Macrophage-tropic, non-syncytium-inducing, HIV-1 variants predominate in the asymptomatic phase of infection and may be responsible for establishing infection in an individual exposed to the mixture of HIV-1 variants. Here, genotypical and phenotypical characteristics of virus populations, present in sexual, parenteral, or vertical donor-recipient pairs, were studied. Sequence analysis of the V3 domain confirmed the presence of a homogeneous virus population in recently infected individuals. Biological HIV-1 clones were further characterized for syncytium inducing capacity on the MT2 cell line and for macrophage tropism as defined by the appearance of proviral DNA upon inoculation of monocyte-derived macrophages. Both sexual and parenteral transmission cases revealed a selective outgrowth in the recipient of the most macrophage-tropic variant(s) present in the donor. In three out of five vertical transmission cases, more than one highly macrophage-tropic virus variant was present in the child shortly after birth, suggestive of transmission of multiple variants. In three primary infection cases, homogeneous virus populations of macrophagetropic, non-syncytium-inducing variants were present prior to seroconversion, thus excluding humoral immunity as the selective pressure in favour of macrophage-tropic variants. These observations may have important implications for vaccine development. (J. Clin. Invest. 1994. 94
ABSTRACT. Introduction. Growth failure is a common feature of children with human immunodeficiency virus type 1 (HIV-1) infection. Children who are treated with mono or dual nucleoside analogue reverse transcriptase inhibitor (NRTI) therapy show a temporary increase in weight gain and linear growth rate. In adults, protease-inhibitor-containing antiretroviral therapy is associated with a sustained weight gain and increased body mass index (BMI). Experience with protease inhibitors and growth in children is still limited. The data mainly deal with short-term effects on growth.Objective. To evaluate the effect of highly active antiretroviral therapy (HAART) on growth in children with HIV-1 infection.Design and Methods. We analyzed selected growth parameters, clinical data, and laboratory results as part of a prospective, open, uncontrolled, multicenter study to evaluate the clinical, immunologic, and virologic response to HAART consisting of indinavir, zidovudine, and lamivudine in children with HIV-1 infection. Height and weight were measured at 0, 12, 24, 36, 48, 60, 72, 84, and 96 weeks after initiation of HAART. Information about the children's growth before enrollment in the study was retrieved from the hospital medical records and/or the school doctor or health center. BMI was calculated. z Scores were used to express the standard deviation (SD) in SD units from the Dutch reference curves for age and gender. Viral loads and CD4 ؉ T-cell counts were examined prospectively and related to these growth parameters. z Scores were also calculated for CD4 ؉ T-cell counts to correct for age-related differences. A z score of 0 represents the P50, which is exactly the age/sex-appropriate median. A height z score of ؊1 indicates that a child's height is 1 SD below the age-and gender-specific median height for the normal population. Virologic responders were defined as those who either reached an undetectable viral load (<500 copies/mL) or had a >1.5 log reduction in viral load compared with baseline at week 12 after the initiation of HAART, which was maintained during the follow-up period.Results. Patients. Twenty-four patients were included (age: 0.4 -16.3 years at baseline), with a median HIV-1 RNA load of 105 925 copies/mL (5.03 log), a median CD4 ؉ T-cell count of 0.586 ؋ 10 9 /L (median z score: ؊2.28 SD), a median height z score of ؊1.22, a median weight z score of ؊0.74, and a median baseline BMI z score of ؊0.32. Eleven patients were naive to antiretroviral therapy, and 13 patients had received previous treatment with NRTI monotherapy. Twenty children used indinavir and 4 children used nelfinavir as part of HAART.Virologic and immunologic responses to HAART. Seventeen children were virologic responders, and 7 children were virologic nonresponders. In patients naive to NRTIs, median baseline viral loads were significantly higher than in pretreated patients. However, at weeks 48 and 96, there was no significant difference between the viral loads of both groups. At baseline, there was no significant difference in C...
In children with HIV, even when long-term clinically and virologically controlled, we found lower brain volumes, a higher WMH load, and poorer WM integrity compared to matched controls. These differences occur in the context of a poor cognitive performance in the HIV-infected group, and larger, longitudinal studies are needed to increase our understanding of the pathogenesis of cerebral injury in perinatally HIV-infected children.
Our results show that cognitive performance of HIV-infected children is poor compared with that of SES-matched healthy controls. Gaining insight into these cognitive deficits is essential, as subtle impairments may progress to more pronounced complications that will influence future intellectual performance, job opportunities, and community participation of HIV-infected children.
The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV‐1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short‐term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long‐term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first‐ and second‐line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART ‘pipeline’ of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained.
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