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A Landay

Publications and source records attributed to A Landay.

At least 19 recordsLinked to original sources
PubMed2004

Evaluation of the impact of highly active antiretroviral therapy on immune recovery in antiretroviral naive patients.

OBJECTIVES: To examine the extent of immune reconstitution in treatment-naive patients with CD4 T-cell counts <500 cells/microL following 48 weeks of highly active antiretroviral therapy (HAART). METHODS: Thirteen antiretroviral naive patients were evaluated longitudinally for 48 weeks on HAART utilizing immune functional and lymphocyte phenotyping assays, including lymphocyte proliferation assay, flow cytometric evaluation of cell surface markers, and delayed type hypersensitivity skin tests. Virologic responses were monitored using commercially available viral load assays and gag/pol mRNA quantification using simultaneous immunophenotyping/UltraSensitive fluorescence in situ hybridization (ViroTect In Cell HIV-1 Detection Kit; Invirion, Frankfort, MI). Thymic function was evaluated for a subset of four patients using real-time polymerase chain reaction (PCR) for T-cell receptor excision circle (TREC) quantification and thymic scans using computerized axial tomography (CT) of the thymus. RESULTS: HAART initiation resulted in a significant decline in plasma viremia and percentage of infected peripheral blood cells, and a rise in CD4 T cells from a baseline median of 207 cells/microL to a week-48 median of 617 cells/microL. The rise was predominately in CD4 memory cells. Naive T cells also increased in number, but at a slower rate. Activated (HLA-DR CD38) CD4 and CD8 T cells were elevated at baseline (24 and 62%, respectively) and declined by week 48 (17 and 36%, respectively) but did not reach normal levels. The number of Fas CD4 T cells increased from a baseline median of 169 to 381 cells/microL at week 48. Both soluble interleukin (IL)-2 and tumour necrosis factor (TNF) II receptors declined by week 48. HIV p24 lymphocyte proliferation assay responses were transiently detected in three patients. TREC values increased from a median 6400 copies/microg at baseline to a week-48 median value of 26 697 copies/microg. CONCLUSION: Immune functional reconstitution was not achieved in these HAART naive patients.

Adult↗
PubMed2001

Determinants of HIV-1 shedding in the genital tract of women.

BACKGROUND: Plasma HIV-1 RNA concentration has been the best predictor for risk of heterosexual and perinatal transmission. However, direct contact with HIV-1 present locally in the genital tract might be necessary for transmission. We aimed to assess the relation between HIV-1 shedding (RNA or culturable virus) in female genital secretions and other factors that might affect HIV-1 shedding. METHODS: This was a cross-sectional study within the Women's Interagency HIV Study (WIHS), a prospective longitudinal cohort study of HIV-infected women. We enrolled 311 HIV positive women from Jan 30, 1997 to July 1, 1998. We did clinical assessments, cultured HIV-1, and measured RNA in peripheral blood mononuclear cells (PBMC) and genital secretions. We compared the results with univariate and multivariate analyses. Presence of HIV-1 RNA or culturable virus in genital secretions was defined as HIV-1 shedding. FINDINGS: HIV-1 RNA was present in genital secretions of 57% (152/268) of women whereas infectious virus was detected only in 6% (17/271). Genital tract HIV-1 shedding was found in 80% (130/163) of women with detectable plasma RNA and 78% (116/148) of women with positive PBMC cultures. 33% (27/83) of women with less than 500 copies/mL plasma RNA and 39% (35/90) of those with negative PBMC cultures also had genital tract shedding. INTERPRETATION: Plasma RNA concentration, both qualitatively and quantitatively, was the most important factor in predicting genital HIV-1 shedding, even among women receiving potent antiretroviral therapy. However, HIV-1 shedding did occur in women with less than 500 copies/mL plasma HIV-1 RNA. This finding suggests that a separate reservoir of HIV-1 replication may exist in some women.

