Thread by @PaulSaxMD

Yesterday I posted a long thread on the extraordinary progress we’ve made in HIV care and research since report of the first cases 40 years ago. Now for Part 2!

(I stopped at around year 20. Here’s the link to Part 1, in case you want to catch up

https://twitter.com/PaulSaxMD/status/1462035443827023883?s=20

)
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When we left off, we'd experienced the thrill of effective combination ART. Our 2 major news magazines featured advances in HIV on their covers! One of these guys was a basketball star, the other an HIV researcher -- see if you can guess which one is which

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But the excitement of having effective ART was tempered by the realization that these treatments had major issues, including side effects, high pill burdens, and low resistance barriers. The "when to start?" question became a central part of HIV care

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How did we move forward? First, the limitations of early ART stimulated drug development, with substantial improvements that made older treatments mostly obsolete

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Second, the AIDS Conference in Durban in 2000 was a wake-up call to the world that HIV treatment was *desperately* needed around the globe -- where ART worked just as well as it did in richer countries, despite ill-informed skepticism or irrational fears

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Further progress: Carefully done large research studies on both intermittent Rx (SMART) or early Rx (START) clearly established that suppressive ART -- before immunosuppression -- was key to improving clinical outcomes, outweighing toxicity and resistance concerns

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Results from the SMART and START studies, and better drugs, meant that virologic suppression became the norm, not the exception. Here's one of many cohort studies showing this wonderful trend

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Remember that discouraging study from Hopkins with only 37% suppression in 1998? They repeated their analysis in 2011, and rate was now up to 87% -- especially notable in this challenging patient population
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doi.org/10.1093/cid/ci…

In response, I wrote an editorial highlighting the timelines for various advances in ART.

TL/DR: *Lots* to celebrate here

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One of the most important advances was the introduction of the first INSTI (raltegravir) in 2007, which meant that even people with multi-drug resistance HIV could achieve viral suppression. Many experienced "undetectable" for the 1st time in the late 2000s -- so great

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Of course this integrase inhibitor drug class was just getting started. Look at on-treatment responses today using dolutegravir and bictegravir-containing regimens. And this with no treatment-emergent resistance

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The apotheosis of the high resistance barrier concept is demonstrated in the recently published NADIA trial, demonstrating that both DTG and DRV/r achieve high rates of viral suppression even with no predicted activity from TDF/3TC or ZDV/3TC. Still amazed by these results!

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And it's not just treatment of HIV that has had extraordinary advances. Let me shift now to prevention, which has been equally miraculous

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We can start with the fact that we've had *amazingly* accurate diagnostic test for HIV almost as long as we've known about the virus. This rapidly made the blood supply so much safer. Risk for transfusion-related HIV now one in approximately 1.5 to 2 million units

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Next up is 076, which demonstrated that maternal zidovudine markedly reduced the risk of mother-to-child transmission of HIV. This came in the early 1990s, when we really needed a win for HIV research, and was so welcome

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It took some time for the next great advance in HIV prevention, but wow it was a big one -- HPTN 052 conclusively showed that treatment of HIV reduced the risk of sexual transmission of the virus. Such a motivator for PWH to start and stay on ART

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Follow-up observational studies in serodiscordant couples choosing not to use condoms have confirmed that U most definitely equals U! ART as prevention has a staggeringly powerful effect

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The next advance in prevention was PrEP. It's a strategy that once would have been unfathomable due to drug toxicity -- but with TDF/FTC, TAF/FTC, and soon cabotegravir, it can be widely and safely deployed

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Are we done yet? Of course not -- still plenty to accomplish if we want to end the HIV epidemic. The scientific challenges of an HIV cure and effective vaccine remain formidable, and sadly there are still residual inequities in access to diagnosis and treatment

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But challenges notwithstanding, it has been a privilege to watch (and be a small part) of this extraordinary progress. As we approach #WorldAIDSDay and Thanksgiving, I am so grateful for it, and hope we can apply what we've learned from HIV to our current pandemic

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Here's a link to the full slide set. Thanks to all for the feedback, and to Fundacion Fernandez-Cruz for inviting me to give this talk -- it was a joy to put together
(Woof.)
dropbox.com/s/zgihz3p3431m…
fin.