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Background Knowledge on tuberculosis (TB) infection epidemiology in women of reproductive age living in TB-endemic areas is limited. We used a composite definition of TB infection in a cohort of pregnant women recruited in an Ethiopian city as a model for TB exposure patterns, and to identify factors associated with TB infection. Methods Women seeking antenatal care at public health facilities underwent structured interviews, physical examination, and QuantiFERON-TB Gold-Plus (QFT) testing. Women with symptoms compatible with TB disease, and all human immunodeficiency virus (HIV)–positive women, were investigated for active TB by sputum bacteriological testing. TB infection (TB+) was defined as either positive QFT (≥ 0.35 IU/mL), self-reported previous active TB, or current active TB. Associations between TB infection and clinical, demographic, and socioeconomic characteristics were tested in multiple logistic regression analysis. Results Among 1834 participants, 679 (37.0%) met criteria for TB+ (80 [4.4%] previous active TB, 5 [0.3%] current active TB, and 594 [32.4%] QFT-positive without previous or current active TB). Age (annual adjusted odds ratio [AOR], 1.069 [95% confidence interval {CI}, 1.045–1.093]) and HIV infection (AOR, 1.43 [95% CI, 1.033–1.988]) were independently associated with TB+. The relationship with increasing age was only observed in HIV-negative women, and translated to an estimated annual risk of TB infection of 2.1% in HIV-negative women. Conclusions TB infection in women of reproductive age in Ethiopia was independently associated with HIV infection and increasing age, suggesting exposure to contagious TB and continuous acquisition of TB infection in this population., In this cross-sectional study of pregnant women in Ethiopia, 679 of 1834 (37.0%) had tuberculosis infection, which was associated with HIV infection and increasing age (estimated at an annual risk of 2.1% among HIV-negative women), suggesting continuous exposure to contagious tuberculosis.

HIV-1 disease is often associated with CD4+ T lymphopenia as well as quantitative reductions in naive CD8+ T cells and cytopenias involving nonlymphoid hemopoietic lineages. Studies in HIV-1-infected humans as well as in animal models of lentivirus disease indicate that these effects may be secondary to infection and destruction of multilineage and lineage-restricted hemopoietic progenitor cells. To define the stages of T cell differentiation that might be susceptible to HIV-1, we performed flow cytometric analysis of the surface expression of CXCR4 and CCR5 on T cells and their progenitors from fetal tissue, cord blood, SCID-hu Thy/Liv mice, and adult peripheral blood. We found that CXCR4 is expressed at low levels on hemopoietic progenitors in the bone marrow, is highly expressed on immature (CD3−CD4+CD8−) T cell progenitors in the thymus, and then is down-regulated during thymocyte differentiation. As thymocytes leave the thymus and enter the peripheral circulation, the expression of CXCR4 is again up-regulated. In contrast, CCR5 is undetectable on most hemopoietic progenitors in the bone marrow and on intrathymic T progenitor cells. It is up-regulated when thymocytes coexpress CD4 and CD8, then down-regulated either in the thymus (CD4+ cells) or during exit from the thymus (CD8+ cells). These results indicate that discrete, lineage-related populations of T cell progenitors may vary widely in their potential to respond to chemokines and to be infected by HIV-1, and that T lymphoid differentiation is particularly vulnerable to CXCR4-using viruses.

As the immune system develops, T cells are selected or regulated to become tolerant of self antigens and reactive against foreign antigens. In mice, the induction of such tolerance is thought to be attributable to the deletion of self-reactive cells. Here, we show that the human fetal immune system takes advantage of an additional mechanism: the generation of regulatory T cells (Tregs) that suppress fetal immune responses. We find that substantial numbers of maternal cells cross the placenta to reside in fetal lymph nodes, inducing the development of CD4+CD25highFoxP3+ Tregsthat suppress fetal antimaternal immunity and persist at least until early adulthood. These findings reveal a form of antigen-specific tolerance in humans, induced in utero and probably active in regulating immune responses after birth.