Adult↗
PubMed2001

T cell receptor excision circle (TREC) content following maximum HIV suppression is equivalent in HIV-infected and HIV-uninfected individuals.

BACKGROUND: The adult human thymus contributes to de novo T cell synthesis; such synthesis can be assessed by analyzing T cell receptor excision circles (TREC). METHODS: TREC levels were measured in total peripheral blood mononuclear cells (PBMC) and CD4- and CD8-enriched cells of 29 HIV-positive patients with maximal viral suppression. The expression of CD45RA+CD45RO-, CD45RA+CD62L+, CD45RO-CD27+CD95low and HLA-DR+CD38+ was assessed using three-color flow cytometric analysis of whole blood. Thymic index score was based on computed tomographic scans of the thymus. The relationship of TREC with thymic index and the expression of the naive phenotypes was evaluated. RESULTS: TREC expression was not statistically different in these HIV-positive patients from that in age-matched HIV-negative controls. Among HIV-positive patients with CD4 cell count of > 500 x 10(6) cells/l after antiretroviral therapy (n = 15), PBMC TREC levels correlated with the expression of CD45RA+CD45RO- and CD45RA+CD62L+ naive phenotypes, and inversely correlated with the expression of HLA-DR+CD38+. The change between pre- and post-therapy CD4 cell counts for these 15 patients significantly correlated with both thymic index and expression of the CD45RA+CD45RO- phenotype. CONCLUSIONS: The finding that TREC expression was equivalent between HIV-positive patients after therapy and HIV-negative donors suggests that there is no reduction in thymic output among HIV-positive individuals after therapy. Given that TREC is inversely correlated with HLA-DR/CD38 expression, its analysis in studies of thymopoiesis should be evaluated in the context of maximum viral suppression to reduce HIV-mediated immune activation and/or by normalizing for cell turnover.

Adult↗
PubMed2001

Persistence of intracellular HIV-1 mRNA correlates with HIV-1-specific immune responses in infected subjects on stable HAART.

OBJECTIVE: To determine if low level, persistent, HIV-1 replication within specific immune cells contributes to HIV-1-specific immune responsiveness. DESIGN: We analyzed 59 HIV-1-infected subjects on stable highly active antiretroviral therapy (HAART) therapy (not including zidovudine) with suppressed plasma viremia (< 400 copies/ml) for phenotypic and lymphoproliferative correlates of immune function. METHODS: Peripheral blood mononuclear cells were collected for immunophenotyping, lymphoproliferative assays, and simultaneous immunophenotyping/ultrasensitive in situ hybridization. Plasma was collected for plasma viral load as determined by the Ultra Sensitive Roche Amplicor RT-PCR. Descriptive statistics (mean and SD, median, first and third quartiles) were determined for all variables in two groups defined as having persistent viral replication present or absent. The two-sided Wilcoxon test (continuity correction, 0.5) was used to compare lymphocyte phenotypes, lymphoproliferative assay responses, intracellular gag-pol mRNA, lowest CD4 counts and CD4% of these two groups. RESULTS: HIV-1 replication in CD4, CD45RO memory T lymphocytes persists in spite of undetectable plasma viral load. Patients (n = 24) with persistent intracellular expression of HIV-1 mRNA (> 0.3%) showed significant in vitro proliferative responses to HIV-1 p24 (stimulation index > or = 10) compared to patients (n = 35) without persistent intracellular replication. The group with persistent HIV-1 replication in cells showed no significant response to the recall antigen tetanus toxoid but a trend toward higher responses to pathogen antigens. There were no differences between the groups in the prevalence of AIDS or occurrences of opportunistic infections; however, the high viral persistence group was more HAART experienced (P < 0.05). CONCLUSIONS: These results suggest that HIV-1-specific immune responses correlate with evidence of ongoing HIV-1 replication.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Multiple CD4+ cell kinetic patterns and their relationships with baseline factors and virological responses in HIV type 1 patients receiving highly active antiretroviral therapy.

