Browsing by Author "Janoff, Edward N."
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Item The Evidence For Using Conjugate Vaccines To Protect HIV-Infected Children Against Pneumococcal Disease(The Lancet infectious diseases, 2008) Bliss, Sandra J.; O’Brien, Katherine L.; Janoff, Edward N.; Cotton, Mark F.; Musoke, Philippa; Coovadia, Hoosen; Levine, Orin S.Pneumococcal conjugate vaccines (PCVs) are a potentially useful complement to existing treatment strategies in HIV-infected children, for whom pneumococcal infections are common and serious. This Review summarises available data on the burden of pneumococcal disease and the safety and efficacy of PCVs in HIV-infected children. The data demonstrate that children with HIV have significantly increased risk of pneumococcal disease compared with uninfected children; the serotypes included in currently licensed or near-licensure conjugate vaccines include most serotypes that cause invasive pneumococcal disease (IPD) in HIV-infected children and adults; PCVs provide substantial protection against IPD and clinical pneumonia when given to HIV-infected infants; and HIV-infected adults gain an indirect benefit when children in the community are vaccinated. PCV should be considered as an important intervention for improving the lives of HIV-infected children.Item Impaired Haemophilus influenzae Type b Transplacental Antibody Transmission and Declining Antibody Avidity through the First Year of Life Represent Potential Vulnerabilities for HIV-Exposed but -Uninfected Infants(Clinical and Vaccine Immunology, 2014) Gaensbauer, James T.; Rakhola, Jeremy T.; Onyango-Makumbi, Carolyne; Mubiru, Michael; Westcott, Jamie E.; Krebs, Nancy F.; Asturias, Edwin J.; Fowler, Mary Glenn; McFarland, Elizabeth; Janoff, Edward N.To determine whether immune function is impaired among HIV-exposed but -uninfected (HEU) infants born to HIV-infected mothers and to identify potential vulnerabilities to vaccine-preventable infection, we characterized the mother-to-infant placen- tal transfer of Haemophilus influenzae type b-specific IgG (Hib-IgG) and its levels and avidity after vaccination in Ugandan HEU infants and in HIV-unexposed U.S. infants. Hib-IgG was measured by enzyme-linked immunosorbent assay in 57 Ugandan HIV- infected mothers prenatally and in their vaccinated HEU infants and 14 HIV-unexposed U.S. infants at birth and 12, 24, and 48 weeks of age. Antibody avidity at birth and 48 weeks of age was determined with 1 M ammonium thiocyanate. A median of 43% of maternal Hib-IgG was transferred to HEU infants. Although its level was lower in HEU infants than in U.S. infants at birth (P < 0.001), Hib-IgG was present at protective levels (>1.0 - g/ml) at birth in 90% of HEU infants and all U.S. infants. HEU in- fants had robust Hib-IgG responses to a primary vaccination. Although Hib-IgG levels declined from 24 to 48 weeks of age in HEU infants, they were higher than those in U.S. infants (P 0.002). Antibody avidity, comparable at birth, declined by 48 weeks of age in both populations. Early vaccination of HEU infants may limit an initial vulnerability to Hib disease resulting from impaired transplacental antibody transfer. While initial Hib vaccine responses appeared adequate, the confluence of lower antibody avidity and declining Hib-IgG levels in HEU infants by 12 months support Hib booster vaccination at 1 year. Potential immunologic impairments of HEU infants should be considered in the development of vaccine platforms for populations with high maternal HIV prevalence.Item Kinetics of Nevirapine and Its Impact on HIV-1 RNA Levels in Maternal Plasma and Breast Milk Over Time After Perinatal Single-Dose Nevirapine(JAIDS Journal of Acquired Immune Deficiency Syndromes, 2012) Aizire, Jim; McConnell, Michelle S.; Mudiope, Peter; Mubiru, Michael; Matovu, Flavia; Parsons, Teresa L.; Elbireer, Ali ,; Nolan, Monica; Janoff, Edward N.; Glenn Fowler, MaryTo determine kinetics after single-dose nevirapine and the impact on HIV RNA [viral load (VL)] in maternal plasma and breast milk (BM). Methods: Cohort of 120 HIV-1–infected pregnant Ugandan women received perinatal single-dose nevirapine alone and followed up with their infants through 24 weeks postdelivery. We assessed the relationship of nevirapine concentration (tandem mass spectroscopy) and HIV-1 VL (Roche AMPLICOR HIV-1 Kit, version 1.5) in maternal plasma and BM over time. Results: At week 1 postpartum, NVP ($10 ng/mL) was detected in all 53 plasma and 47 of 51 (92.2%) BM samples with median (inter- quartile ranges) of, respectively, 171 (78–214) ng/mL and 112 (64–158) ng/mL, P = 0.075, which decreased subsequently with traces persisting through week 4 in plasma. Plasma and BM VL dropped by week 1 and were highly correlated at delivery (R = 0.71, P , 0.001) and week 1 (R = 0.69, P , 0.001) but not thereafter. At week 1, VL correlated inversely with NVP concentra- tion in plasma (R = 0.39, P = 0.004) and BM (R = 0.48, P = 0.013). There was a VL rebound in both compartments, which peaked at week 4 to levels greater than those at week 1 [significantly in plasma (P , 0.001) but not in BM] and remained stable thereafter. Median VL was consistently greater (11- to 50-fold) in plasma than BM at all time points (all P , 0.001). Conclusions: After single-dose nevirapine, NVP concentration was comparably high through week 1, accompanied by suppression of plasma and BM VL. A longer “tail” (.1 week) of potent postnatal antiretroviral drugs is warranted to minimize the observed VL rebound and potential for NVP resistance as a result of persistent NVP traces