HIV Care Cost in England

A Cross-Sectional Analysis of Antiretroviral Treatment and the Impact of Generic Introduction

KJ Ong; AJ van Hoek; RJ Harris; J Figueroa; L Waters; C Chau; S Croxford; P Kirwan; A Brown; MJ Postma; ON Gill; V Delpech

Disclosures

HIV Medicine. 2019;20(6):377-391.

Abstract and Introduction

Abstract

Objectives: Reliable and timely HIV care cost estimates are important for policy option appraisals of HIV treatment and prevention strategies. As HIV clinical management and outcomes have changed, we aimed to update profiles of antiretroviral (ARV) usage pattern, patent/market exclusivity details and management costs in adults (≥ 18 years old) accessing HIV specialist care in England.

Methods: The data reported quarterly to the HIV and AIDS Reporting System in England was used to identify ARV usage pattern, and were combined with British National Formulary (BNF) prices, non-ARV care costs and patent/market exclusivity information to generate average survival-adjusted lifetime care costs. The cumulative budget impact from 2018 to the year in which all current ARVs were expected to lose market exclusivity was calculated for a hypothetical 85 000 (± 5000) person cohort, which provided an illustration of potential financial savings afforded by bioequivalent generic switches. Price scenarios explored BNF70 (September 2015) prices and generics at 10/20/30/50% of proprietary prices. The analyses took National Health Service (NHS) England's perspective (as the payer), and results are presented in 2016/2017 British pounds.

Results: By 2033, most currently available ARVs would lose market exclusivity; that is, generics could be available. Average per person lifetime HIV cost was ~£200 000 (3.5% annual discount) or ~£400 000 (undiscounted), reducing to ~£70 000 (3.5% annual discount; ~£120 000 undiscounted) with the use of generics (assuming that generics cost 10% of proprietary prices). The cumulative budget to cover 85 000 (± 5000) persons for 16 years (2018–2033) was £10.5 (± 0.6) billion, reducing to £3.6 (± 0.2) billion with the use of generics.

Conclusions: HIV management costs are high but financial efficiency could be improved by optimizing generic use for treatment and prevention to mitigate the high cost of lifelong HIV treatment. Earlier implementation of generics as they become available offers the potential to maximize the scale of the financial savings.

Introduction

HIV causes a chronic infection that can be controlled by life-long antiretroviral (ARV) use. Reliable estimates of lifetime HIV care costs aid policy decision-making around treatment optimization and HIV prevention strategies such as HIV testing or the offer of pre-exposure prophylaxis (PrEP). Such estimates are challenging to derive because of the complex and changing treatment options, variation in stages of HIV progression, the long time-scale of treatment, and the introduction of generics over time. In the UK, there is open access to free testing for and treatment of HIV infection through the National Health Service (NHS).

In 2016, 96% of the 84 725 persons living with diagnosed HIV infection accessing specialist HIV care in England were receiving ARV treatment (ART).^[1] National spending on HIV specialized services in 2016/2017 was close to £540 million, with slightly more than three-quarters of this total being spent on ART (;^[2] A. Duncan, Department of Health, personal communications). The lifetime HIV care cost has been estimated at £360 800 (undiscounted, 2013 values), modelled on men who have sex with men (MSM) aged 30 years and estimated to live for another 41.5 years to reach the age of 71.5 years.^[3] This cost was lower (£179 600) when assuming an 80% discount on list price 3 years after ARV patent expiry. The ART regime was based on 2012 British HIV Association treatment guidelines. The analysis used non-ARV HIV care costs derived from cohort data recorded over the years 1996–2008, for persons starting ART with two nucleoside reverse transcriptase inhibitors (NRTIs) in combination with a nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI).^[4] New ARVs with better side-effect profiles have since been introduced, and patient outcome improvements were observed in the UK Collaborative HIV Cohort (UK CHIC) data over the years 2000–2007.^[5] At the same time, life expectancy in persons living with diagnosed HIV infection has also improved.^[6] Given such changes in disease diagnosis and management landscapes, it is prudent to revisit the future resources needed for HIV care, including both ARV and non-ARV costs.

The objectives of this study were to generate a profile of ARV usage patterns for adults aged ≥ 18 years living with diagnosed HIV infection in England, collate details of patent and market exclusivity for currently available ARVs, and model the lifetime cost per person applicable in technology appraisals and annual budget impact analysis at a cohort level for HIV care payers. In the estimates of lifetime cost and annual budget impact, potential financial savings from switches to bioequivalent generics were considered.

