Thread by @PaulSaxMD

The "History of HIV" talk I gave last week actually has this title, which I don't think is an overstatement. Posting it now with gratitude, just in time for Thanksgiving (my favorite holiday -- the gratitude and family part).

(Part 1 thread)
1/x

Must start with this 1981 @CDCMMWR report of 5 cases of PCP in Los Angeles. Have already commented on the surprising page 2 placement. There's a story behind it, right @deborahcottonmd? (Later moved to Page 1 on reprints.) Note “blue diazo” slide style

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During my first year of med school, we had one lecture on AIDS, with putative causes. Not an auspicious start.
(Yes, 1983. I'm old.)

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Huge breakthrough later that year with the discovery of the virus, eventually earning lead-author Françoise Barré-Sinoussi the Nobel Prize in Medicine in 2008. Specimen obtained from man with lymphadenopathy and night sweats, then cultured in lab, T-cell tropic

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This is the first patient I saw during medical school with AIDS -- it was so sad. Prognosis was grim, median survival after OI was 10 months. Though he improved with experimental therapy (DHPG, later called ganciclovir), he died soon after

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Big news in 1987 was approval of zidovudine (AZT) for treatment, based on this placebo-controlled study. Will never forget the mortality benefit: 19 subjects in the placebo group and 1 in the AZT group died during the study

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Alas, the benefits of AZT were temporary -- due to resistance, toxicity, cost -- and a period of therapeutic nihilism started. This reached its nadir during the 1993 Berlin AIDS Conference, when the negative results from the CONCORDE study were released

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HIV had became the leading cause of death among young adults as I finished my residency and started in ID, with deaths peaking in the early 1990s. For me, the striking thing about the AIDS quilt is to read ages of those who died. People in their 20s, 30s, 40s ...

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Everything changed in 1996! Highlighting this study led by Trip Gulick*, as it showed sustained viral suppression with combination ART for the first time. I remember Doug Richman saying, if no replication, no resistance -- so this could last!
(*we were co-ID fellows!)
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Why 1996? We now had sufficient drugs for combination therapy. Credit to Marty Hirsch (and others) for studying combination ART in vitro, demonstrating additive and sometimes synergistic activity. It worked!

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The clinical benefits came rapidly -- like a bright light suddenly illuminating a dark room. Deaths from AIDS plummeted. One of my pts went to hospice in early 1996 with likely PML -- & today she is fine! Everyone cited this figure, which I like to call "the Palella-gram"

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But soon after, strange side effects appeared, which initially were hidden by the dramatic benefits of treating uncontrolled HIV and restoration of immune function. All my talks on Rx in late 90s/early 2000s included this cartoon and photo collage

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In addition, the regimens were so tough to take that “real world” experience fell far short of the clinical trials -- this study from Hopkins often cited. Many argued to defer ART until CD4 was < 350 -- or even 200!

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Meanwhile, a global catastrophe was unfolding, esp in Sub-Saharan Africa. The HIV field was going through a tragic paradox, where PWH in rich countries wanted to stop therapy, whereas those in poor regions were desperate to start it

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Tomorrow I'll finish this story and bring us up to today -- and why progress in HIV care and research truly is a "medical miracle". (I'll also post a link to the full slide set.)

Thanks for sticking around so far.

fin