This exploratory analyses characterizes patterns of lymphocyte recovery in HIV-1-infected patients treated with highly active antiretroviral therapy (HAART) and investigates their relationship with baseline indices and virologic responses. We modeled kinetics of total CD4+ lymphocytes, as well as naive (CD45RA+ CD62L+), and memory (CD45RA- CD45RO+) subsets in 48 patients treated with AZT/3TC/Ritonavir for 48 weeks in ACTG protocol 315. Cell kinetic indices were estimated by nonlinear regression methods and were correlated with baseline factors and virologic responses. Five different kinetic patterns were identified, including biphasic growth, growth-plateau, growth-depletion, decay-recovery, and biphasic decay. Although overall mean lymphocyte responses showed a biphasic increase in cell number, a careful investigation reveals that only one-third of patients actually followed the biphasic growth pattern in CD4+ cell response, while 44% of 48 patients from this study followed the growth-depletion pattern. CD4+ cell recovery during the first phase and the 48-week study period were negatively correlated with baseline CD4+ cell counts, and positively correlated with baseline viral load. Memory CD4+ cell recovery during the first phase was also negatively correlated with baseline memory CD4+ and total CD4+ cell number, but the recovery rate of memory CD4+ cells during the second phase was positively correlated with baseline CD4+ cell number. Patients with a decay in CD4+ cell count during treatment were more likely to have experienced virological rebound (58%) than patients with nondecay patterns (24%). The rate and magnitude of the absolute increase in total CD4+ and memory CD4+ cell number (but not naive CD4+ cells) during the second phase were lower in patients with viral rebound compared with patients with persistent viral suppression. These results show that the kinetics of lymphocyte reconstitution in response to potent antiretroviral therapy in individual patients vary considerably from the "classic" biphasic increase that characterizes the mean or median response pattern. Pattern analysis of lymphocyte kinetics may be useful for testing relationships among factors that modulate the response to treatment.

Anti-HIV Agents↗
PubMed2001

A menstrual cycle pattern for cytokine levels exists in HIV-positive women: implication for HIV vaginal and plasma shedding.

OBJECTIVES: To evaluate the effect of the menstrual cycle in HIV-positive women on plasma and genital cytokine levels, interrelationships between vaginal and plasma cytokines, CD4 and CD8 T cell fluctuations, and genital and plasma viral loads. METHODS: Plasma and cervicovaginal lavage specimens were collected from 55 HIV-positive women with CD4 cell counts < 350 cells/microl during phases of the menstrual cycle. Samples were assayed for IL-1beta, IL-6, IL-4, IL-8, IL-10, TGFbeta, TNFalpha, INFgamma, MIP1alpha, MIP1beta, RANTES, and TNFR-II using enzyme-linked immunosorbent assays. CD4 and CD8 T cell expression was evaluated by flow cytometry. Repeated measures regression models were used to assess the effect of the menstrual cycle on cytokines and viral load. Multivariate repeated regression models were used to assess the correlation among selected cytokines and between selected cytokines and HIV viral load. RESULTS: Vaginal IL-1beta, IL-4, IL-6, IL-8, IL-10, MIP1beta, RANTES, TGFbeta, and TNFR-II were significantly elevated during menses but were not altered during other phases. Plasma cytokine levels were not altered during the menstrual cycle. A positive Candida culture increased vaginal IL-8 during menses, whereas vaginal discharge was associated with a reduction in vaginal IL-4, IL-10, and RANTES. CD4 and CD8 cell numbers did not vary with the menstrual cycle. Vaginal cytokine levels correlated only with vaginal viral load, in a sampling method-dependent manner. CONCLUSION: We provide evidence of elevated vaginal cytokine levels during menses, which appear to regulate vaginal and not plasma HIV shedding, suggesting that a menstrual cycle pattern exists for cytokine production in HIV-positive women impacting vaginal shedding of HIV.

Adolescent↗
PubMed2001

A potential role for interleukin-7 in T-cell homeostasis.

