By David Evans
While the world’s top HIV experts reported no earth shattering progress in preventing, treating or curing HIV at the 9th IAS Conference on HIV Science (IAS 2017), which took place in July in Paris, it did serve as an important marker of progress. HIV researchers revealed new data that further strengthened the case for PrEP and HIV treatment as prevention — and issued a resounding declaration that a person with full viral suppression is essentially incapable of passing on HIV to their sex partners.
On the other hand, a joint meeting of HIV and cancer scientists, just before IAS 2017, ended on a more somber note. Though noting the rapid progress in our knowledge of the underlying mechanisms that make both HIV-infected cells and cancerous cells so hard for the body to get rid of, experts there also acknowledged that while long-term viral remission — with HIV still present in the body — can likely be achieved in many people, completely eliminating the virus will remain rare.
Here are some key highlights from the conference.
HIV Treatment Scale-up, Treatment as Prevention, and U=U
Two presentations and one issuance of a declaration statement, when combined, demonstrated just how much progress we are making at simultaneously improving the physical, mental and social health of people with HIV and substantially reducing the number of new HIV infections around the globe.
In terms of the societal impact of HIV treatment scale up and viral suppression, a new study out of Swaziland in the Kwazulu-Natal province in South Africa found that doubling the number of people with HIV who had full viral suppression was accompanied by a 50% drop in new infections. Though previous studies in multiple countries and cities had demonstrated less directly that increasing the number of people with HIV on ART was associated with significant drops in new HIV cases, this study represents the most direct correlation between viral suppression and HIV incidence to date.
A second presentation took these data to a very personal level. The previously reported PARTNER study, which predominantly enrolled heterosexual mixed HIV status couples, found zero cases of HIV transmission between people with HIV who had fully suppressed virus and their HIV-negative primary partner, despite thousands of condomless sex acts. The PARTNER study did enroll couples where both partners were male and where condomless anal sex was the primary risk, but the numbers were so small it was not possible to derive firm conclusions other than that lower HIV levels did offer good protection.
The Opposites Atract study focused solely on male-male mixed HIV status couples, and also found zero new infections between positive and negative partners despite nearly 17,000 condomless sex acts, a fair number of them occurring when the HIV-positive partner also had a sexually transmitted infection. Combined with the original PARTNER study, the top experts who convened the IAS 2017 conference, and high level officials from the U.S. government issued a strong declaration in support of the Undetectable = Untransmittable (U=U) campaign from the Prevention Action Campaign, which stresses the critical importance for people with HIV and the communities they live in to be aware of the fact that when a person living with HIV is on ART with a persistently undetectable viral load there is a negligible risk that they can transmit HIV to their sex partners. Growing consensus around this statement, and gaining buy-in and support from medical societies and various branches of government could considerably improve the physical, emotional and social well-being not only of people with HIV, but others in their communities.
Perhaps the most helpful presentation on pre-exposure prophylaxis (PrEP) came from a second look at data from the IPERGAY study, which took place in France and Canada a couple of years ago, and which studied intermittent rather than continuous daily PrEP. Though efficacy rates were very high in IPERGAY — an 86% reduction in new HIV infections overall, but zero new infections in people who actually took their medication as directed — a critical uncertainty remained. Since the protocol recommended PrEP just before, during and after sex, and because so many participants had a lot of sex, a lot of the guys in the study were essentially taking daily PrEP.
The re-analysis of data on the subset of people who did go for longer stretches between sexual encounters, and who therefore could be considered as truly taking intermittent PrEP, showed that they also had high levels of protection against HIV transmission. It thus seems pretty clear that intermittent PrEP is a reasonable approach for those who go for longer periods between having condomless anal sex (provided that it is taken similarly to the protocol used in IPERGAY). It also lends further weight to the argument that even daily oral PrEP is likely to be incredibly forgiving of missed doses in those whose HIV risk is from condomless anal sex.
Pathway to a Cure
Since approximately 2010, when the world’s top scientists and government agencies began openly using the word “cure” as an achievable goal in the fight against HIV, we have gone from an initial burst of exuberance to an attitude of more sober optimism — the result of repeated experiments documenting the stubborn persistence of the virus and its ability to surge back to life when ART is stopped, even when the most sensitive tests seeking a trace of it come up blank over months or years.
Interestingly, as the consensus among scientists is that total elimination of the virus from a person’s body is highly unlikely, but that a long-lasting remission free of ART might be, we are now most intensively utilizing drugs designed for another condition where the word remission is the key: cancer.
Because both HIV-infected and cancerous cells hijack the biological machinery that protects the immune cells from attack by most viral infections, the IAS 2017 organizers convened a small pre-conference devoted to exploring the commonalities and the ways that some of the newest cancer drugs might also be promising as part of a combination approach to achieving long-lasting suppression of HIV when people stop taking ART.
Predominantly, those drugs are focused on the molecular markers on the outside of CD4 and CD8 cells that communicate with other immune cells. These checkpoint markers can affect whether a cell that has been activated by the presence of a virus essentially goes to sleep and becomes invisible to the rest of the immune system. While this is a desirable ability if we want to retain cells that can immediately mount strong immune response if we are exposed to a virus a second time, it is a total liability if those cells harbor reproducible portions of genetic material that can lead to the reemergence of HIV disease or cancer.
The good news is that several of the immune check-point blockers are so much more potent against some cancers than previous drugs, also appear to enhance the immune system to recognize and eliminate cells that are latently infected with HIV. Unfortunately, the drugs approved so far stop or reverse tumor growth in only about half of people with cancer, and the drugs almost always lose potency over time. This is leading researchers to believe that immune-checkpoint blocker therapy for cancer is possibly going to look a lot more like modern ART — combinations of drugs used together over the course of a person’s life.
Though sobered by these realities, however, the two-day pre-conference ended on a note of determination to succeed with the same zeal that delivered the medications that are making ending the epidemic a plausible reality for many parts of the globe.