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Annals of Internal Medicine
Generic Antiretrovirals and the Uncertain Future of HIV Care in the
eneric antiretroviral drugs have contributed to re- ity of regimens that contain generic antiretrovirals and de-
markable achievements in the global HIV epidemic.
fining differences in adherence, virologic success, and
Mortality has decreased by 24% since 2005, new HIV
health care use. How these studies will be supported is
infections have decreased by 20% since 2001, and 8 mil-
lion persons are receiving treatment (1). In the United
Angst and uncertainty about HIV care abound at this
States, 10 available generic antiretrovirals have been used
time. According to the national version of the “Gardner
infrequently because of greater toxicity and inferior effi-
Cascade,” fewer than one third of PLWHIV in the United
cacy. However, when generic efavirenz becomes available
States have sufficient disease control with treatment, and
in 2013, a regimen of generic efavirenz and lamivudine
fewer than half (36%) are reliably receiving care (11).
with branded tenofovir will become a credible alternative
This unacceptably poor performance is worthy of soul-
searching. Fortunately, the National AIDS Strategy offers
In this issue, Walensky and colleagues (2) mathemat-
measured and specific guidance to our response to expand
ically model the effect of the substitution of generic efa-
HIV testing and improve recruitment and retention in care
virenz and lamivudine in all people living with HIV
(12, 13). Nonetheless, our HIV care “system” is a fragile
(PLWHIV) in the United States who were assumed to
edifice with disparate parts. Public sources, such as Medic-
receive the branded coformulation of these drugs with
aid, Medicare, and the Ryan White Care Act, support 80%
tenofovir. They found a 50% reduction in drug costs and a
of care for PLWHIV, and the Ryan White Care Act covers
savings of $960 million in care costs in 1 year. They also
only care, drugs, and services that are not supported by
found reduced treatment efficacy, resulting in 4.4 months
Medicare and Medicaid. Under the Affordable Care Act
of life lost per patient lifetime. Even with substantial vari-
(ACA), 32 million uninsured Americans will enter Medic-
ations in the model’s assumptions, large-scale cost savings
aid starting in 2014, but of 37 states under single-party
were achieved, and the comparative cost-effectiveness of
control, 24 are hostile to ACA and 20 currently plan not to
branded antiretrovirals exceeded the standard threshold of
participate in Medicaid expansion (14). Making matters
$100 000 per quality-adjusted life-year. Recent studies in
worse, rules for ACA that were recently issued left the
Europe and the United Kingdom also report substantial
definition of “essential health benefits” and drug formulary
savings with generic antiretrovirals (3–5).
composition up to states (15). As a result, existing state-
Can a regimen of combined generic and branded anti-
to-state disparities in HIV care and access to antiretrovirals
retrovirals perform as well as a preferred branded 1-pill,
once-daily coformulation? Current HIV treatment guide-lines uniformly recommend the use of coformulated anti-
In addition to these strains, the Ryan White Care Act,
retrovirals because of convenience, superior patient adher-
which serves more than 500 000 PLWHIV and provides
ence, patient and clinician preference, and lower insurance
treatment for 200 000 persons, is up for reauthorization in
copayments. Most available evidence support these recom-
2013. High-quality HIV care evolved within the HIV multi-
mendations (6). In 1 exception, once-daily regimens of 2
disciplinary team with guidance, training, and funding
or 3 equipotent antiretrovirals were not inferior to a
from the act. Many care innovations—such as the HIV
branded once-daily coformulation (7). Similarly, although
medical home and HIV prevention and treatment inte-
guidelines recommend once-daily dosing when possible, 1
grated with maternal– child health, mental health, and sub-
of 4 “preferred” initial regimens is dosed twice daily, and 7
stance abuse treatment—may be at risk if the act is sub-
of 11 studies in a meta-analysis found no difference be-
sumed into Medicaid under ACA (16). Community health
tween once- and twice-daily regimens (8).
centers are prioritized under ACA, but many lack skills and
Would even a small reduction in efficacy be accept-
capacity for HIV care and will require training. The act’s
able? In the study by Walensky and colleagues, poorer sur-
budgets will probably be further strained in states opting
vival with generics resulted from minor differences of un-
out of Medicaid expansion (17). Because half of its expen-
certain clinical significance between lamivudine and
ditures are for medications, generic antiretrovirals will be a
emtricitabine in resistance outcomes and virologic efficacy
critical issue in the reauthorization debate and in state
from limited trial data (9, 10). The best regimen choice in
Medicaid formulary budgets. Vigilance by HIV advocates
their model was generic efavirenz and coformulated emtric-
will be critical at the federal and state levels to ensure that
itabine plus tenofovir, a 2-pill, once-daily option with sim-
the act has sufficient flexibility to improve outcomes in
ilar efficacy and lower cost. Large-scale effectiveness trials
states that expand Medicaid eligibility to include most
that compare generics, including abacavir, with branded
PLWHIV and in states that decline Medicaid expansion.
coformulations will be critical in assessing the comparabil-
Activism to persuade reluctant states to expand Medicaid
2013 American College of Physicians 133
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Editorial Generic Antiretrovirals and HIV Care in the United States
eligibility and to safeguard multidisciplinary HIV care
3. Stoll M, Kollan C, Bergmann F, Bogner J, Faetkenheuer G, Fritzsche C, et
models in the transition into Medicaid will also be crucial.
al; ClinSurv Study Group.