Interleukin (IL)-7 is known to up-regulate thymopoietic pathways of T-cell regeneration. Recent work also has shown it to potently enhance thymic-independent peripheral expansion and to restore immunocompetence in athymic T-cell-depleted hosts. We hypothesized that endogenous IL-7 could contribute to the restoration of T-cell homeostasis following T-cell depletion. To analyze this, we evaluated circulating IL-7 levels and lymphocyte subsets in multiple clinical cohorts with T-cell depletion of varying etiologies. In pediatric (n = 41) and adult (n = 51) human immunodeficiency virus-infected CD4-depleted patients, there were strong inverse correlations between IL-7 levels and CD4 counts (r = -0.77, P <.0001, and r = -0.68, P <.0001). Declines in IL-7 were temporally correlated with recovery of CD4 counts. Similar patterns were observed in CD4-depleted patients receiving cancer chemotherapy (r = -0.65, P =.009). Therefore, in 2 disparate clinical scenarios involving CD4 depletion, IL-7 levels dynamically respond to changes in CD4 T-cell number, making this cytokine uniquely suited as a candidate regulator of T-cell homeostasis. Furthermore, in patients with idiopathic CD4 lymphopenia, a much weaker relationship between IL-7 levels and peripheral blood CD4 counts was observed, suggesting that an impaired IL-7 response to CD4 depletion may contribute to the impaired lymphocyte homeostasis observed in this population. In light of the known effects of IL-7 on T-cell regeneration, we postulate that increased availability of IL-7 could play a critical role in restoring T-cell homeostasis following T-cell depletion.

Adolescent↗
PubMed2001

Leukemia inhibitory factor inhibits HIV-1 replication and is upregulated in placentae from nontransmitting women.

The placenta may play a critical role in inhibiting vertical transmission of HIV-1. Here we demonstrate that leukemia inhibitory factor (LIF) is a potent endogenous HIV-1-suppressive factor produced locally in placentae. In vitro, LIF exerted a potent, gp130-LIFRbeta-dependent, HIV coreceptor-independent inhibition of HIV-1 replication with IC50 values between 0.1 pg/ml and 0.7 pg/ml, depending on the HIV-1 isolate. LIF also inhibited HIV-1 in placenta and thymus tissues grown in ex vivo organ culture. The level of LIF mRNA and the incidence of LIF protein-expressing cells were significantly greater in placentae from HIV-1-infected women who did not transmit HIV-1 to their fetuses compared with women who transmitted the infection, but they were not significantly different from placentae of uninfected mothers. These findings demonstrate a novel pathway for endogenous HIV suppression that may prove to be an effective immune therapy for HIV infection.

Adult↗
PubMed2000

Cellular restoration in HIV infected persons treated with abacavir and a protease inhibitor: age inversely predicts naive CD4 cell count increase.

OBJECTIVE: To characterize early and later indices of cellular restoration among HIV-1 infected persons treated with abacavir and one protease inhibitor and to identify predictors of CD4 cell increases. METHODS: Flow-cytometric analyses of lymphocyte phenotypes among 71 antiretroviral treatment naive adults in a 48 week treatment trial. RESULTS: During the first 4 weeks of therapy, increases in naive and memory CD4 cells and in B cells were seen; naive CD8 cells increased while CD8 cells remained stable as memory CD8 cells decreased. During the second phase total CD4 and naive CD4 and CD8 cells increased while total CD8 and memory CD8 cells decreased. The numbers of CD4 cells that expressed CD28 increased from a median of 308 x 10(6)/l at baseline to 477 x 10(6)/l at week 48. Higher baseline plasma HIV-1 RNA levels predicted the magnitude of early CD4 (r = 0.35; P = 0.01), memory CD4 (r = 0.38; P = 0.001) and CD28 CD4 cell (r = 0.29; P = 0.01) restoration but was not related to second phase changes. Younger age predicted a greater second phase (but not first phase) increase in naive CD4 cells (r = -0.31; P = 0.03). CONCLUSIONS: Higher baseline levels of HIV-1 replication determine the magnitude of first phase CD4 cell increases after suppression of HIV-1 replication. Second phase (primarily naive) CD4 cell increases are not related to HIV-1 replication but are inversely relate to age suggesting that thymic potential is a major determinant of long term cellular restoration in HIV-1 infected persons receiving antiretroviral therapy.

