Scientists know that in heterosexual partnerships, women get infected with HIV more often than men. But new research shows that when transmission occurs in either sex, it is usually only the hardiest strains of the virus that survive and thrive. So, there may be a way for doctors to attack and defeat weaker strains of the virus before it spreads in a newly infected person.
Countless genetic variations of the HIV virus live inside each infected host. HIV is a replication powerhouse. On average, the crafty virus mutates once each time it copies itself, constantly evolving and puzzling scientists. But it often becomes much weaker when it mutates away from a primary strain, also known as a “consensus sequence.”
Researchers offer new insights into these phenomena in a paper published today in Science. Scientists from the Emory Vaccine Center/Center for AIDS Research teamed up with lead author Jonathan Carlson of Microsoft Research to study the genetic sequences of HIV found in heterosexual partners about 46 days after transmission occurred.
They followed the evolution of the viruses for two years among 137 opposite-sex couples in Zambia. Virus strains presented with a low barrier to infection — as is often the case in women, who are believed to have more vulnerable cells in their genitalia — tended to be less hearty. But in otherwise healthy men who did become infected, despite having a higher barrier to infection, it was only extraordinarily hearty strains that succeeded. Ultimately, such strains represent a more severe progression of HIV.
Men who had inflammation in their genitalia from conditions such as herpes, and so had a much lower barrier to transmission than usual, became infected with less hearty strains, much like women. In all cases, the successful strains had to make it through a so-called “genetic bottleneck” in order to establish an infection.
The bottleneck means that when a person becomes infected, he or she is exposed to many strains of HIV, but they are quickly whittled down to only the strongest — the one that most closely resembles the "consensus sequence."
A Window of Opportunity
“The best explanation for what we are seeing is that frequently, after exposure to HIV, a few cells in the genital tract are infected, without establishment of a systemic infection,” the researchers wrote in a joint press statement. “We now have evidence that the game isn’t lost as soon as the first target cells is infected. This suggests that any approach that makes it more difficult for the virus to replicate in a cell, or that targets infected cells for killing before they can create new viruses, will reduce the probability of systemic infection.”
What this means is that even if a person is infected with HIV during sex, there is a chance that doctors can head off the infection before it replicates and becomes widespread in the person's body.
Healthline asked the researchers what implications this new information has for the use of medications for PrEP, or pre-exposure prophylaxis, and PEP, post-exposure prophylaxis. These medications can be taken to prevent HIV infections.
“In terms of PrEP, the approach is effectively to raise the barrier of transmission, which means we’ll fall into the paradox of more severe disease when transmission does occur,” the authors replied in a joint statement. “As an aside, our data also provide a better understanding of how PrEP works. In order for a fitness bottleneck to occur, it must frequently be the case that target cells are infected without leading to systemic infection, which provides a window when drugs, or T-cell based vaccines, may be able to work.”
PEP, PrEP, and the Promise of a Vaccine
PEP, taken after exposure to HIV, is intended to reduce the chance of infection by reducing the amount of circulating virus in a person's body. But, the researchers noted, “With any drug therapy, we have to worry about resistance mutations, which lead to viral rebound. The encouraging aspect of our study is that, while resistance mutations nullify the drug, they often weaken the virus in the process. If this is the case, then transmission rates will still be reduced relative to what they would have been in the absence of PEP.”
Dr. Robert Grant, a professor at the University of California, San Francisco and chief medical officer of the San Francisco AIDS Foundation, told Healthline the research shows why PEP and PrEP have proven highly effective. “This important study reveals a point of vulnerability for HIV as it passes from person to person. Reduced to small numbers in newly exposed people, the HIV population’s ‘away team’ can be disabled by chance mutations in its genetic code, or poor luck in finding host cells to foster its growth.”
The research, if it is replicated by other scientists, may also be helpful for vaccine development, said Dr. Cristian Apetrei, a professor at the University of Pittsburgh's Center for Vaccine Research. That is because it could help identify characteristics of the so-called "consensus sequence" that doctors can then attack.
“Once we can define 'consensus' we can induce responses through vaccines,” Apetrei told Healthline. “This of course has to be tested, but it would be very good news to everyone if it were demonstrated.”