Even using very conservative estimates of efficacy, using
two generic HIV drugs plus one branded one in the most popular first-line
regimen instead of using all three in a single-pill fixed-dose combination
would save $4000 per quality-adjusted year of life (QALY) for each individual
on treatment in the USA, and would save the country $920 million on its annual
drugs bill, the 19th
International AIDS Conference was told yesterday.
These estimates were arrived at by Rochelle Walensky and colleagues
from Harvard Medical School, using a mathematical model called the
Cost-Effectiveness of Preventing AIDS Complications in the US (CEPAC-US) model.
The single most popular first-line therapy in the US and the
first-place recommended regimen in the US
CDC treatment guidelines is tenofovir/FTC/efavirenz, usually given as the
fixed-dose combination pill Atripla. Lamivudine
is usually regarded as almost equivalent to FTC (emtricitabine) in terms of
efficacy and resistance profile, has
recently come off patent and efavirenz will do so next year. This allows for
doctors to substitute a three-pill regimen using the two generic drugs instead
Walensky’s team compared the likely clinical outcomes in
cost and life expectancy on people given no antiretroviral therapy (ART), Atripla or generic 3TC and efavirenz plus branded tenofovir (Viread) in the current on-treatment US
They built some conservative assumptions into the model.
They assumed that tenofovir/generic 3TC/generic efavirenz would be 7% less
virologically effective than Atripla,
achieving viral undetectability in 78% of patients within six months instead of
85% of patients. They also assumed more than twice the rate of virological
failure after the first six months, using a failure rate of 5.41% a year
instead of 2.52% a year as is the case with Atripla.
They assumed a 75% price reduction for the two generic drugs, leading to a 40%
reduction in the total regimen, from $15,300 a year down to $9,200, thus saving
$6,100 a year.
Using these figures, they calculated that patients on the
generic-based combination would have an extra life expectancy of 8.03
quality-adjusted life years (QALYs) over patients not taking ART, and patients
on Atripla 8.40 QALYs. This
difference in life expectancy, which we must remember is based on very pessimistic
assumptions of efficacy for the generic regimen, amounts to an extra 4.5 months
of life. The lifetime cost to the health system of a person not on ART would be
$131,200, on the generic-based regimen $300,300 and Atripla $342,800.
The threshold for cost-effectiveness of a drug regimen is
usually set at $100,000 per extra QALY gained in the USA. The generic-based
regimen would cost $21,100 per QALY and Atripla
$25,200 per QALY. This means that the extra 4.5 months of life gained would
cost $114,800 per QALY. If the pessimistic efficacy assumptions turn out to be
true, then, the incremental cost of using Atripla
would place it beyond the normally used bounds of cost-effectiveness.
Walensky acknowledged that talking about forgoing small
individual survival benefits for large national savings was an uncomfortable
subject, especially in the US. She also added that the savings cited would, in
practice, vary a lot according to who is paying for the drugs, whether they are
state AIDS Drug Assistance Programs (ADAPs), state Medicaid programmes, the US
Veterans Administration, or others. And she emphasised that there was no
guarantee that the extra money saved would be reinvested in HIV care.
However, she added, the CDC has recommended that any generic
regimen should be equivalent in efficacy for the branded drug(s) it replaces.
If this was the case, then there would be considerably greater savings per
It might be possible to negotiate a greater than 75% reduction
in price for the generics, too. She gave the example of three drugs. The price
of simvastatin was reduced by 66% when it came off-patent and of
methylphenidate by 72%, but the price of the blood-thinning drug warfarin came
down by 85% when it went generic.
What could the extra money pay for? Walensky said that
President Obama’s 2010 National HIV/AIDS Strategy must be explicitly financed
by “re-purposed” rather than new funds. This is an opportunity for treatment
providers to recommend that the money saved is re-invested into other treatment
programmes for people with HIV, such as the new hepatitis C drugs, which are
currently covered by less than 50% of ADAPs.