Adolescent↗
PubMed2000

Mechanisms of HIV-associated lymphocyte apoptosis.

Infection with the human immunodeficiency virus (HIV) is associated with a progressive decrease in CD4 T-cell number and a consequent impairment in host immune defenses. Analysis of T cells from patients infected with HIV, or of T cells infected in vitro with HIV, demonstrates a significant fraction of both infected and uninfected cells dying by apoptosis. The many mechanisms that contribute to HIV-associated lymphocyte apoptosis include chronic immunologic activation; gp120/160 ligation of the CD4 receptor; enhanced production of cytotoxic ligands or viral proteins by monocytes, macrophages, B cells, and CD8 T cells from HIV-infected patients that kill uninfected CD4 T cells; and direct infection of target cells by HIV, resulting in apoptosis. Although HIV infection results in T-cell apoptosis, under some circumstances HIV infection of resting T cells or macrophages does not result in apoptosis; this may be a critical step in the development of viral reservoirs. Recent therapies for HIV effectively reduce lymphoid and peripheral T-cell apoptosis, reduce viral replication, and enhance cellular immune competence; however, they do not alter viral reservoirs. Further understanding the regulation of apoptosis in HIV disease is required to develop novel immune-based therapies aimed at modifying HIV-induced apoptosis to the benefit of patients infected with HIV.

Apoptosis↗
PubMed2000

Normalization of immune activation in lymphoid tissue following highly active antiretroviral therapy.

Although significant progress has been made in understanding immune reconstitution in peripheral blood following highly active antiretroviral therapy (HAART), less is known about immune changes in lymphoid tissue. Here, the expression of cytokine proteins (interferon gamma [IFN-gamma], interleukin [IL]-2, IL-4, IL-10, IL-1alpha, and IL-1beta) and surface antigens (CD4, CD8, CD1a, CD68) as well as cellular proviral HIV-1 DNA were determined in sequential tonsil biopsies before and at 4, 12, and 48 to 56 weeks posttherapy by quantitative in situ image analysis and fluorescent in situ 5;-nuclease assay (FISNA). Despite plasma virus suppression, a fraction of tonsil cells harbored pro-viral DNA for up to 1 year. A fourfold to eightfold increase in CD8+ T cells in tissue compared with seronegative controls and an increased frequency of CD1a+ dendritic cells prior to HAART reached control levels at week 56. The frequency of IFN-gamma expressing cells was 10-to 15-fold higher than controls before therapy and was comparable with findings in seronegative controls by week 56. Elevated baseline expression of IL-1alpha and IL-1beta was reduced by week 4 but IL-1alpha levels remained elevated in 1 of 3 patients at week 56. These findings suggest that with effective viral suppression the immune system in tissue may return to a more resting state.

Antiretroviral Therapy, Highly Active↗
PubMed2000

Maximum suppression of HIV replication leads to the restoration of HIV-specific responses in early HIV disease.

