Andrew Wiznia

Stony Brook University, Stony Brook, New York, United States

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Publications (80)394.13 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background. IMPAACT P1066 is a Phase I/II open label multicenter trial to evaluate safety, pharmacokinetics (PK), tolerability and efficacy of multiple raltegravir (RAL) formulations in HIV-infected youth. Methods. Dose selection for each cohort (I: 12 to <19 years; II: 6 to<12 years; and III: 2 to<6 years) was based on review of short term safety (4 weeks) and intensive pharmacokinetic (PK) evaluation. Safety data through Weeks 24 and 48, and Grade >3 or serious adverse events (AE) were assessed. The primary virologic endpoint was achieving HIV RNA<400 copies/mL or ≥1 log10 reduction between baseline and week 24. Results. The targeted PK parameters (AUC0-12 hr and C12 hr) were achieved for each cohort allowing dose selection for two formulations. Of 96 final dose subjects, there were 15 subjects with Grade 3+ clinical AEs (1 subject with drug related [DR] psychomotor hyperactivity and insomnia); 16 subjects with Grade 3+ laboratory AEs (1 with DR transaminase elevation); 15 subjects with serious clinical AEs (1 with DR rash); 2 subjects with serious laboratory AEs (1 with DR transaminase increased). There were no discontinuations due to AEs and no DR deaths. Favorable virologic responses at Week 48 were observed in 78.9%, with a mean CD4 increase of 156 cells/uL (4.6%). Conclusions. 400 mg BID of RAL film-coated tablet (6 to <19 years, and ≥25 kg) and 6 mg/kg BID (maximum dose 300 mg) of RAL chewable tablet (2 to<12 years) were well-tolerated and showed favorable virologic and immunologic responses.
    Clinical Infectious Diseases 10/2013; · 9.37 Impact Factor
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    ABSTRACT: APOBEC3 proteins mediate potent anti-retroviral activity by hypermutating the retroviral genome during reverse transcription. To counteract APOBEC3 and gain a replicative advantage, lentiviruses such as HIV-1 and SIV have evolved the Vif protein, which targets APOBEC3 proteins for proteasomal degradation. However, the proteasome plays a critical role in the generation of T cell peptide epitopes. Whether Vif-mediated destruction of APOBEC3 proteins leads to the generation and presentation of APOBEC3-derived T cell epitopes on the surface of lentivirus-infected cells remains unknown. Here, using peptides derived from multiple Vif-sensitive APOBEC3 proteins, we identified APOBEC3-specific T cell responses in both HIV-1-infected patients and SIV-infected rhesus macaques. These results raise the possibility that these T cell responses may be part of the larger anti-retroviral immune response.
    Journal of Virology 03/2013; · 5.08 Impact Factor
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    ABSTRACT: The introduction of combination antiretroviral therapy has resulted in improved survival and quality of life for individuals infected with the human immunodeficiency virus (HIV). There is, as expected, a growing population of perinatally HIV-infected women who are, have been, or will become pregnant. We describe a large cohort of perinatally infected women, compare it with a similar age-matched behaviorally HIV-infected group, and examine factors affecting maternal and infant health. We reviewed the records of 30 perinatally infected women who gave birth at two hospitals between January 2000 and December 2011. The comparison group comprised behaviorally infected women who delivered at these hospitals during the same period. The outcome measures were differences in CD4 counts and viral load between the cohorts, and comparisons of maternal morbidity, mortality, and mother-to-child HIV transmission. Median CD4 counts were significantly lower in the perinatal group before, during, and after pregnancy. The median viral load was significantly higher in the perinatal group. Interval prepregnancy to post partum viral load decline was also greater in the behavioral group. Viral load decreases in the perinatal population were not sustained in the post partum period, at which time viral load trended back to prepregnancy levels. There was one mother-to-child HIV transmission in a perinatally infected woman. Over an extended 4 years of follow-up, there were four deaths in the perinatal group and none in the behavioral group. After delivery, the differences between perinatally and behaviorally infected mothers accentuate, with immunologic deterioration in the former group. The perinatal population may require novel management strategies to ensure outcomes comparable with those observed in the behavioral group.
