Dynamics of leukocyte telomere length in pregnant women living with HIV, and HIV-negative pregnant women: A longitudinal observational study

Abstract

Background HIV-mediated inflammation and immune activation can accelerate telomere attrition. In addition, antiretrovirals can inhibit telomerase, possibly shortening telomeres. We examined the longitudinal dynamics of leukocyte telomere length (LTL) during pregnancy in a unique cohort of women living with HIV (WLWH) treated with combination antiretroviral therapy (cART), and HIV-negative control women. Methods Blood was collected at three visits during pregnancy, at 13–23, >23–30, and >30–40 weeks of gestation, and for WLWH only, at 6 weeks post-partum. LTL was measured by qPCR and both cross-sectional and longitudinal (MANOVA) models were used to examine possible predictors of LTL among participants who attended all three visits during pregnancy. Results Among WLWH (n = 64) and HIV-negative women (n = 41), within participant LTL were correlated throughout pregnancy (p<0.001). LTL was shorter among WLWH at first visit, but this difference waned by the second visit. WLWH who discontinued cART post-partum experienced a decrease in LTL. Longitudinally, LTL was similar in both groups and increased as gestation progressed, a change that was more pronounced among women under 35 years. Among WLWH, both smoking throughout pregnancy (p = 0.04) and receiving a ritonavir-boosted protease inhibitor-based regimen (p = 0.03) were independently associated with shorter LTL. Conclusions LTL increases as pregnancy progresses; the reasons for this are unknown but may relate to changes in blood volume, hormones, and/or cell subset distribution. While our observations need confirmation in an independent cohort, our data suggest that although some cART regimens may influence LTL, being on cART appears overall protective and that stopping cART post-partum may negatively impact LTL. The effect of smoking on LTL is clearly negative, stressing the importance of smoking cessation.

Association between micronutrients and maternal leukocyte telomere length in early pregnancy in Rwanda

“…We found evidence of leukocyte telomere length as a marker of biological aging in Rwandan women and also of possible associations between maternal micronutrient status and leukocyte telomere length in pregnant women in Rwanda. Other leukocyte telomere length studies with pregnant women have been conducted primarily in the European and North American context, which presents a different environmental milieu in terms of overall burden of infectious disease and maternal nutritional health [38,39]. In contrast with these other studies, the endemicity of infectious diseases in Kigali, Rwanda, including clinical and subclinical infections such as a higher prevalence of sexually transmitted infections and endemicity of malaria, provides a different context to assess the association between maternal leukocyte telomere length and birth outcomes [40].…”

“…We found no association between biomarkers for inflammation and infection including sexually transmitted infections and leukocyte telomere length, although in bivariate analyses, any presence of sexually transmitted infection and infection with chlamydia trachomatis approached statistical significance for shorter leukocyte telomere length. Previous studies of infectious disease, specifically HIV in South Africa, have found shorter leukocyte telomere length with infection [59] although other studies with HIV infected individuals did not find any association, primary in the context of antiretroviral therapy immune reconstitution [38,60]. Additional studies evaluating multiple pathogens have found that the association between shorter leukocyte telomere and infection may be pathogen specific [61].…”

Correlates of telomere length shortening in peripheral leukocytes of HIV-infected individuals and association with leukoaraiosis

“…We observed that shorter LTLs in HIV + individuals were strongly associated with advancing age, cART without INSTI, failure to achieve viral control after initiation of cART, and substance use. In previous reports, cART and substance abuse have sometimes been associated with LTL shortening in HIV + individuals [25, 26]. Antiretroviral drug-induced toxicity is an important complication of cART, particularly for regimens containing protease inhibitors (PIs).…”

Daily Oral Supplementation with 60 mg of Elemental Iron for 12 Weeks Alters Blood Mitochondrial DNA Content, but Not Leukocyte Telomere Length in Cambodian Women

“…Telomere attrition typically occurs gradually in adults, although the inter-individual variability is high [31]. Nevertheless, studies have detected changes in LTL in response to various interventions (e.g., calorie-restricted diet resulting in weight loss, exercise, and meditation) and pregnancy in less than 12 weeks [32][33][34][35]. There remains an extensive gap in the literature regarding short-term changes in telomere length.…”