HIV and ID Observations

Hey Image Creator, make a holiday greeting card in mid-century modern with dogs.

A bunch of ID (and a few non-ID) items of note as you prepare for the peak of the holiday season.

The President of IDSA has written an open letter to the American Board of Internal Medicine (ABIM) asking for changes to the recertification process. Current IDSA President Dr. Steven Schmitt proposes several modifications, all designed to reduce the burden and cost to the doctors. It importantly includes results from a member survey that shows a majority of ID docs believe the program “adds no clinical value, does not positively impact clinical practice and contributes to burnout.” A whopping 92% of early career ID doctors find the cost a burden. Note that it’s hard to find any survey that has responses so overwhelmingly negative about an ostensibly educational program.

Here’s part two of my commentary on this ABIM issue. In this update, the current president of ABIM gets mad, says something he later regrets (maybe), apologizes (accepted, thank you!), but sticks to his guns anyway. After reading this, my ID colleague/pal John Badley kindly sent me an email stating, “Paul, you and your blog are not despicable.” Thanks for the reassurance, John! And let me be clear once again — I do believe that it’s essential physicians continue to learn, and to keep their clinical practice updated, but I’m increasingly aware that the recertification process as currently designed has major limitations.

Patients who had recently used PrEP and acquired HIV were 7 times more likely to have baseline resistance at HIV diagnosis than those who never used it. The most likely explanation for this excess resistance is that PrEP was stopped, and then re-started after HIV was acquired. The most common mutation detected was M184V (lamivudine and emtricitabine resistance), so DTG and BIC-based three-drug therapy still should be active. Rather than use these data to discourage use of PrEP, we should leverage it to encourage better adherence and more regular follow-up.

Two investigational antivirals hastened time to recovery in people with COVID-19 compared to placebo. VV116 is a remdesivir oral analogue, and leritrelvir is a SARS-CoV-2 protease inhibitor given without ritonavir. Neither study reported significant safety concerns, and both would have fewer drug interactions than nirmatrelvir/r (Paxlovid), especially VV116. While the authors didn’t comment on rebound, recall that this issue does not happen with IV remdesivir. These two drugs (VV116 in particular) along with ensitrelvir all appear to have major advantages over our existing options for outpatients. As cases rise again this December (as they have every December since 2020), I eagerly — and confess impatiently — await better alternatives!

For children presenting to emergency departments with acute gastroenteritis, molecular testing led to a significant increase in identification of a potential pathogen and decreased the need for follow-up visits. The diagnostic yield increased from 3% in the pre-intervention period compared to a whopping 74% with molecular testing. Molecular testing was associated with a 21% reduction in the odds of any return visit, a clinical benefit strongly endorsed by my pediatrician wife (fewer “he had another loose poop” calls). These results remind me of one of the early studies of enterovirus PCR for meningitis, showing that even when you don’t have a treatment, sometimes just knowing the diagnosis can have benefits.

Treatment of men with UTIs and fever is one of the exceptions to the “shorter is better” rule of antibiotic courses. More relapses and treatment failures occurred after the 7 vs. 14 day course; strongly suspect prostate infection is the nidus for recurrence. I’d add high-risk vertebral osteomyelitis to this short list of conditions that may require longer treatment, based on both a prior observational study and anecdotal experience.

A microbiology laboratory tested 85 clinical isolates of beta streptococci for susceptibility to trimethoprim-sulfamethoxazole, clindamycin, and doxycycline. The surprise (to some) winner?  Trim-sulfa (100%), followed by clindamycin (85%), with every ID doc’s favorite doxycycline bringing up the rear, with only 57% susceptible. Some would argue that this in vitro activity of trim-sulfa vs. strep has long been proven in clinical studies of skin and soft tissue infections (such as one in kids and one in kids and adults), but that hasn’t stopped clinicians from frequently choosing double therapy with beta lactams plus trim sulfa for outpatient treatment of these infections. Guidelines, too, steer people away from trim sulfa for strep. Trim sulfa’s bad reputation vs. strep stems from an artifact introduced in a now outdated method of resistance testing, which had high thymidine content of the test media inhibiting the activity of the drug.

Weight gain after switching an NNRTI-based regimen to tenofovir DF/lamivudine/dolutegravir occurred only in those whose pre-switch NNRTI was efavirenz — not nevirapine. As previously observed, the women gained more weight than men. Also previously noted is that efavirenz has a weight-suppressive effect, which is not observed in other drugs in the NNRTI class — rilpivirine and doravirine also do not suppress weight. The mechanism by which efavirenz has this effect remains unclear, but I’m betting that this is an off-target toxicity. One confounder in this study is that most of the participants on NVP were on AZT/3TC, most on EFV were on TDF/3TC, and these NRTIs also influence weight.