    Adolescent Health, Medicine and Therapeutics 01/2013; 4:51-8.
  • Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 11/2012; 109(5):A34-A34. · 3.45 Impact Factor
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    ABSTRACT: This study prospectively examines the effects of maternal and child HIV infection on youth penetrative and unprotected penetrative sex, as well as the role of internal contextual, external contextual, social and self-regulatory factors in influencing the sexual behaviors of HIV-infected (PHIV+), HIV-affected (uninfected with an HIV+ caregiver), and HIV unaffected (uninfected with an HIV- caregiver) youth over time. Data (N=420) were drawn from two longitudinal studies focused on the effects of pediatric or maternal HIV on youth (51% female; 39% PHIV+) and their caregivers (92% female; 46% HIV+). PHIV+ youth were significantly less likely to engage in penetrative sex than HIV- youth at follow-up, after adjusting for contextual, social, and self-regulatory factors. Other individual- and contextual-level factors such as youth alcohol and marijuana use, residing with a biological parent, caregiver employment, caregiver marijuana use, and youth self-concept were also associated with penetrative sex. Youth who used alcohol were significantly more likely to engage in unprotected penetrative sex. Data suggest that, despite contextual, social, and self-regulatory risk factors, PHIV+ youth are less likely to engage in sexual behavior compared to HIV- youth from similar environments. Further research is required to understand delays in sexual activity in PHIV+ youth and also to understand potential factors that promote resiliency, particularly as they age into older adolescence and young adulthood.
    AIDS patient care and STDs 06/2012; 26(7):411-22. · 2.68 Impact Factor
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    ABSTRACT: As the pediatric HIV epidemic in resource-rich countries evolves into an adolescent epidemic, there is a substantive need for studies elucidating mental health needs of perinatally HIV-infected (PHIV +) youth as they transition through adolescence. This article examines the role of perinatal HIV infection in influencing mental health by comparing the changes in psychiatric disorders and substance use disorders (SUD) in PHIV + and perinatally HIV-exposed, but uninfected (PHIV -) youth over time. Participants were recruited from four medical centers in New York City. Individual interviews were administered at baseline and 18-month follow-up to 166 PHIV + and 114 PHIV- youth (49% male, age 9-16 years at baseline). Youth psychiatric disorder was assessed using the caregiver and youth versions of the Diagnostic Interview Schedule for Children (DISC-IV). Over two-thirds of participants met criteria for at least one psychiatric disorder at either baseline or follow-up, with few group differences. Among PHIV + youth, there was a significant decrease in the prevalence of any psychiatric disorder, as well as anxiety disorders specifically over time, whereas the prevalence of any psychiatric disorder among PHIV- youth remained the same and mood disorders increased. Rates of SUD were low in both groups, increasing slightly by follow-up. PHIV + youth reported more use of mental health services at follow-up. CD4 count and HIV RNA viral load were not associated with the presence or absence of disorder at either time point. In conclusion, among PHIV + and PHIV- youth, the rates of psychiatric disorder were high, even compared to other vulnerable populations, suggesting that factors other than perinatal HIV infection may be important determinants of mental health. PHIV + youth were more likely to improve over the observation period. The data underscore the critical need for mental health interventions for both PHIV + and PHIV- youth.
