HIV and ID Observations

The Lyme Laser.

For those venturing next week to IDWeek here in Boston, fall gives us our very best weather. Comfortable sunny days with brilliant blue skies, cool evenings, low humidity — great weather for exercising and sleeping. Usually you just need a light jacket. And now, after one of the rainiest Septembers on record (boo!), October has so far has been heavenly (yay!).

But you don’t come to this site for a New England weather report, which might change day-by-day anyway.

Let’s go to the links, starting with ID topics:

• Lyme vaccine clinical trials continue, and one candidate is quite far along. Fingers crossed, at least one of these two vaccines will be safe and effective, then widely adopted in highly endemic areas. My non-medical friends here frequently wonder why there is no vaccine for humans if their dogs can get one. I tell them there was one — but it got caught up in the controversial cloud that follows this disease around like dust over Pigpen.
• How’s this for an example of this dust? Or crap, to be more accurate: You can get treatment with a “Lyme Laser”. It “addresses the concern of the biofilm established in the advanced stages of Lyme disease,” and “enhances the body’s natural abilities to improve function and regeneration.” Seriously, the unvalidated and potentially dangerous “treatments” offered for this serious infection continue to strain imagination. Note that pricing on this site (and others just like it) is conspicuously absent.
• The NIH-sponsored clinical trial ACTIV6 for COVID-19 is still open, evaluating metformin. The study will (I hope) confirm the benefits seen in the COVID-OUT trial, in which metformin reduced the incidence of long COVID by 41%. Importantly, people can also take other COVID-19 treatments and still participate. I’m particularly interested to see if it can reduce the incidence of rebound after nirmatrelvir/r, which remains a bedeviling problem.
• PEPFAR may be in trouble. Could a rare example of bipartisan political support for a hugely successful public health program come to an end? That’s the worrisome message expressed in recent coverage of PEPFAR, which pays for HIV treatment in resource-constrained countries with high HIV prevalence, especially in Africa. At last estimates, the program has saved 25 million lives. Wow.
• The CDC called for comments on the use of doxycycline for post-exposure prophylaxis for STI prevention. You will not find them by clicking this link, and getting to them is tricky, so here are “guidelines” on how to find the draft guidelines: Go this YouTube video, watch the summary of the evidence, and eventually (at 15:15) you’ll reach this:
• In related news, this modeling study shows that adopting doxycycline for STI PEP using these criteria would be an efficient use of resources. Monitoring for STI resistance will be critical.
• Can oral swabs run on a multiplex PCR platform help diagnose community acquired pneumonia? In this study, correlation between oral and lower respiratory results was high when S. pneumoniae and H. influenzae were the cause of the pneumonia. Sure would be easier than trying to get an induced sputum.
• Ceftobiprole was noninferior to daptomycin in treatment of Staph aureus bacteremia. Wow, talk about a blast from the past — I thought this cephalosporin (with activity against MRSA) had long been abandoned, but here it is again! Look for this paper in many ID and medicine journal clubs over the next few months, as there are numerous questions about the study design and the clinical implications. I worry in particular about the control arm — daptomycin (not oxacillin or cefazolin) for MSSA (76% of study participants)? And was daptomycin underdosed?
• In other MSSA bacteremia research, here’s a different prospective randomized clinical trial: The study compared cloxacillin alone vs. cloxacillin plus fosfomycin. The combination regimen failed to show superiority, despite more rapid clearance of bacteremia at day 3 — reminds me of adjunctive gentamicin in this regard. Great to see these studies of Staph aureus bacteremia, which is almost certainly the most common reason for inpatient ID consults, at least in the United States.
• Herpes simplex encephalitis has a high rate of subsequent neurologic complications, with immune-mediated choreoathetosis particularly common. This in-depth study suggests corticosteroid treatment of this late complication is warranted. And it’s a reminder that despite being “treatable” with high dose intravenous acyclovir, HSV encephalitis remains a devastating diagnosis — patients and their families should be counseled up front about the potentially serious outcomes.
• The viral dynamics of COVID-19 have dramatically changed in relation to symptom onset since the start of the pandemic. Viral loads of SARS-CoV-2 now peak at day 4 of symptoms (not at or right before symptoms start), with rapid antigen testing gradually increasing in sensitivity over symptom-days 1-4. The results clearly emphasize the need to re-test in patients with negative tests early in the illness, and also have infection control implications. Our broad pre-existing immunity is responsible for this “new normal”.
• The WHO endorsed use of a highly effective malaria vaccine, the second vaccine now available. Work on malaria vaccines has been a struggle for decades, so this progress is a welcome advance indeed — because in separate news, the mosquitoes appear to be winning. Global malaria deaths are ticking up, and other mosquito-borne diseases such as dengue and chikungunya continue to spread.
• These authors provide an interesting perspective on those annoying low-level viral load results that create all kinds of anxiety — namely, that the labs and clinicians should focus on the 200 copies/mL threshold as the important one for “U=U,” as this was the lowest threshold used in the large studies evaluating HIV viral load and transmission. While I agree that this is a reasonable approach (and the one I use in clinic), there is some uncertainty around this threshold, since most of the people in these studies of transmission on ART had undetectable viral loads — the 50-200 sample was necessarily small. Nonetheless, I 100% agree that flagging these results with a big red exclamation point is unnecessary. And check out panel 4 in the figure.
• The Nobel Prize in Medicine went to Katalin Karikó and Drew Weissman, whose work led to the development of mRNA vaccines against COVID-19. Lots of chatter about how Karikó “failed” in traditional academic research, which prompted her to leave her university lab setting because she was unable to get grant support. Let’s face it, the weeding out process in academic medicine specifically and science in general will definitely overlook some innovative geniuses, as grant-review committees are famously conservative in favor of established researchers and familiar strategies.
• You know that strange sensation of time distortion since the start of the COVID-19 pandemic? “Pandemic skip” is a great descriptive term. And though the writer of this piece is just 30, it applies to every age, doesn’t it? And sometimes it feels like just a few months since those terrible dark days in 2020, and at other times it feels like it must have been many, MANY years ago, certainly much more than just 3. Don’t you agree?
• Here’s a poetic rumination on microbial odors. Impressive alliteration on display: “From the fungal fragrances that sing of environmental mold to the bacterial bouquet that warns us off week-old leftovers, our air comprises a microbial miasma of information, ripe for research and exploration.” I’m sure Cliff, the C. diff-sniffing dog, would agree!

