COVID Vaccination and Preeclampsia; Menstrual Blood for HPV Testing

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of Texas Tech Health El Paso, look at the top medical stories of the week.

This week’s topics include COVID vaccination and preeclampsia, HIV injection medicines, mpox treatment, and menstrual blood for HPV testing.

Program notes:

0:37 HIV treatment monthly injections

1:37 Long-acting and effective

2:37 Some didn’t come for monthly injections

3:16 COVID vaccination and preeclampsia rate

4:16 In two successive cohorts during pandemic

5:16 Pre-existing morbidity 58% reduction

6:15 COVID cytokine storm?

6:45 Mpox treatment

7:45 Randomized to placebo or smallpox drug

8:50 Menstrual blood to test for HPV

9:50 Minipad essentially the same as clinician collection

10:45 Can make it cost effective?

11:49 End

Transcript:

Elizabeth: Does COVID vaccination protect against preeclampsia?

Rick: Does treatment for smallpox work for people with monkeypox?

Elizabeth: Can we detect human papillomavirus in menstrual blood?

Rick: Treating people with HIV who have trouble taking oral pills regularly.

Elizabeth: That’s what we’re talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I’m Rick Lange, president of Texas Tech Health El Paso.

Elizabeth: Rick, if it’s okay with you, I’d like to turn first to NEJM. This ongoing issue of, “Gosh, how do we manage people who have HIV?” And this study takes a look at those folks who have challenges taking oral meds on a daily basis.

Rick: What’s clear after decades of studies and experiences is that antiretroviral therapy lowers mortality, it slows the progression of disease among patients that have HIV, and it also prevents the transmission of HIV. In most individuals that are treated, we use fixed-dose combination daily oral tablets. Unfortunately, it’s estimated that only about two-thirds of individuals on these actually end up with viral suppression because there are some challenges to taking oral antiretroviral therapy — social and structural barriers, side effects or stigma, and then people have other competing priorities.

About 4 years ago, the FDA actually approved the combination of long-acting injectable antiretroviral therapy. Cabotegravir plus rilpivirine can be injected on a once-monthly basis. For people that can’t regularly or won’t take oral antiretroviral therapy, is the long-acting effective in terms of preventing regimen failure? They took 450 individuals who weren’t controlled very well on oral therapy, and in step 1, they spent up to 24 weeks giving them support, conditional economic incentives, and then treating them with oral antiretroviral therapy.

From that group, about 300 were actually effective in terms of meeting the goals. So they took those, and they randomized them either to continue on oral therapy or put them on the long-acting injectable that was given once a month, and they followed these individuals over the course of 48 weeks. Those in whom they spent a lot of time teaching them how to give oral therapy, at the end of the 48 weeks, the regimen failure rate was about 41%, compared to about 23% in those that received the injectable form.

Elizabeth: Okay. So how do we account for the 20%+ failure rate among the people who got the injectable?

Rick: The same thing — it is they had to come for their monthly injections, and so over the course of 48 weeks, there were some individuals that just didn’t do it. So it didn’t completely ameliorate all the regimen failure, but it reduced it substantially.

Elizabeth: How did these things compare on a cost basis?

Rick: This particular study didn’t address that. It did look at the adverse event rate, and they were equal between the injectable and the oral.

Elizabeth: More data needed, no doubt. Well, we know that there’s also a regimen that has been tested that’s only an injectable twice a year. I’m wondering how that might compare with this.

Rick: That’s a great question. So, Elizabeth, this study was done because they were recommending this monthly injection for individuals that were not adherent, but nobody had ever done a study to show whether it was effective or not. And so this follows up on the FDA recommendations to prove, in fact, that it does help.

Elizabeth: Since we’re talking about infectious disease, then why don’t we turn to The Lancet? And this is a very interesting study that’s taking a look at whether women who are pregnant and are vaccinated against COVID-19 experience more, less, or the same amount of preeclampsia as those women who don’t get vaccinated during pregnancy.

And it’s a provocative thing. I do have to note that we’ve talked before about multiple benefits of vaccinations in reducing inflammation. And specifically, I refer to the shingles vaccine and the tantalizing data relative to dementia, as well as the flu vaccine and data relative to MIs [myocardial infarctions] experienced by those folks.

So this study looked at individual-level data from women who were pregnant who were prospectively enrolled from 18 countries in two consecutive cohorts between 2020 and 2022 during the COVID pandemic. They had a total of 6,527 women who were pregnant; 33% were diagnosed with COVID and 57% were unvaccinated. Of the vaccinated women, the vast majority received mRNA vaccines. About a third of them received an initial regimen plus a booster dose. Most of those also were the mRNA vaccine.

They confirmed an independent association between COVID-19 and preeclampsia. And that had been noted previously, of course, in lots of other studies. They especially noted that in unvaccinated women, what happens when we give a vaccination? They found that any vaccination gave a protective effect against preeclampsia during the index pregnancy. And that effect was stronger with a booster dose, reducing the odds ratio by about a third. Among women with preexisting morbidities who received a booster dose, their odds were reduced by 58%. This is pretty powerful evidence that, “Gosh, if you’re pregnant and there’s COVID running around, getting a vaccine and getting a booster is probably a good idea.”