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Abstract and Introduction
Methods
Results
Discussion
Appendix
References

Table 1. Number (%) of persons on individual antiretrovirals (ARVs) in 2016 in England ( n = 68 801*), estimated timing of generic availability, and British National Formulary (BNF) 70 (September 2015) list price and proprietary price for each individual ARV
ARV	Proprietary name	Estimated year of generic availability, unless stated otherwise	BNF70 (September 2015) price per person per year (proprietary price, if different)
Where specific ARV prescribed is known
> 5% of persons prescribed each of these ARVs in 2016
Abacavir + lamivudine	Kivexa	2019	£3645
Darunavir	Prezista	2020	£5439
Efavirenz + emtricitabine + tenofovir disoproxil fumarate	Atripla	Off-patent^†	£6488
Emtricitabine + tenofovir disoproxil fumarate	Truvada	2021	£4331
Ritonavir - any dose	Norvir	Off-patent^†	£2840
Ritonavir boosting dose	Norvir	Off-patent^†	£473
Tenofovir	Viread	Off-patent^†	£2488
1%-5% of persons prescribed each of these ARVs in 2016
Abacavir	Ziagen	2019	£2162
Atazanavir	Reyataz	2019	£3694
Efavirenz	Sustiva	Off-patent^†	£1251 (£2438)
Emtricitabine	Emtriva	2021^‡	£1692
Emtricitabine + rilpivirine + tenofovir disoproxil fumarate	Eviplera	2027	£6403
Lamivudine	Epivir	Off-patent^†	£669 (£1918)
Nevirapine	Viramune	Off-patent^†	£2070
Raltegravir	Isentress	2024	£5739
Rilpivirine	Edurant	2027	£2438
< 1% of persons prescribed each of these ARVs in 2016
Abacavir + lamivudine + zidovudine	Trizivir	2019	£5268
Didanosine	Videx	Off-patent^†	£1877
Enfuvirtide	Fuzeon	Keep originator price due to small market size	£13 168
Etravirine	Intelence	2024	£3668
Fosamprenavir	Telzir	Keep originator price, off-patent but no generics	£2680
Indinavir	Crixivan	Keep originator price, off-patent but no generics	£2204
Lamivudine + zidovudine	Combivir	Off-patent^†	£860 (£3654)
Lopinavir	Kaletra	Off-patent^†	£3475
Maraviroc	Celsentri	2023	£5372
Ritonavir-boosted lopinavir	Kaletra	Off-patent^†	£3475
Saquinavir	Invirase	Keep originator price, off-patent but no generics	£3059
Stavudine	Zerit	Keep originator price, off-patent but no generics	£1965
Tipranavir	Aptivus	Keep originator price due to small market size	£5369
Zidovudine	Retrovir	Off-patent^†	£1476 (£2432)
Where specific ARV prescribed is not known
> 5% of persons prescribed this category of ARVs in 2016
Newer generation ARVs^§		2033^¶	£4150
< 1% of persons prescribed this category of ARVs in 2016
First ARV regimen^#		Keep originator price, specific ARV not known	£7625 (£7907)
Second and subsequent ARV regimens^#		Keep originator price, specific ARV not known	£7977 (£8226)
Complex ARV^#		Keep originator price, specific ARV not known	£10 583 (£10 873)
Other NNRTI^††		Keep originator price, specific ARV not known	£2330 (£2725)
Other NRTI^††		Keep originator price, specific ARV not known	£1927 (£2242)
Other PI^††		Keep originator price, specific ARV not known	£3595
Not known		Keep originator price, specific ARV not known	£4355 (£4434)
Blinded treatment in clinical trials		Keep originator price, specific ARV not known	£0

NNRTI, nonnucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
*Of whom 2614 persons were not on antiretroviral therapy (ART). The list excludes amprenavir (proprietary name Agenerase; coded as used by < 5 persons) and nelfinavir (Viracept; coded as used by eight persons), which have been withdrawn from the market [15]. ^†Assumed generics available from 2018, which is the model first calendar year. ^‡Considered used in combination with TDF in Truvada and the estimated year it became available was the same as the estimated year in which the generic tenofovir disoproxil (any salt form) + emtricitabine combination pill became available. ^§The specific newer generation ARVs could not be determined from the codes available for use under the HIV and AIDS Reporting System (HARS) 2016 (clinics could only code them as "Other drugs"). These drugs included cobicistat, dolutegravir, elvitegravir, tenofovir alafenamide or their combination products with other ARVs; the price was calculated as the average of the cobicistat, dolutegravir and elvitegravir prices. ^¶Actual ARV was unknown (as in note §) but was estimated based on maximum expiry for tenofovir alafenamide. ^#Specific ARV was unknown. The cost was calculated by using a combination of HARS coding for treatment complexity level (first-line, second- or subsequent-line, or complex ART). ^††Specific ARV unknown. The cost was calculated from average prices of ARVs within the same class.

