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N Profizi

Publications and source records attributed to N Profizi.

At least 19 recordsLinked to original sources
PubMed1999

Long-term evaluation of triple nucleoside therapy administered from primary HIV-1 infection.

OBJECTIVE: To study the long-term effect of triple-drug therapy initiated at the time of primary HIV-1 Infection and to evaluate the persistance of replication-competent virus in responding patients. METHODS: Prospective open-label pilot study. Patients received a combination of zidovudine, didanosine and lamivudine. Viral sequencing of the reverse transcriptase gene was performed before therapy and during follow-up. HIV-1 RNA and DNA as well as CD4 and CD8 T lymphocyte subsets were measured in blood and in lymph node biopsies during therapy. Isolated blood CD4 T cells were cultured in conditions that improved HIV isolation. Three patients received in vivo interleukin-2 and gamma-interferon in order to try to identify intracellular pools of replication-competent virus. SETTING: A tertiary care general hospital. PATIENTS: Fifteen patients observed within 28 days following the acute retroviral syndrome. RESULTS: After a mean follow-up of 27.5+/-2.9 months, plasma RNA remained < 20 copies/ml (four patients), fluctuated between 20 and 120 copies/ml (six patients) or rebounded (five patients). M184V and/or T215Y mutations were demonstrated in two of these last five patients. Proviral DNA in peripheral blood mononuclear cells (PBMC) decreased by an average of -1 log after 16+/-3 months, reaching undetectable levels in three patients. The culture of isolated CD4 T cells yielded virus in all but two patients. These last were characterized by a waning antibody reactivity on the Western blot, undetectable proviral DNA in PBMC and undetectable RNA in lymph nodes. Cytokine administration in vivo had no effect in one patient and unmasked plasma RNA in the other. Stopping therapy in the first patient led to a rebound in plasma RNA. CONCLUSION: Despite a lack of detectable plasma viral activity in some patients after 3 years of triple nucleoside therapy administered since the acute retroviral syndrome, replication-competent virus can still be demonstrated.

Adult↗
PubMed1998

Residual human immunodeficiency virus type 1 RNA in lymphoid tissue of patients with sustained plasma RNA of <200 copies/mL.

Human immunodeficiency virus type 1 (HIV-1) RNA was measured in lymph node (LN) mononuclear cells of 50 patients with sustained plasma RNA of <200 copies/mL with therapy. Six patients had received a combination of three reverse transcriptase inhibitors (RTIs) since primary infection, 11 received this same combination during chronic disease, 21 received a combination of two RTIs plus a protease inhibitor (PI), and 12 received three RTIs plus a PI. The mean overall duration of therapy was 8.9 +/- 0.5 months (range, 5-24), with no significant difference between groups. LN HIV-1 RNA levels varied from undetectable to 1.7 million copies/10(6) cells according to cases. The mean LN HIV-1 RNA level was 2.99 +/- 0.42 log10 copies/10(6) cells in the 17 patients receiving three RTIs compared with 1.93 +/- 0.25 log10 copies/10(6) cells in the 33 patients receiving a PI (t test, P = .02). These data demonstrate that highly active antiretroviral regimens have unequivalent effects on LNs and invite redefinition of suboptimal therapy at this level.

Adult↗
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

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↗
PubMedDate not supplied

Quantitative molecular monitoring of HIV-1 RNA during antiretroviral therapy.

Plasma HIV-1 RNA testing was used to monitor 43 HIV-1 infected patients newly placed on antiretroviral therapy or whose therapy had been recently changed. A polymerase chain reaction kit was used to measure HIV-1 RNA in clinical samples or frozen plasma. The cutoff of this test was 200 RNA copies/ml. The first group (11 patients) was stable on long-term zidovudine monotherapy when switched to stavudine. The HIV-1 RNA of three patients who had a regular decline in CD4+ T cell count did not change despite this switch, with a mean follow-up of 630 days. The HIV-1 RNA copy numbers of eight patients whose CD4+ T cell counts were stable declined an average of 0.53 log10 between days 90 and 650. The second group (14 patients) was on long-term zidovudine monotherapy and had declining CD4+ T cell counts over the past 6 months. Lamivudine was added to this regimen on day 0. HIV-1 RNA copy number decreased rapidly within 30 d, reaching -0.86 log10 on day 90, and this effect was maintained thereafter, with a mean follow-up of 161 days. There was a concomitant mean gain of +33 CD4+ T cells on day 90. The third group (nine patients) had never received anti-retroviral therapy and was given zidovudine+didanosine. HIV-1 RNA copy number decreased in all cases but one, reaching -1.31 log10 on day 150. This decrease was transient in three cases. The last group (nine patients) had also not had previous anti-retroviral therapy and was given zidovudine + didanosine + lamivudine in combination. HIV-1 RNA copy numbers declined rapidly in all cases, to below the cutoff in eight cases within a mean period of 50.5 days. The CD4+ cell counts increased by 164 cells/microliter on day 14 and by 201 cells/microliter on day 180. The response to therapy of the total population of 43 patients varied according to cases. The relative changes in p24 antigen compared to HIV-1 RNA also differed between patients. Measurement of HIV-1 viremia appears to be a valuable tool in current practice for individualizing therapy.

Adult↗
PubMedDate not supplied

HIV-1 replication in the plasma and cerebrospinal fluid.

The HIV-1 RNA in plasma and CSF samples from 40 HIV-1 infected patients was measured by a polymerase chain reaction (PCR) technique. The possible implication of cytokines in HIV-1 replication was investigated by measuring the concentrations of tumor necrosis factor alpha (TNF-alpha), macrophage colony stimulation factor (M-CSF) and interleukin-6 (IL-6) in these fluids. HIV-1 RNA was quantified in all plasma samples and in 87.5% of the CSF samples. CSF HIV-1 RNA titers did not correlate with the stage of disease or the CD4+ T cell counts, unlike the plasma HIV-1 RNA titers. These results were confirmed when patients with a blood brain barrier damage, as assessed by the CSF/ plasma albumin ratio, were excluded from the analysis. TNF-alpha levels were statistically correlated with the HIV-1 RNA in plasma and CSF. These data demonstrate that HIV-1 replication in the CSF at each clinical stage can be accurately measured with PCR and, although the titers of HIV-1 RNA copies in the CSF are correlated with those in the plasma, the magnitude of HIV-1 replication in CSF is not directly linked to the stage of disease, or to the CD4+ T cell count. The significance of early high levels of HIV-1 RNA in CSF is now being studied prospectively.

Adult↗
PubMedDate not supplied

Role of autoimmunity in protein S deficiency during HIV-1 infection.

The objective of the study was to evaluate the role of autoimmune mechanisms in the pathophysiology of protein S deficiency during HIV-1 infection. In a prospective study the correlation between protein S activity and the presence of anti-protein S autoantibodies or anti-cardiolipin antibodies in HIV-1-positive patients and in a population of patients without HIV infection was investigated. Fifty-five HIV-1-infected patients and 15 hospitalized patients without HIV infection were analysed for protein S activity (functional assay), complement system activation, presence of autoantibodies against protein S (Dot Immunobinding) and levels of anti-cardiolipin IgG antibodies (ELISA). The presence of anti-protein S antibodies was detected in 31 (56.36%) out of the 55 HIV-1-positive patients and in three (20%) of the 15 control patients (Fisher's exact test, p = 0.012). The average value (+/- standard deviation) of protein S activity was 100.93 (14.73)% in the control group. For the HIV-1-infected patients it was 73.70 (20.67)% in those with anti-protein S antibodies compared to 88.08 (25.48)% in those without (Mann-Whitney U Test, p = 0.01). In the HIV-1-positive group protein S activity was correlated with concentrations of circulating immune complexes (Spearman rank sum test, r = -0.41, p = 0.018) and in the control group with concentrations of anti-cardiolipin antibodies (Spearman rank sum test, r = 0.709, p = 0.032). In conclusion, HIV-1 infection is associated with a high prevalence of antibodies against protein S. These antibodies are associated with a significantly low protein S activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