Rick: Yeah. So we’ve talked years ago about how the COVID-19 vaccination decreases the severity of COVID infections and also decreases mortality. This is the first time it actually looked at preeclampsia. This extends the benefits of COVID-19 vaccination, not only with disease severity and mortality, but also decreasing the risk of preeclampsia in a substantial way.

Elizabeth: I was really interested in their speculations on the mechanism by which this vaccination might do this. And basically, they put forward this idea that viral infections are linked to pulmonary embolism through placental dysfunction, syncytiotrophoblast stress — I love that word, by the way — and through inflammation, of course, which we’ve speculated many times is the final common pathway. And we know that COVID, of course, typically produces a cytokine storm and has direct vascular endothelial damage. So that makes some sense to me why it might be protective.

Rick: Yeah. And, Elizabeth, I’m aware of at least 11 different viruses that have been associated with the increased risk of preeclampsia, again, for the reasons you mentioned. It’s not just the COVID-19, but really any viral infection at all that a woman may get, even something as “innocuous” as influenza can increase the risk of preeclampsia.

Elizabeth: Let’s turn back to the New England Journal for your second one.

Rick: Yep. And we’ve talked before, I think, one time about the human monkeypox virus. It’s an important public health threat worldwide. So far, it’s caused at least 100,000 infections and about 220 deaths across more than 100 different countries where the Mpox, or what we’ve previously called monkeypox, has been reported. It’s very transmissible.

There’s a similar orthopoxvirus called smallpox and there’s a treatment for it called tecovirimat. It’s approved by the FDA for the treatment of smallpox. And at least in some studies, both in in vitro and preclinical studies, it suggests that the same treatment may be effective against monkeypox because it targets a very similar protein — that’s what’s called the p37 envelope protein — in both smallpox and in monkeypox. So the question is, is it effective in resolving monkeypox in people that have become infected?

So this is a phase 3, international, double-blind, randomized, placebo-controlled trial of individuals that have laboratory-confirmed monkeypox. They were randomized to receive either placebo or tecovirimat for 14 days. And the primary outcome was, did it resolve clinically and did the active skin or mucosal lesions go away? And the secondary outcome was, did it reduce the pain that’s associated with monkeypox?

So they had 412 individuals that received placebo or tecovirimat, the vast majority of whom had laboratory-confirmed monkeypox. And I’m unfortunately sad to report that there was no benefit at all. The clinical resolution was the same. No change in lesion healing or viral DNA clearance. Finally, no difference in pain. So, unfortunately, it doesn’t sound like it’s worth giving to patients with monkeypox.

Elizabeth: Is there anything else, did they mention, that’s on the horizon that might be helpful in this regard?

Rick: No, Elizabeth, they don’t. And I did not do a search to see what else is on the horizon. It’s interesting because this has been used by some practitioners because of the similarities of smallpox and monkeypox. But, again, this is really the importance of doing a randomized controlled trial to see whether it’s effective or not.

Elizabeth: Back to the drawing board, it sounds like.

Finally, let’s turn to The BMJ. And this is a study that is using menstrual blood to test for human papillomavirus for cervical cancer screening. They wanted to compare the diagnostic accuracy of minipad-collected menstrual blood versus clinician-collected cervical samples to test for HPV in the detection of cervical intraepithelial neoplasia, the precursors for cervical cancer, early stages or later.

This is a cross-sectional population-based study. They had almost 3,100 women, 20 to 54 years of age, with regular menstrual cycles. What they did was test for HPV using a minipad-collected menstrual blood sample that the woman collected herself. They also looked at clinician-collected cervical samples and thin prep cytology for the presence of potential neoplasia.

What they found is that this little minipad, which right now it sounds like unfortunately is not commercially available, essentially the same with regard to clinician-based HPV testing. Among this cohort, these women preferred it to going in and having a clinician-collected sample. So it sounds like something that if we can commercialize it, it could be very acceptable, and it could result in much more robust HPV screening and heading off cervical cancer development.

Rick: Having to rely upon a clinician to collect samples to test for HPV, there’s privacy issues for women, there’s stigma associated with it, and there are healthcare costs. If we can actually have women provide samples from home, that alleviates some of those issues. And previously, there were some home diagnostic tests that usually involved a vaginal swab, which is still somewhat invasive and unacceptable to many women. If we can make it cost-effective, this will remove many of the barriers to getting women tested for HPV, which is obviously associated with an increased risk of cervical cancer.

Elizabeth: They describe the process and it just really is not a big deal. It’s just this little strip that then once it gets the sample on it, you remove it, put it into a collection container that’s got a solution, and mail it off, and it gets tested. So it seems extremely simple to me and, of course, is similar in many ways to lots and lots of other self-collected specimens we’re seeing these days. And I would point to Cologuard, for example, as something that’s been very acceptable and has performed well.

Rick: But it’s only useful if it’s not only available and cost-effective, but if it’s accurate as well. And what this study shows is that it has comparable diagnostic accuracy to clinician-collected cervical samples.

Elizabeth: I suspect we’ll see some more of this. That’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.

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