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1.  CD4/CD8 Ratio for Diagnosis of HIV-1 Infection in Infants: The Women and Infants Transmission Study 
Pediatrics  2008;122(2):331-339.
Early diagnosis of HIV infection in infants with perinatal HIV exposure is critical for clinical management decisions. Positive HIV nucleic acid detection represents the gold standard for the diagnosis of HIV infection status in infants prior to age 18 months, but this test is not universally available, especially in resource poor regions of the world. In this study we tested the hypothesis that the CD4/CD8 T cell ratio can predict HIV infection status in HIV-exposed infants.
CD4/CD8 T cell ratios were determined from data of live born, singleton infants who had been prospectively enrolled in the Women and Infants Transmission Study (WITS). Data from 2208 infants with known HIV infection status (179 HIV infected, 2029 uninfected) were analyzed.
Receiver Operating Characteristic (ROC) curves indicated that CD4/CD8 ratio performed better than CD4% for diagnosis of HIV infection as early as age 2 months (p=0.018), and this relationship was unaffected by adjusting for maternal race/ethnicity, infant birth weight, gestational age and gender. At age 4 mos., 90% specificity for HIV diagnosis was associated with 60% sensitivity. For ease of utilization, longitudinal LMS profile-based percentile curves were developed for sensitivity/specificity of CD4/CD8 ratios in HIV-infected and -uninfected infants until age 12 months. At age 6 months, a simplified equation that incorporated sequential CD4/CD8 ratios and hematocrit values resulted in improved ROCs with 94% positive predictive value (PPV) and 98% negative predictive value (NPV). The PPV and NPV remained above 90% in simulated infant populations over a wide range of prevalence of HIV infection.
In the absence of virologic diagnosis, a presumptive diagnosis of HIV- infection status may be made on the basis of CD4/CD8 ratios in HIV-1-exposed infants after age 2 months; sensitivity and specificity can be further improved at 6 months by using a discriminant analysis equation.
PMCID: PMC4699439  PMID: 18676551
HIV diagnosis; perinatal HIV transmission; HIV exposed infants; CD4/CD8 ratio
2.  A Phase II, Randomized, Safety and Immunogenicity Trial of a Re-Derived, Live-Attenuated Dengue Virus Vaccine in Healthy Children and Adults Living in Puerto Rico 
This was a double-blind, randomized, controlled, phase II clinical trial, two dose study of re-derived, live-attenuated, tetravalent dengue virus (TDEN) vaccine (two formulations) or placebo in subjects 1–50 years of age. Among the 636 subjects enrolled, 331 (52%) were primed, that is, baseline seropositive to at least one dengue virus (DENV) type. Baseline seropositivity prevalence increased with age (10% [< 2 years], 26% [2–4 years], 60% [5–20 years], and 93% [21–50 years]). Safety profiles of TDEN vaccines were similar to placebo regardless of priming status. No vaccine-related serious adverse events (SAEs) were reported. Among unprimed subjects, immunogenicity (geometric mean antibody titers [GMT] and seropositivity rates) for each DENV increased substantially in both TDEN vaccine groups with at least 74.6% seropositive for four DENV types. The TDEN vaccine candidate showed an acceptable safety and immunogenicity profile in children and adults ranging from 1 to 50 years of age, regardless of priming status. NCT00468858.
PMCID: PMC4559678  PMID: 26175027
3.  Safety and Immunogenicity of Human Serum Albumin-Free MMR Vaccine in US Children Aged 12–15 Months 
M-M-RTMII (MMRII; Merck & Co) is currently the only measles-mumps-rubella (MMR) vaccine licensed in the United States. Another licensed vaccine would reinforce MMR supply. This study assessed the immunogenicity of a candidate vaccine (PriorixTM, GlaxoSmithKline Vaccines [MMR-RIT]) when used as a first dose among eligible children in the United States.
In this exploratory Phase-2, multicenter, observer-blind study, 1220 healthy subjects aged 12–15 months were randomized (3:3:3:3) and received 1 dose of 1 of 3 MMR-RIT lots with differing mumps virus titers (MMR-RIT-1 [4.8 log10]; MMR-RIT-2 [4.1 log10]; MMR-RIT-3 [3.7 log10] CCID50) or MMRII co-administered with hepatitis A vaccine (HAV), varicella vaccine (VAR) and 7-valent pneumococcal conjugate vaccine (PCV7). Immune response to measles, mumps, and rubella viruses was evaluated at Day 42 post-vaccination. Incidence of solicited injection site, general, and serious adverse events was assessed.
Seroresponse rates for MMR vaccine viral components in MMR-RIT lots were 98.3–99.2% (measles), 89.7–90.7% (mumps), and 97.5–98.8% (rubella), and for MMRII were 99.6%, 91.1%, and 100%, respectively. Immune responses to HAV, VAR, and PCV7 were similar when co-administered with any of the 3 MMR-RIT lots or MMRII. There were no apparent differences in solicited or serious adverse events among the 4 groups.
Immune responses were above threshold levels for projected protection against the 3 viruses from MMR-RIT lots with differing mumps virus titers. MMR-RIT had an acceptable safety profile when co-administered with HAV, VAR, and PCV7.
