Any rise in the use of cheaper, non-branded HIV drugs could see more patients with treatment failure, doctors warn.
Soon-to-be available generic medicines could save the US health care system nearly $1bn a year, they say in the journal Annals of Internal Medicine.
But trial data suggests generic drugs might be slightly less effective.
And they require users to take three daily pills instead of one, increasing the risk some patients may miss doses.
The doctors calculate reduced treatment efficacy could result in 4.4 months of life lost per patient lifetime.
At the same time the lifetime financial savings would be $42,500 (£26,500) per patient, say the Massachusetts General Hospital investigators.
The currently recommended treatment for newly diagnosed patients is a single pill (Atripla) taken daily that combines three brand-name antiretrovirals - tenofovir (Viread), emtricitabine (Emtriva) and efavirenz (Sustiva).
A generic form of a drug that has a similar mechanism of action to emtricitabine became available in January 2012, and a generic version of efavirenz is expected in the relatively near future.
Patients could soon take these two less expensive generic drugs alongside the brand drug tenofovir.
Lead researcher Dr Rochelle Walensky said: "This is a trade-off that many of us will find emotionally difficult, and perhaps even ethically impossible, to recommend."
For patients who took their medications well and adhered to the medical regimen, the generic option would be a bit more complex but could be as effective as the standard regimen, she said.
But those who missed a dose faced treatment failure.
She said this trade-off might be more acceptable if the financial savings were redirected to other aspects of HIV medicine.
The researchers calculate that for every 15 patients switched to the generic-based regimen, one who is also infected with hepatitis C could be treated and potentially cured of that infection.
Jason Warriner, of the Terrence Higgins Trust, a UK HIV charity, said: "We welcome this research, which couldn't be more timely.
"There are around 7,000 people diagnosed annually in the UK, meaning the cost of anti-HIV drugs is rising year on year.
"With the NHS under unprecedented financial pressure, the spread of the epidemic is a challenge not just for public health but for the public purse.
"Introducing generic medications would be one way for the health service to reduce expenditure, but this must not be at the expense of patient health.
"Anything that compromises the effectiveness of anti-HIV drugs, or makes people less likely to stick to treatments, would be a false economy.
"Currently, ensuring people with HIV are diagnosed and on treatment is a cornerstone of HIV prevention efforts.
"Effective medications not only keep those living with the virus fit and well, they also help to keep down new infections."