CD57(+) expression in T lymphocytes has been recognized for decades as a marker of in vitro replicative senescence. In recent years, accumulating evidences have pointed on the utility of this marker to measure functional immune deficiency in patients with autoimmune disease, infectious diseases, and cancers. We review here the relevant literature and implications in clinical settings.

https://jlb.onlinelibrary.wiley.com/doi/epdf/10.1189/jlb.0809566

CD57+ T lymphocytes and functional immune deficiency.

Few studies address the use of paediatric highly active antiretroviral therapy (HAART) in Africa. We performed a retrospective cohort study to investigate preliminary outcomes of all children eligible for HAART at Sinikithemba HIV/AIDS clinic in KwaZulu-Natal, South Africa. Immunologic, virologic, clinical, mortality, primary caregiver, and psychosocial variables were collected and analyzed. From August 31, 2003 until October 31, 2005, 151 children initiated HAART. The median age at HAART initiation was 5.7 years (range 0.3–15.4). Median follow-up time of the cohort after HAART initiation was 8 months (IQR 3.5–13.5). The median change in CD4% from baseline (p 95%adherence). Seventeen patients (11.3%) had a regimen change; two (1.3%) were due to antiretroviral toxicity. The Kaplan-Meier one year survival estimate was 90.9% (95%confidence interval (CI) 84.8–94.6). Thirteen children died during follow-up (8.6%), one changed service provider, and no children were lost to follow-up. All 13 deaths occurred in children with advanced HIV disease within 5 months of treatment initiation. In multivariate analysis of baseline variables against mortality using Cox proportional-hazards model, chronic gastroenteritis was associated with death [hazard ratio (HR), 12.34; 95%CI, 1.27–119.71) and an HIV-positive primary caregiver was found to be protective against mortality [HR, 0.12; 95%CI, 0.02–0.88). Age, orphanhood, baseline CD4%, and hemoglobin were not predicators of mortality in our cohort. Fifty-two percent of the cohort had at least one HIV-positive primary caregiver, and 38.4% had at least one primary caregiver also on HAART at Sinikithemba clinic. This report suggests that paediatric HAART can be effective despite the challenges of a resource-limited setting.

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Preliminary outcomes of a paediatric highly active antiretroviral therapy cohort from KwaZulu-Natal, South Africa.

Background. Recent evidence suggests that decreases in morbidity and mortality in cohorts of adults infected with human immunodeficiency virus (HIV) are showing signs of reversal. We describe changes over time in these characteristics and in the response to treatment among children in the United Kingdom and Ireland with perinatally acquired HIV infection, many of whom are now adolescents. Methods. We analyzed prospective cohort data reported to the National Study of HIV in Pregnancy and Childhood (NSHPC) and the Collaborative HIV Paediatric Study. Results. By mid 2006, 1441 HIV-infected children were reported to NSHPC; 40% were 10 years old at their most recent follow-up visit, and 34% were receiving care outside London. The proportion of children born abroad increased from 24% during 1994–1996 to 64% during 2003–2006. The percentage of total child time during which children received highly active antiretroviral therapy (HAART) increased from 36% during 1997–1999 to 61% during 2000–2002 and 63% during 2003–2006. Of children who were naive to antiretroviral therapy at the start of HAART, the percentage with an HIV-1 RNA load of !400 copies/mL after 12 months increased from 52% during 1997–1999 to 79% during 2003–2006. In multivariate analysis, only calendar time predicted virological response, whereas both younger age and lower CD4 cell percentage at HAART initiation predicted increases of 110% in the CD4 cell percentage. A total of 31% of children aged 5–14 years and 38% aged 15 years at their most recent follow-up visit had been exposed to drugs from each of the 3 main HAART classes. The rate of AIDS and mortality combined decreased from 13.3 cases per 100 person-years before 1997 to 3.1 and 2.5 cases per 100 person-years, respectively, during 2000–2002 and 2003–2006; rates of hospital admission also declined during this interval. Of 18 children known to have died since 2003, 9 died within 1 month after presentation. Conclusions. Morbidity and mortality rates among HIV-infected children continue to decrease over time. Because these children are increasingly dispersed outside London, specialist care is now provided in national clinical networks. Transition pathways to adolescent and adult services and long-term observation to monitor the effects of prolonged exposure to both HIV and HAART are required.

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Morbidity, mortality, and response to treatment by children in the United Kingdom and Ireland with perinatally acquired HIV infection during 1996-2006: planning for teenage and adult care.

Objectives
To describe the early response to World Health Organization (WHO)–recommended nonnucleoside reverse transcriptase inhibitor (NNRTI)–based first-line highly active antiretroviral therapy (HAART) in HIV-1–infected Kenyan children unexposed to nevirapine.

Early response to highly active antiretroviral therapy in HIV-1-infected Kenyan children.

