An ongoing dialogue on HIV/AIDS, infectious diseases,
June 20th, 2024
Early Heatwave ID Link-o-Rama
We’ll get to the links in a moment, but first, a little poll. You might have heard that there’s a new Editor-in-Chief at NEJM Journal Watch, Dr. Raja-Elie Abdulnour. We met recently, and discussed this column or blog or newsletter or whatever you want to call it.
A topic came up that we’ve been wondering about for a while — who are you, the readers of this thing? If you could take a moment to vote, I’d very much appreciate it.
Feel free to elaborate further in the comments. I promise that no one will follow up asking you to explain how to determine the length of antibiotic therapy, why learning the names of HIV drugs is so difficult, or the reason why medical students know more about listeria than any other bacterial infection.
On to the links we go!
In a randomized clinical trial of pre-exposure prophylaxis for prevention of HIV in women, twice-yearly injectable lenacapavir was superior to the oral options TDF/FTC (Truvada) or TAF/FTC (Descovy). None — that’s right ZERO! — of the 2134 women who received lenacapavir contracted HIV, versus 16 of 1068 on TDF/FTC, and 39 of 2136 on TAF/FTC. Study was conducted in 25 sites in South Africa and in Uganda. Many more details on this important study undoubtedly to come at this summer’s AIDS 2024 conference in Munich, but based on these results alone, it’s a major advance in HIV prevention strategies.
In antibiotic treatment of sepsis, continuous versus intermittent β-lactam antibiotic infusions did not significantly reduce 90-day mortality. The study, cleverly called BLING III (“Beta-Lactam Infusion Group”), promises to generate lots of controversy, as there was an observed benefit — just not enough to be statistically significant for the primary endpoint. Another way of looking at it is that there could be benefit for this critically ill population. Suspect many will continue to use continuous infusion therapy unless there’s shown to be some harm.
Compared to vancomycin plus cefepime, a cohort study showed an association between use of vancomycin and piperacillin-tazobactam and increased mortality. The study design took advantage of a “natural experiment,” one driven by a shortage of the pip-tazo. The leading hypothesis for the results is that the extra anaerobic coverage of pip-tazo is harmful. Alternatively, perhaps this is just an association due to the different time periods, with actual no causation — remember, the randomized ACORN trial showed no difference in major clinical outcomes between pip-tazo and cefepime as empiric therapy.
In a prospective analysis of a large patient population switching to tenofovir/lamivudine/dolutegravir (TLD), virologic failure with resistance occurred, but was rare. Switching to this regimen while viremic was a risk factor. With over 20 million people on this treatment globally, ongoing monitoring for emergent integrase inhibitor resistance will be critical — as will transmitted resistance, as the default first-line and second-line therapy in most of the world is now TLD.
Brief aside — I learned recently from my brilliant colleague Dr. Emily Hyle that a month of TLD now costs around $3 in Africa, while a resistance genotype is still $300! In an era where another molecular test, the GeneXpert for TB, is widely available in this region, this high price of HIV resistance testing is an absurdity that must end soon.
Is there a role for two-drug HIV therapy in Africa? From a medical perspective, the answer to this question is of course there is — there’s a role for such treatment now in the developed world, with dolutegravir/lamivudine and long-acting injectable cabotegravir and rilpivirine being the most important options. But availability of lab testing is a major barrier, with limited access to renal monitoring, assessment of hepatitis B status, and the already called-out HIV resistance testing. Not so bold prediction: In the not-so-distant future, we will be hearing a lot about tenofovir DF complications (renal, bone disease) in older PWH globally, especially those with comorbidities.
Pivmecillinam is now FDA-approved for treatment of uncomplicated UTIs in the United States. In case you’re surprised at the development of this “new” antibiotic for this indication (raises hand!), there’s a reason I put new in quotes — it’s been available in other countries for decades. Despite broad use in some European countries, this review found resistance to be uncommon. I’ve been told by one of our ID pharmacists that it won’t be available in our pharmacies here in the USA until 2025.
An insider monkey.
The metropolitan area in the United States with the highest HIV rate is in southern Florida, the Miami-Fort Lauderdale area. Caveat — this list is from a link found on Yahoo Finance called Insider Monkey, and though they used CDC data, I didn’t check their methodology. But the results show no major surprises — most of the top cities are either in the South, or the big metropolitan areas in the Northeast (south of New England) and California.
Patients who had de-escalation of broad-spectrum beta-lactam therapy experienced a reduced risk for emergent gram-negative infections compared to those who did not. While the results could be confounded by baseline differences in patient characteristics, this result makes abundant sense. In other words, let’s change that meropenem to ceftriaxone when we can!
In a prospective study of healthcare workers who did not respond to hepatitis B vaccination, two doses of the adjuvanted hepatitis B vaccine elicited serologic responses in 91%. Participants had to have non-response to five doses of the standard vaccine, hence these are impressive results. Though not a comparative clinical trial, how long before this vaccine is the default recommended strategy for this population at high-risk for occupational exposure?