Table 2. Estimated total lifetime HIV care cost for selected HIV exposure categories and CD4 count at diagnosis, based on differential assumptions around generic discounting, adjusted by mean age at diagnosis and estimated life expectancy
	Mean age at diagnosis	Estimated no. of remaining life years from diagnosis	Median estimated HIV life expectancy*	Annual discount rate applied to future values
				3.50%					0.00%
				BNF70 prices	Generics at 10% of proprietary prices	Generics at 20% of proprietary prices	Generics at 30% of proprietary prices	Generics at 50% of proprietary prices	BNF70 prices	Generics at 10% of proprietary prices	Generics at 20% of proprietary prices	Generics at 30% of proprietary prices	Generics at 50% of proprietary prices
Model 1
Overall†	35	43	78	£202.3K	£73.3K	£88.3K	£103.2K	£125.1K	£404.3K	£124.1K	£156.5K	£188.9K	£234.6K
CD4 < 200 cells/μL at diagnosis	39	40	79	£201.7K	£72.4K	£87.5K	£102.4K	£124.0K	£387.3K	£118.2K	£149.7K	£181.0K	£225.7K
CD4 ≥ 200 cells/μL at diagnosis	35	45	80	£206.2K	£76.0K	£91.1K	£106.1K	£129.1K	£417.4K	£131.0K	£164.1K	£197.1K	£246.5K
MSM	35	44	79	£208.3K	£77.2K	£92.4K	£107.6K	£130.1K	£420.8K	£130.9K	£164.5K	£175.9K	£217.3K
PWID	34	20	54	£134.1K	£55.5K	£64.7K	£73.4K	£85.7K	£201.9K	£74.4K	£89.1K	£103.2K	£123.3K
Heterosexuals	36	45	81	£199.0K	£71.1K	£86.0K	£100.8K	£123.5K	£394.9K	£121.8K	£153.6K	£164.5K	£206.4K
Model 2
Overall	35	43	78	£193.8K	£70.2K	£84.6K	£98.9K	£123.0K	£375.3K	£119.0K	£148.7K	£178.4K	£228.1K

*Median HIV life expectancy calculated based on assumptions of proportional hazards in HIV-positive persons compared with Office for National Statistics (ONS) survival estimates, which were derived using cohort life expectancy projections. ^†Ratio of antiretroviral:nonantiretroviral costs under different price scenarios: British National Formulary (BNF) 70 (86:14), and generics at 10% of proprietary prices (49:51), 20% of proprietary prices (61:39), 30% of proprietary prices (68:32) and 50% of proprietary prices (75:25).

Table A1. Data completeness for each variable of interest ( N = 82 749 adults aged ≥18 years); complete observations excludes unknown values
Variable	Complete observations (n)	Complete observations (n/N%)
Year of birth	82 749	100
Gender	82 749	100
Year of diagnosis*	82 749	100
Years living with diagnosed HIV*	82 749	100
HIV clinic location	82 421	100
Ethnicity	81 640	99
Exposure route (risk category)	81 101	98
Year of ART Initiation^†	80 484	97
ART regime complexity level^‡	72 827	88
ARV1 code^§	72 827	88
First CD4+ count	67 594	82

*Exclude diagnoses coded as occurring before 1981 or after 2016, the same apply for years living with diagnosed HIV as this was calculated from year of diagnosis; †Exclude two observations whereby the year of ART initial was before 1981; ‡This has been cleaned to be consistent with ARV codes, where there was a code for ARV but ART regime complexity recorded patient "not on ARV" or "missing", changed to "on ART, regimen unknown"; n = 8890 observations were coded as "on ART, regimen unknown"; §This has been cleaned to be consistent with ART regime complexity, where there was a missing code for ARV but ART regime complexity recorded patient as on first-, second- or subsequent-line or complext ART or "not on ARV", updated ARV1 codes according to ART regime complexity; n = 6489 observations were recoded as first-line ART regime (n = 575), second- or subsequent-line ART regime (n = 1515), complex ART regime (n = 63), and not on ART (n = 4336) from 16 411 observations with missing values, leaving 9922 observations with missing values.

