Utrecht conference focuses on HIV sequence analysis and modeling

It’s probably safe to say that the conference on “HIV Dynamics & Evolution”, in Utrecht, in the Netherlands, was somewhat unusual: It featured a lot of research involving HIV sequence analysis and mathematical modeling. And yes, many of the talks at the conference, which ended yesterday, came with differential equations (don’t worry, I won’t get into that in this post.)

One rare exception was the Keynote lecture by Asier Sáez-Cirión from the Institut Pasteur in Paris. He presented his data on the so-called VISCONTI cohort of 14 HIV-infected individuals who started antiretroviral treatment early and were later able to control HIV infection after stopping treatment (see Is it Ever Too Early?, IAVI Report, Sep.-Oct. 2012). He said that after he published his results in March, he has been contacted by researchers all over the world who found about 20 additional cases of post-treatment controllers, adding that all such cases worldwide will be collected in an international cohort, the formation of which will be announced at the upcoming International AIDS Society conference in Kuala Lumpur.

Sáez-Cirión stressed that his and other studies now strongly suggest that HIV-infected people should start treatment as early as possible. That’s why he was happy, he said, that the U.S. Preventive Services Task Force recently recommended HIV testing of all people between the ages of 15 and 65, regardless of whether they are at a high risk of HIV infection.

In the discussion after the talk, John Coffin of Tufts University in Boston urged Sáez-Cirión to sequence the HIV variants in the VISCONTI individuals, to determine if there is any ongoing evolution (and therefore low-level replication). That would clarify if these individuals are more similar to naturally occurring elite controllers (who show ongoing virus evolution) or to people on combination antiretroviral therapy (or cART), where the virus stops evolving, Coffin said.

Coffin, for his part, presented a case study of an HIV-infected person who became resistant to his cART regimen after 11 years. The case is unusual because sequencing of his HIV RNA revealed not only drug-resistant HIV, but also wild type, drug-sensitive HIV variants. While switching the patient’s treatment to a new cART regimen reduced the level of the resistant variants, it didn’t affect the wild type variants much, if at all. 

Because the patient had oral cancer at the time, the wild type HIV variants probably came from infected cells that were multiplying (instead of replicating virus), Coffin said. This would explain why the cART didn’t affect the wild type virus, he said; it could also be bad news for efforts to try to eradicate HIV in infected people, because it suggests that multiplying HIV-infected cells are another, underappreciated source for persistent HIV viremia in people treated with cART. 

Coffin’s study was one of many presented at the conference that involved analysis of HIV sequences. Some of them used sequences to identify HIV transmission networks. For example, Sanjay Mehta from the University of California in San Diego and his colleagues analyzed over 1000 HIV Pol sequences of mostly men who have sex with men determined within weeks to a few months after infection in the San Diego area between 1996 and 2012. For 565 of them, he knew the ZIP codes of their place of residence. Using this information, he mapped the epicenter of the HIV epidemic in San Diego to the Hillcrest neighborhood and found, surprisingly, that most of the infected people in Hillcrest were infected by people who reside in other areas. 

To Mehta, the likely reason for this is that there is more agressive HIV testing in Hillcrest. Because of that, HIV cases in Hillcrest are detected and treated earlier, which makes them less likely to transmit HIV to others. This shows that aggressive testing does have positive effects, Mehta said. 

The last session of the conference yesterday focused on HIV evolution. Most studies presented there dealt with models or sequence analysis. For example, Samuel Alizon, a researcher from Montpellier, France, compared many different sequences to show that HIV evolves more quickly within the same host than between different hosts. Until now, he said, this has only been shown for portions of the env gene, but Alizon reported that it is actually the case for the entire HIV genome. 

This means that HIV variants that are transmitted to another person aren’t the most highly evolved viruses in that person, and that HIV strains that are less adapted to the host have a transmission advantage. In other words, many HIV variants have evolved so much to their host that they lose some of their ability to infect another person. The variants that are eventually transmitted are likely ”stored” from an earlier stage of infection in latent T cells, Alizon said.  

Alizon agrees that the conference is quite unique. “[It’s] probably the only HIV conference I go to,” he said. “I am really an evolutionary biologist by training. This is really a unique conference, because it ranges from clinicians to very theoretical people.”