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      Antiretroviral Therapy Initiation Before, During, or After Pregnancy in HIV-1-Infected Women: Maternal Virologic, Immunologic, and Clinical Response

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          Abstract

          Background

          Pregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART) era. The effect of timing of HAART initiation relative to pregnancy on maternal virologic, immunologic and clinical outcomes has not been assessed.

          Methods

          We conducted a retrospective cohort study from 1997–2005 among 112 pregnant HIV-infected women who started HAART before (N = 12), during (N = 70) or after pregnancy (N = 30).

          Results

          Women initiating HAART before pregnancy had lower CD4+ nadir and higher baseline HIV-1 RNA. Women initiating HAART after pregnancy were more likely to receive triple-nucleoside reverse transcriptase inhibitors. Multivariable analyses adjusted for baseline CD4+ lymphocytes, baseline HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, history of ADE, prior use of non-HAART ART, type of HAART regimen, prior pregnancies, and date of HAART start. In these models, women initiating HAART during pregnancy had better 6-month HIV-1 RNA and CD4+ changes than those initiating HAART after pregnancy (−0.35 vs. 0.10 log 10 copies/mL, P = 0.03 and 183.8 vs. −70.8 cells/mm 3, P = 0.03, respectively) but similar to those initiating HAART before pregnancy (−0.32 log 10 copies/mL, P = 0.96 and 155.8 cells/mm 3, P = 0.81, respectively). There were 3 (25%) AIDS-defining events or deaths in women initiating HAART before pregnancy, 3 (4%) in those initiating HAART during pregnancy, and 5 (17%) in those initiating after pregnancy ( P = 0.01). There were no statistical differences in rates of HIV disease progression between groups.

          Conclusions

          HAART initiation during pregnancy was associated with better immunologic and virologic responses than initiation after pregnancy.

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          Most cited references45

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          A new and improved population-based Canadian reference for birth weight for gestational age.

          Existing fetal growth references all suffer from 1 or more major methodologic problems, including errors in reported gestational age, biologically implausible birth weight for gestational age, insufficient sample sizes at low gestational age, single-hospital or other non-population-based samples, and inadequate statistical modeling techniques. We used the newly developed Canadian national linked file of singleton births and infant deaths for births between 1994 and 1996, for which gestational age is largely based on early ultrasound estimates. Assuming a normal distribution for birth weight at each gestational age, we used the expectation-maximization algorithm to exclude infants with gestational ages that were more consistent with 40-week births than with the observed gestational age. Distributions of birth weight at the corrected gestational ages were then statistically smoothed. The resulting male and female curves provide smooth and biologically plausible means, standard deviations, and percentile cutoffs for defining small- and large-for-gestational-age births. Large-for-gestational age cutoffs (90th percentile) at low gestational ages are considerably lower than those of existing references, whereas small-for-gestational-age cutoffs (10th percentile) postterm are higher. For example, compared with the current World Health Organization reference from California (Williams et al, 1982) and a recently proposed US national reference (Alexander et al, 1996), the 90th percentiles for singleton males at 30 weeks are 1837 versus 2159 and 2710 g. The corresponding 10th percentiles at 42 weeks are 3233 versus 3086 and 2998 g. This new sex-specific, population-based reference should improve clinical assessment of growth in individual newborns, population-based surveillance of geographic and temporal trends in birth weight for gestational age, and evaluation of clinical or public health interventions to enhance fetal growth. fetal growth, birth weight, gestational age, preterm birth, postterm birth.
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            Natural regulatory T cells in infectious disease.

            This review discusses the control exerted by natural CD4(+) CD25(+) regulatory T cells (natural T(reg) cells) during infectious processes. Natural T(reg) cells may limit the magnitude of effector responses, which may result in failure to adequately control infection. However, natural T(reg) cells also help limit collateral tissue damage caused by vigorous antimicrobial immune responses. We describe here various situations in which the balance between natural T(reg) cells and effector immune functions influences the outcome of infection and discuss how manipulating this equilibrium might be exploited therapeutically.
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              Non-adherence to highly active antiretroviral therapy predicts progression to AIDS.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2009
                9 September 2009
                : 4
                : 9
                : e6961
                Affiliations
                [1 ]Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
                [2 ]Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
                [3 ]Comprehensive Care Center, Nashville, Tennessee, United States of America
                [4 ]Center for Health Services Research, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
                University of Cape Town, South Africa
                Author notes

                Conceived and designed the experiments: VVM TS. Performed the experiments: VVM. Analyzed the data: VVM BS. Contributed reagents/materials/analysis tools: VVM BS SES PFR GB SPR TS. Wrote the paper: VVM BS SES PFR TS.

                Article
                09-PONE-RA-10381R1
                10.1371/journal.pone.0006961
                2734183
                19742315
                d1ef8594-1625-4a58-8ca5-526e64fe6966
                Melekhin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 13 May 2009
                : 12 August 2009
                Page count
                Pages: 11
                Categories
                Research Article
                Infectious Diseases/HIV Infection and AIDS
                Obstetrics/Pregnancy
                Women's Health/Sexually Transmitted Diseases

                Uncategorized
                Uncategorized

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