The X4 phenotype of HIV type 1 evolves from R5 in two children of mothers, carrying X4, and is not linked to transmission.

Previously, we found that emergence of the X4 viral phenotype in HIV-1-infected children was related to the presence of X4 in their mothers (C.H. Casper et al., J Infect Dis 2002; 186:914-921). Here, we investigated the origin of the X4 phenotype in the child, analyzing two mother-child pairs (Ma-Ca, Mb-Cb) where the mothers carried X4 and their children developed X4 after an initial presence of R5. We used nested polymerase chain reaction of the env V3 region to generate 203 HIV-1 clones for sequencing (Ma, n = 44; Ca, n = 73; Mb, n = 61; Cb, n = 25) from DNA of peripheral blood mononuclear cell (PBMC) lysates, altogether 167 clones, or from cDNA of plasma RNA, 36 clones. PBMC and plasma isolate sequences from each time point enabled us to assign the probable phenotype to clone sequences in a phylogenetic tree. The transmission and evolution were reconstructed using the maximum likelihood method. In mother-child pair Ma-Ca, one maternal R5 isolate clustered with the child's R5 sequences, at the earliest time when R5 was isolated in the child, confirming this as a likely source of the transmitted R5 phenotype. At age 3, an X4 population was present in the child that had evolved from the child's own R5-associated population, clearly distinct from the maternal X4 sequences. The second mother-child pair (Mb-Cb) displayed a similar pattern. Amino acid substitution patterns corroborated the conclusions from the phylogenetic tree. Thus, in both children, the X4 virus developed from their own R5 population, and was not caused by transmission of X4.

HIV and child-bearing: clinical outcome and aspects of mother-to-infant transmission.

Forty-four HIV-1-seropositive women and their children were followed-up and examined in connection with the course of pregnancy, mother-to-infant transmission of HIV and clinical outcome. Twelve out of 48 children were known to be infected and two children were lost to follow-up. Of the remaining 34 children, 22 are not infected, and 12 are clinically and immunologically normal at less than 18 months. There was no difference in intrauterine growth between infected and uninfected children. Forty-six per cent of the 39 mothers seen after delivery progressed to a more advanced stage of HIV infection during a mean follow-up time of 33 months after delivery. Although comparable in age, clinical and immunological status at delivery, and follow-up time, mothers of infected children had longer durations of HIV infection and were symptomatic and/or had low CD4 cell counts to a significantly greater extent at follow-up than mothers of uninfected children.

Influence of donor and recipient ages and sex on graft function after pediatric renal transplantation.

BACKGROUND: Adult donor grafts adapt to the smaller size of the child recipient by reducing their absolute glomerular filtration rate (GFR) (ml/min). The question arises whether these grafts can increase the absolute GFR when the child recipient grows or whether a child donor graft can better increase its function. The aim of this study was to evaluate the influence of donor and recipient ages and sex on renal function. METHODS: Eighty-five children and adolescents, aged 0.4-20.5 years at transplantation, were monitored annually, by GFR and effective renal plasma flow (ERPF), determined by clearances of inulin and para-aminohippuric acid. The patients received 90 grafts from donors aged 3-67 years. Follow-up time was around 5 years. RESULTS: Absolute GFR and ERPF (ml/min) of grafts from donors <20 years of age (all cadaveric donor grafts) increased during follow-up, resulting in a constant relative GFR and ERPF (ml/min/1.73 m2), whereas absolute GFR and ERPF of grafts from donors >20 years of age remained constant during follow-up, resulting in a significant decrease in relative values. Relative GFR and ERPF fell during follow-up in young recipients (<12 years of age), but remained constant in older recipients (>12 years). Donor and recipient sex did not influence renal function. CONCLUSIONS: Child donor grafts seem better able to increase their function with the growth of the child recipient than adult grafts. However, the limited access to pediatric grafts and the fact that pediatric cadaveric grafts might involve technical problems in connection with grafting restrict their use.

Renal transplantation in children less than two years old.

Twenty-one infants, 2 years old or younger, received 21 renal transplants between 1983 and 1995. Six of the transplantations were performed from 1983 to 1989, and the remaining 15 were performed from 1990 to 1995. The median age at transplantation was 16.0 months and the median body weight was 9.0 kg. Living-related donor kidneys were used in 15 cases, an adult cadaveric donor kidney was used in one case, and pediatric cadaveric donor kidneys were used in five cases. All grafts were placed intra-abdominally. The immunosuppressive therapy consisted of cyclosporine, azathioprine, and prednisolone. No prophylactic antithymocyte globulins were used. Five infants have died, one with a functioning graft and four after loss of graft function. All graft losses and deaths occurred during the first 6 months after transplantation. The 5-year patient survival and graft survival rates were 87% for recipients of living donor grafts and 44% for recipients of cadaveric grafts. The median height SD score increased from -3.7 before operation to -1.9 at 1 year, -0.7 at 3 years, and -1.1 at 5 years. The glomerular filtration rate in absolute values remained stable in all infants, whereas a reduction in glomerular filtration rate related to body surface area was seen at follow-up, 5 years after transplantation. We conclude that renal transplantation can be performed with good long-term results in children less than 2 years old.