BACKGROUND: There is a recognized gap in the evidence base relating to the nature and components of interventions to address the psycho-social needs of HIV positive young people. We used mixed methods research to strengthen a community support group intervention for HIV positive young people based in Harare, Zimbabwe. METHODS: A quantitative questionnaire was administered to HIV positive Africaid support group attendees. Afterwards, qualitative data were collected from young people aged 15-18 through tape-recorded in-depth interviews (n=10), 3 focus group discussions (FGDs) and 16 life history narratives. Data were also collected from caregivers, health care workers, and community members through FGDs (n=6 groups) and in-depth interviews (n=12). Quantitative data were processed and analysed using STATA 10. Qualitative data were analysed using thematic analysis. RESULTS: 229/310 young people completed the quantitative questionnaire (74% participation). Median age was 14 (range 6-18 years); 59% were female. Self-reported adherence to antiretrovirals was sub-optimal. Psychological well being was poor (median score on Shona Symptom Questionnaire 9/14); 63% were at risk of depression. Qualitative findings suggested that challenges faced by positive children include verbal abuse, stigma, and discrimination. While data showed that support group attendance is helpful, young people stressed that life outside the confines of the group was more challenging. Caregivers felt ill-equipped to support the children in their care. These data, combined with a previously validated conceptual framework for family-centred interventions, were used to guide the development of the existing programme of adolescent support groups into a more comprehensive evidence-based psychosocial support programme encompassing caregiver and household members. CONCLUSIONS: This study allowed us to describe the lived experiences of HIV positive young people and their caregivers in Zimbabwe. The findings contributed to the enhancement of Africaid's existing programme of support to better promote psychological well being and ART adherence.

/pdf/enhancing-psychosocial-support-for-hiv-positive-adolescents-10ifpy5bnn.pdf

Enhancing Psychosocial Support for HIV Positive Adolescents in Harare, Zimbabwe

Background Use of antiretroviral therapy has resulted in a decrease in morbidity and mortality rates in human immunodeficiency virus type 1 (HIV-1)-infected childrenMethods We performed a retrospective study involving 427 children to determine the effectiveness of different antiretroviral therapy protocols on clinical outcome The follow-up period was divided into 5 calendar periods (CPs): CP1 (1980-1989), before antiretroviral therapy was administered; CP2 (1990-1993), when monotherapy was administered; CP3 (1994-1996), when combined therapy was administered; CP4 (1997-1998), when /=60% of children were receiving HAARTResults Children experienced a progressive increase in the CD4(+) cell count and decrease in the viral load from 1997 onwards A lower number of AIDS cases and deaths occurred during CP5 than during the other CPs (P 20 and a relative risk of survival of >30 The AIDS rate was >50% in CP1; we observed a very strong decrease to 14% in CP2, to 16% in CP3, to 7% in CP4, and to 2% in CP5 The mortality rates in CP2 and CP3 were >6% and thereafter decreased to 05% in CP5 The relative risks for no hospital admission in CP4 and CP5 were >35 The total rates of hospital admission in CP1, CP2, and CP3 were >30%; we observed a decrease in CP4 and CP5 The duration of hospitalization decreased during the follow-up period, and it was higher in CP1 (~30 days) than in the other periodsConclusions We observed that HAART produces a decrease in adverse clinical outcomes (ie, hospital admission, AIDS, and death) in children with vertical HIV-1 infection in Madrid, Spain

/pdf/clinical-outcomes-improve-with-highly-active-antiretroviral-5d40odili6.pdf

Clinical outcomes improve with highly active antiretroviral therapy in vertically HIV type-1-infected children.

Background
Protease inhibitors (PIs) have been associated with metabolic complications. There is a trend to switch to simpler therapy to improve these disturbances. We report a case-series describing the effects in metabolic abnormalities in seven HIV-infected children, previously treated with protease inhibitor (PI) after switching to nevirapine.

/pdf/outcome-of-protease-inhibitor-substitution-with-nevirapine-4j5j22zbyi.pdf

Outcome of protease inhibitor substitution with nevirapine in HIV-1 infected children

We evaluated the effect of salvage antiretroviral therapy with lopinavir/ritonavir (LPV/r) on the immune system of heavily antiretroviral pretreated HIV-infected children. We carried out a longitudinal study in 20 antiretroviral experienced HIV-infected children to determine the changes in several immunological parameters (T cell subsets, thymic function) every 3 months during 18 months of follow-up on salvage therapy with LPV/r. Statistical analyses were performed with the Wilcoxon test, taking as a reference the basal value at the entry in the study. HIV-infected children showed an increase of CD4+T cells, a decrease in CD8+ T cells, and an increase in T cell rearrangement excision circle (TRECs) levels. The percentage of HIV children with undetectable viral load (VL ≤400 copies/ml) increased significantly (p = 0.007) and the percentage with SI viral phenotype decreased significantly (p = 0.002) at the end of the study. Thus, the viral phenotype changed to NSI/R5 after salvage therapy with LPV/r. Intere...

Pablo Martín Fontelos

Papers

Clinical outcomes improve with highly active antiretroviral therapy in vertically HIV type-1-infected children.

Outcome of protease inhibitor substitution with nevirapine in HIV-1 infected children

Immunological changes after highly active antiretroviral therapy with lopinavir-ritonavir in heavily pretreated HIV-infected children.