High seroprevalence of human herpes virus 8 (HHV-8) antibodies among vertically HIV-infected pediatric patients living in Germany

Background: Human herpes virus 8 (HHV-8), a gamma herpes virus, is the etiological agent for Kaposi sarcoma (KS). HIV-infected adults with advanced immunodeficiency are at risk. Prevalence data of HHV-8 infection in HIV-infected children living in non-endemic areas are limited. Serologic studies indicate low seroprevalence rates of 3–4% for healthy children living in United States and Germany [1]. Purpose of the study: The aim of the study was to determine the seroprevalence of HHV-8 antibodies among vertically HIV-infected pediatric patients in Germany and to evaluate their association with age, gender, ethnicity, and other demographic factors. Methods: In 2012, a multi-center cross-sectional study was conducted in four University Hospitals in Germany. Stored frozen serum specimens obtained from vertically HIV-infected children and adolescents were tested for antibodies against lytic and latent HHV-8 antigens. Data on patients' demographic characteristics and medical history were recorded. Results: A total of 214 HIV-infected children and adolescents (105 males, 109 females) were included. The median age was 10.2 years (range 1 months–22.6 years). A high proportion of these children (62%) was born in Western Europe, whereas 65% (139/214) of their mothers were born in countries outside Western Europe. The majoritiy (91%) of the children had been treated with highly active antiretroviral therapy and 55.2% (116/210) had a HIV-viral load<50 copies/mL. The median CD4 cell count was 1000/L (range 3–4400). The overall seroprevalence of HHV-8 antibodies was 23.8% (51/214). Seroprevalence rates did not show significant differences between age or gender. In the group of young children aged 1 month to 35 months, 19.4% (46/31) had HHV-8 antibodies, compared to 25% (25/100) in children aged 36 months to 11 years, and 24.1% (20/83) children 12 years and older. In the study group, seroprevalence rates were significantly lower in children who were born in Western Europe (p <0.01) compared to those born in Africa, Asia, or Eastern Europe. Clinical symptoms of HHV-8 infection were reported to be uncommon; only one child had a history of KS at 2 years of age. Conclusions: Vertically HIV-infected pediatric patients living in Germany showed a high HHV-8 seroprevalence of 23.8%. These rates were higher as expected in the normal pediatric population. The findings suggest that HHV-8 infection occurred already in the first years of life

Hematological Changes in Women and Infants Exposed to an AZT-Containing Regimen for Prevention of Mother-to-child-transmission of HIV in Tanzania.

Tanzanian guidelines for prevention of mother-to-child-transmission of HIV (PMTCT) recommend an antiretroviral combination regimen involving zidovudine (AZT) during pregnancy, single-dosed nevirapine at labor onset, AZT plus Lamivudine (3TC) during delivery, and AZT/3TC for 1-4 weeks postpartum. As drug toxicities are a relevant concern, we assessed hematological alterations in AZT-exposed women and their infants. A cohort of HIV-positive women, either with AZT intake (n = 82, group 1) or without AZT intake (n = 62, group 2) for PMTCT during pregnancy, was established at Kyela District Hospital, Tanzania. The cohort also included the infants of group 1 with an in-utero AZT exposure ≥4 weeks, receiving AZT for 1 week postpartum (n = 41), and infants of group 2 without in-utero AZT exposure, receiving a prolonged 4-week AZT tail (n = 58). Complete blood counts were evaluated during pregnancy, birth, weeks 4-6 and 12. For women of group 1 with antenatal AZT intake, we found a statistically significant decrease in hemoglobin level, red blood cells, white blood cells, granulocytes, as well as an increase in red cell distribution width and platelet count. At delivery, the median red blood cell count was significantly lower and the median platelet count was significantly higher in women of group 1 compared to group 2. At birth, infants from group 1 showed a lower median hemoglobin level and granulocyte count and a higher frequency of anemia and granulocytopenia. At 4-6 weeks postpartum, the mean neutrophil granulocyte count was significantly lower and neutropenia was significantly more frequent in infants of group 2. AZT exposure during pregnancy as well as after birth resulted in significant hematological alterations for women and their newborns, although these changes were mostly mild and transient in nature. Research involving larger cohorts is needed to further analyze the impact of AZT-containing regimens on maternal and infant health

Granulysin-Expressing CD4+ T Cells as Candidate Immune Marker for Tuberculosis during Childhood and Adolescence

