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

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