Table A2. Summary overview of HARS 2016 observations for all adults aged ≥18 years, stratified by observations with complete values for variables of interest (dates of diagnosis and ART initiation, and ARV codes; n = 68 801) and those with incomplete observations ( n = 13 948)
(a*)
HIV exposure category	No. (%) of observations		Mean (SD; IQR) age at diagnosis; unit: years		Mean (SD; IQR) years living with diagnosed HIV
HIV exposure category	Complete observations	Incomplete observations	Complete observations	Incomplete observations	Complete observations	Incomplete observations
Overall	68 801	13 948	36.3 (10.1; 29–42)	36.2 (10.1; 29–42)	10.5 (6.6; 5–14)	10.4 (7.0; 4–15)
MSM	32 262 (46.9%)	6783 (48.6%)	35.6 (10.0; 28–42)	35.4 (9.5; 28–41)	10.6 (7.5; 5–15)	10.7 (7.6; 4–16)
Hets	33 327 (48.4%)	6354 (45.6%)	36.9 (10.1; 30–43)	37.2 (10.1; 30–43)	10.5 (5.6; 6–14)	10.6 (6.1; 6–15)
MTCT	222 (0.3%)	139 (1.0%)	22.9 (7.5; 18–25)	20.2 (3.9; 18–21)	5.0 (3.9; 2–7)	3.9 (2.6; 2–5)
PWID	1210 (1.8%)	191 (1.4%)	34.9 (8.1; 29–40)	35.1 (8.1; 29–41)	12.0 (8.3; 5–17)	10.8 (7.9; 4–15)
Blood products	519 (0.8%)	94 (0.7%)	35.9 (11.9; 26–43)	39.3 (14.7; 26–51)	13.4 (9.5; 5–19)	11.4 (8.3; 4–18)
CD4+<200 at diagnosis†	15 945 (27.7%)	2545 (25.2%)	39.1 (10.4; 32–45)	38.4 (10.1; 31–45)	9.9 (5.5; 6–14)	10.8 (6.0; 6–15)
CD4+≥200 at diagnosis^†	41 541 (72.3%)	7563 (74.8%)	35.2 (10.1; 28–41)	35.3 (09.9; 28–41)	9.5 (6.2; 4–13)	8.8 (6.0; 4–13)
(b*)
HIV exposure category	No. (% of all diagnoses)^† of very late diagnoses	Ethnicity						Mean (SD) no. of medical consultations in 2016^‡
	No. (% of all diagnoses)^† of very late diagnoses	White (%)		Black (%)		Other (%)		Mean (SD) no. of medical consultations in 2016^‡
	Complete observations	Incomplete observations	Complete observations	Incomplete observations	Complete observations	Incomplete observations	Complete observations	Incomplete observations	Complete observations	Incomplete observations
Overall	15 945 (28%)	2545 (25%)	36 917 (55.2%)	6534 (49.2%)	23 900 (35.7%)	5086 (38.3%)	6070 (9.1%)	1662 (12.5%)	3.4 (2.3)	2.7 (2.1)
MSM	4880 (18%)	877 (17%)	27 575 (86.6%)	5052 (76.4%)	1469 (4.6%)	532 (8.0%)	2807 (8.8%)	1029 (15.6%)	3.6 (2.4)	2.8 (2.1)
Hets	10 297 (37%)	1567 (34%)	8000 (24.2%)	1257 (20.1%)	22 049 (66.6%)	4415 (70.6%)	3056 (9.2%)	579 (9.3%)	3.2 (2.1)	2.7 (2.0)
MTCT	68 (34%)	23 (32%)	37 (17.1%)	07 (5.1%)	150 (69.1%)	108 (78.8%)	30 (13.8%)	22 (16.1%)	3.7 (2.6)	2.4 (1.7)
PWID	263 (28%)	25 (23%)	1034 (86.1%)	160 (85.1%)	65 (5.4%)	10 (5.3%)	102 (8.5%)	18 (9.6%)	3.7 (2.5)	2.8 (2.1)
Blood products	117 (33%)	11 (24%)	271 (52.8%)	58 (62.4%)	167 (32.6%)	21 (22.6%)	75 (14.6%)	14 (15.1%)	3.4 (2.4)	3.2 (2.7)
CD4+<200 at diagnosis^†	15 945 (100%)	2545 (100%)	6559 (41.5%)	905 (36.3%)	7741 (49.0%)	1294 (51.9%)	1507 (9.5%)	294 (11.8%)	3.4 (2.3)	2.6 (2.0)
CD4+≥200 at diagnosis^†	0 (0%)	0 (0%)	24 406 (59.5%)	3886 (52.8%)	12 774 (31.1%)	2441 (33.2%)	3870 (9.4%)	1031 (14.0%)	3.5 (2.3)	2.6 (1.9)

*Table broken down to two parts to make readable; †CD4+<200 at diagnoses represented very late diagnoses; ‡Excluded attendances above 14 times a year (99th percentile).