Women with HIV Demonstrate Greater Mortality Risk vs Men

In a past international study, investigators showed an association of the female sex and an increased risk of mortality in people with HIV (PWH) with CD4 <100 cells/μL who were initiating antiretroviral therapy (ART).

These investigators wanted to do a follow-up to examine in a secondary analysis from a prospective study that included PWH with CD4 <100 cells/μL who had not begun ART regimen. Participants included people from the United States, Kenya, and Thailand, and they initiated ART between December 2006 to March 2013. They were followed up for nearly a year (48 weeks).

The investigators compared differences in biomarkers at baseline including C-reactive protein (CRP), hyaluronic acid (HA), hepcidin, IP-10, IL-2, -6, -8, -10, -17, IFN-γ, myeloperoxidase (MPO), sCD14, sCD163, tissue factor, TNF, and d-dimer, which did not differ by sex after adjusting for multiple comparisons, they reported.

Figure courtesy of the investigators and CROI.

To capture the biomarker data, they utilized multivariable regression models, associations between the odds of death and baseline biomarkers by sex using logistic regression models, and hazards of death using Cox proportional hazards models. All analyses were adjusted for site of enrollment.

Overall, they examined the biomarkers of 506 PWH, with 39.3%(N=199) of whom were assigned female at birth. The investigators reported that the baseline age, CD4 count, and HIV viral load were not significantly different by sex.

The results of this follow-up analysis were reported at this week’s ongoing Conference on Retroviruses and Opportunistic Infections (CROI) in Denver, CO.

Specifically, the new data being reported showed that although they did not see any major differences in biomarkers, CD4 count, or viral load in PWH with CD4 <100 cells/μL starting ART, females were associated with increased mortality odds.

“Within 6 months of initiating ART, 31 (6.5%) participants died, 17 of whom were female (55%). Female sex was associated with increased hazards of mortality, particularly in the first 30 days after ART initiation (HR 3.34, P=0.038). Increased CRP, increased IL-27, and decreased body mass index were associated with increased odds of death in both sexes; increased IL-8, -10, HA, MPO, and d-dimer were associated with increased odds of death in females but not males, while elevated white blood cell count and decreased hemoglobin were associated with increased odds in males but not females,” the investigators wrote.

The investigators suggested that in females there might be a “distinct pathophysiologic mechanisms that account for the observed increased risk of death.” Still this conclusion warrants further studies they wrote.

Reference

Wang J, Rupert A, Sheikh H, et al. Evaluating Biomarkers and Mortality by Sex in People With Late HIV Starting Antiretroviral Therapy. Poster #358 presented at CROI 2024. March 3-6, 2023. Denver, CO.