OBJECTIVES: It is predicted that HIV-infected individuals in early HIV disease are the most likely group to achieve immune reconstitution following highly active antiretroviral treatment. We assessed whether suppression of HIV replication in this group would improve immune function. METHODS: Seventeen antiretroviral-naïve patients in early HIV disease were evaluated for immune function and lymphocyte phenotyping using standard immunological assays. RESULTS: Absolute CD4+ T-cell number increased from a median of 550 to 800 x 10(6) cells/l while CD8+ T-cell numbers were reduced. The decrease in CD8+ cells correlated with a decrease in the CD8+ memory phenotype. Kinetics of CD4+ naïve and memory T-cell rise indicated that 80% of the maximum CD4+ naïve increase was achieved within 18 weeks whereas maximum CD4+ memory T-cell rise was achieved within 36 weeks. Activation markers (HLA-DR, CD38) and an apoptosis-related marker (CD95) were reduced on CD4+ and CD8+ T cells. Lymphocyte proliferation responses to tetanus toxoid, alloantigen, and anti-CD3/CD28 were restored in patients that were initially unresponsive. At baseline, 31% of the patients responded to HIV p24, which increased to 69% post-therapy. The inducible RANTES response was normalized following therapy whereas inducible interferon-gamma, interleukin (IL)-12, and MIP1beta were elevated. The depressed inducible IL-10 response, however, was not altered after therapy. CONCLUSIONS: This is one of the first studies to demonstrate the restoration of HIV-1 specific responses in non-acute HIV infection, suggesting early intervention with potent antiretroviral therapy may reverse immune-mediated damage not seen with treated patients who have more advanced disease.

Adolescent↗
PubMed2000

Detection of T cell receptor circles (TRECs) as biomarkers for de novo T cell synthesis using a quantitative polymerase chain reaction-enzyme linked immunosorbent assay (PCR-ELISA).

Currently, phenotypic markers that distinguish between recent thymic emigrants/de novo T cells and the rest of the peripheral T cell pool are lacking. This distinction is critical in studies aimed at evaluating immune reconstitution following intensive chemotherapy, in immunodeficiency-related therapies, or in the elucidation of the kinetics of thymic function. During V(D)J T cell receptor rearrangement, DNA extrachromosomal excision products are generated. These products, known as T cell receptor excision circles (TRECs), are not replicated during mitosis and are thus diluted with each round of cell division. Therefore, TRECs can be used as an indicator of recent thymic emigrants. Thus far, quantitative competitive-polymerase chain reaction (QC-PCR) and real time PCR were used to measure TREC levels. However, QC-PCR relies on radioactivity, is cumbersome when processing many samples at once and the cost of real time PCR does not make it a viable option for many laboratories. We describe here the development of a quantitative PCR-ELISA method for the measurement of coding joint TRECs generated from ValphaJalpha recombination. Our assay is ultra sensitive, relies on biotin labeling rather than radioactivity, is based on a 96-well format making multiple process sampling relatively easy, and is cost effective. Using this PCR-ELISA method, we evaluated thymic output among 22 normal subjects, ranging in age from 22-53 years, and among HIV-infected individuals following highly active antiretroviral therapy (HAART). We demonstrate that an inverse relationship exists between TREC levels and aging in normal individuals and that, among some HIV patients, HAART treatment leads to enhanced thymic output. Our assay has direct relevance in projects examining normal and abnormal thymic function and in immune reconstitution studies.

Adult↗
PubMed2000

Response to immunization with recall and neoantigens after prolonged administration of an HIV-1 protease inhibitor-containing regimen. ACTG 375 team. AIDS Clinical Trials Group.

OBJECTIVES: To ascertain if immunization results in the restoration of responses to recall antigens, in the development of responses to presumed neoantigens, and to identify the virologic and immunologic correlates of these responses in persons with HIV-1 infection. DESIGN AND SETTING: Open-label study carried out at three university-affiliated AIDS Clinical Trials Units in the United States. SUBJECTS AND METHODS: Thirty-one subjects participating in AIDS Clinical Trials Group Protocol 375 who had received zidovudine, lamivudine, and ritonavir for at least 48 weeks. Subjects were immunized with tetanus toxoid (TT) at entry and with inactivated hepatitis A vaccine (hep A) and keyhole limpet hemocyanin (KLH) at entry and 6 weeks. The development of antibody, lymphocyte proliferative assay (LPA), and delayed-type hypersensitivity (DTH) responses after immunization were monitored. RESULTS: The LPA and DTH responses to TT improved in 57 and 68% of participants, respectively; 73 and 65% developed enhanced LPA and DTH responses to KLH. Forty-eight percent of patients developed a four-fold increase in antibody concentration to tetanus. Seventy-three percent of patients without detectable hepatitis A antibodies at baseline developed antibodies after immunization. Eighty-three percent of patients experienced at least a four-fold rise in KLH antibody concentration. Immune activation and viral load predicted poor recall responses and the number of memory CD4+ T-cells predicted good responses to recall antigens. Naïve CD4+ T-cell numbers, decrease in viral load, increases in CD4+ and CD28+ cells, and decreases in immune activation were associated with responses to presumed neoantigens. CONCLUSIONS: Most HIV-infected patients treated with potent combination antiretrovirals develop responses to recall and presumed neoantigens after immunization. Functional immune restoration in response to immunization is related to control of viral replication, decreased immune activation as well as to both quantitative and qualitative restoration of circulating T- lymphocyte subpopulations.

