Biomarkers from late pregnancy to 6 weeks postpartum in HIV-infected women who continue versus discontinue antiretroviral therapy after delivery

Abstract

Background: Women who use antiretroviral therapy (ART) solely for the prevention of mother-to-child transmission of HIV discontinue postpartum. We hypothesized that women discontinuing ART by 6 weeks postpartum ("discontinuers") would have elevated postpartum inflammatory biomarker levels relative to women remaining on ART postpartum ("continuers").

Methods: Data from HIV-infected pregnant women enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group P1025 with CD4 counts >350 cells per cubic millimeter before initiating ART or first pregnancy CD4 counts >400 cells per cubic millimeter after starting ART and with available stored plasma samples at >20 weeks of gestation, delivery, and 6 weeks postpartum were analyzed. Plasma samples were tested for highly sensitive C-reactive protein, D-dimer, and interleukin-6. We used longitudinal linear spline regression to model biomarkers over time.

Results: Data from 128 women (65 continuers and 63 discontinuers) were analyzed. All biomarkers increased from late pregnancy to delivery, then decreased postpartum (slopes different from 0, P < 0.001). Continuers had a steeper decrease in log D-dimer between delivery and 6 weeks postpartum than discontinuers (P = 0.002).

Conclusions: In contrast to results from treatment interruption studies in adults, both ART continuers and ART discontinuers had significant decreases in the levels of D-dimer, highly sensitive C-reactive protein, or interleukin-6 postpartum. Continuation was associated with a more rapid decline in D-dimer levels compared with discontinuation.

FIGURE 1

Median (Q1, Q3) biomarker levels. All biomarker levels were highest at time of delivery, then decreased postpartum to a level comparable with or lower than the level during pregnancy. Quest reference range: (1) hsCRP: >3–10 mg/L is considered high risk and <1 mg/L low risk; (2) D-dimer upper limit of normal is 0.50 µg/mL; (3) IL-6 (highly sensitive) lower limit of detection is −0.31pg/mL. Data gathered from http://www.questdiagnostics.com/testcenter and http://www.specialtylabs.com/clients/gbmc/details.asp?id=S51587&spt=true.

FIGURE 2

Estimated log biomarker trajectories by ART status group. Displays predicted values at selected time points from longitudinal regression models. All biomarkers increased from the third trimester of pregnancy to delivery and decreased by 6 weeks postpartum to levels below those seen in pregnancy. *One woman was missing the D-dimer measurements.

FIGURE 3

Estimated log D-dimer trajectory by ART status and viral load at 6 weeks postpartum. Displays predicted values at selected time points from longitudinal regression models. D-dimer levels were significantly higher among women when early and late discontinuers were combined into 1 group (above) and in women with viral loads greater than 400 copies per milliliter (below). *One woman was missing the D-dimer measurements. Viral load at 6 weeks postpartum was only available in 77 women (43 continuers and 34 discontinuers).

FIGURE 4

Biomarker trajectories in women with and without pregnancy/delivery complications. Displays predicted values at selected time points from longitudinal regression models. IL-6 trajectory was significantly different in women who experienced at least 1 pregnancy/delivery complication compared with those who did not. At each time point, D-dimer and hsCRP levels were higher in women who experienced at least 1 pregnancy/delivery complication compared with those who did not, but these differences were not statistically significant.