At the 2024 Conference on Retroviruses and Opportunistic Infections (CROI 2024) Terri Wilder, M.S.W., visited a poster presentation by Rebecca A. Abelman, M.D., titled “Age Modifies the Association Between Sex and the Plasma Inflammatory Proteome in Treated HIV.” Abelman is an assistant professor within the University of California-San Francisco Infectious Diseases Division.
Their conversation, transcribed below, highlights the differences between women and men who have suppressed HIV on antiretroviral therapy by looking at a number of inflammatory proteins, while adjusting for age and other variables.
This transcript has been edited for clarity.
Terri Wilder, M.S.W.: There’s a strong interest in HIV and aging because many folks who were diagnosed in the ’80s and ’90s are now in their 50s, 60s, and 70s. Would you talk a little bit about the motivation for this study?
Rebecca Abelman, M.D.: Sure. This study is within the CNICS cohort, which is a cohort of women and men with HIV across the United States. And we were really interested in looking to see if there were sex differences in inflammatory proteins and whether there was an age effect, as well.
Some of the precursors for this work were in the same cohort, and they were looking at a small number of immune activation biomarkers and saw that many of those immune activation biomarkers, consistent with other published data, were higher in women with HIV, as compared to men. But intriguingly, in women above age 47, many of those biomarkers were higher and, actually, in women they were more strongly predictive of clinical events.
We wanted to expand on that and so we used the [Olink Explore Inflammation] panel. So that allows us to have a far higher number of proteins. So, this had a total of 363 proteins. And we looked at first if there were differences in some of these proteins by sex, and then we later stratified by age to see if some of those differences changed based on age.
The other thing we did was look at these various proteins and their associations with mortality in the overall cohort. So, we wanted to see if there were also any differences in mortality by sex associated with any of these proteins.
In short, we found that there were many [differences]; there was evidence of sex differences in many proteins. We saw in 39 of the proteins that there was evidence of a sex difference and that many of those proteins were higher in women compared to men.
Then subsequently, when we stratified by age (we used the median age of 47) whereas in the cohort that was less than age 47, there were some proteins that were higher in women compared to men with HIV, but there were overall smaller amounts. And many of the proteins that were higher in women were more immunoregulatory than inflammatory.
In people who were over age 47, there were far more proteins that were higher in women when compared to men with HIV, and many of those proteins were associated with increased mortality in the overall cohort.
Overall, taken together, it suggested that inflammation tended to be more predictive with mortality in women than in men, and that women in general had more inflammation than men, particularly at higher ages.
I think the big question that we have and what we think is one of the potential drivers of this is menopause, and if there’s a menopausal effect that’s driving some of this. So, we’re looking into that further.
Wilder: I’m very intrigued by one bullet point in your conclusion: “This may suggest a mechanism to explain the loss of ‘female advantage’ in life expectancy in people with HIV.” Are you referring to how people believe that women live longer than men?
Abelman: Yes. So, women live longer than men. And then there’s been some data looking at mortality associations in people with HIV in that some of those differences with women living longer actually are less [in women with HIV]. So, we’re wondering if perhaps having higher inflammation might be one of the mechanisms that in women that might lead to essentially equalizing the life expectancy between women and men with HIV.
Wilder: Can you tell me a little bit about the women in this study?
Abelman: These were all virally suppressed individuals who were at outpatient clinics within the United States.
In the overall cohort, 46% of participants identified as Black, whereas 77% of women (of the 169 women) and 40% of the men [were Black]. Eleven percent of the overall cohort identified as Hispanic.
Women had slightly higher BMIs, [at] 30.3 [kg/m2], as compared to 26.1[kg/m2] in the overall cohort. CD4 nadirs were pretty similar across all groups and they were all virally suppressed.
And then looking at other clinical risk factors: ASCVD [atherosclerotic cardiovascular disease], the overall ASCVD [risk score] was 4.5% in the cohort; in women it was 3.1%. And we had slightly higher hepatitis C in women with HIV as compared to men, and slightly higher smoking rates, but similar amounts of ever intravenous drug use.
Wilder: If we’re looking at this inflammatory process, what can be done clinically?
Abelman: That’s a great question. I think there’s still a lot to investigate. I think this is, hopefully, a first step in trying to understand some of the underlying mechanisms that can be used to develop further therapeutics.
And then, from a clinical perspective, my personal research interest is in menopause and trying to understand some of the consequences of menopause and some of the underlying causal changes that happen with estrogen and whether, for example, things like hormone therapy might be beneficial in this group. We still don’t know, but it’s an area of active research.
Wilder: I’m also wondering about anti-inflammatory medications that might help.
Abelman: I think what’s useful about this type of approach is that it allows you to look at a bunch of different potential pathways. There’s no clear one pathway that’s leading to this inflammation. So, based on what we know now, there’s no one magic drug that will decrease all this inflammation. And there may be multiple mechanisms that are contributing.