AIDS-Related Opportunistic Infections↗
PubMed2000

Changes in human immunodeficiency virus type 1 virus load during mobilization and harvesting of hemopoietic progenitor cells. Adult AIDS Clinical Trials Group 285 Study Team.

Genetic modification of hemopoietic progenitor cells ex vivo, followed by the infusion of the genetically modified cells into the human immunodeficiency virus-1 (HIV-1) infected donor, has been proposed as a treatment for HIV-1 infection. The current study was undertaken to evaluate the effect of hemopoietic stem cell mobilization and harvesting on HIV-1 replication in persons with HIV-1 infection. Eighteen HIV-1-infected persons received recombinant granulocyte colony-stimulating factor (G-CSF; Filgrastim) 10 microg/kg per day, for 7 days. On days 4 and 5, peripheral blood mononuclear cells were harvested by leukapheresis. The CD4+ lymphocyte count at entry was >500/microL for 6 subjects, 200 to 500/microL for 6 subjects, and <200/microL for 6 subjects. For 9 of 18 subjects, plasma HIV-1 RNA levels increased 4- to 100-fold (>0.6 log(10)) above baseline between days 4 and 7 and returned to baseline by day 27. Significant increases of plasma HIV-1 RNA levels occurred in 5 subjects despite 3-drug antiretroviral therapy. Changes in CD4+ and CD34+ cells during mobilization and harvesting were similar in all subjects whether they had or did not have increased plasma HIV-1 RNA levels. Thus, mobilization and harvesting of bone marrow progenitor cells from persons infected with HIV-1 induced a transient increase in viral replication in some patients but was not associated with adverse effects. (Blood. 2000;95: 48-55)

Adult↗
PubMed2000

Evaluation of thymopoiesis using T cell receptor excision circles (TRECs): differential correlation between adult and pediatric TRECs and naïve phenotypes.

To determine whether the thymus is still functional despite age-related involution, we measured a biomarker for thymopoiesis known as the T cell receptor excision circle (TREC) from peripheral blood mononuclear cells (PBMCs) of 148 healthy children and from PBMCs, CD4(+), and CD8(+) cells of 32, 30, and 50 healthy adults, respectively. We demonstrate that during the first 5 years of life, thymic output is decreased (P 0.002) but not dramatically (r = -0. 282). Among adults aged 23-58, thymic output was inversely correlated with age, as measured from PBMCs (r = -0.628, P < 0.0005), CD4(+) (r = -0.530, P 0.003), and CD8(+) fractions (r = -0.385, P 0. 006). A strong correlation existed between pediatric PBMC TRECs and the expression of three naïve phenotypic markers (CD45RA(+)CD45RO(-), CD45RA(+)CD62L(+), and CD45RO(-)CD27(+)CD95(low)). Adult PBMC TRECs correlated only with the expression of CD45RA(+)CD45RO(-) (r = 0.459, P 0.012). Our data suggest that in adults CD45RA(+)CD45RO(-) may be enriched for TRECs and add to a growing body of evidence illustrating intact thymic function in adulthood.

Adolescent↗