August–October 2015 or 2017.
TDF: tenofovir disoproxil fumarate; TAF: tenofovir alafenamide; HIV: human immunodeficiency virus.
Our audit was designed to provide a representative snapshot of antiretroviral prescribing through our clinic. We may have potentially missed some of our regular patients, who might have collected more than four months of medication close to but outside of the sampling window. We were also not able to match different medications with clinical data on renal function or bone density results to determine if actual toxicities, rather than the concern about toxicities, had driven this change in prescribing. Not all patients transitioned off their efavirenz-based therapy, possibly because no TAF combination exists containing efavirenz. Antiretroviral prescribing within our service was predominately restricted to five full-time HIV specialists who do not work in other disease areas. These clinicians have autonomy in their choice of HIV medications (within national guidelines) and would therefore be considered to be knowledgeable on antiretroviral issues. Although generic versions of TDF will become available in Australia within the next few months, it is unlikely that these will have significant impact on TAF-based prescribing patterns, as they do not have any direct impact on choice consideration for either prescribers or patients in terms of their lower cost, as all antiretrovirals are completely reimbursed through the PBS system. Conversely, TAF-based prescribing may further increase once the protease inhibitor – TAF combination tablet (TAF 10 mg/emtricitabine 200 mg/cobicistat 150 mg/darunavir 800 mg) obtains PBS approval.
TAF does not accumulate within renal proximal tubule cells as occurs with TDF and thus does not induce the phosphate wasting and osteomalacia associated with TDF. 6 It therefore likely represents a safer long-term treatment option for HIV-infected patients.
Footnotes
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.