HIV and ID Observations

Word cloud from submitted questions.

Going to take a partial break from all things COVID-19 today and recap some of the terrific questions we received in our course, Infectious Diseases in Primary Care.

Not surprisingly, there were plenty of COVID-19 questions but also the usual mix of practical queries from everyday practice.

Front-line clinicians doing office-based practice attend this course, and every year, they remind us of the common problems and quandaries they face in their day-to-day work. It’s a great mix of general internists, family practitioners, nurse practitioners, and PAs.

This year, of course, we held it virtually due to the pandemic, bringing with it predictable trade-offs.

On the plus side, more people could attend, the lectures are available to watch on-demand (at least for a while), and also the barrier to asking questions was lower — just type in a question and send!

On the other hand, we missed the personal interactions with participants and couldn’t get immediate feedback on whether what we were teaching was useful — watching people during teaching gives you a real sense of whether they’re with you on the topic or perplexed. Finally, humor during teaching is all but impossible to gauge — did the jokes land or fall flat?

But we got some amazing questions and didn’t have time to answer them all, so here’s a baker’s dozen and some quick answers.

Question #1:  Would you give the recombinant zoster vaccine to someone who is 40 and at high risk because they are immunocompromised?

Answer: The quick answer is that the ACIP doesn’t yet recommend it in this population, but it has been studied in a variety of immunocompromised hosts (autologous stem cell transplants, rheumatoid arthritis), and it is safe and effective. So in general, the answer is don’t give it to people younger than 50, or to the severely immunosuppressed, at least for now; future guidelines may change, so stay tuned. (And of course, insurance may not cover it in this population.)

Question #2:  Can you address the sensitivity/specificity of the rapid antigen tests for COVID-19 and the problem of low vs high pretest probability?

Answer: Since the antigen tests do not have an amplification step (unlike the PCR), they are less sensitive for detection of the virus. Despite this drawback, their rapid turnaround time makes them quite useful in certain settings. In a case where the pre-test probability is low — such as in an asymptomatic person with few or no high-risk exposures — a negative test further reduces the post-test probability that the person has asymptomatic COVID-19. Antigen tests are also quite likely to be positive in those who are most infectious.

By contrast, in a person who has compatible symptoms, a negative antigen test would not be sufficient to rule out the disease, especially in the hospital. Stick with PCR for those cases.

Question #3:  What do I do when a job requires varicella titers, and they come back negative? The patients did receive their primary varicella vaccine series.

Answer: The varicella titers we do in clinical practice do not reliably assess for vaccine-induced immunity. Hence, we do not recommend them for this purpose, and the patient should provide proof of having had the primary series as sufficient evidence.

Question #4:  Do we need to give a hepatitis B booster if it’s been a long time since the primary vaccine series? Someone recently told me he received it more than 30 years ago.

Answer: In general, boosters are not recommended after the hepatitis B vaccine series — especially if follow-up titers showed that at some point after the vaccine, the patient responded. (Checking is recommended for healthcare workers.) Even if the titer is now negative, exposure to hepatitis B will induce an anamnestic (always hard to pronounce!) response, so people will be protected.

One common exception to this rule is for people on hemodialysis. A repeat vaccine would be indicated if their titers all below 10 mIU/mL. Some people also recommend this strategy for other immunocompromised hosts, but this is not yet fully endorsed in guidelines. Here’s a great list of hepatitis B FAQs from the CDC.

Question #5: For fecal transplants, why do we not accept stool from obese donors?

Answer: There is evidence that the microbiome of normal versus overweight people differs and also that antibiotic administration (at least in childhood) leads to weight gain — remember, this is why livestock and poultry receive antibiotics, to fatten them up! Plus there’s at least one case report of emergent obesity after fecal transplant from an overweight donor. Unfortunately, we don’t have evidence yet of the converse — that normal-weight donors lead to weight loss in those who are overweight.

Question #6:  Any evidence that vitamin D supplementation prevents or treats COVID-19?

Answer: Studies have shown that there is an association between low vitamin D levels and a higher risk of testing positive for COVID-19 and that people hospitalized with the disease have lower levels than population-based controls. One small, randomized trial also suggested a possible benefit of giving vitamin D.

While these data suggest that supplementation will help, remember that low vitamin D levels correlate with poor health in general and that the road is littered with failed studies of vitamin D treatment for a wide range of conditions, including critically ill people with respiratory failure. Pending the results of a fully powered study of vitamin D in COVID-19, we don’t currently recommend it.

Question #7:  For our stable HIV patients, please specify which statins can be given safely with ART. (Note: I didn’t write “HAART”.)