A detailed virologic study of 563 HIV isolates from blood donors from 2015–2020 found PI, NRTI, and NNRTI resistance mutations in 5.0%, 4.6% and 13.9% of sequenced samples. The overwhelming majority (96%) were subtype B. Resistance declined over time. Two samples (0.4%) had the M184V mutation, including one that also had K65R — perhaps in a person who had taken PrEP? Unfortunately, no sequencing of integrase inhibitor mutations was performed.
Here are some ID-related “therapeutic myths” in solid-organ transplantation. Highlights include treatment of all asymptomatic bacteriuria after kidney transplant (don’t), giving antibiotic prophylaxis for dental work (don’t again), and the lack of evidence for vaccinations inducing rejection. Good graphic summary.
The FDA advised companies to update the COVID vaccines to target the KP.2 strain. This is a descendent of the JN.1 variant that circulated widely this past winter. COVID cases will inevitably increase this respiratory virus season (mid-late November is when it typically kicks into high gear), so having an updated vaccine for people at high risk for complications is a good idea. The question remains whether all previously immunized and infected people need annual boosters — hope one day we get a good trial to answer that question.
Believe it or not, there’s another pneumococcal vaccine coming. This version covers 21 serotypes, just 1 more numerically than the PCV-20. However, the serotypes are different, including 8 not covered by other currently available pneumococcal vaccines. The manufacturer has data that these serotypes more closely match the disease-causing strains in adults. On June 27, the CDC’s Advisory Committee on Immunization Practices will meet to review how it should fit in with currently available options.
Staph aureus susceptibilities over a 10-year period showed a rising rate of resistance to tetracyclines and trimethoprim sulfamethoxazole, especially in MRSA strains. The study included 382 149 isolates from 2010–2019, stratified by MRSA versus non-MRSA. Among MRSA strains, tetracycline resistance increased from 3.6% in 2010 to 12.8% in 2019; for TMP-SMX, it increased from 2.6% to 9.2%. The good news? The proportion overall that were MRSA declined from 53.6% in 2010 to 38.8%, a favorable (and mysterious) trend seen previously in other studies that no one has been able to explain.
A review of over 60,000 inpatient ID consults at an academic medical center from 2014–2023 found a high proportion were done on patients with terminal or incurable illness, with a 7.5% mortality during the admission. There were two striking findings in this study. First, the obvious one, which is that people who need ID consults are really sick. Second, the volume of ID consults has nearly doubled over the past decade — from 5.0/100 to 9.9/100 patients. If you think you’ve been increasingly busy on your inpatient consult service, this is no illusion.
In a randomized clinical trial, povidone iodine in alcohol was noninferior to chlorhexidine gluconate in alcohol to prevent infection after cardiac or abdominal surgery. The importance of the study is the much-lower cost of the povidine iodine, and chlorhexidine is therefore much less widely available globally. Hey, I believe this is the first time I’ve covered a topical antimicrobial study in a Link-o-Rama!
Before we wrap up, first, don’t forget to take the poll (see above); and second, a little childhood history for those of a certain age (mine, or a bit older).
In the 1960s, I learned there was an important debate about the best baseball player in the world, Willie Mays or Mickey Mantle. Increasingly obsessed with this sport to the point that I bored my parents senseless with my endless ruminations on this and other baseball-related topics, I intensively studied biographies and statistics of these two players, wanting ever so much for Mickey Mantle to be the winner with a passion that makes absolutely no sense today.
Turns out, no matter how I twisted the data — focusing only on their best years, or most heroic moments, or their potential without injuries — the answer came back the same again and again.
Willie was better. Possibly best ever. Rest in peace, Say Hey Kid!
19 Responses to “Early Heatwave ID Link-o-Rama”
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
Biography | Disclosures | Summaries
Learn more about HIV and ID Observations.
NEJM Journal Watch — Recent Infectious Disease Articles- When it Comes to Antimicrobial Stewardship, Is a Boost Better Than a Nudge?
- HIV Prevention and Treatment: Updated Recommendations from the International AIDS Society–USA
- Observations from ID and Beyond: Dr. Thomas O'Brien — Expert in Antimicrobial Resistance and Giant in His Field (Literally)
- How Serious Is Artemisinin Partial Resistance in African Malaria Parasites?
- Observations from ID and Beyond: Who's Going to Get Lenacapavir for HIV Prevention?
I checked the “other” box. Although I retired from pharmacy practice 5 years ago, and was forced out of HIV clinical practice 19 years ago, I still enjoy keeping up from a distance, and reading Dr. Sax’s entertaining blog.
About the BLING III RCT comparing intermittent vs continuous beta-lactam infusions in sepsis patients in critical illness:
I was shocked to see that the JAMA editors agreed with this conclusion:
The observed difference in 90-day mortality between
continuous vs intermittent infusions of β-lactam antibiotics did not meet statistical
significance in the primary analysis. However, the confidence interval around the effect
estimate includes the possibility of both no important effect and a clinically important benefit
in the use of continuous infusions in this group of patients.
