An AIDS-Free Generation: A Rallying Cry or Really Just Hype?

Each International AIDS Society Conference (aka: IAS, IAC, World AIDS Conference, WAC, AIDS [fill in the year]) has its own semi-official theme. More than slogan-ism, these motifs can be useful in setting agendas as well as expectations for the global HIV community. We will always have Vancouver. The spectacular initial results from studies of combination HIV therapies presented at this conference in 1996 created a giddiness among the attendees that sparked an optimism that endures. And who can forget Durban 2000? Under the Southern Cross, unseen hands conducted us to sing in unison that access to antiretrovirals was achievable for all - raising millions of hopes and dollars.

This year, at a conference symbolic in its return to the US, we were directed to contemplate the end of AIDS. Hillary asked us to envision an “AIDS-free generation”. NIAID Director Tony Fauci gave a run down of the tools we have at hand to halt the spread of HIV and extinguish the epidemic and Phil Wilson of the Black AIDS Institute challenged us to use them. In the audience, there were hallelujahs among the believers. But, others (dare we say, skeptics?) could not be faulted for wondering where did all this end of AIDS talk come from and why was this not on our radars before coming to DC?

Serious consideration of an HIV epidemic endgame started with a thought experiment. In 2008, Rueben Granich and colleagues from the World Health Organization (WHO) published the results from simulations they did modeling the dynamics of the HIV epidemic after pushing variables such as HIV testing and antiretroviral coverage to extremes. According to their math, elimination of HIV transmission was achievable. It would take 50 years and an effort to scale up testing and immediate treatment that could only be achieved if Mao Tse Tung were put in charge, but it was possible. Simplistic by necessity, the model nonetheless propped open the end-of-the-epidemic door – an opening widened with the results from HPTN 052 (showing nicely that successful treatment of an infected individual renders them nearly un-infectious) and other studies of treatment as prevention.

At IAC/IAS/WAC we saw the idea of epidemic extinction transmute into agenda gold. With antiretrovirals cleansing body fluids of circulating virus and cure approaches trying to mop up the latently infected pool, it seemed like we could be at a tipping point. In enumerating the arrows in our quiver, Dr. Fauci was painting a target and egging us on to aim high.

But, this was not Vancouver and while it was exciting to think about the beginning of an end to the epidemic, for some this was overreaching. One activist I spoke to told me that such talk is premature and minimizes the substantial challenges we face in diagnosing and treating those who are currently infected. With almost 50,000 new cases of HIV annually just in the US and less than a third of those with HIV in the nation treated successfully, talk of eradication of HIV can ring hollow. Furthermore, where does ending the epidemic leave those who are now living with the virus or those who become infected today, this month or this year?

As a provider who tends to see the glass half full when it comes to HIV care, I don’t feel compelled to choose sides in the ‘yes, we can’ versus ‘no, we can’t’ debate and I see how hype can be useful for advancing noble causes. Plus, our collective attention is not quite zero-sum, and I believe we can focus on prevention of new infections and the care for those living with the virus at the same time. For me, the raising of the prospect of an AIDS-free generation in our lifetime is akin to JFK’s declaration that the US would blast a man to the moon and back. Fantastic, expensive, complicated? Yes. Thrilling? Yes.

Without the dream, there would be no reality. In Berlin, a few years ago some hematologists figured they could possibly (not probably) cure a man with cancer of his HIV infection. Cleverly, they found a bone marrow match that was also homozygous for the CCR5-delta deletion. It worked and in DC he walked into an elevator smiled at me and announced unsolicited that he was the first man cured of HIV (and, would I mind pressing the 7 button for him). I shook his hand – touching for myself the realized dream.

Meanwhile, for those of you whose heads are not spent in clouds of possibility but rather in the medical records of the newly HIV-diagnosed young man, the treatment-experienced woman about to start her fifth antiretroviral regimen, and the suppressed patient with a Framingham Risk Score that made you cringe, the end of the HIV epidemic can seem about as likely as your best ever fantasy football team coming over to your house to convince you to become their team doctor and director of all social activities during all away-games. Front line providers, these few practical IAC/IAS/WAC highlights are for you:

  • Dolutegravir vs. Raltegravir: One is a lonely number and the integrase class is about to get a bit less roomy. In the SPRING-2 trial comparing dolutegravir to its classmate raltegravir in treatment naïve patients also receiving TDF/FTC or ABC/3TC, the newcomer performed well with 88% achieving an HIV RNA level below 50 copies/mL at week 48 compared to 85% in the raltegravir arm – a statistical dead heat. Toxicity was rare and similar across the arms. Among the small number of patients in each arm experiencing virologic failure who had genotypes able to be performed, none of those failing doultegravir had detected resistance mutations in the integrase or reverse transcriptase regions. In contrast, 1 of 18 participants on raltegravir who were failing and had resistance testing performed had integrase resistance and 4 of 19 had nucleoside resistance. With plans to be formulated in a fixed dose with the comeback combo, ABC/3TC, this is not a me-too drug.
  • Simplification with TDF/FTC/Rilpivirine: A common use for this newer fixed dose single tablet regimen is as a switch from more complicated combinations in suppressed patients. In the SPIRIT study, this strategy was compared in patients on a ritonavir-boosted protease inhibitor and two NRTIs with undetectable viremia and no history of drug resistance. At 24 weeks, 94% switching to TDF/FTC/Rilpivirine had a viral load <50 copies/mL compared to 90% of those staying on their entry regimen (non-inferiority achieved). Historic baseline viral load (i.e., before entry regimen) above or below 100,000 copies/mL did not influence the efficacy results - indicating that pre-treatment viral load (a prickly problem in the ECHO Trial) is not an issue when switching stably suppressed patients to this regimen. As expected, gastrointestinal symptoms and lipids improved with the switch from PI therapy.
  • NRTI-Sparing with Maraviroc+Boosted Atazanavir: You say you want a nuke-sparing regimen, well, you know, we all want to change the world. You tell me that its evolution, but you just can’t change the fact that despite numerous attempts over many years, no such revolution to free us from NRTI domination has succeeded. The latest attempt looked at a combination of maraviroc plus ritonavir-boosted atazanavir, compared to the same PI with TDF/FTC in 121 treatment-naïve patients harboring R5 tropic virus. In a presentation that I think may have used Jedi mind tricks, the 96-week performance of the NRTI-sparing regimen (68% with viral load < 50 copies/mL) compared to the TDF/FTC arm (82%!) was considered to be, you know, sort of, close enough. No statistics were applied, as the study was “small”. Also, no mention how the NRTI-sparing performance looked much like the underwhelming results seen with darunavir/ritonavir+raltegravir in ACTG study A5262, a study which helped put the kibosh on the PI+integrase strategy. This trial again shows that, for reasons yet to be fully explained, it does seem that a drug that works at the reverse transcriptase is key to optimal success of PI-based therapy.
  • And there was a bunch of stuff on pre-exposure prophylaxis.

Looking ahead to AIDS 2014, to be held in Melbourne, Australia (!), I do not know what the theme will be, but it will be hard to top ending the epidemic. I am sure we will think of something.