Unique Profile of Inflammation and Immune Activation in Pregnant People With HIV in the United States

Abstract

Background: Little is known about inflammation/immune activation during pregnancy in people with HIV (PWH) and growth in their children who are HIV-exposed and uninfected (CHEU).

Methods: Using data from the Pediatric HIV/AIDS Cohort Study and an HIV-seronegative comparison group, we assessed associations of (1) HIV status, mode of HIV acquisition (perinatally vs nonperinatally acquired), and type of antiretroviral therapy (ART) with inflammation/immune activation in pregnancy; and (2) inflammation/immune activation in pregnancy with growth of CHEU at 12 months. Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble(s) TNF-α receptor 1 and 2 (sTNFR1, sTNFR2), sCD14, and sCD163 were measured between 13 and 27 weeks' gestation. Linear regression models were fit to estimate differences between groups for each log-transformed biomarker, adjusted for confounders.

Results: Pregnant PWH (188 total, 39 perinatally acquired, 149 nonperinatally acquired) and 76 HIV-seronegative persons were included. PWH had higher IL-6, sTNFR1, sCD14, and sCD163 and lower sTNFR2 compared to HIV-seronegative persons in adjusted models. Among PWH, sCD163 was higher in those with perinatally versus nonperinatally acquired HIV and on PI-based versus INSTI-based ART. Higher maternal concentrations of IL-6, sTNFR2, and hs-CRP were associated with poorer growth at 12 months.

Conclusions: Maternal HIV status is associated with a distinct profile of inflammation/immune activation during pregnancy, which may influence child growth.

Keywords: HIV; HIV-exposed uninfected; immune activation; inflammation; pediatrics; pregnancy.

Figure 1.

Estimated mean differences in log-transformed biomarkers during pregnancy, by exposures. For analyses of the associations between (A) HIV status [PWH versus HIV-seronegative (reference)], (B) mode of HIV acquisition [perinatally versus nonperinatally-acquired HIV (reference)], and (C) ART regimen [ART regimens versus INSTI-based ART (reference)] with biomarkers, generalized linear regression models with robust standard errors were fit to estimate the difference in mean log-transformed biomarker concentrations between exposure groups for each biomarker, unadjusted and adjusted for maternal age at conception, education, prepregnancy/first-trimester obesity, any substance use in the first trimester, and any sexually transmitted infection. For analyses to assess the association between mode of HIV acquisition and biomarkers we additionally adjusted for HIV RNA concentration. For analyses to assess the association between ART regimen and biomarkers, we additionally adjusted for HIV RNA concentration and mode of maternal HIV acquisition. Numbers of participants included in adjusted analysis were (A) HIV status, n = 151; (B) mode of HIV acquisition, n = 151; (C) ART regimen, n = 147. Abbreviations: ART, antiretroviral therapy; CI, confidence interval; HIV, human immunodeficiency virus; hsCRP, high-sensitivity C-reactive protein; IL-6, interleukin 6; INSTI, integrase strand transfer inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor; PWH, people with HIV; sCD14, soluble CD14; sCD163, soluble CD163; sTNFR1, soluble TNF-α receptor 1; sTNFR2, soluble TNF-α receptor 2.

Figure 2.

Adjusted associations of log-transformed maternal inflammation and immune activation biomarker concentrations with growth outcomes at 12 months of age in HIV-exposed uninfected infants. Difference in adjusted mean growth z-score at 12 months of age or change in growth z-score from birth to 12 months of age, per 1-unit increase in a specific log-transformed biomarker concentration. Separate generalized linear regression model with robust standard error was fit for each biomarker, adjusting for maternal age at conception, education, prepregnancy/first-trimester obesity, any substance use in the first trimester, type 1/2 or gestational diabetes, PI use during pregnancy, HIV RNA viral load, and mode of maternal HIV acquisition. Numbers of participants included in adjusted analysis were weight-for-age z-score at 12 months, n = 106; height-for-age z-score at 12 months, n = 105; weight-for-length z-score at 12 months, n = 105; change in weight-for-age z-score from birth to 12 months, n = 105; change in height-for-age z-score from birth to 12 months, n = 94. Abbreviations: HIV, human immunodeficiency virus; hs-CRP, high-sensitivity C-reactive protein; IL-6, interleukin 6; sCD14, soluble CD14; sCD163, soluble CD163; sTNFR1, soluble TNF-α receptor 1; sTNFR2, soluble TNF-α receptor 2.