Calculation of direct antiretroviral treatment costs
and potential cost savings by using generics in the German HIV ClinSurv cohort.
HIV advocates and caregivers might more readily em-
PLoS One. 2011;6:e23946. [PMID: 21931626]
brace generic antiretrovirals if, as Walensky and colleagues
4. Gazzard B, Moecklinghoff C, Hill A.
New strategies for lowering the costs of
suggest, the savings were diverted to address other funding
antiretroviral treatment and care for people with HIV/AIDS in the United King-
needs within the field of HIV medicine, but no such mech-
dom. Clinicoecon Outcomes Res. 2012;4:193-200. [PMID: 22888265]
5. Sloan CE, Champenois K, Choisy P, Losina E, Walensky RP, Schackman
anism exists. Perhaps a large, simple trial should be con-
BR, et al; Cost-Effectiveness of Preventing AIDS Complications (CEPAC)
ducted in which generic and branded antiretrovirals are
Newer drugs and earlier treatment: impact on lifetime cost of care
compared and patients in the generic group are allowed to
for HIV-infected adults. AIDS. 2012;26:45-56. [PMID: 22008655]
use the cost savings of their regimen to support their an-
6. Llibre JM, Arribas JR, Domingo P, Gatell JM, Lozano F, Santos JR, et al;
Spanish Group for FDAC Evaluation.
Clinical implications of fixed-dose cofor-
nual health insurance premiums, in which case I predict
mulations of antiretrovirals on the outcome of HIV-1 therapy. AIDS. 2011;25:
rapid accrual. In any case, Walensky and colleagues’ study
is a wake-up call to PLWHIV and their clinicians: The era
7. Buscher A, Hartman C, Kallen MA, Giordano TP.
Impact of antiretroviral
dosing frequency and pill burden on adherence among newly diagnosed,
of generic antiretrovirals in the United States has come.
antiretroviral-naive HIV patients. Int J STD AIDS. 2012;23:351-5. [PMID:
The noted infectious diseases physician John G. Bartlett
has predicted that the annual cost of antiretrovirals in 10
8. Parienti JJ, Bangsberg DR, Verdon R, Gardner EM.
Better adherence with
years will be less than $200, and he has not often been
once-daily antiretroviral regimens: a meta-analysis. Clin Infect Dis. 2009;48:484-8. [PMID: 19140758]
wrong when forecasting HIV care trends in the United
9. Svicher V, Alteri C, Artese A, Forbici F, Santoro MM, Schols D, et al.
Different evolution of genotypic resistance profiles to emtricitabine versus lami-vudine in tenofovir-containing regimens. J Acquir Immune Defic Syndr. 2010;
10. Gallant JE, Staszewski S, Pozniak AL, DeJesus E, Suleiman JM, Miller
MD, et al; 903 Study Group.
Efficacy and safety of tenofovir DF vs stavudine in
combination therapy in antiretroviral-naive patients: a 3-year randomized trial.
JAMA. 2004;292:191-201. [PMID: 15249568]
Potential Conflicts of Interest:
Disclosures can be viewed at www
11. Centers for Disease Control and Prevention (CDC).
Vital signs: HIV pre-
vention through care and treatment—United States. MMWR Morb Mortal
Wkly Rep. 2011;60:1618-23. [PMID: 22129997]
12. The White House Office of National AIDS Policy.
Strategy for the United States. Washington, DC: The White House Office of
Requests for Single Reprints:
Renslow Sherer, MD, Section of Infec-
tious Diseases and Global Health, Department of Medicine, University
13. Thompson MA, Mugavero MJ, Amico KR, Cargill VA, Chang LW, Gross
of Chicago, 5841 South Maryland Avenue, MC5065, Chicago, IL
R, et al.
Guidelines for improving entry into and retention in care and antiret-
roviral adherence for persons with HIV: evidence-based recommendations froman International Association of Physicians in AIDS Care panel. Ann Intern Med.
2012;156:817-33. [PMID: 22393036]
Ann Intern Med.
14. Davey M.
One-party control opens states to partisan rush. New York Times.
22 November 2012:A1.
15. U.S. Department of Health and Human Services.
Essential Health Benefits,
Actuarial Value, and Accreditation Standards: Ensuring Meaningful, Affordable
Coverage. Washington, DC: U.S. Department of Health and Human Services;
1. Joint United Nations Programme on HIV/AIDS.
Global Report: UNAIDS
2012. Accessed at www.healthcare.gov/news/factsheets/2012/11/ehb11202012a
Report on the Global AIDS Epidemic 2012. Geneva: Joint United Nations
16. Martin EG, Schackman BR.
What does U.S. health reform mean for HIV
clinical care? J Acquir Immune Defic Syndr. 2012;60:72-6. [PMID: 22517415]
/20121120_UNAIDS_Global_Report_2012_en.pdf on 12 November 2012.
17. Sherer R.
The future of HIV care in the USA. Sex Transm Infect. 2012;88:
2. Walensky RP, Sax PE, Nakamura YM, Weinstein MC, Pei PP, Freedberg
KA, et al.
Economic savings versus health losses: the cost-effectiveness of generic
18. Maxmen A.
Generic HIV drugs will widen US treatment net. Nature. 2012;
antiretroviral therapy in the United States. Ann Intern Med. 2013;158:84-92.
15 January 2013 Annals of Internal Medicine Volume 158 • Number 2
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