Inflammation, antiretroviral therapy continuation, and HIV disease progression in postpartum women with HIV

Abstract

Background: Higher levels of inflammation are associated with increased HIV disease progression, but data are lacking in postpartum women with HIV (WHIV), who generally have a distinct immune profile. Further, the impact of discontinuation of antiretroviral therapy (ART) on inflammation is not well understood for postpartum women. We studied the relationship of ART discontinuation, inflammation, and HIV disease progression in postpartum WHIV.

Setting: We conducted a 1:3 case-control study (N=347) nested within a multi-country randomized trial comparing postpartum ART continuation vs. discontinuation in WHIV with WHO clinical stage 1 disease and who did not meet criteria for ART at the time. Median follow-up time was 97.1 weeks.

Methods: Cases were defined as WHIV who progressed to HIV disease stage 2 or greater during follow-up. Controls were selected using a risk set sampling strategy. Plasma levels of inflammatory biomarkers interleukin-6 (IL-6), interferon γ (IFNγ), tumor necrosis factor α (TNFα), intestinal fatty acid-binding protein (I-FABP), soluble CD14(sCD14) and CD163 (sCD163) before (i.e., baseline) and 4 weeks after randomization were measured using immunoassays. Weighted multivariable regression models assessed the association between inflammation with HIV disease progression, by randomization arm (ART continuation vs. discontinuation).

Results: Postpartum WHIV with higher levels of baseline I-FABP and persistently high levels of IFNγ and TNFα had increased hazards of HIV disease progression. Significantly larger increases in I-FABP and sCD14, and smaller increases in TNFα and sCD163 between baseline and week 4 were observed for postpartum participants who continued ART than among those who discontinued ART.

Conclusion: Postpartum WHIV with higher levels of immune biomarkers have increased hazards of HIV disease progression, suggesting an important role for inflammation in HIV treatment outcomes. Our results showed that continuation of ART compared to discontinuation had differential impacts on various immune markers, with the discontinuation results relevant in settings of poor adherence, or treatment interruption.

Keywords: ART discontinuation; HIV clinical treatment failure; gut integrity; immune activation; monocyte activation.