Robust tobacco smoking self-report in two cohorts: pregnant women or men and women living with or without HIV

Abstract Understanding the true burden of tobacco smoking on adverse pregnancy outcomes is critical in generating appropriate interventions to improve outcomes. Self-reporting of human behaviour that is associated with stigma is associated with underreporting in general and may bias the impact of smoking in studies; however, self-reporting is frequently the most practical method of gleaning this information. The objective of this study was to evaluate concordance between self-reported smoking and concentrations of plasma cotinine, a biomarker of smoking, among participants enrolled in two related HIV cohorts. A total of 100 pregnant women (76 living with HIV [LWH] and 24 negative controls) in their third trimester, and 100 men and non-pregnant women (43 LWH and 57 negative controls) were included. Among all participants, 43 pregnant women (49% LWH and 25% negative controls) and 50 men and non-pregnant women (58% LWH and 44% negative controls) were self-reported smokers. The odds of discordance between self-reported smoking and cotinine levels were not significantly different between self-reported smokers and non-smokers, nor between pregnant women and others, but were significantly increased, regardless of self-reported status, among people LWH compared to negative controls. The overall concordance between plasma cotinine and self-reported data among all participants was 94% with a sensitivity and specificity of 90% and 96%, respectively. Taken together, these data demonstrate that participant surveying in a non-judgemental context can lead to accurate and robust self-report smoking data among both persons LWH and not, including in the context of pregnancy

Evidence of Subclinical mtDNA Alterations in HIV-Infected Pregnant Women Receiving Combination Antiretroviral Therapy Compared to HIV-Negative Pregnant Women.

Combination antiretroviral therapy (cART) can effectively prevent vertical transmission of HIV but there is potential risk of adverse maternal, foetal or infant effects. Specifically, the effect of cART use during pregnancy on mitochondrial DNA (mtDNA) content in HIV-positive (HIV+) women is unclear. We sought to characterize subclinical alterations in peripheral blood mtDNA levels in cART-treated HIV+ women during pregnancy and the postpartum period.This prospective longitudinal observational cohort study enrolled both HIV+ and HIV-negative (HIV-) pregnant women. Clinical data and blood samples were collected at three time points in pregnancy (13-<23 weeks, 23-<30 weeks, 30-40 weeks), and at delivery and six weeks post-partum in HIV+ women. Peripheral blood mtDNA to nuclear DNA (nDNA) ratio was measured by qPCR.Over a four year period, 63 HIV+ and 42 HIV- women were enrolled. HIV+ women showed significantly lower mtDNA/nDNA ratios compared to HIV- women during pregnancy (p = 0.003), after controlling for platelet count and repeated measurements using a multivariable mixed-effects model. Ethnicity, gestational age (GA) and substance use were also significantly associated with mtDNA/nDNA ratio (p≤0.02). Among HIV+ women, higher CD4 nadir was associated with higher mtDNA/nDNA ratios (p<0.0001), and these ratio were significantly lower during pregnancy compared to the postpartum period (p<0.0001).In the context of this study, it was not possible to distinguish between mtDNA effects related to HIV infection versus cART therapy. Nevertheless, while mtDNA levels were relatively stable over time in both groups during pregnancy, they were significantly lower in HIV+ women compared to HIV- women. Although no immediate clinical impact was observed on maternal or infant health, lower maternal mtDNA levels may exert long-term effects on women and children and remain a concern. Improved knowledge of such subclinical alterations is another step toward optimizing the safety and efficacy of cART regimens during pregnancy

Temporal variation in mtDNA/nDNA ratio during pregnancy, at delivery and postpartum for the HIV+ cohort.

