Drug cost savings from routine use of generic ARVs: safety and efficacy in practice
Simon Collins, HIV i-Base
Several presentations provided results on commissioning guidelines relating to use of generic versions of commonly used HIV drugs. These showed the potential for large savings was driven by routine switching to generics with minor gains from other approaches.
NHS England saves £10 million from use of generics
The first of these was an oral presentation by Laura Waters from Mortimer Market Centre, on behalf of the NHS England HIV Clinical Reference Group (CRG). These were results for 2016/17 from a pharmacy audit of five clinically appropriate and acceptable prescribing switches that were aimed to save 2.5% from the £429m costs for 2015/16. 
This involved both new prescriptions for participants starting ART and switches for people currently stable on ART. The programme was developed by a multidisciplinary group, including doctors, pharmacists, patient representatives and commissioners.
The generic switches included switching to generic versions of abacavir/3TC, efavirenz, nevirapine and to coformulated cobicistat rather than separate ritonavir with darunavir or atazanavir. This results in total savings of almost £10m, driven mainly by use of generic abacavir/3TC and efavirenz, see Table 1.
Table 1: Drug switches and savings by NHS England 2016/17
|Switch ARVs||2016/17 savings (£)|
|Abacavir/lamivudine – originator to generic||6,946,811|
|Atripla to Truvada + generic efavirenz||1,131,212|
|Nevirapine PR – originator to generic||722,022|
|Darunavir/ritonavir to Rezolsta||752,172|
|Atazanavir/ritonavir to Evotaz||240,404|
Even though this programme was not fully rolled out in all regions, with some areas starting later, the switches reduced the drug budget to $413.7m, achieving a 3.5% saving compared to the total ARV budget compared to 2015/16. An additional £2m savings were made in other secondary savings.
Additional costs, however, were not adjusted for or included in these results, for example, from more frequent clinic visits, switching back when appropriate, and the suspension of VAT-free prescribing. Also, this was only a financial analysis, with no details on clinical outcomes.
Clear communication to individual patients and community engagement in this process overall were both emphasised as being essential. The lack of an updated CRG website to help with information and transparency was noted as a weakness.
Allowance for additional visits and switch-backs
In a second oral presentation in the same conference session, Elizabeth Okecha from Manchester University NHS Trust presented a review of total costs from a case note review of 432 patients from single clinic in Manchester (The Hathersage Centre). 
This involved some of the same switches to the CRG study reported above, but also included switching from the fixed dose combination (FDC) of dolutegravir/abacavir/3TC to separate dolutegravir plus generic abacavir/3TC.
In addition to drug savings, results were also presented for additional costs including clinic visits and drug wastage. Although large savings were switching to generic formulations, especially from the two FDC Atripla and Triumeq, addtional costs from extra clinic visits and drug wastage resulted in increased costs when switching to darunaivr/cobicistat coformuation, see Table 2.
Table 2: Drug switches and savings in Manchester clinics (n=432)
|Switch ARVs||n||Further switches
|extra visits||extra clinic costs (£)||drug wastage (£)||Net saving (6 months)|
|Atripla to Truvada + generic efavirenz||187||8||11||4550||4654||£71,319|
|Triumeq to dolutegravir plus generic abacavir/3TC||76||10||14||5997||3193||£42,760|
|Darunavir/ritonavir to Rezolsta||152||11||59||20,346||4515||–£7,132|
|Atazanavir/ritonavir to Evotaz)||17||0||5||1,755||0||£227|
The results included the 29/432 of people who had to modify treatment again after the first switch, requiring an additional 89 clinic visits.
Two cases of viral failure were reported in patients who were previously on stable ART, one with resistance to efavirenz (K103N) and one with resistance to lamivudine (M184V).
Overall patient acceptability however was reported as good.
Several posters presented additional aspects relating to switching and implications for costs and savings.
Complications from switching ritonavir to cobicistat
A poster presented by Colver et al from Luton Sexual Health presented results from a case note review of 48 patients who switched from ritonavir- to cobicistat-boosted PIs. NHS England CRG has set target to switch 50% of patients on darunavir and 60% on atazanavir to the FDCs Rezolsta and Evotaz, respectively. 
Mean age of this group was 44 (range: 29 to 56), with 77% black African and 56% women. Most people were on daruanvir (65%), with one third on atazanavir. Overall 8-5% were using tenofovirDF/FTC backbone but only 39/48 had viral load <40 copies/mL) before the switch (those with detectable ranged from 116 to 4935 copies/mL).
New side effects were reported by 21% of patients (including headache, diarrhoea, generalised itch, leg/foot pain and rash) resulting in four individuals switching back to ritonavir (8%).
Although the poster concluded that majority of patients switching from ritonavir to cobicistat benefit from a reduced pill burden, a small number switch back to their original regimen because of side effects. They recommended using a short course of the cobicistat-containing regimen first to avoid wasting larger quantities in those who do switch back.
A second poster on switching to cobicistat was presented by Pires and colleagues from the Lawson Unit in Brighton. 
This case note review included 173 patients who switched from darunavir plus ritonavir to darunavir/cobicistat. Of these, 15/173 (8.6%) later discontinued darunavir/cobicistat, with 7/15 returning back to ritonavir: 3/7 tablet size; 3/7 side effects (stomach cramps, headache, foot pain) and 1 due to patient choice. Of the 8/15 changing to alternative combinations, 5/8 were due to diarrhoea, 3/8 for cardiovascular risk and 1/8 due to pill burden and raised creatinine.
Of the 17 people on atazanavir, 2/17 returned to atazanavir/ritonavir (1 due to dizziness, 1 to acne and alopecia) and 2/17 changed to alternative combinations (1 due to pill burden and jaundice and 1 for simplification).
