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Change of HIV-1 coreceptor use has been connected to progression of disease in children infected with HIV-1, presumably subtype B. It has not been possible to discern whether the appearance of new viral phenotypes precedes disease development or comes as a consequence of it. We studied the evolution of coreceptor use in HIV-1 isolates from 24 vertically infected children. Their clinical, virological, and immunological status was recorded and the env V3 subtype was determined by DNA sequencing. Coreceptor use was tested on human cell lines, expressing CD4 together with CCR5, CXCR4, and other chemokine receptors. The children carried five different env subtypes (nine A, five B, four C, three D, and one G) and one circulating recombinant form, CRF01_AE (n = 2). Of the 143 isolates, 86 originated from peripheral blood mononuclear cells (PBMCs) and 57 originated from plasma, received at 90 time points. In 52 of 54 paired plasma and PBMC isolates the coreceptor use was concordant. All 74 isolates obtained at 41 time points during the first year of life used CCR5. A change from use of CCR5 to use of CXCR4 occurred in four children infected with subtype A, D, or CRF01_AE after they had reached 1.5 to 5.8 years of age. There was a significant association with decreased CD4+ cell levels and severity of disease but, interestingly, the coreceptor change appeared months or even years after the beginning of the immunological deterioration. Thus CXCR4-using virus may emerge as a possible consequence of immune deficiency. The results provide new insights into AIDS development in children.

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BACKGROUND: A specialized antenatal care unit was set up for counseling and care of HIV-infected pregnant women. The team consisted of gynecologists, a midwife, a social worker and pediatricians. METHODS: The women were referred from departments of infectious diseases, venereology or institutions for drug addicts, antenatal care units and abortion clinics, or applied themselves. Women identified in the pregnancy HIV screening program were informed primarily by the team. The women were counseled along with their partners and cared for during abortion or the antenatal period, delivery and post partum. Contraceptive services were offered and psychosocial support was given. RESULTS: Between April 1985 and March 1997, 95 HIV-infected women with 122 pregnancies attended. Twenty-one per cent were or had been drug users, 2% had been infected by transfused blood and 77% were classified as having been sexually infected, two thirds of whom were Africans. The mean age was 27.8 years. In 54 of 93 pregnancies (58%) in which the woman could make an informed decision, she elected abortion -- in 37 cases for HIV related reasons. Significantly more women with an uninfected steady partner, compared to women without a steady partner, chose to continue the pregnancy, as did women in a relatively stable social situation. Of the partners, 68 were HIV-negative, 36 HIV-positive and 18 not tested. No severe HIV-related complications occurred during pregnancy. Seven of 40 (18%) children with a known infection status were infected. During the course of follow-up, nine mothers, two fathers and three children have died. Seventeen children were at risk of being orphaned, and another five were placed in foster care. CONCLUSION: Although it is possible to reduce mother-to-infant transmission by zidovudine therapy, the negative consequences of HIV and childbearing are still substantial. Therefore HIV screening during pregnancy and pre-pregnancy counseling are important issues for the health care system.

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PIP: "Children living in a world with AIDS" was the theme of a UNAIDS campaign launched because 1 million children are infected with HIV and 9 million children have become orphans due to AIDS (90% in sub-Saharan Africa). During 1996 alone, 400,000 children were infected: 90% were infected during pregnancy, delivery, or while breast feeding; the remaining 10% were infected sexually or via blood or blood products. In Africa, only one-third of HIV-infected children survive their 3rd birthday, and 8% of all children in Zimbabwe have lost their mothers to AIDS. A similar situation is rapidly evolving in Asia and South America. In Spain and Italy, more than 600 children have AIDS; most of them were infected through drug-abusing mothers. In France the figure is comparable, but here a large segment is represented by children of mothers from African countries. The total number of children with AIDS in the European Community is 2800: 86% were infected through their mothers. Romania has 4000 children with AIDS, who were predominantly infected via nonsterile syringes and blood transfusion. The European Commission has a specific AIDS prevention program, which addresses the measurement of disease spread, counteracting the disease, information and education, support for persons with HIV/AIDS, and countering discrimination. The risk of mother-to-child HIV transmission can be reduced from 25% to 8% by zidovudine (AZT) treatment during pregnancy and delivery.^ieng

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OBJECTIVE: To determine the effectiveness of a national screening programme for HIV infection in pregnant women. DESIGN: Observational study. SUBJECTS: All pregnant women presenting to antenatal or abortion clinics. SETTING: Sweden, September 1987 to December 1991. MAIN OUTCOME MEASURES: Number and characteristics of infected women. RESULTS: By the end of the study period 510,000 tests had been performed and 54 women with HIV infection identified (1.06/10,000). Of the 33 women identified in Stockholm, 14 women (4.4/10,000) had attended abortion clinics and 19 antenatal clinics (1.8/10,000; p < 0.05). Three women had been intravenous drug users, one was infected through a blood transfusion, and 50 were probably infected sexually. Of the 20 women who attended antenatal clinics early enough to allow an abortion, 12 continued with their pregnancies. CONCLUSIONS: Testing of all women, not just those perceived to be at risk, probably contributed to the high uptake of HIV testing. With high uptake such screening provides valuable data on spread of HIV in the heterosexual population and presents opportunity for preventing transmission of HIV to children and partners.

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PIP: Since the end of the 1980s the increase in the heterosexual spread if HIV infection in Sweden has led to infection of women and their children. The family and social care consultation at the psychiatric clinic of Huddinge hospital outside of Stockholm has been active in treating and providing support for pregnant women and their partners with such problems since the mid-1980s. In 1986 a pilot project was launched with the involvement of 22 maternal health care wards and 3 abortion counseling sites and districts with the aim of implementing voluntary HIV testing of all pregnant women. 99% consented, and 1 out of 2500 was found HIV-positive. As a result, all pregnant women are routinely offered an HIV test. The consultation team consists of a midwife, a counselor, a gynecologist, a pediatrician, and a psychiatrist. The team advises them and their partner about the risks to them and the child and about the options of keeping or aborting the child. Another group of HIV-infected women comes from Roslagstulls hospital; these women aware of their condition. Some take the 70% chance of giving birth to a healthy HIV-free child, but others choose abortion to avoid the 30% chance of having an HIV-infected child. The patient newly diagnosed with HIV is referred to a doctor to be informed of new treatment methods in time. The consultation also tries to mitigate the isolation and loneliness of infected patients. If the child is born, it is checked for HIV infection, and it can be declared free of it at the age of 18 months. Breast feeding is not recommended. The ethical questions concerning having a child when both parents are infected and the attitudes of staff towards HIV-positive human beings are also mentioned.^ieng

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Serum gamma-glutamyl transferase was analyzed in 669 pregnant women. They were interviewed with special emphasis on their consumption of alcohol during the first trimester. Thirteen percent admitted a consumption of greater than 30 gm of pure alcohol per day, and 3%, greater than 125 gm per day. One child with a complete fetal alcohol syndrome and one with a partial one were born to mothers with a high consumption of alcohol and elevated serum gamma-glutamyl transferase. The ninety-fifth percentile for serum gamma-glutamyl transferase in women classified as low consumers (less than 30 gm of alcohol per day) was 0.44 mukat/L. With this 95% specificity level used as a cutoff, the sensitivity of the serum gamma-glutamyl transferase test in identifying those who consumed more than 30 gm of alcohol per day was 25%. The conclusion was that screening based on analyses of serum gamma-glutamyl transferase is not to be recommended for routine use in prenatal care.

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