HIV probably arrived in the U.S. around 1971—a decade before AIDS was recognized as a disease and a dozen years before scientists discovered the virus that causes it—according to a new analysis of viral genomes from New York City and San Francisco. The genetic evidence upends a longstanding myth that a French-Canadian flight attendant started the U.S. epidemic when he slept with men in California and New York in the early 1980s.
This revised timeline comes from a close examination of blood samples taken from men in the late 1970s for hepatitis B testing and that of the man blamed for being the U.S. epidemic’s “Patient Zero.” For this new work researchers managed to isolate HIV in eight of those 1970s blood samples and sequence the viruses’ genomes. The genetic diversity of the HIV samples from those early dates lays bare the fact that the virus had been circulating—and mutating—in the country throughout the 1970s. The team’s molecular clock work even suggests that the U.S. strain of the virus had hopped from Africa to the Caribbean by about 1967, moved to New York City by about 1971 and from there to San Francisco by about 1976.
The virus’s family tree was sketched out by a group of international disease experts and a medical historian. They sequenced HIV genomes from patient blood samples and examined how the virus mutated over time. By comparing the eight genome sequences to HIV samples from the Caribbean and Africa and assuming certain rates of mutation, the researchers found that there was already striking genomic diversity in the virus around the U.S. by the late 1970s. This suggests HIV had already been evolving within U.S. hosts for years. Similar genetic clock methods have also cleared 2014 World Cup soccer tournament fans of introducing the Zika virus to the Americas, and have helped epidemiologists track foodborne outbreaks.
The scientist who led the new HIV research, Michael Worobey, had published a paper in Proceedings of the National Academy of Sciences in 2007 suggesting a similar early introduction of HIV into the U.S.—but this drew serious skepticism. In this earlier work Worobey and his colleagues cited less-definitive evidence: They had studied viral gene samples from the 1980s, not whole genome sequencing from the late 1970s. With this new work, “there will be very few people left who will take issue with this early timing,” says Worobey, head of the Department of Ecology and Evolutionary Biology at the University of Arizona.
Worobey’s new study, published Wednesday in Nature, relied on virus isolated from blood serum samples from 1978 and 1979—mostly collected for unrelated studies on hepatitis B among men who had sex with men in San Francisco and New York City. His research team scoured the samples for signs of HIV, and studied the makeup of those viral samples’ sequences. His team then concluded that the viral genome from the supposed Patient Zero most closely resembled later samples of HIV—those with mutations that placed them in the middle of the HIV family tree—making it very unlikely that he was Patient Zero when the virus had apparently been circulating in the country for a decade. The result of this work “puts to rest this silly Patient Zero story,” says Beatrice Hahn, a professor of medicine who works on HIV at the University of Pennsylvania and was not involved in the study. “It’s pretty clear that the 1978 and 1979 samples definitely predated the description of the disease in the 1980s and there wasn’t just one person infected at that time—people were infected in NYC and San Francisco,” she says.
Gaetan Dugas, the flight attendant from Quebec who came to be labeled Patient Zero and died in 1984, reported approximately 250 different sexual partners a year between 1979 and 1981. Epidemiologists trying to understand the then-unknown virus and its transmission in the early 1980s interviewed symptomatic patients including Dugas and discovered that he or his partners had sexual contact with multiple other patients who later reported similar sets of symptoms. Armed with that information, investigators at the U.S. Centers for Disease Control and Prevention created diagrams with arrows and circles that pointed to Dugas as a likely source of disease transmission. Of the 72 sexual partners whose names Dugas shared with the CDC, a total of eight in southern California and New York City were found to have AIDS.
Several factors then led to the Dugas-as-Patient-Zero narrative. He remembered the names of many of his partners when other men did not, so researchers had a more extensive list connecting him to other infected patients. And in the early 1980s doctors and epidemiologists thought the virus had a short incubation time—about 10.5 months—so some researchers wondered if Dugas introduced the virus to North America and played a large role spreading the disease via his relationships. The authors of the CDC paper that mapped the contacts between Dugas and other patients (formally called a cluster study) maintained that Dugas was likely not the HIV vector for the wider U.S. epidemic. But the term Patient Zero had already taken off.
This labeling of Dugas was also fueled by an earlier mix-up, Worobey’s team says. William Darrow, one of the CDC investigators involved in the earlier HIV cluster study, has stated that the agency’s records of Dugas referred to him as “patient O”—the letter O, meant to abbreviate the patient’s “Out[side]-of-California” residential status in order to distinguish him in their records—yet somehow that title eventually evolved within the CDC to become the numerical “Patient 0.”
Whatever the reason for the initial title snafu, Dugas’s status as North America’s Patient Zero was cemented in the public consciousness by the late 1980s. The CDC never publicly disclosed his identity, although they did share information about him with other epidemiologists and physicians who cared for him. Randy Shilts, a journalist who wrote about the early years of HIV in the country in his 1987 book And the Band Played On: Politics, People and the AIDS Epidemic, was able to piece together Dugas’s identity through interviews with some of those clinicians. Shilts’ account, which suggests Dugas picked up the disease in France, referred to Dugas as a “Quebecois version of Typhoid Mary” who refused to give up unprotected sex despite his symptoms and diagnosis. Shilts detailed how Dugas allegedly ignored the pleas of his doctors and friends, and continued to engage in unprotected sex—supposedly only informing his partners afterward that he was sick, and that they would probably get sick, too. There is no guarantee that someone will contract HIV even if he or she has sexual contact with someone who is infected with the virus, however.
Indeed, despite those alarming reports, the new molecular clock study clears Dugas not only of importing the virus into the U.S. but also of helping it make an initial jump from one side of the country to the other. Genome sequences of HIV on the east coast are much more similar to the main early California virus than to the virus from Dugas, Worobey and colleagues note. “While he did link AIDS cases in New York and Los Angeles through sexual contact, our results refute the widespread misinterpretation that he also infected them with HIV-1,” the authors wrote. “The point was those people were already infected and no one knew about it because they weren’t symptomatic and there was no way of finding they had a virus that no one knew existed,” Hahn adds.
“Whether Gaetan Dugas actually was the person who brought AIDS to North America remains a question of debate and is ultimately unanswerable,” Shilts wrote in his book. Almost 30 years later—and decades after Shilts died from AIDS—it appears we finally have our answer.