BACKGROUND: Granulysin produced by cytolytic T cells directly contributes to immune defense against tuberculosis (TB). We investigated granulysin as a candidate immune marker for childhood and adolescent TB. METHODS: Peripheral blood mononuclear cells (PBMC) from children and adolescents (1-17 years) with active TB, latent TB infection (LTBI), nontuberculous mycobacteria (NTM) infection and from uninfected controls were isolated and restimulated in a 7-day restimulation assay. Intracellular staining was then performed to analyze antigen-specific induction of activation markers and cytotoxic proteins, notably, granulysin in CD4(+) CD45RO(+) memory T cells. RESULTS: CD4(+) CD45RO(+) T cells co-expressing granulysin with specificity for Mycobacterium tuberculosis (Mtb) were present in high frequency in TB-experienced children and adolescents. Proliferating memory T cells (CFSE(low)CD4(+)CD45RO(+)) were identified as main source of granulysin and these cells expressed both central and effector memory phenotype. PBMC from study participants after TB drug therapy revealed that granulysin-expressing CD4(+) T cells are long-lived, and express several activation and cytotoxicity markers with a proportion of cells being interferon-gamma-positive. In addition, granulysin-expressing T cell lines showed cytolytic activity against Mtb-infected target cells. CONCLUSIONS: Our data suggest granulysin expression by CD4(+) memory T cells as candidate immune marker for TB infection, notably, in childhood and adolescence

Guidelines and practice of breastfeeding in women living with HIV—Results from the European INSURE survey

Introduction: Antiretroviral therapy (ART) is integral to HIV prevention, including averting vertical transmission. The World Health Organization (WHO) recommends ART and breastfeeding for all women living with HIV for at least 12 months post-partum [1, 2]. Much of the data on HIV transmission through breastfeeding comes from low-resource settings, with a paucity of data on breastfeeding-related HIV transmission in women living with HIV in other settings. Women Against Viruses in Europe (WAVE), part of the European AIDS Clinical Society (EACS), aims to improve the standard of care for women living with HIV and sought to gain an understanding of breastfeeding guidelines and practice in women living with HIV across Europe.// Methods: A steering group convened by WAVE developed a survey to collate information on breastfeeding trends, practice, and guideline recommendations for women living with HIV in Europe and to establish interest in becoming involved in a collaborative breastfeeding network. The survey was disseminated to 31 countries in March 2022.// Results: In total, 25 eligible responses were received: 23/25 (92%) countries have HIV and pregnancy guidelines; 23/23 (100%) guidelines refer specifically to breastfeeding; 12/23 (52%) recommend against breastfeeding; 11/23 (48%) offer an option if certain criteria are met; 12/25 (48%) reported that the number of women living with HIV who breastfeed is increasing; 24/25 (96%) respondents were interested in joining a network on breastfeeding in women living with HIV.// Conclusions: Recommendations vary, and nearly half of the guidelines recommend against breastfeeding. Many countries report an increase in breastfeeding. WAVE will establish a collaborative network to bridge data gaps, conduct research, and improve support for women living with HIV who choose to breastfeed

Immunopathogenic and clinical implications of advanced tissue analysis in non-tuberculous mycobacterial infections in children

Objectives: Infections with non-tuberculous mycobacteria (NTM) in children usually affect the lymph nodes and surrounding tissue. Although the infection is typically self-limiting, it carries a substantial risk of complications due to persistent inflammation and invasive therapeutic interventions. Yet, the immunopathogenesis of the disease is obscure, as are biomarkers guiding treatment decisions.Methods: In this observational study, we analyzed histological samples collected in the NTMkids study to identify parameters associated with impaired wound healing and complicated disease progression. Samples from 33 patients (median age at first presentation 33 months) were investigated, with two consecutive biopsies in 9 patients.Results: Germinal centers, a scattered distribution of granuloma associated CD4+ T-cells, higher CD8+ T-cell density inside the necrosis and foamy epitheloid cells were associated with a favorable outcome. Tissue damage presenting clinically as liquefaction was associated with an adverse outcome.Conclusions: The identified tissue reaction patterns in NTM infections provide insights into the biology of NTM lymphadenitis in children and may aid in more precise treatment decisions

Vigilância do desenvolvimento neuropsicomotor de crianças de um programa DST/AIDS

