"It is with great sadness that I announce that Timothy passed away... this afternoon surrounded by myself and friends, after a 5 month battle with leukemia," his partner Tim Hoeffgen said in a post on Facebook.
Brown, born on March 11, 1966, became known as the "Berlin Patient" after his HIV was eradicated by treatment there in 2007.
The American's case fascinated and inspired a generation of HIV doctors as well as patients infected with the virus that causes AIDS, offering a glimmer of hope that one day a cure will be found that eventually ends the AIDS pandemic.
Adeeba Kamarulzaman, president of the International AIDS Society, said he would mourn Brown "with a profoundly heavy heart." "We owe Timothy and his doctor, Gero Huetter, a great deal of gratitude for opening the door for scientists to explore the concept that a cure for HIV is possible," said Kamarulzaman, who is also a professor of medicine and infectious diseases at Malaya University.
Brown was diagnosed with HIV in 1995 while living in the German capital, and in 2006 was also diagnosed with a type of blood cancer known as acute myeloid leukemia.
While Brown remained clear of HIV for more than a decade after being treated, he had suffered a relapse of the leukemia in the past year. His doctors said the blood cancer had spread to his spine and brain, and he had recently been in hospice care in his home town of Palm Springs, California.
For Huetter, the German doctor caring for him in 2007, Brown's case was a shot in the dark. The treatment involved the destruction of Brown's immune system and the transplanting of stem cells with a gene mutation called CCR5 that resists HIV.
Only a tiny proportion of people — most of them of northern European descent — have the CCR5 mutation that makes them resistant to the AIDS-causing virus.
This and other factors made the treatment Brown had expensive, complex and highly risky. Most experts say it could never become a way to cure all HIV patients, since many of them would risk death from the procedure itself.
More than 37 million people worldwide are currently infected with HIV, and the AIDS pandemic has killed about 35 million people since it began in the 1980s.
Medical advances over the past three decades have led to the development of drug combinations known as antiretroviral therapies that can keep the virus in check, allowing many HIV positive people to live with the virus for years.
A second HIV patient, Adam Castillejo, who was known as "the London patient" until he revealed his identity this year, is also thought to be in remission from HIV after having a transplant in 2016 similar to the one Brown had.
"Although the cases of Timothy and Adam are not a viable large-scale strategy for a cure, they do represent a critical moment in the search for an HIV cure," said Sharon Lewin, a professor and HIV specialist at Australia's Doherty Institute.
She said Brown was a "a champion and advocate for keeping an HIV cure on the political and scientific agenda," and added:"It is the hope of the scientific community that one day we can honor his legacy with a safe, cost-effective and widely accessible strategy to achieve HIV remission and cure."