BACKGROUND Protease inhibitor (PI)-based combination antiretroviral therapy is often indicated for treatment of maternal HIV disease, but little is known about PI pharmacokinetics during pregnancy. Increased cytochrome P450 activity may affect the disposition of PI and decrease drug exposure. METHODS Steady-state PI pharmacokinetics, measured by the area under the plasma concentration versus time curve (AUC(tau)), were evaluated in women on stable antiretroviral regimens containing nelfinavir (n = 9) or indinavir (n = 4) with or without ritonavir (n = 2) during the second and third trimesters of pregnancy and postpartum. Cytochrome P450 activity was assessed by measuring the urine 6 beta-hydroxycortisol to cortisol ratio (6 beta-OHF/F). RESULTS AUC(tau) in women on indinavir alone decreased and 6 beta-OHF/F ratios increased during pregnancy compared with postpartum control values (n = 2). Nelfinavir results demonstrated no clear change and were highly variable. CONCLUSIONS The results for indinavir suggest that metabolic induction occurs during pregnancy, which apparently resolves spontaneously postpartum. This may warrant dosage adjustment during pregnancy. This induction is offset by concomitant use of ritonavir. Nelfinavir results were variable and, therefore, the impact of pregnancy on nelfinavir disposition was not fully determined.

This editorial argues that antiretroviral drugs to combat vertical transmission must be chosen and administered without causing eventual drug resistance. The writer states that although active deployment of Petra A or B or HIVNET 012 drug protocols in the developing world may prevent hundreds of thousands of pediatric AIDS infections these same women and their infected children exposed to short-course zidovudine plus lamivudine or single-dose nevirapine will be at substantial risk of treatment failure when antiretroviral therapy becomes available. Given the pending crisis of Africas AIDS orphans policymakers should consider more carefully treatment programs that save the lives of mothers.

In a recent Oregon case, the state successfully sued for custody of an infant to prevent his human immunodeficiency virus (HIV)‐infected mother from breastfeeding him and to require antiretroviral prophylaxis. As more HIV-infected women give birth, pediatricians may increasingly face dilemmas when parents reject medical recommendations to forgo breastfeeding and to administer antiretroviral prophylaxis to the infant. Such disagreements create ethical dilemmas because pediatricians have an obligation to both protect the infant and respect parental decision making. Pediatricians need to balance these obligations in deciding whether to ask the courts to intervene on the infant’s behalf. To that end, we analyze the legal and ethical issues that arise when an HIV-infected mother refuses interventions to reduce neonatal transmission of HIV to her infant, provide an approach for addressing these disagreements, and present illustrative scenarios in which pediatricians should, may, and should not seek a court order to intervene. Arch Pediatr Adolesc Med. 2001;155:927-933

Assessing the activity of CYP3A4 is important for predicting the pharmacokinetic behavior of protease inhibitors in HIV positive patients, especially in pregnant women. The endogenous hormonal ratio of 6beta-hydroxycortisol (beta-OHF) to cortisol (F) in the urine is an index for metabolic enzyme activity of cytochrome p-450 (CYP) 3A4. Because the ratio is a unique way to assess the enzyme activity without using any exogenous probes for this isozyme, it is practical for use in pregnant women. In this paper, we describe a method using high performance liquid chromatography (HPLC) for 6beta-OHF in urine from pregnant women to estimate the ratio of 6beta-OHF/F. Urinary 6beta-OHF was measured by using C18-cartridge solid phase extraction and isocratic HPLC. Aliquots (1 ml) of urine samples spiked with internal standard, 6beta-hydroxyprednisolone (6beta-OHPSL), were alkalinized with NaOH, then applied to C18-cartridges, which were washed with water and hexane and eluted with ethyl acetate. After the effluents were dried and reconstituted in 10% acetonitrile, the samples were analyzed by HPLC using an isocratic mobile phase (acetic acid/acetonitrile/50 mM potassium dihydrogenphosphate: 0.2/9/90.8; v/v) and ultraviolet detection at 245 nm. The recoveries of 6beta-OHF from C18 cartridges were 93.2 and 93.9% when the authentic 6beta-OHF was added to the urine sample at the concentration of 50 and 300 ng/ml, respectively. Intra- and inter-day variations estimated at concentrations of 113-674 ng/ml were 2.9-5.6 and 4.9-8.1%, respectively. The method was applied to morning urine samples collected from HIV-positive pregnant women managed with protease inhibitor containing anti-retroviral regimens.