Bone Age and Mineral Density Assessments Using Plain Roentgenograms in Tenofovir-exposed Infants in Malawi and Brazil Enrolled in HIV Prevention Trials Network 057.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) use during pregnancy has been increasing, and studies linking bone toxicity with exposure to TDF have raised concern for its use in infants. METHODS: Hand/wrist and spine radiographs were obtained at 3 days and 12 weeks of age in infants born to HIV-infected pregnant women enrolled in the HIV Prevention Trials Network 057 pharmacokinetic study of TDF conducted in Malawi and Brazil assigned to 3 TDF dosing cohorts. In cohort 1, mothers received 600 mg of TDF during labor. In cohort 2, infants received 4 mg/kg dose on days 0, 3 and 5. In cohort 3, a 900 mg maternal dose was given during labor, followed by a 6 mg/kg infant dose on days 0, 3 and 5 of life. RESULTS: Across all 3 cohorts, 89 infants had radiographs performed at either time point, and 85 had radiographs performed at both time points. Metaphyseal lucency was present in 1 case in Brazil and 2 in Malawi. Fifteen percent of infants from Brazil and 9% of infants from Malawi presented bone age discrepancies. No other abnormalities were identified in Brazil, whereas in Malawi, there were 7 more cases of wrist osteopenia, 2 of spine osteopenia and 3 other abnormalities. CONCLUSION: Bone abnormalities were not uncommon in the overall cohort of HIV-exposed infants. Because of very limited study drug exposure at the time of birth, it is unlikely that TDF was associated with these findings. Untreated maternal HIV disease and/or maternal nutritional status could potentially be related to fetal bone development. This association should be explored in future cohort studies.

Supranormal thymic output up to 2 decades after HIV-1 infection.

OBJECTIVES: AIDS is caused by CD4 T-cell depletion. Although combination antiretroviral therapy can restore blood T-cell numbers, the clonal diversity of the reconstituting cells, critical for immunocompetence, is not well defined. METHODS: We performed an extensive analysis of parameters of thymic function in perinatally HIV-1-infected (n = 39) and control (n = 28) participants ranging from 13 to 23 years of age. CD4 T cells including naive (CD27 CD45RA) and recent thymic emigrant (RTE) (CD31/CD45RA) cells, were quantified by flow cytometry. Deep sequencing was used to examine T-cell receptor (TCR) sequence diversity in sorted RTE CD4 T cells. RESULTS: Infected participants had reduced CD4 T-cell levels with predominant depletion of the memory subset and preservation of naive cells. RTE CD4 T-cell levels were normal in most infected individuals, and enhanced thymopoiesis was indicated by higher proportions of CD4 T cells containing TCR recombination excision circles. Memory CD4 T-cell depletion was highly associated with CD8 T-cell activation in HIV-1-infected persons and plasma interlekin-7 levels were correlated with naive CD4 T cells, suggesting activation-driven loss and compensatory enhancement of thymopoiesis. Deep sequencing of CD4 T-cell receptor sequences in well compensated infected persons demonstrated supranormal diversity, providing additional evidence of enhanced thymic output. CONCLUSION: Despite up to two decades of infection, many individuals have remarkable thymic reserve to compensate for ongoing CD4 T-cell loss, although there is ongoing viral replication and immune activation despite combination antiretroviral therapy. The longer term sustainability of this physiology remains to be determined.

World Federation of Pediatric Imaging (WFPI) volunteer outreach through tele-reading: the pilot project in South Africa.

BACKGROUND: Shortages in radiology services are estimated to affect 3.5-4.7 billion people worldwide. Teleradiology is a potential means of alleviating this shortage. OBJECTIVE: This paper examines the practicality and sustainability of a pilot pediatric teleradiology project at the Khayelitsha District Hospital in sub-Saharan Africa. We analyze how this World Federation of Pediatric Imaging (WFPI) program fares against the global challenges described in the current literature facing these practice types. MATERIALS AND METHODS: A teleradiology pilot was developed to provide coverage to the Khayelitsha District Hospital after the district pediatrician requested assistance in interpreting radiographs. This program utilized a network of WFPI volunteer pediatric radiologists, direct JPEG conversion of digital radiographic images, and an e-mail delivery system of images, referral requests and teleradiology opinion. Data were collected retrospectively from referral cards and JPEG images of radiographs, as well as from the volunteer officer database. RESULTS: A total of 555 referral cards and 1,106 radiographs were submitted for teleradiology opinion during the course of this pilot program; 74.6% of requests for image interpretation were chest radiographs and 14.2% of those were for the evaluation of tuberculosis. There were 40 volunteer teleradiologists from 17 countries; all spoke English, and 14 were bilingual (8 fluent in Spanish, 5 in Portuguese, and 1 in Italian). CONCLUSION: Teleradiology is a viable option to alleviate radiologist shortages in underserved areas, but there are many challenges to designing an adequate teleradiology system. The WFPI pilot teleradiology program can be considered a successful one.

Thymic volume, T-cell populations, and parameters of thymopoiesis in adolescent and adult survivors of HIV infection acquired in infancy.

OBJECTIVES: Antiretroviral therapy has significantly prolonged the lifespan of children who acquire HIV infection in infancy, but the impact of HIV on thymus-mediated maintenance of T lymphocytes has not been studied. To examine the long-term effects of HIV infection in childhood on thymopoiesis, thymic volume and parameters of thymic function from clinically stable adolescents and young adults with HIV infection acquired in infancy were compared with those from uninfected controls. METHODS: Thymic volume was determined using three-dimensional reconstruction and volumetric analysis of non-contrast enhanced computed tomography images of the upper chest. The degree of fat involution was assessed using a semiquantitive scoring system. CD4 and CD8 T cell populations and T cell receptor recombination excision circles (TREC) concentrations in peripheral blood lymphocytes were measured in all subjects. RESULTS: Twenty youths (aged 17.6 +/- 2.5 years) with HIV infection acquired perinatally (n = 18) or by neonatal transfusion (n = 2) were enrolled whose HIV plasma viral load had been undetectable for a median of 3.1 years, along with 18 seronegative healthy young adults (aged 20.6 +/- 1.3 years). HIV infected subjects and controls had indistinguishable CD4 T cell counts, thymus volumes (20.5 versus 15.8 cm), thymic index scores, and TREC values. Thymic volume correlated with the number and percentage of CD4 T lymphocytes in the control group and with the number of TREC in CD4 lymphocytes in the HIV infected group. CONCLUSIONS: Long term survivors of pediatric HIV infection appear to have retained or recovered thymic volume and thymic activity approximating uninfected youths.