    AIDS Care 04/2012; 24(8):953-62. · 1.60 Impact Factor
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    Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 01/2012; 22(6):442-4. · 1.89 Impact Factor
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    ABSTRACT: In the USA, most HIV-1 infected children are on antiretroviral drug regimens, with many individuals surviving through adolescence and into adulthood. The course of HIV-1 infection in these children is variable, and understudied. We determined whether qualitative differences in immune cell subsets could explain a slower disease course in long term survivors with no evidence of immune suppression (LTS-NS; CD4%≥25%) compared to those with severe immune suppression (LTS-SS; CD4%≤15%). Subjects in the LTS-NS group had significantly higher frequencies of naïve (CCR7+CD45RA+) and central memory (CCR7+CD45RA-) CD4+ T cells compared to LTS-SS subjects (p = 0.0005 and <0.0001, respectively). Subjects in the rapid progressing group had significantly higher levels of CD4+ T(EMRA) (CCR7-CD45RA+) cells compared to slow progressing subjects (p<0.0001). Rapid disease progression in vertical infection is associated with significantly higher levels of CD4+ T(EMRA) (CCR7-CD45RA+) cells.
    PLoS ONE 01/2012; 7(1):e29154. · 3.73 Impact Factor
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    ABSTRACT: As perinatally HIV-1-infected children grow into adolescents and young adults, they are increasingly burdened with the long-term consequences of chronic HIV-1 infection, with long-term morbidity due to inadequate immunity. In progressive HIV-1 infection in horizontally infected adults, inflammation, T cell activation, and perturbed T cell differentiation lead to an "immune exhaustion", with decline in T cell effector functions. T effector cells develop an increased expression of CD57 and loss of CD28, with an increase in co-inhibitory receptors such as PD-1 and Tim-3. Very little is known about HIV-1 induced T cell dysfunction in vertical infection. In two perinatally antiretroviral drug treated HIV-1-infected groups with median ages of 11.2 yr and 18.5 yr, matched for viral load, we found no difference in the proportion of senescent CD28(-)CD57(+)CD8(+) T cells between the groups. However, the frequency of Tim-3(+)CD8(+) and Tim-3(+)CD4(+) exhausted T cells, but not PD-1(+) T cells, was significantly increased in the adolescents with longer duration of infection compared to the children with shorter duration of HIV-1 infection. PD-1(+)CD8(+) T cells were directly associated with T cell immune activation in children. The frequency of Tim-3(+)CD8(+) T cells positively correlated with HIV-1 plasma viral load in the adolescents but not in the children. These data suggest that Tim-3 upregulation was driven by both HIV-1 viral replication and increased age, whereas PD-1 expression is associated with immune activation. These findings also suggest that the Tim-3 immune exhaustion phenotype rather than PD-1 or senescent cells plays an important role in age-related T cell dysfunction in perinatal HIV-1 infection. Targeting Tim-3 may serve as a novel therapeutic approach to improve immune control of virus replication and mitigate age related T cell exhaustion.
    PLoS ONE 01/2012; 7(9):e45733. · 3.73 Impact Factor
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    ABSTRACT: HIV-infected children may be at risk for premature cardiovascular disease. We compared levels of biomarkers of vascular dysfunction in HIV-infected children (with and without hyperlipidaemia) with those in HIV-exposed, uninfected (HEU) children enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS), and determined factors associated with these biomarkers. A prospective cohort study was carried out. Biomarkers of inflammation [C-reactive protein (CRP), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP1)], coagulant dysfunction (fibrinogen and P-selectin), endothelial dysfunction [soluble intracellular cell adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM) and E-selectin], and metabolic dysfunction (adiponectin) were measured in 226 HIV-infected and 140 HEU children. Anthropometry, body composition, lipids, glucose, insulin, HIV disease severity, and antiretroviral therapy were recorded. The median ages of the children were 12.3 years in the HIV-infected group and 10.1 years in the HEU group. Body mass index (BMI) z-scores, waist and hip circumferences, and percentage body fat were lower in the HIV-infected children. Total and non-high-density lipoprotein (HDL) cholesterol and triglycerides were higher in HIV-infected children. HIV-infected children also had higher MCP-1, fibrinogen, sICAM and sVCAM levels. In multivariable analyses in the HIV-infected children alone, BMI z-score was associated with higher CRP and fibrinogen, but lower MCP-1 and sVCAM. Unfavourable lipid profiles were positively associated with IL-6, MCP-1, fibrinogen, and P- and E-selectin, whereas increased HIV viral load was associated with markers of inflammation (MCP-1 and CRP) and endothelial dysfunction (sICAM and sVCAM). HIV-infected children have higher levels of biomarkers of vascular dysfunction than do HEU children. Risk factors associated with higher biomarkers include unfavourable lipid levels and active HIV replication.