In a placebo-controlled, randomized clinical trial, vitamin D did not lower the risk of upper respiratory tract infection in older adults. A large study, involving 16,000 participants, this is another negative vitamin D supplementation randomized trial we can add to a large pile. Oddly, in a prespecified analysis, the researchers observed a significantly lower occurrence of URI in the vitamin D group, compared to placebo, during summer only — exactly the opposite of what I’d expect. A protective effect also was seen in Black participants.

A synbiotic preparation called SIM01 improved certain symptoms of long COVID significantly more than placebo. These symptoms included fatigue, “general unwellness,” memory loss, gastrointestinal upset, and difficulty in concentration. There was a corresponding alteration in the treatment group’s gut microbiome. Confess I didn’t know what constituted “synbiotics” before this study — it means “a mixture of probiotics and prebiotics that beneficially affects the host by improving the survival and activity of beneficial microorganisms in the gut.” And in case you’re counting, this is the third COVID-19-related randomized clinical trial coming from China I’ve chosen to highlight.

A graphic designer provided a detailed account of her devastating symptoms from long COVID. This is a long, quite heartbreaking piece, beautifully depicted, painful to read. Clinicians will appreciate that for some patients, the meticulous record keeping provides some solace, the sheer volume of it starting in 2020 no doubt correlating with the severity of her symptoms. She writes, “I thought that if I collected enough data, I would eventually figure out what was going wrong. But no matter how much data I collected or how many correlations I tried to draw, answers eluded me. Still, I couldn’t stop tracking. My spreadsheet was the only thing I could control in a life I no longer recognized.”

A detailed pharmacokinetics study evaluated bictegravir/FTC/TAF in 29 virologically suppressed pregnant women with HIV. The main findings were that while concentrations of all three drugs during the second and third trimester were lower than postpartum levels (roughly 40-80% of postpartum levels, biggest reduction for bictegravir), the mean bictegravir exposures were still more than 6.5-fold greater than the protein-adjusted 95% effective concentration. No virologic failure or infant transmissions occurred. This regimen — the most commonly used in the U.S. right now — is still listed as having “insufficient data” in pregnancy guidelines. I wonder if this small study will change that category.

Latent infection with Toxoplasma gondii was associated with increased mortality. Note that I wrote “associated” and not “causes”, as this large observational study found marked demographic differences between those who were seropositive and seronegative. One also wonders why the tests were sent to begin with — certainly it’s not a commonly ordered test, done only in very specific clinical circumstances. Nonetheless, it’s worth remembering that even latent infections can have consequences, as is increasingly evident with studies on CMV.

A Mostly Non-ID Section:

The story behind the “booming business” of cutting under a baby’s tongue to improve breastfeeding. Although well intentioned, this procedure has minimal evidence to support its now growing use despite being widely recommended by certain lactation specialists. It also takes advantage of parents during a time of great emotional vulnerability when there is already enormous pressure to breastfeed. Here’s what we do know:  it’s very profitable for the doctors and dentists doing the procedure, and it can have serious complications. I’ve been listening to wise pediatricians — especially one very close to me! — express concerns about this procedure for years, so it’s gratifying to see this exposed.

A survey of nearly 19,000 physicians found that nearly a third had a moderate or high “intention to leave” practice within 2 years. With the caveat that any survey may select only for those who are unhappy and want to express their discontent, the most striking figure from the paper places medical specialties in 4 different quadrants — along the vertical axis professional fulfillment, the horizontal proportion with burnout. Trust me, we don’t want to be in the bottom right (low professional fulfillment, high burnout). I was pleased to see that ID just escaped, sitting in the upper right — scoring higher than average on the burnout side of things (bad), but also higher on professional fulfillment (good)

A general internist wrote about the patients who fired him. In this excellent account of a difficult subject — and the valuable things he learned through the process — he tells the story of four such patients who left his practice. He concludes by writing:  “To keep this reflection under 2000 words, I leave out the stories of two other patients. I am also not sure I could have tolerated writing more.” We need more of these stories in clinical medicine to balance out the “I came in and saved the day” anecdotes — which not surprisingly are much more common!

Hey, happy holidays everyone! Let’s wrap up the year with these American-born dancers living in Galway performing to a song written and performed by a singer-guitarist from Puerto Rico, who quite amazingly was born blind and started playing the guitar at age nine.