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UBC Theses and Dissertations

Blood telomere length in infants and their HIV-infected mothers exposed to antiretroviral therapy during pregnancy Imam, Tuhina


Background/Objectives: Nucleoside reverse transcriptase inhibitors (NRTIs) are part of the antiretroviral therapy (ART) given to HIV-infected pregnant women to prevent vertical HIV transmission. The NRTI zidovudine (AZT) is a known inhibitor of human telomerase, the enzyme responsible for telomere elongation. We hypothesized that average telomere length (ATL) may be shorter in infants born to HIV-infected mothers and exposed to ART in utero, compared to ART-unexposed infants. Methods: Two independent cohorts of pregnant women and their infants were studied, spanning 1990-2000 (SJ) and 2005-2009 (Pregnancy). SJ included 120 HIV⁺ exposed and unexposed pregnancies while Pregnancy included 99 HIV⁺ highly active antiretroviral therapy (HAART)-exposed and HIV⁻ pregnancies. Dried blood spots (SJ) or whole blood (Pregnancy) were collected from the pregnant women and their infants. Relative ATL (rATL) was measured by quantitative PCR. The differences in rATL between HAART/ART-exposed and unexposed maternal, infant and cord blood (CB) were investigated using ANCOVA, adjusting for maternal age, gestational age, smoking (cigarette/marijuana) and illicit drug/methadone use ever in pregnancy. For the HIV/HAART group, additional parameters included CD4+ count, HIV plasma viral load near delivery, length of HAART exposure, HCV infection and ethnicity. Relationships between maternal and infant rATL were also investigated. Results: Infant rATL were significantly longer than maternal rATL for both cohorts (p<0.0001). Exposed CB rATL was shorter than controls (p=0.042) but the differences became non-significant after adjusting for covariates. Although a consistent pattern was seen whereby the rATL were 2-6% shorter in the exposed samples compared to the unexposed ones, this difference never reached statistical significance. In the SJ but not the Pregnancy cohort, smoking and illicit drug use in pregnancy were associated with shorter infant (p=0.033) and maternal (p=0.035) blood rATL. In the pregnancy cohort, among the HIV⁺ HAART-exposed, higher CD4+ count (p=0.047) and longer HIV duration (p=0.016) were independently associated with shorter maternal rATL. Maternal and infant rATL were significantly correlated (r=0.43, p=0.002) in the pregnancy but not in the SJ cohort. Conclusion: These results suggest that, if HIV and/or ART/HAART is a risk for telomere attrition in the context of this study, it is less important than other recognized risks.

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