Now, a brief non-ID section:

• Over in The New England Journal of Medicine (the Mother Ship of this Journal Watch enterprise), the editors kindly published how I felt when the news broke about a business decision that will dramatically reshape the clinical, research, and training experience in Boston — the departure of Dana-Farber Cancer Institute from Brigham and Women’s Hospital, where I work. Still can’t believe this is happening. Makes me very sad.
• These two oncologists provide a highly critical viewpoint on Maintenance of Certification by the American Board of Internal Medicine. Interesting to contrast their approach with my more ruminative account, but both ultimately come to a similar conclusion, which is that there must be something better.
• Here’s a wonderful essay for those of us of a certain age, contrasting the experience of travel both with, and without, illness. On the topic of the ailments that start accumulating as you age: “It’s as if we were all devices made by some big tech company, designed to start falling apart the instant the warranty expires and to be ingeniously difficult to repair, with zero support for older models.” Wow, wish I’d written that sentence.
• You can now order medical care on Amazon. My wife, a primary care pediatrician, says that everyone knows this by now, but somehow I missed it. But look — plenty of infections on the list! UTI, HSV, vaginal yeast infections, sinusitis. Text- or video-visit based care. And if your diagnosis is COVID-19, it’s $35 for text care, $75 for a video. Stuff like this makes you wonder about this future of healthcare, for better and (mostly) for worse, doesn’t it?
• You don’t have to be a baseball fan to find this documentary of Yogi Berra joyful and fun. Berra seemed to be the kind of person everyone loved — such a desirable trait! That he happened to be a world-class athlete (and kind of unusual looking, with quotable quotes) added to the charm. I’m sure that his very charismatic granddaughter, Lindsay, will no doubt wonder what she and her famous grandfather are doing on an ID blog.

Since people will be coming from all over the world to IDWeek, how about this impressive and nimble take on country-specific accents? Wow, what talent. What’s your favorite?

Hope to see many of you at IDWeek!