There were no virological failures from switching to cobicistat. Although the study reported saving approximately £25,000 from this switch, the poster was unclear whether additional costs from clinic vists and additional treatment changes had been included.
Switching from Atripla to generic efavirenz plus separate TDF/FTC
Three posters provided more details from switching from the FDC Atripla to generic efavirenz plus separate TDF/FTC.
The first, from the large Chelsea and Westminster cohort, was presented by Tyler and colleagues. 
The database review identified 2547 patients in April 2016 who were taking Atripla, Since then, 1556/2547 (61%) switched to generic efavirenz plus TDF/FTC and 48 (2%) to generic efavirenz with new NRTIs, Of the 648 patients (25%) switching to alternative combinations, 31/648 (5%) changed to an alternative single pill combination.
The remaining 295/2547 (12%) who did not switch are either lost to follow-up, have not yet been reviewed or have died.
Of the people who switched, 94% remained on generic efavirenz and 6% (n=97) subsequently switched to an alternative ART.
The most common reason for switching from generic efavirenz were: side effects (75/97; including CNS in 63/75), drug-drug interactions (10/97), single pill request (6/97), TDF side effects (4/97) and viral failure (2/97).
Notably, approximately half of the people stopping due to side effects reported that these were new-onset with the generic formulation.
The second was a case note review from Nottingham University Hospital presented by Darley and colleagues. 
Switching from Atripla was discussed with 157/188 patients (88%) recorded as taking Atripla in December 2016. Of these, 21 were not offered this switch because ATP was no longer suitable due to side effects (14), drug interactions (5) or virologic failure (2): showing the importance of regular assessment of stable ART. One patient was identified as not being suitable for a switch.
At this time, switch was voluntary, with 110 people accepting the switch and 47 continuing with the FDC (largely to avoid increase in pill count). Of the 110 who switched, 11/110 (10%) switched back due to new side effects (9/11) or problems with pill swallowing (2/11).
In this Atripla cohort overall, 99/188 (52%) have successfully switched to generic efavirenz with 30% remaining on Artipla and 18% switching to alternative combinations.
Although not meeting the commissioner target to switch 60% of patients on the FDC, this group reported that patient education and clear explanations were particularly important for switching to be successful and that switches for cost-saving rather than clinical need should not be compulsory.
Finally, the NHS commissioning response in Birmingham stopped prescription of Atripla entirely, with the Trust no longer ordering supplies. 
Patients were informed of the new policy at their routine clinic and they were assured that their new two-pill combination contained the same medicines as Atripla. 
Of the 445 people switching (63% men, 37% women), 97% of who had viral load <40 copies/mL pre-switch, 436/445 (98%) had undetectable viral load six months after the switch to the generic.
The led to an annual saving of almost £2m with an average annual saving of £4336 per patient who switched from Atripla, reducing the overall drug cost in the Atripla cohort from £2,877,498 to £948,042.
As with all other health areas, the routine switch to generic drugs enables the NHS to continue to provide free HIV testing and treatment. The policy also led to successful price reductions by originator companies. For example, ViiV Healthcare reduced the price for Triumeq to match comparable generic prices for the abacavir/3TC components.
These overall savings on the drug budget were made despite increasing numbers of people each year, related to annual HIV incidence and earlier use of ART.
However, even for simple switches, the importance of generally rare reactions is important in the framework of individualised care. This becomes even more important when commissioning guidelines are based on target goals (CQUINS etc) for cost-based prescribing. The use of the MHRA yellow card reported scheme is important for all such cases. 
Patient engagement and accurate information seems key to successful switching programmes and can lead to significant savings.
Unless stated otherwise, all references are to the Programme and Abstracts of the 4th Joint BHIVA/BASHH Conference, 17 – 20 April 2018, Edinburgh. HIV Medicine (2018), 19 (Suppl. 2).
- Waters L et al. Was the pain worth the gain? Antiretroviral (ARV) savings from the Improving Value project and generics use in England . 4th BHIVA/BASHH, 17-20 April 2018, Edinburgh. Oral abstract O1. HIV Medicine, 19 (Suppl. 2), s5–s20.
- Okecha E et al. NHS England commissioning for value: what is the hidden cost? 4th BHIVA/BASHH, 17-20 April 2018, Edinburgh. Oral abstract O2. HIV Medicine, 19 (Suppl. 2), s5–s20.
- Colver H et al. Cost-effectiveness switching from ritonavir- to cobicistat-boosted PIs: is simplification as straightforward as it sounds? 4th Joint BHIVA/BASHH Conference, 17 – 20 April 2018, Edinburgh. Poster abstract P6. HIV Medicine, 19 (Suppl. 2), s21–s152.
- Pires S et al. Tolerability, efficacy and cost savings associated with switching ritonavir to cobicistat. 4th BHIVA/BASHH, 17-20 April 2018, Edinburgh. Poster abstract P28.
- Tyler S et al. A review of switching people living with HIV (PLWH) from Atripla to Truvada and generic efavirenz (gEFV). 4th Joint BHIVA/BASHH Conference, 17 – 20 April 2018, Edinburgh. Poster abstract P2. HIV Medicine, 19 (Suppl. 2), s21–s152.
- Darley A et al. Did commissioning for value provide good value? 4th Joint BHIVA/BASHH Conference, 17 – 20 April 2018, Edinburgh. Poster abstract P7. HIV Medicine, 19 (Suppl. 2), s21–s152.
- Manavi K. Virological and financial impact of switching HIV-infected patients to generic components. 4th Joint BHIVA/BASHH Conference, 17 – 20 April 2018, Edinburgh. Poster abstract P30. HIV Medicine, 19 (Suppl. 2), s21–s152.
- MHRA yellow card reporting scheme.