Search

Measles vaccination is currently recommended at 9 months, since maternal antibodies are supposed to protect infants until that age. In this study of 6‐month‐old Malawian infants 98.3% (58/59) had non‐protective IgG levels against measles, irrespective of HIV exposure. Anticipating the first dose at 6 months could be considered. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the immune response to HBV vaccine in HIV‐exposed infants and to correlate it to HBV infection acquisition. Protective anti‐HBs levels (>10 mIU/mL) were found in 54/58 (93.2%) infants at 6 months, 126/144 (87.5%) at 12 months and 141/176 (80.1%) children at 24 months. HBV infection (seven children were HBsAg + at Month 24) occurred also in the presence of levels above 10 mIU/mL. Our findings indicate limited impact of HIV exposure on anti‐HBV immune response, but suggest that levels >10 mIU/mL may be required to confer protection in this context. [ABSTRACT FROM AUTHOR]

Abstract: Problem: Data on soluble CD14 (sCD14) during pregnancy and lactation are scarce. We assessed the levels of sCD14 in plasma and breastmilk of Malawian HIV‐positive women and evaluated the possible association with morbidity and mortality in the HIV‐exposed children. Method of study: One hundred and forty‐nine mother/child pairs were studied. Women received antiretroviral therapy from 26 weeks of gestation to at least 6 months of exclusive breastfeeding. sCD14 concentrations were determined using an enzyme‐linked immunosorbent assay. Results: sCD14 levels measured at 26 weeks of pregnancy (median: 1418 ng/mL, IQR: 1086‐1757) were inversely correlated to maternal CD4+ cell count (r = −.283, P = .001) and to neonatal birthweight (r = −.233, P = .008). At 6 months, sCD14 plasma levels were significantly higher compared to baseline (1993 ng/mL, IQR: 1482‐2604, P < .001), and breastmilk sCD14 levels (7668 ng/mL, IQR: 5495‐10207) were 4‐fold higher than in plasma (although the concentrations in the two compartments were not correlated). No association was found between sCD14 levels in plasma or breastmilk and morbidity or mortality in children. Conclusion: Higher sCD14 levels in HIV‐positive women were associated with a more compromised maternal immunological status and to a lower neonatal birthweight, but not to poorer clinical outcomes in the HIV‐exposed children. [ABSTRACT FROM AUTHOR]

Introduction HIV infection is characterized by a persistent immune activation associated to a compromised gut barrier immunity and alterations in the profile of the fecal flora linked with the progression of inflammatory symptoms. The effects of high concentration multistrain probiotic (Vivomixx®, Viale del Policlinico 155, Rome, Italy in EU; Visbiome®, Dupont, Madison, Wisconsin in USA) on several aspects of intestinal immunity in ART-experienced HIV-1 patients was evaluated. Methods A sub-study of a longitudinal pilot study was performed in HIV-1 patients who received the probiotic supplement twice a day for 6 months (T6). T-cell activation and CD4+ and CD8+ T-cell subsets expressing IFNγ (Th1, Tc1) or IL-17A (Th17, Tc17) were stained by cytoflorimetric analysis. Histological and immunohistochemical analyses were performed on intestinal biopsies while enterocytes apoptosis index was determined by TUNEL assay. Results A reduction in the frequencies of CD4+ and CD8+ T-cell subsets, expressing CD38+, HLA-DR+, or both, and an increase in the percentage of Th17 cell subsets, especially those with central or effector memory phenotype, was recorded in the peripheral blood and in gut-associated lymphoid tissue (GALT) after probiotic intervention. Conversely, Tc1 and Tc17 levels remained substantially unchanged at T6, while Th1 cell subsets increase in the GALT. Probiotic supplementation was also associated to a recovery of the integrity of the gut epithelial barrier, a reduction of both intraepithelial lymphocytes density and enterocyte apoptosis and, an improvement of mitochondrial morphology sustained in part by a modulation of heat shock protein 60. Conclusions These findings highlight the potential beneficial effects of probiotic supplementation for the reconstitution of physical and immunological integrity of the mucosal intestinal barrier in ART-treated HIV-1-positive patients. [ABSTRACT FROM AUTHOR]