A terapia anti-retroviral de alta potência (TARV) é uma forma eficaz de prevenção da transmissão do vírus HIV de mãe para filho. No entanto, os estudos ainda investigam os efeitos da exposição intraútero à TARV, dentre eles o atraso no desenvolvimento neuropsicomotor (DNPM). O presente estudo apresenta o relato de um projeto de extensão, cujos objetivos foram verificar o DNPM de crianças de um programa DST/AIDS, orientar as famílias considerando seu contexto socioeconômico e realizar encaminhamentos para serviços de saúde específicos. A vigilância do DNPM foi feita em três etapas: (1) avaliação em ambulatório; (2) avaliação e orientações em domicílio; (3) elaboração de relatórios aos gestores de saúde. Foram utilizados os testes DENVER II e o PEDI, além de um questionário socioeconômico. Participam do programa DST/AIDS 15 crianças, sendo 12 soro-revertidas, 1 soropositiva e 2 indefinidas. Doze crianças foram avaliadas, e os domínios mais comprometidos foram linguagem, pessoal-social e motor fino, respectivamente. Quanto ao nível econômico, 73,3% pertenciam ao nível E, e 58,3% das mães eram analfabetas ou cursaram apenas o primário. Crianças filhas de mães HIV positivo, além de fatores biológicos, geralmente estão expostas a fatores de risco ambientais que contribuem para alterações do DNPM. Desta forma, o acompanhamento por uma equipe de profissionais de saúde, em parceria com a família da criança, torna-se uma importante ferramenta para a identificação e intervenção precoce.Highly active antiretroviral therapy (HAART) is an effective way of preventing mother-to-child transmission of HIV. However, further studies investigate the effects of short and long term exposure to HAART in-utero and its consequence on child neuropsychomotor development (NPMD). The paper presents a report and discussion of results of an extension project whose objectives were to verify the NPMD of children participating of the STD/AIDS program, to orientate families according to their socioeconomic context and make referrals to specific health services. The NPMD surveillance was divided into three parts: (1) ambulatory evaluation; (2) home evaluation and orientations; (3) reporting health managers. DENVER II and PEDI tests were used and also a socioeconomic questionnaire. Fifteen children were on the program of which 12 uninfected, 1 HIV+ and 2 indeterminate. Twelve children were evaluated and the most impaired domain were language, personal-social and fine motor, respectively. Regarding to socioeconomic status, 73,3% were E level and 58,3% of mothers were analphabet or had primary school. Children born of infected mothers, besides the biological risks, usually are exposed to environment/social risks that can affect the NPMD. Thus, monitoring by a team of health professionals, in partnership with the child's family, becomes an important tool for identification and early intervention

Effect of Maternal HIV-1 Status and Antiretroviral Drugs on Haematological Profiles of South African Infants in Early Life

Maternal HIV-1 status and antiretroviral drug exposure may influence the haematological profiles of infants. We recruited infants from 118 uninfected control women and from 483 HIV-1 infected women who received no antiretroviral drugs (n=28), or received single-dose Nevirapine (sdNVP) (n=424) or triple-drug combination therapy (n=31) to reduce HIV-1 transmission. Blood was drawn from infants within 24 hours of delivery or 6-12 weeks post-delivery and full blood counts performed using a fully automated AcT-5-diff haematology analyser and reference controls. Exposed uninfected (EU; no NVP) differed from control infants only in having lower basophil counts and percentages. In all infant groups, leukocyte profiles showed characteristic quantitative changes with age in the first 6 weeks of life. HIV-1 infected infants displayed by 6 weeks elevations in white blood cells, lymphocyte, monocyte and basophil counts, and monocyte and basophil percentages, when compared to EU infants. At birth EU NVP-treated infants exhibited elevated monocyte percentages and counts and basophil counts that did not persist at 6 weeks. Interestingly, EU newborns of mothers with high CD4 counts (> 500 cells/μl) that had taken sdNVP had significantly elevated white blood cell, monocyte and basophil counts when compared to newborn infants of mothers with similar CD4 counts that had not taken sdNVP; this was not evident in infants of mothers with CD4 counts <200 cells/μl. These previously undescribed features may affect immune response capability in early life and clinical consequences of such changes need to be further investigated

Increased thymic output after initiation of antiretroviral therapy in human immunodeficiency virus type 1-infected children in the Paediatric European Network for Treatment of AIDS (PENTA) 5 trial

To investigate the thymic contribution to immune reconstitution during antiretroviral therapy (ART), T cell receptor gene rearrangement excision circles (TRECs) were measured in peripheral blood mononuclear cells (PBMC) and CD4 cells from 33 human immunodeficiency virus (HIV) type 1-infected children monitored for 96 weeks after ART initiation. Baseline TREC levels were associated positively with baseline CD4 cell percentage and inversely with age and HIV-1 RNA load. During therapy, TREC level changes in PBMC and CD4 cells were fairly comparable. TREC level changes were inversely related to baseline CD4 cell percentage and positively associated with CD4 cell percentage increases, the main source being naive CD4 cells. TREC changes were independent of age and baseline HIV-1 RNA load; however, HIV-1 suppression was independently associated with smaller TREC changes. Thymic output appears to be the main source of CD4 cell repopulation in children receiving ART. Recovery of thymic function is independent of age and influenced by the status of peripheral CD4 cell depletion and HIV-1 suppression

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch