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Biomedical subjects

A Lafeuillade

Publications and source records attributed to A Lafeuillade.

At least 37 records · Page 2Linked to original sources
PubMed1997

V delta 1 T cells expanded in the blood throughout HIV infection display a cytotoxic activity and are primed for TNF-alpha and IFN-gamma production but are not selected in lymph nodes.

We have previously reported significant alterations of gamma delta subset distribution in the peripheral blood of HIV-infected donors. These modifications are characterized by the depletion of the V delta 2 subset associated with a strong increase in peripheral V delta 1 T cells. In addition, the latter exhibit ex vivo an activated phenotype and show a restricted complementarity-determining region 3 (CDR3) repertoire. In the present report we first address the question of the origin of these expanded cells. The lack of expansion and the Gaussian complementarity-determining region 3 size distribution of lymph node V delta 1 T cells suggest that lymph nodes do not represent the site of specific activation of this subset. The function of blood V delta 1 T cells was also explored. We report that patients' V delta 1 T cells express high levels of perforin and display an in vitro cytotoxic activity, whose characteristics are different from those of NK and LAK cells. In addition, single cell analysis of cytokine production revealed that, in contrast to V delta 1 T cells from control donors, patients' V delta 1 T cells are primed in vivo for IFN-gamma and TNF-alpha production. Together, these results indicate that in the course of HIV infection, expanded blood V delta 1 T cells are differentiated into a functional subset and raise the question of the contribution of this subset to AIDS pathogenesis.

Cell Differentiation↗
PubMed1997

Effects of a combination of zidovudine, didanosine, and lamivudine on primary human immunodeficiency virus type 1 infection.

A combination of zidovudine, didanosine, and lamivudine was used to treat 10 patients with primary human immunodeficiency virus type 1 (HIV-1) infection 5-28 days after the onset of symptoms. When therapy began, the mean plasma HIV-1 RNA level was 5.31 +/- 0.33 log10 copies/mL and the mean CD4 T cell count was 630 +/- 112 x 10(6)/L. The plasma HIV-1 RNA level decreased rapidly, and levels dropped below the cutoff in each case after 108 +/- 32 days. Lymph nodes from 5 patients were biopsied before therapy and during follow-up. Infectious HIV-1 could not be cultivated from any lymph node mononuclear cells taken on day 90, and HIV-1 RNA was at very low levels in lymph nodes after 1 year. In some cases, waning of the antibody response to HIV-1 was shown by Western blot after several months of undetectable plasma RNA. These data demonstrate that triple-drug therapy has a potent antiviral effect during primary HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Human immunodeficiency virus type 1 dynamics in different lymphoid tissue compartments.

Human immunodeficiency virus type 1 (HIV-1) RNA was measured in total lymph node (LN) tissue and isolated LN mononuclear cells (LNMC) in sequential LN biopsy samples from 1 patient with primary HIV-1 infection and from 5 previously untreated patients with chronic disease. HIV-1 RNA levels were an average of 210-fold higher in total LN tissue compared with levels in LNMC, even during primary infection, when circulating antibodies were absent. After the patients were treated with a three- or four-drug regimen, total HIV-1 RNA decreased exponentially in total LN tissue and in LNMC (mean half-lives of 8.5 +/- 1.8 and 7.9 +/- 2.2 days, respectively). In addition, the evolution of the infectious virus in LNMC was analyzed for the 5 patients with chronic disease: Titers decreased, with a mean half-life of 7.5 +/- 2.3 days. Extracellular virions are the most important virus compartments in LNs; however, they exhibit the same dynamics as virions situated in LNMC, with a mean virus decay half-life of approximately 1 week.

Adult↗
PubMed1997

Lymph node expansion of CD4+ lymphocytes during antiretroviral therapy.

The evolution of lymphocyte subsets was analyzed in sequential lymph nodes (LN) biopsies and compared with that in the blood of 25 human immunodeficiency virus type 1 (HIV-1)-infected patients receiving highly active antiretroviral therapy. An average of 3 biopsies were obtained from each patient, with a mean follow-up of 5.6 +/- 0.6 months. A correlation was found between the CD4:CD8 ratio in blood and in LN at baseline but not after > or = 2 months of therapy. With therapy, there was a significant increase in CD2+ cells and a much higher CD4+ cell increase and CD8+ cell decrease in LNs compared with levels in blood. A subset of patients had increased expression of Ki-67 and a decreased expression of CD8CD38 or CD3HLA-DR. Expanded CD4+ cells in LNs were mainly CD45RO+, and changes were concomitant with a decrease in LN virus load. These data demonstrate that CD4 cell reconstitution in HIV-1 infection takes place primarily in secondary lymphoid organs and is not related to a simple redistribution of cells.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Antiretroviral effect of zidovudine-didanosine combination on blood and lymph nodes.

OBJECTIVE: To evaluate the antiretroviral effect of a combination of zidovudine (ZDV) and didanosine (ddl) on plasma, peripheral blood mononuclear cells (PBMC) and lymph nodes after 24 weeks. METHODS: Eight patients naive of antiretroviral therapy were followed by monthly blood samples and two surgical lymph-node biopsies taken at baseline and after 24 weeks. CD4+ T cells were counted monthly by flow cytometry. Plasma HIV-1 RNA was measured monthly by polymerase chain reaction (PCR). Infectious cellular viraemia was measured monthly by a culture technique. Proviral DNA titres in PBMC were measured by endpoint dilution PCR at baseline and 24 weeks. Infectious HIV-1 and proviral DNA titres were measured in the lymph-node mononuclear cells (LNMC). The total HIV-1 RNA content of lymph nodes was measured by PCR. In some cases, phenotypic resistance to ZDV was measured, and codon 215 and 74 mutations in PBMC and LNMC were analysed. RESULTS: A mean increase in CD4 cell count of 122 x 10(6)/l, a mean decrease in HIV-1 RNA of 1.47 log10 in plasma and a mean decrease in HIV-1 DNA titre of 0.63 log10 were found after 24 weeks of therapy. Nevertheless, there were no statistically significant changes in the mean infectious HIV-1 titre in PBMC and LNMC, in the HIV-1 DNA titre in LNMC or in the total lymph-node HIV-1 RNA burden at week 24. Phenotypic or genotypic markers of drug resistance were rarely found in PBMC at week 24, although they were detected in LNMC from some patients. CONCLUSION: A discrepancy in the therapeutic effect can be observed between lymphoid organs and blood after 24 weeks of therapy with ZDV and ddl. This difference could be explained by the insufficient antiretroviral potency of this combination facing the significant viral burden present in lymph nodes. Development of drug resistance in this compartment prior to blood can be demonstrated in some cases, although other mechanisms remain to be investigated in future studies to explain this difference.

Adult↗
PubMed1997

Quantification of HIV-1 viral load in lymphoid and blood cells: assessment during four-drug combination therapy.

OBJECTIVE: To assess the antiretroviral effect of a combination of zidovudine, didanosine, lamivudine and saquinavir in plasma, peripheral blood mononuclear cells (PBMC) and lymph-node mononuclear cells (LNMC) after 8 weeks. METHODS: Ten HIV-1 antiretroviral therapy-naive patients were given a combination of oral zidovudine (200 mg three times daily), oral didanosine (200 twice a day), oral lamivudine (150 mg twice a day) and oral saquinavir (600 mg three times daily). HIV-1 plasma RNA was measured by quantitative reverse transcriptase (RT)-polymerase chain reaction (PCR). Infectious HIV-1 in PBMC and LNMC was measured by a coculture technique. HIV-1 RNA in PBMC and LNMC was quantified by RT-PCR. Proviral DNA titres in PBMC and LNMC were measured by endpoint dilution PCR. CD4 T-cells were analysed by flow cytometry. RESULTS: CD4 cell counts rose in all patients (mean increase of 125 +/- 71 CD4 cells x 10(6)/l) and the benefit was greater for patients with fewer than 350 CD4 cells x 10(6)/l (mean increase of 159 +/- 74 CD4 cells x 10(6)/l). Plasma HIV-1 RNA decreased exponentially in all patients (mean decrease of 3.1 log10 after 8 weeks with a mean half-life of 2.2 +/- 0.6 days). HIV-1 RNA showed a decrease of 3.07 log10 in PBMC and of 2.1 log10 in LNMC. The decrease in plasma HIV-1 RNA was consistently associated with the decrease in LNMC. These data were supported by a concomitant drop of HIV-1 infectious titres in PBMC (mean decrease of 1.41 log10) and in LNMC (mean decrease of 2.54 log). CONCLUSIONS: These data show a significant antiretroviral effect of this four-drug combination in blood and lymphoid tissues. However, a greater decrease in HIV-1 RNA was observed in PBMC and in plasma than in lymph node cells.

Adult↗
PubMed1997

A pilot study of a combination of three reverse transcriptase inhibitors in HIV-1 infection.

The objective of this study was to evaluate the efficacy and tolerability of a combination of three reverse transcriptase inhibitors in patients with human immunodeficiency virus type 1 (HIV-1) infection. The investigation was an open pilot study of 48 weeks duration. Forty-five patients with CD4 cell counts between 50 and 500 cells/mm3 received a combination of oral zidovudine (200 mg three times daily) plus didanosine (200 mg twice daily) and lamivudine (150 mg twice daily). Plasma HIV-1 RNA and CD4 cell levels were measured weekly during the first month, at weeks 6, 8 and monthly thereafter. HIV-1 RNA levels were also measured sequentially in the lymph nodes of five patients after the initiation of therapy, and after several months of undetectable plasma RNA in 10 additional cases. Sequencing was performed on virus from the peripheral blood mononuclear cells of a subset of 14 patients after a mean period of 11+/-1 months on therapy. The mean (+/-SE) plasma viral load was 5.04+/-0.09 log10 copies/ml and the mean CD4 cell count was 339+/-14 cells/mm3 at baseline. Plasma HIV-1 RNA levels decreased exponentially in each case and became undetectable in 36 out of 42 cases who continued therapy for 24 weeks. HIV-1 RNA levels were < 20 copies/ml in 73% of these cases with undetectable HIV RNA. HIV-1 RNA decreased exponentially in lymph nodes after the initiation of therapy. The mean residual lymph node HIV-1 RNA level was 3.06+/-0.58 log10 copies/10(6) cells in 10 patients evaluated after several months of having undetectable plasma HIV RNA levels. A mean gain of 212 and 237 CD4 cells/mm3 was observed at 24 and 48 weeks, respectively. Proviral DNA sequencing showed that the main resistance codon mutations were absent in each case. Only one patient presented with a mutation resulting in the K219Q substitution, and one other with a T200I substitution. We conclude that this combination can achieve a significant decrease in HIV-1 replication in both plasma and lymph nodes in most cases. It is safe, able to delay the selection of resistant mutants, and keeps open the option for the use of protease inhibitors in case of therapeutic failure.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Assessment of a standardized reverse-transcriptase PCR assay for quantifying HIV-1 RNA in plasma and serum.

The analytical variability of the new commercially available Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) assay, Amplicor HIV-1 Monitor, has been assessed to establish criteria for assessing the significance of HIV-1 RNA level measurements. Estimations of the standard deviations (SD) of log-copies in inter-assay (mean 0.09 log) and in inter-laboratory (mean 0.14 log) reproducibility experiments demonstrated that the assay can discriminate with 95% confidence between 3-fold (inter-assay) and 5-fold differences (inter-laboratory). The inter-lot reproducibility (mean 0.10 log) was similar to the inter-assay reproducibility. The HIV-1 RNA concentrations measured in plasma collected in potassium EDTA anticoagulant were slightly higher than those measured in plasma collected in sodium citrate. The HIV-1 RNA concentrations measured in sera were about 50% of the HIV-1 RNA concentrations measured in paired plasma samples. However, there was a strong correlation between these two measurements (P < 0.0001). The assay was used to measure viral RNA in the plasma of 50 HIV-1 positive individuals at different stages of infection. All the individuals had detectable HIV-1 RNA (300-957000 copies/ml). There was no correlation between HIV-1 RNA and Immune Complex Dissociated (ICD) p24 antigen, but HIV-1 RNA was correlated with CD4+ cell counts (P < 0.0001) and the clinical stage (P = 0.0042), with higher HIV-1 RNA concentrations in patients with a more advanced stage of the disease. The significant association of HIV-1 RNA with major markers of HIV infection and the reliability of this sensitive, easy-to-use RT-PCR assay indicate its suitability for use in clinical trials and suggest that this assay is appropriate for routine clinical applications.

Adult↗
PubMed1996

Human immunodeficiency virus type 1 kinetics in lymph nodes compared with plasma.

As lymphoid organs are the major reservoir of human immunodeficiency virus type 1 (HIV-1), the rates at which HIV-1 RNA decreases from the plasma and from a series of lymph node biopsies from 4 patients treated with a combination of zidovudine, didanosine, and lamivudine were measured. The concentrations of HIV-1 RNA in the plasma and in lymph nodes declined exponentially, with mean half-lives of 1.88 +/- 0.86 days for plasma and 6.01 +/- 3.44 days for lymph nodes. These data show that most of the HIV-1 in lymphoid organs is due to the infection of new cells and demonstrate that a triple-drug combination is able to target this compartment.

Antiviral Agents↗
PubMed1996

Search for the presence of six Mycoplasma species in peripheral blood mononuclear cells of subjects seropositive and seronegative for human immunodeficiency virus.

The prevalence of Mycoplasma fermentans, Mycoplasma pirum, Mycoplasma genitalium, Mycoplasma pneumoniae, Mycoplasma hominis, and Mycoplasma penetrans was investigated by using specific PCR assays with peripheral blood mononuclear cells from subjects infected or not infected with the human immunodeficiency virus (HIV). Only M. fermentans was detected in 5.8% of 154 HIV-seropositive and 11.1% of 90 HIV-seronegative subjects.

AIDS-Related Opportunistic Infections↗
PubMed1995

Association of Mycoplasma penetrans with human immunodeficiency virus infection.

A cross-sectional study was done to determine the seroprevalence of Mycoplasma penetrans in human immunodeficiency virus (HIV) type 1-seropositive and -seronegative persons recruited in France. The data were analyzed with respect to the sociodemographic, clinical, and biologic status of the patients. M. penetrans seropositivity was associated with HIV infection (18.2% of HIV-seropositive vs. 1.3% of HIV-seronegative persons were M. penetrans-seropositive; P < .001). M. penetrans infection was predominantly but not exclusively associated with homosexual practices in HIV-seropositive subjects and thus presumably sexually transmitted. M. penetrans seroprevalence increased with progression of HIV-associated disease. No association was found between M. penetrans and Kaposi's sarcoma. Thus, there is an unambiguous association between M. penetrans and HIV, particularly among homosexual persons, but its clinical significance remains to be investigated.

AIDS-Related Opportunistic Infections↗