Clinical Trials Registration
NCT00861744; etrack; 111870
PMCID: PMC4681379  PMID: 26582873
co-administration; immunogenicity; measles; mumps; rubella
In 2011, research educators face significant challenges. Training programs in Clinical and Translational Research need to develop or enhance their curriculum to comply with new scientific trends and government policies. Curricula must impart the skills and competencies needed to help facilitate the dissemination and transfer of scientific advances at a faster pace than current health policy and practice. Clinical and translational researchers are facing also the need of new paradigms for effective collaboration, and resource sharing while using the best educational models. Both government and public policy makers emphasize addressing the goals of improving health quality and elimination of health disparities. To help achieve this goal, our academic institution is taking an active role and striving to develop an environment that fosters the career development of clinical and translational researchers. Consonant with this vision, in 2002 the University of Puerto Rico, Medical Sciences Campus School of Health Professions and School of Medicine initiated a multidisciplinary post-doctoral Master of Science in Clinical Research focused in training Hispanics who will address minority health and health disparities research. Recently, we proposed a curriculum revision to enhance this commitment in promoting competency-based curricula for clinician-scientists in clinical and translational sciences. The revised program will be a post-doctoral Master of Science in Clinical and Translational Research (MCTR), expanding its outreach by actively engaging in establishing new collaborations and partnerships that will increase our capability to diversify our educational efforts and make significant contributions to help reduce and eliminate the gap in health disparities.
PMCID: PMC3446207  PMID: 22263296
Research career development; clinical and translational research; minority health; health disparities; Hispanic researchers
Immunoreconstitution of HIV-infected (HIV+) patients after treatment with highly antiretroviral therapy (HAART) appears to provoke inflammatory diseases.
Determine whether HIV+ children on HAART (HIV+ HAART+) have a higher incidence of asthma than HIV+ children not on HAART (HIV+ HAART−).
To investigate this possibility, 2,664 children (193 HIV+, 2,471 HIV−) born to HIV+ women were evaluated for the incidence and prevalence of asthma (i.e., asthma medication use), and change of CD4+ T cell percentage with time.
The HIV+ HAART+ children had higher CD4+ T cell percentages, lower CD8+ T cell percentages, and lower viral burdens than the HIV+ HAART− children (P≤0.05 to P≤0.01). The cumulative incidence of asthma medication use in HIV+ HAART+ children at 13.5 year rose to 33.5% vs. 11.5% in HIV+ HAART− children (hazard ratio=3.34, P=0.01) and was equal to that in the HIV− children. In children born prior to the HAART era, the prevalence of asthma medication use for HIV+ HAART+ children at 11 years of age was 10.4% vs. 3.8% for HIV+ HAART− children (odds ratio=3.38, P=0.02) and was equal to that of the HIV− children. The rate of change of CD4+ T cells (percent/year) around the time of first asthma medication for HIV+ HAART+ vs. HIV+ HAART− children was 0.81 vs. −1.43 (P=0.01).
The increased incidence of asthma in HIV+ HAART+ children may be driven by immunoreconstitution of CD4+ T cells.
This HIV model of pediatric asthma may yield clues to help explain the epidemic of asthma in the general pediatric population.
PMCID: PMC3246282  PMID: 18547627
pediatric HIV infection; CD4+ T cell mediated induction of asthma; HAART-produced immunoreconstitution
6.  Early Immunological Predictors of Neurodevelopmental Outcomes in HIV-Infected Children 
Background. A previous analysis of children infected with human immunodeficiency virus (HIV) in the Women and Infants Transmission Study showed a strong correlation between low activated CD8+ T lymphocytes in the first 2 months of life and good immunological prognosis. We sought to extend these observations to neurodevelopmental prognosis.
Methods. Ninety-eight HIV-infected children born before 1994 with flow cytometric data from the first 2 months of life and adequate neurodevelopmental testing through age 30 months were studied. Children were divided into those with low (⩽5% CD8+HLA-DR+ cells or ⩽25% CD8+CD38+ cells) or high (>5% CD8+HLA-DR+ cells or >25% CD8+CD38+ cells) immune activation at 1 and/or 2 months of age. Analysis was performed using survival analysis, Cox's proportional hazard regression, and longitudinal regression models.
Results. Absence of immune activation, measured as ⩽5% CD8+HLA-DR+ cells, was strongly associated with better performance on the psychomotor developmental index of the Bayley scales of infant development through the third year of life. This association persisted after adjustment for CD4 cell count, viral load, and progression to acquired immunodeficiency syndrome (P=.005). An association with the mental development index was also present (P=.048). Significant association between neurodevelopmental outcomes and ⩽25% CD8+CD38+ cells was not seen.
Conclusions. In this prospective cohort study of HIV-infected children, there was a significant favorable association of low immune activation in peripheral T cells at age 1 or 2 months, measured by a low percentage of CD8+HLA-DR+ cells, with subsequent psychomotor and mental development. This association was independent of other indices of severity and progression of HIV infection.
PMCID: PMC3671733  PMID: 19115969
7.  Maternal Neutralizing Antibody and Transmission of HCV to her Infant 
The Journal of infectious diseases  2008;198(11):1651-1655.
To determine if lower levels of hepatitis C virus (HCV)-specific neutralizing antibodies (nAb) are associated with an increased risk of mother-to-child transmission (MTCT) of HCV, anti-HCV nAb titers were assessed in 63 mothers co-infected with HCV and human immunodeficiency virus type 1 (HIV). Among the mothers, 16 transmitted HCV to their infant but no difference was detected between the ability of maternal plasma from transmitters and non-transmitters to neutralize heterologous HCV pseudoparticles (median nAb titer 1:125 vs. 1:100, P=0.23). In the setting of HIV/HCV co-infection, we found no evidence that anti-HCV nAbs are associated with prevention of MTCT of HCV.
PMCID: PMC2777710  PMID: 18928374
HCV; HIV; mother-to-infant transmission; perinatal transmission; hepatitis C virus; neutralizing antibody; HCVpp; MTCT

Results 1-7 (7)