This is exactly what 95CI intervals do!.
Regarding the poll, I’m a clinical research oriented pediatric oncologist and I’m a long time fan of this blog.
I’m a PharmD working in HIV treatment/prevention and this is a blog I always read and recommend to others!
I’m a family doc who thinks ID docs are the unsung heros of the medical world, fights for antibiotic stewardship daily, and is a big baseball and Red Sox fan.
Scientist. Also Gay, immigrant, male in HIV discordant marriage, caretaker, medical decision maker for spouse who has mild HAND / memory loss and cognitive impairment and HIV associated atherosclerosis with hx of cardiac event, BMI of 24, exercise enthusiast, 25+ yrs poz, tx compliant to a fault and yet viral load detectable > 500 copies. Current tx guidelines are obsolete. HIV undetectable in plasma is not good enough considering Pattern Recognition Receptors detect HIV / proteins in lymphatic tissue resulting in HAND, CAD and more. Since 2020, ID docs have breathlessly lectured the world 24/7 about long-term COVID. HIV associated inflammatory syndromes in undetectable / low viremia: crickets. Do better.
I am on Ob/gyn who just loves this column. I get a little lost in the HIV world, but I can get enough.
SO amused picturing earnest little baseball-fanatic Paul boring his parents senseless…especially as the grandmother of two of that species.
Just a former editor of AIDS Clinical Care here, back in the days of print newsletters, and a fan of Paul Sax ever since. Checked “other.”
“Say hey, kid”, Paul. I’m old enough to have seen both play a little (not in person). Sorry, but Willie was the man! Thanks
Paul, I find your little newsletter tremendously helpful-I don’t always get a chance to discuss “regular” ID things with colleagues, and I appreciate your take on the issues. I really like the curated discussion as well.
WRT dual therapy in Africa, another major challenge is the supply chain. Dual therapy with DTG will most likely be DTG/3TC which means 2 pills-probably. This is double the chance of a stockout. Personally I am holding out for Len/Cab, but with the positions the drug companies have taken it may be wishful thinking.
Best,
Katy
Regarding Vanc + Pip/Tazo v Cefepime … the timeline for ACORN was 14-day mortality but for the new study you cite was 90 days – it may be that microbiome-mediated changes/risk (or other effects of anti-anaerobic therapy) take longer than 14 days to evolve and increase risk. All of the studies are helpful, but evaluate different metrics.
I’m a PCP who trained across the street with the ID great Dr. Bob Moellering when HIV was HTLV-3. Ever since muddling through COVID, my younger peers seem to be retiring. I read this blog because it reminds of the joy of practicing medicine. I may learn a few facts, but what I most enjoy now is the shared pleasure working with other happy members of this ever-humbling profession.
P.S. I remember seeing Willie Mays play.
Med/Peds doctor in central Africa.
TLD is the first line where I work. As was noted above, genotype testing is very expensive, and is only available in the capital city here. Country wide, 34% of people living with HIV have had viral load testing and 58% of them had an undetectable viral load.
I’m a pharmacist by training but have been doing medical writing for years. ID is one of my favorite topics (along with toxicology)–unfortunately I do not get to write about ID much since antibiotic development doesn’t generate money 🙂 Love the blog and the baseball references!
Enjoy reading the blog as a cardiologist who works in the CICU. Having ID updates is so important given the changing population we have seen in the last 20 years with the pts no longer primarily ACS, but CHF with multiorgan failure and sepsis
PCP, mid-career. Similar to James Howe above, I love this blog because of its:
1. spirit of curious inquiry and joy/enjoyment of ongoing learning in pursuit of being and doing better in patient care
2. occasional rants about healthcare delivery system / business decisions
3. consolidated tidbits about ID that are directly applicable (UTI treatment in the US) and not directly applicable for me but superinteresting and important (twice a year injectable PrEP in Africa led to NO new HIV cases??? AWESOME.)
Retired med educator/rheumatologist ex-spouse of ID doc disciple of revered Don Armstrong, may he rest in peace, at Memorial Sloan Kettering, whose intercity ID Rounds helped identify the first cluster by promoting discussions across the medical centers, and who many attribute changing GRID (Gay related immunodeficiency syndrome) to AIDS. Loved attending the earliest international AIDS meetings – when I could still understand Fauci’s annually projected cartoon of the then-known immunology – the progress year to year was staggering.
Love this blog and connection to that historical time: despite the ongoing tragedy of loss of so many young patients and colleagues, there was much excitement in the community of physicians, care givers, and investigators watching progress unfold.
I am a Family Physician, but never miss your blog. I voted in the first category because it is my job to both prescribe PReP and treat infectious diseases.
I guess I’m “other”. I was a postdoc at UNC and started working on HIV as soon as the virus and a cell line it would grow in became available in 1985. I looked at antivirals and synergy of them before most were approved. I worked on HIV off and on through my career, and although I’m retired, I love to read your HIV & ID Observations blog.