    HIV Medicine 12/2011; 13(5):264-75. · 3.16 Impact Factor
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    ABSTRACT: Our objective was to determine whether monitoring HIV-1 DNA concentration or new resistance mutations in peripheral blood mononuclear cells (PBMCs) during effective antiretroviral therapy (ART) predicts virologic failure. A retrospective analysis used blood specimens and clinical data from three nevirapine containing arms of a four-arm, open-label, randomized trial comparing ART regimens in HIV-1-infected children who had failed mono- or dual-nucleoside therapy. Sensitive assays compared cell-associated HIV-1 DNA concentrations and nevirapine (NVP) and lamivudine (3TC) resistance mutations in children with plasma HIV-1 RNA <400 copies(c)/ml who did or did not experience subsequent virologic failure. Forty-six children were analyzed through the last available follow-up specimen, collected at 48 (n=16) or 96 (n=30) weeks of ART. Thirty-five (76%) had sustained viral suppression and 11 (24%) had plasma viral rebound to ≥ 400 c/ml (virologic failure detected at a median of 36 weeks). HIV-1 DNA levels at baseline, 24, 48, and 96 weeks of ART were similar in children who did vs. did not experience virologic failure (p=0.82). HIV-1 DNA levels did not increase prior to viral rebound. NVP resistance mutations were detected in 91% of subjects in the failure group vs. 3% in the suppressed group (p <0.0001). Among nine evaluable children, NVP mutations were first detected prior to virologic failure in two (22%), at viral rebound in five (56%), and after failure in two (22%) children. HIV-1 DNA concentrations did not predict virologic failure in this cohort. New drug resistance mutations were detected in the PBMCs of a minority of virologically suppressed children who subsequently failed ART.
    AIDS research and human retroviruses 11/2011; 28(8):780-8. · 2.18 Impact Factor
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    ABSTRACT: Human endogenous retrovirus (HERV)-specific T cell responses in HIV-1-infected adults have been reported. Whether HERV-specific immunity exists in vertically HIV-1-infected children is unknown. We performed a cross-sectional analysis of HERV-specific T cell responses in 42 vertically HIV-1-infected children. HERV (-H, -K, and -L family)-specific T cell responses were identified in 26 of 42 subjects, with the greatest magnitude observed for the responses to HERV-L. These HERV-specific T cell responses were inversely correlated with the HIV-1 plasma viral load and positively correlated with CD4(+) T cell counts. These data indicate that HERV-specific T cells may participate in controlling HIV-1 replication and that certain highly conserved HERV-derived proteins may serve as promising therapeutic vaccine targets in HIV-1-infected children.