Answer: It all depends whether the ART (and thank you for not saying “H—T”!) contains the pharmacokinetic boosters ritonavir or cobicistat, which can dangerously increase levels of certain statins, especially simvastatin. If not, especially if they’re on a dolutegravir- or bictegravir-containing regimen (as so many people with HIV are these days), then you can use any statin.

But if ritonavir or cobicistat is in the mix, go with low-dose atorvastatin (10-20 mg daily), as levels will increase 2-4 fold. Another alternative is pitavastatin — no interaction potential — though insurance sometimes doesn’t cover this one. Finally, efavirenz lowers atorvastatin levels somewhat, so starting with a slightly higher dose is reasonable. And if you’re not using the Liverpool HIV Drug Interactions site, start now!

Question #8:  How should we dose trimethoprim/sulfamethoxazole for skin and soft tissue infections?

Answer: While a pivotal large clinical trial used two double-strength tablets twice daily, observational studies show no difference in outcomes between this and the standard 1 DS twice-daily approach. PharmD Bryan Hayes provides a nice summary of this controversy.

My practice is to recommend 2 DS twice daily for large and young people, and 1 DS twice daily for smaller and elderly patients — I’ll let you decide if this seems like a reasonable approach. And for the non-pediatricians out there, remember that each double-strength tablet contains 160 mg trimethoprim and 800 mg sulfamethoxazole — amazing how few clinicians of adults know that!

Question #9:  It is my understanding that a tick must be attached for over 24 hours for a patient to get Lyme disease. Is that correct? Does this influence your approach to preventive therapy?

Answer: You are correct about the need for tick attachment for at least 24 hours before Lyme transmission, but the practical problem is that the ticks don’t provide us time-stamped receipts for how long they’ve been snacking on our blood. (So inconsiderate of them.)

So unless one has clear evidence about timing — went for a hike in the afternoon, tick found that evening — we tend to be quite liberal in our administration of preventive therapy, meaning that pretty much anyone who asks for it gets it. This goes against the guidelines, but it’s a much more real-world approach! Remember, too, that black-legged ticks are now ubiquitous in our region — one can pick them up doing pretty much any outdoor activity.

Question #10:  If I treat someone for early Lyme, is there any reason to get a follow-up Lyme titer to confirm that my clinical diagnosis was correct?

Answer:  Generally not — both because it won’t alter your approach to future therapy (people can get Lyme multiple times) and because there is some evidence that early antibiotic therapy blunts the antibody response to this infection. Some might argue that it’s good to have a baseline for future evaluations or to check based on curiosity alone, but neither reason in my opinion is sufficient to warrant doing the test. And yes, that’s two Lyme questions in a row — hey, this is New England!

Question #11: Corticosteroids used to be recommended for herpes zoster for prevention of the post-herpetic neuralgia. Can you comment on this?

Answer:  While some older clinical trials suggested that steroids helped reduce pain in patients with acute herpes zoster, a Cochrane review of several randomized studies showed no aggregate benefit. A further limitation is that many of the studies excluded patients with even small contraindications to steroid treatment, such as having diabetes or being on immunosuppressive therapy. As a result, we ID docs don’t routinely recommend them — but the neurologists still sometimes do, and admittedly, a short course is unlikely to be harmful.

Question #12:  What negative side effects of long term antibiotics do you educate patients about? (I have some on antibiotics for years from ‘Lyme specialists’.)

Answer:  While the adverse effects of this strategy are well-documented (line infections, resistance, C. diff), it can sometimes be difficult to communicate this in a non-judgmental way. One sometimes useful strategy is to refer them either to the CDC site or, if they want something with a bit more narrative and without government associations, the Lyme Science site. The latter is a remarkable (and quite frightening) resource. Sorry, yet another Lyme question — there were so many!

Question #13:  My patient had an illness consistent with COVID-19 in the spring but was never tested since there was such a shortage. Now he has prolonged post-illness fatigue and “brain fog” and wonders if he has “long COVID.” His antibody test is negative. Help!

Answer:  This is a huge challenge on multiple fronts, as it’s possible he had COVID-19 in April but that his antibody titer has declined — it’s highly variable from person-to-person and also depends on what assay is being used. We unfortunately have no routine way to measure cellular immunity. Of course, it’s also possible he had a different viral respiratory tract infection.

Since I ended on this difficult topic of COVID-19 long-term symptoms, time to plug our latest podcast on Open Forum Infectious Diseases. Joining me is Dr. Vinay Prasad from UCSF, covering a wide range of COVID-19 issues, including treatments, research, long COVID, publications, and policies.

He has some remarkable (and controversial, no surprise) insights. You won’t regret it.

(Transcript here.)