Ten years' experience of renal transplantation in children in the cyclosporine era.

Sixty renal transplantations were performed in 53 children, 0.4-16.0 years of age during the last 10 years. Fifty-five percent of the children were < or = 7 years at transplantation and 23% were < or = 2 years. Congenital nephropathies were the primary disease in 79%. Preemptive transplantation was performed in 24 first transplantations. Forty-two grafts came from living related donors and 18 came from cadaveric donors. The 1- and 5-year patient survival rates in the 0- to 7.0-year age group were 83% and 83%, respectively, and in the 7.1- to 16.0-year age group, 100% and 93%. The 1- and 5-year graft survival rates were 77% and 77% and 90% and 74% in the two groups, respectively. In children < or = 2 years old at transplantation, the 1- and 5-year patient and graft survival rates were the same, 86% and 86% in living related donors recipients, whereas they were 40% and 40% in cadaveric donors recipients. Six patients died, 3 with functioning grafts. An additional 7 grafts were lost in 6 patients, all of whom were subsequently retransplanted. The median height SD scores at transplantation was -2.98 SD in children with congenital diseases and -0.48 SD in children with acquired diseases. The median height SD scores of the 22 children followed for 3 years after transplantation was -1.06 SD. It is concluded that the survival rates obtained are satisfactory, despite the fact that the majority of the children were transplanted at a comparatively young age because of a high frequency of congenital renal disorders.

Coreceptor change appears after immune deficiency is established in children infected with different HIV-1 subtypes.

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.

Prognosis of children admitted to institutional care during infancy.

The present study has investigated the prognosis of infants admitted to institutional care. The follow-up was made after five and ten years. Three groups of children were studied: those who were in adoptive homes, foster homes and biological homes, respectively, at the time of the investigation. Approximately 50% of the total population was treated in hospital after the neonatal period. More children in foster and biological homes were hospitalized because of trauma. At 4 years of age the psychomotor development was considered normal in 77% of the adopted children compared to approximately 55% in the other two groups. Furthermore, the children in foster and biological homes demonstrated a higher rate of psychological or behavioral disturbances. The children who were in foster homes had experienced more separations and 39% of them had been subjected to 6 or more placements. The experiences of institutional care per se in infancy do not predispose the child to health and behavioral problems. The determining factor for optimal development seems to be permanency of care and parenting capability.

Screening for HIV-1 antibodies in pregnancy: results from the Swedish national programme.

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.

[Mother-to-child transmission of HIV infections. Antiviral agents and Cesarean section reduce the risk of transmission]. / HIV-smitta från mor till barn. Läkemedel och kejsarsnitt minskar risk för smitta.

There has been a substantial decrease in maternal-infant transmission of HIV in many European and North American countries during the past five years, from 15-25 per cent to approximately 5%. Reasons include the prophylactic administration of zidovudine to mother and child, more effective treatment strategies leading to decreased viral load during pregnancy, and increased use of elective Caesarean section. In developing countries however, the vertical transmission rate of HIV is still high at 25-40 per cent. Simpler and less expensive prophylactic regimens, such as nevirapine to mother and child at delivery and after birth, respectively, have raised hope. Drug resistance and the risk of adverse effects of antiretroviral drugs on the child are threats to the prevention of mother-to-infant transmission of HIV.

[Children of HIV-infected women. An exposed group]. / HIV-infekterade kvinnors barn. En utsatt grupp.

PIP: In order to describe the social situation of children of HIV-infected mothers, an investigation was carried out between November 1991 and February 1992. A questionnaire inquiring about children (under 18) of HIV-infected mothers was sent out to all HIV treatment wards in Stockholm and institutes engaging in family and social care. The mothers (21-45 years old, average age 32 years) were divided into 4 groups: 1) known or probable infection through sexual contact in Europe (mainly in Sweden), 2) known or probable infection through sexual contact in the rest of the world (mainly in Africa), 3) infection via blood products, and 4) infection via intravenous drug abuse. Data were received about 92 living mothers and their 144 children under 18 years of age. Almost two-thirds of the mothers' infection were known to be or probably sexually transmitted, and of these more than two-thirds were from countries outside Europe, mainly from Africa. Only 32% of mothers were infected by IV drug use, and the remaining 6% via blood products. 24% of all children had mothers with an advanced stage of the disease (AIDS or severely reduced immune response). All children 11-18 years old were HIV negative, while 10 children of 105 who were under 11 years of age were infected with HIV, and 15 had a still undetermined HIV status. In all, 63% (91/144) of children had a known living father, 40% of whom (36/91) were infected with HIV. 40% of all children (58/144) had regular contact with their fathers, while only 1 child of 20 children who were under guardian care had regular contact. 74% of the children faced the risk of being left without parents.^ieng

[The year of the world aids day: children in a world of AIDS]. / Arets världsaidsdag: barn i en värld med aids.

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