    Journal of Virology 08/2011; 85(21):11526-31. · 5.08 Impact Factor
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    ABSTRACT: HIV-infected children are treated with tenofovir in combination with other, potentially interacting, antiretroviral agents. We report the pharmacokinetic parameters of tenofovir in combination with efavirenz, darunavir-ritonavir, or atazanavir-ritonavir in HIV-infected children. HIV-infected patients 8 to 18 years of age receiving a tenofovir (300 mg)-based regimen containing efavirenz (300 or 600 mg) once daily (group 1), darunavir (300 or 600 mg)-ritonavir (100 mg) twice daily (group 2), or atazanavir (150 to 400 mg)-ritonavir (100 mg) once daily (group 3) were enrolled. Plasma samples were collected over a 24-h time interval. The 90% confidence intervals (90% CI) of the geometric means for the area under the plasma concentration-time curve (AUC) and the minimum concentration of drug in serum (C(min)) of each antiretroviral were computed and checked for overlap with intervals bracketing published values obtained in adult or pediatric studies demonstrating safety and/or efficacy. Group 1 efavirenz plasma concentrations were observed to be higher in patients receiving fixed-dose combination tablets compared with subjects receiving the individual formulation. In group 2, tenofovir and darunavir exposure was observed to be lower than expected. In group 3, tenofovir and atazanavir administered concomitantly produced exposures similar to those published for adult patients. The 90% CI of AUC and C(min) for tenofovir overlapped the target range for all combinations. Informal comparisons of treatment groups did not indicate any advantage to any combination with respect to tenofovir exposure. Further study of exposures achieved with antiretrovirals administered in combination is warranted.
    Antimicrobial Agents and Chemotherapy 06/2011; 55(9):4290-4. · 4.57 Impact Factor
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    ABSTRACT: This is a retrospective comparison of pregnant women with perinatally acquired HIV-infection (PAH) with a cohort of pregnant women with behaviorally acquired HIV-infection (BAH). PAH cases (11 women) included all pregnant adolescents followed at our HIV clinic from January 2000 to January 2009. BAH cases (27 women) were randomly selected from all deliveries within the study period at the same institution. Demographics, mode of delivery, CD4+ counts, and viral loads (VLs) before, during, and six months postpartum, as well as neonatal outcomes, were reviewed. CD4 counts were significantly lower in the PAH group. VLs were statistically higher in the PAH group. VLs were undetectable at delivery in 60% of the PAH group compared with 88% of the BAH group. No cases of vertical transmission occurred. PAH women may be at a higher risk for HIV-related disease progression. This may increase vertical transmission risks. Further studies and interventions with this growing population are warranted.
    AIDS Care 05/2011; 23(9):1076-82. · 1.60 Impact Factor
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    ABSTRACT: To assess the characteristics and outcomes of antiretroviral treatment (ART) interruption (TI) in perinatally HIV-infected children. The Adolescent Master Protocol (AMP) of the Pediatric HIV/AIDS Cohort Study is a prospective cohort study that enrolled 7- to 16-year-old perinatally HIV-infected children between 2007 and 2009 from 15 sites in the United States and Puerto Rico. TI was defined as ART discontinuation for ≥ 3 months after ≥ 6 months of continuous ART. Subjects with and without TI were compared. Rates of change (slopes) in CD4 T-lymphocyte (CD4) count and percentage (%) per month during TI were calculated. Factors related to CD4 slope in univariable analyses were included in multivariable linear regression. Of 444 eligible AMP subjects, 101 (23%) had at least one TI. Subjects with TI were born in earlier years but were otherwise similar to those without TI. For 81 TI subjects with complete data, the median (range) CD4% and CD4 count slopes were -0.66% per month (-3.54% to +1.34% per month) and -12.7 cells per cubic millimeter per month (-148 cells/mm to +31 cells/mm per month), respectively. On multivariable linear regression, there was a trend for lower CD4% slope to be associated (P < 0.1) with female sex, higher CD4% at TI, and higher peak viral load before TI. Advanced HIV disease stage and numerous ART regimens were more common in TI subjects in the lowest (fastest declining) CD4% slope quartile. TIs in perinatally HIV-infected youth are common. During TIs, CD4 values decline on average but with high intersubject variability. Factors predicting CD4 slope during TI need further study.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2011; 57(3):223-9. · 4.65 Impact Factor
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    ABSTRACT: Some adolescent girls perinatally infected with HIV (PIH) engage in sexual behavior that poses risks to their own well-being and that of sexual partners. Interventions to promote condom use among girls PIH may be most effective if provided prior to first sexual intercourse. With in-depth interviews, we explored gender- and HIV-specific informational and motivational factors that might be important for sexual risk reduction interventions designed to reach US girls PIH before they first engage in sexual intercourse. Open-ended interview questions and vignettes were employed. The information-motivation-behavioral skills (IMB) model guided descriptive qualitative analyses. Participants (20 girls PIH ages 12-16 years) had experienced kissing (n=12), genital touching (n=6), and oral (n=3), vaginal (n=2), and anal sex (n=1). Most knew sex poses transmission risks but not all knew anal sex is risky. Motivations for and against condom use included concerns about: sexual transmission, psychological barriers, and partners' awareness of the girl's HIV+ status. Girls were highly motivated to prevent transmission, but challenged by lack of condom negotiation skills as well as negative potential consequences of unsafe sex refusal and HIV status disclosure. Perhaps most critical for intervention development is the finding that some girls believe disclosing one's HIV status to a male partner shifts the responsibility of preventing transmission to that partner. These results suggest a modified IMB model that highlights the role of disclosure in affecting condom use among girls PIH and their partners. Implications for cognitive-behavioral interventions are discussed.
