Giving some newly-diagnosed patients an antibiotic would significantly reduce the death toll in the early stages of the disease, they say.
A major study in The Lancet medical journal found it halved mortality.
The World Health Organization already endorses the treatment, but specialists say many people are not given the drug.
Much of the focus of the pharmaceutical battle against HIV has been on antiretroviral drugs, which can greatly extend life.
However, many patients are at greatest risk in the first weeks after diagnosis, with a variety of infections ready to take advantage of their weakened immune systems.
Studies have estimated that as many as a quarter of people who enter antiretroviral drug treatment programmes in sub-Saharan Africa will die in the first year.
But the addition of co-trimoxazole, an inexpensive antibiotic, to the long-term treatment plan of those with the worst affected immune systems appears to prevent many of these deaths.
In HIV infection, it is highly effective for treatment of and prophylaxis against Pneumocystis jirovecii pneumonia, Toxoplasma gondii, Isospora belli, and bacterial infections; it also has antimalarial properties.
The Lancet study, carried out among 3,179 Ugandan patients, suggested a fall of 59% over the first 12 weeks, and 44% between 12 and 72 weeks.
Call for action
Its authors, from the Medical Research Council Clinical Trials Unit and Imperial College in London, and centres in Uganda and Zimbabwe, say the antibiotic is not available in many places.
They say their findings reinforce the need for swifter action by those responsible for drug treatment programmes.
Professor Charles Gilks, who led the study, said any arguments over the effectiveness of the antibiotics were now “well and truly answered”.
He said: “Tens of thousands of lives can be saved by more universal use of the drug, costing just a few pence a day.”
Co-author Professor Diana Gibb, from the Medical Research Council, said the availability and supply of the drug needed to be “ramped up”, and offered to all new patients for the first 18 months.
“There is a significant benefit now – waiting to be grasped,” she said.
In addition to preventing bacterial infections in HIV patients, the drug had a another welcome benefit – it cut the incidence of malaria by a quarter.
Dr Sarah Walker, also from the MRC, said: “The benefits of using this drug are huge, and it’s so simple and cost-effective to administer.”
However, Dr Alvaro Bermejo, the executive director of the International HIV/AIDS Alliance, said access to antiretroviral treatment remained an even bigger problem.
“We need to remember that there are still millions of people in Africa who need antiretrovirals and can’t access them.
“In Uganda the Alliance is seeing people turned away from clinics because they don’t have the treatment available.
“As the study confirms, antiretroviral treatment cuts the risk of death by more than 90% – with co-trimoxazole reducing the risk still further.
“We have the knowledge available to save lives but we need to increase efforts to make sure that everyone who needs treatment can actually access it.”
With files from BBC