<p>A) mtDNA/nDNA ratio in HIV- women (n = 42), HIV+ women who initiated cART prior to conception (n = 17) and continued throughout pregnancy, and HIV+ women who initiated cART during pregnancy (n = 46) at each sample time point (13–22 weeks, 23–30 weeks, 31–40 weeks, delivery, 6 weeks postpartum); mtDNA/ nDNA ratio among HIV+ women (n = 63) for the significant variables of (B) time of visit (13–22 weeks, 23–30 weeks, 31–40 weeks, delivery, 6 weeks postpartum), where the horizontal line in the boxplots indicates the median value, boxes represent the interquartile range, whiskers indicate 1.5 times the interquartile range, while points indicate outliers; (C) CD4 nadir, where the best-fit line from the mixed-effects model is shown.</p

Means, model estimates, and Chi-squared results for the mixed-effects modelling of mtDNA levels within the 63 HIV+ pregnant women.

<p>^a Means (± SEM) are reported for the raw data without correction for covariates.</p><p>^b Estimated effects after taking covariates into account.</p><p>^d LRT = likelihood-ratio test statistic</p><p>SEM, Standard error on the mean</p><p>df, degrees of freedom</p><p>Means, model estimates, and Chi-squared results for the mixed-effects modelling of mtDNA levels within the 63 HIV+ pregnant women.</p

HIV-specific clinical characteristics of HIV+ cohort (n = 63).

<p>HIV-specific clinical characteristics of HIV+ cohort (n = 63).</p

Significant associations between mtDNA/nDNA ratio and variables of interest for both HIV- and HIV+ cohorts (<i>N</i> = 105).

<p>(A) Ethnicity, (B) GA at visit (weeks) and (C) Illicit drug use. In A and C, the horizontal line in the boxplots indicates the median value, boxes represent the interquartile range, whiskers indicate 1.5 times the interquartile range, while points indicate outliers. In B, the best-fit line from the mixed-effects model controlling for platelets and other significant variables is shown. All samples were collected during pregnancy.</p

Means, model estimates, and log-likelihood ratio test Chi-squared results for the mixed-effects modelling of mtDNA levels in all HIV+ and HIV- pregnant women (n = 105).

<p>^a Means (± SEM) are reported for the raw data without correction for covariates.</p><p>^b Estimated effects after taking covariates into account.</p><p>^c The modelling did not differentiate between women using 2 or more illicit drugs during pregnancy and women only taking one illicit drug.</p><p>^d LRT = likelihood-ratio test statistic</p><p>SEM, Standard error on the mean</p><p>df, degrees of freedom</p><p>GA, gestational age</p><p>Means, model estimates, and log-likelihood ratio test Chi-squared results for the mixed-effects modelling of mtDNA levels in all HIV+ and HIV- pregnant women (n = 105).</p

Perinatal and neonatal outcomes for HIV+ (n = 63) and HIV- (n = 42) maternal infant pairs.

<p>^a One infant born to an HIV- mother was stillborn.</p><p>^b Two HIV- control women were considered at high risk of contracting HIV due to drug use and unprotected intercourse with partners with unknown HIV status; therefore, infants were treated with zidovudine (ZDV) and nevirapine (NVP) as per standard of care.</p><p>^c Maternal HIV+ group: pulmonary artery stenosis (n = 2), pyloric stenosis (n = 1), hydronephrosis (n = 1); Maternal HIV- group: hydronephrosis (n = 1).</p><p>^d Maternal HIV+ group: mild respiratory distress (n = 1), respiratory syncytial virus (RSV) infection (n = 1), seizures (n = 1), sepsis (n = 1), apnoea of prematurity (n = 1), pneumonia (n = 1); Maternal HIV- group: mild respiratory distress (n = 1), neonatal intensive care unit for >24 hours (n = 1), hyperbilirubinaemia (n = 1).</p><p>Continuous variables were tested for differences between the groups using t-tests; Apgar scores were compared using a Wilcoxon rank-sum test; categorical variables were compared using Chi Squared tests or Fisher exact tests where appropriate.</p><p>SD, standard deviation</p><p>Perinatal and neonatal outcomes for HIV+ (n = 63) and HIV- (n = 42) maternal infant pairs.</p