    AIDS Care 03/2011; 23(10):1321-8. · 1.60 Impact Factor
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    ABSTRACT: Abstract: RATIONALE : Epidemiologic studies indicate that the development of asthma and allergicsensitization is determined early in life but the underlying immunologic mechanisms have not been well studied. Our study aimed to determine peripheral lymphocyte subsets in associationwith atopy and asthma in the first years of life. METHODS : Twenty-five highly atopic children (age 18 months to 3 years) with history of repeated wheezing and family history of asthma and/or eczema, and 10 healthy children wererecruited. Peripheral blood lymphocyte subpopulations were analyzed by flow cytometry andserum was analyzed for total and allergen specific IgE. RESULTS : The frequency of peripheral CD3+CD8+ T-cells was significantly lower (p=0.03)whereas the frequency of CD3+CD4+ T-cells tended to be higher (p=0.07) in atopic childrencompared to healthy children. In atopic children, the frequency of CD3+CD8+ T-cells within thelymphocyte population negatively predicted total serum IgE (p=0.01). After stratification for useof inhaled corticosteroid, atopic children using steroid inhalers had significantly higher absoluteCD3+ T-cells (p=0.03) and CD8+ T-cells (p=0.01) compared to atopic children without steroiduse. No difference was observed in the frequency or absolute number of T regulatory cells(CD4+CD25+Foxp3+CD127) between healthy and asthmatic children, regardless of steroid use. CONCLUSIONS : Atopic toddlers with history of wheezing had a decreased frequency of peripheral CD8+ T-cells and the frequency of CD8+ T-cells negatively correlated with totalserum IgE within the atopic group. These results indicate a potential role of CD8+ T-cells inallergic sensitization and asthma early in life.
    The Journal of allergy and clinical immunology 02/2011; 127(2):Page AB259. · 12.05 Impact Factor
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    ABSTRACT: The introduction of protease inhibitors (PI) containing antiretroviral regimens in the treatment of HIV infection in infants, children, and adolescents has dramatically decreased morbidity and mortality. Darunavir, the latest PI to be FDA approved for pediatric patients older than 6 years and currently the preferred PI for use in adult patients, was added as an alternative PI for use in children based on a combination of data from both adult and pediatric trials. This review of darunavir in the treatment of HIV-infected children and adolescents looks at the major published clinical trials findings, pharmacokinetic and resistance studies, and preliminary data on use in younger children.
    Adolescent Health, Medicine and Therapeutics 01/2011; 2:85-93.