HIV/HBV co-infection is highly prevalent in sub-Saharan Africa. The aim of this study was to determine if the use of triple combination lamivudine-containing prophylaxis for the prevention of mother-to-infant HIV transmission was associated with the emergence of lamivudine HBV mutations. The study included 21 pregnant co-infected women in Malawi who received either zidovudine or stavudine plus lamivudine and nevirapine from week 25 of gestation until 6 months after delivery or indefinitely if they met the criteria for treatment (CD4+ <350/mm3). HBV-DNA was determined using the Roche COBAS assay. Resistance mutations were assessed by the Trugene assay (Siemens Diagnostics). At baseline 33% of the women were HBeAg positive and had HBV-DNA > 104 IU/ml. Median CD4 count was 237 cells/mm3 and median HIV-RNA was 3.8 log10 copies/ml. After a median of 259 days of treatment, HBV-DNA was detectable in 9 out of 21 patients (42.8%). In three cases the HBV-DNA level was >104 IU/ml. Resistance mutations (M204I in five cases and L180M + M204I/V in one case) were present in 6 (28.6%) patients. Women with a resistant virus had significantly higher baseline HBV-DNA levels than those not developing resistance (1.1 × 107 IU/ml vs. 20.8 IU/ml, P = 0.022). Levels of ALT and AST were higher in women with resistant viruses compared to those retaining a wild-type virus. A high rate of lamivudine resistance was seen in this cohort of pregnant women. Follow-up of these patients will clarify if the presence of resistance has a significant impact on liver disease. J. Med. Virol. 84:1553-1557, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Dendritic cells (DC) generated after a short-term exposure of monocytes to IFN-α and GM-CSF (IFN-DC) are highly effective in inducing cross-priming of CD8T cells against viral antigens. We have investigated the mechanisms responsible for the special attitude of these DC and compared their activity with that of reference DC. Antigen uptake and endosomal processing capabilities were similar for IFN-DC and IL-4-derived DC. Both DC types efficiently cross-presented soluble HCV NS3 protein to the specific CD8 T cell clone, even though IFN-DC were superior in cross-presenting low amounts of viral antigens. Moreover, when DC were pulsed with inactivated HIV-1 and injected into hu-PBL-SCID mice, the generation of virus-specific CD8T cells was markedly higher in animals immunized with IFN-DC than in mice immunized with CD40L-matured IL-4-DC. Of interest, in experiments with purified CD8T cells, IFN-DC were superior with respect to CD40L-matured IL-4-DC in inducing in vitro cross-priming of HIV-specific CD8T cells. This property correlated with enhanced potential to express the specific subunits of the IL-23 and IL-27 cytokines. These results suggest that IFN-DC are directly licensed for an efficient CD8 T cell priming by mechanisms likely involving enhanced antigen presentation and special attitude to produce IL-12 family cytokines. [ABSTRACT FROM AUTHOR]

Several findings support the importance of GM1-enriched lipid microdomains of plasma membrane and of Vav, an essential regulator of actin cytoskeletal rearrangement, in the regulation of T cell activation. Moreover, a functional link among lipid microdomains, Vav and the HIV product Nef has been described. These observations suggest that Nef can modify plasma membrane GM1, affecting the behavior of HIV-infected cells towards antigen recognition and Vav towards counteracting such an effect. We observed that Nef expression, either following viral infection or ectopic expression, significantly decreased the level of plasma membrane GM1 in unstimulated T cells. This down-regulation was associated with the inhibition of NF-AT activation, but not with NF-κB activation inducedby TCR engagement. Dissecting the signaling pathway that regulates NF-AT activation, we found that Nef inhibited exclusively the Ca [ABSTRACT FROM AUTHOR]