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    ABSTRACT: HIV-1 vertically infected children in the USA are living into adolescence and beyond with the widespread use of antiretroviral drugs. These patients exhibit striking differences in the rate of HIV-1 disease progression which could provide insights into mechanisms of control. We hypothesized that differences in the pattern of immunodomination including breadth, magnitude and polyfunctionality of HIV-1 specific CD8+ T cell response could partially explain differences in progression rate. In this study, we mapped, quantified, and assessed the functionality of these responses against individual HIV-1 Gag peptides in 58 HIV-1 vertically infected adolescents. Subjects were divided into two groups depending upon the rate of disease progression: adolescents with a sustained CD4%≥25 were categorized as having no immune suppression (NS), and those with CD4%≤15 categorized as having severe immune suppression (SS). We observed differences in the area of HIV-1-Gag to which the two groups made responses. In addition, subjects who expressed the HLA- B*57 or B*42 alleles were highly likely to restrict their immunodominant response through these alleles. There was a significantly higher frequency of naïve CD8+ T cells in the NS subjects (p = 0.0066) compared to the SS subjects. In contrast, there were no statistically significant differences in any other CD8+ T cell subsets. The differentiation profiles and multifunctionality of Gag-specific CD8+ T cells, regardless of immunodominance, also failed to demonstrate meaningful differences between the two groups. Together, these data suggest that, at least in vertically infected adolescents, the region of HIV-1-Gag targeted by CD8+ T cells and the magnitude of that response relative to other responses may have more importance on the rate of disease progression than their qualitative effector functions.
    PLoS ONE 01/2011; 6(7):e21135. · 3.73 Impact Factor
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    ABSTRACT: The majority of infants born, in developed countries, to HIV-1 positive women are exposed to the HIV-1 virus in utero or peri/post-partum, but are born uninfected. We, and others, have previously shown HIV-1 specific T cell responses in HIV-1 exposed seronegative (HESN) neonates/infants. Our objective in this study was to examine the rate of decay in their HIV-1 specific T cell response over time from birth. Cross-sectional and longitudinal studies of HIV-1 specific T cell responses in HESN infants were performed. Peripheral blood mononuclear cells (PBMC) were isolated from 18 HIV-1 DNA PCR negative infants born to HIV-1 infected mothers receiving care at the Jacobi Medical Center, Bronx, NY, USA. PBMC were examined for T cell responses to HIV-1 antigens by interferon-gamma (IFN-γ) ELISPOT. PBMC from 15 HESN neonates/infants were analyzed. We observed a decay of HIV-1 specific T cell responses from birth at a rate of -0.599 spot forming unit/10⁶ cells per day, with a median half-life decay rate of 21.38 weeks (13.39-115.8). Our results support the dynamic nature of T cell immunity in the context of a developing immune system. The disparate rate of decay with studies of adults placed on antiretroviral drugs suggests that antigen specific T cell responses are driven by the natural rate of decay of the T cell sub-populations themselves.
    Frontiers in Immunology 01/2011; 2:94.

Publication Stats

1k Citations
394.13 Total Impact Points

Institutions

  • 2013
    • Stony Brook University
      Stony Brook, New York, United States
  • 2005–2013
    • University of California, San Francisco
      • • Division of Experimental Medicine
      • • Gladstone Institute
      San Francisco, CA, United States
    • Baylor College of Medicine
      • Department of Pediatrics
      Houston, TX, United States
  • 2012
    • University of Hawaiʻi at Hilo
      Hilo, Hawaii, United States
  • 2009–2012
    • New York State Psychiatric Institute
      New York City, New York, United States
  • 1988–2012
    • Albert Einstein College of Medicine
      • Department of Pediatrics
      New York City, New York, United States
  • 2011
    • University of Toronto
      • Department of Immunology
      Toronto, Ontario, Canada
    • New York Medical College
      New York City, New York, United States
  • 2003–2011
    • University of Alabama at Birmingham
      • Division of Clinical Pharmacology
      Birmingham, Alabama, United States
  • 2002
    • The Rockefeller University
      New York City, New York, United States
  • 1999
    • The University of Manchester
      • School of Mathematics
      Manchester, ENG, United Kingdom
  • 1993
    • Bronx-Lebanon Hospital
      Bronxville, New York, United States