PubMed Health⌕ Search

Biomedical subjects

C Poggi

Publications and source records attributed to C Poggi.

At least 19 recordsLinked to original sources

Predictors of plasma human immunodeficiency virus type 1 RNA control after discontinuation of highly active antiretroviral therapy initiated at acute infection combined with structured treatment interruptions and immune-based therapies.

Thirty patients with acute human immunodeficiency virus (HIV) type 1 infection received a combination of 3 antiretroviral drugs (n=15) or 4 antiretroviral drugs plus hydroxyurea and interleukin-2 (n=15) for 24 months, followed by 1-3 structured therapeutic interruptions (STIs). Viral control, defined as maintaining plasma viremia <5000 copies/mL without therapy, was achieved in 14 cases. Lymphocyte subsets, plasma HIV-1 RNA loads, proviral DNA loads in peripheral blood mononuclear cells (PBMCs), residual HIV-1 RNA loads in PBMCs and in lymph node cells, and anti-p24 lymphoproliferative response were measured. In the multivariate analysis, proviral DNA loads in PBMCs and anti-p24 lymphoproliferative response assessed at 24 months were independently correlated with viral control after STI. These results enabled us to define a subgroup of patients for whom safe discontinuation of therapy initiated at acute infection was suitable and contributed to ascertaining priority for biological parameter assessment in future clinical trials.

Adult↗

HIV-1 induction-maintenance at the lymph node level: the "Apollo-97" Study.

OBJECTIVE: To assess the effects of five-drug combination therapy on HIV-1 load in lymph nodes and subsequent maintenance with four and three drugs. METHODS: Ten pharmacotherapeutically naive patients received a combination of zidovudine, lamivudine, didanosine, ritonavir, and saquinavir for 24 weeks, then zidovudine, lamivudine, didanosine, and saquinavir for the next 24 weeks, and finally zidovudine, lamivudine, and saquinavir for the last 24 weeks. HIV-1 RNA in lymph nodes was measured using quantitative polymerase chain reaction (PCR) at baseline, after 12, 24, 48, and 78 weeks. Plasma HIV-1 RNA, proviral DNA in peripheral blood mononuclear cells (PBMCs), circulating lymphocyte subsets, and protease inhibitor levels in blood were also regularly measured. Genotypic resistance was assessed in the different compartments in 2 patients who were failed by therapy. RESULTS: HIV-1 RNA decreased in lymph nodes in 9 patients and was stable in 1 despite initial control of plasma replication <20 copies/ml in each patient. Lymph node levels rebounded in 1 patient at week 72 as a result of lack of adherence and remained stable in the 8 others despite maintenance regimens. This represents a mean drop of -3.17 log in lymph nodes for the 8 patients maintaining undetectable viremia at 72 weeks. In the patient with stable lymph node viral RNA, selection of the M184V mutation was demonstrated at this level before detection in plasma and low blood saquinavir levels were found throughout the study. Continuous improvements in immune parameters were observed in all cases, although PBMC proviral DNA levels either showed a continuous decrease or stabilized to a plateau. CONCLUSIONS: More complex regimens do not perform better in lymph nodes than classic triple therapy. The persistence of HIV-1 RNA in lymph nodes could be related with cellular resistance mechanisms rather than an insufficient potency of the regimens.

Adult↗

Pilot study of a combination of highly active antiretroviral therapy and cytokines to induce HIV-1 remission.

A pilot study of a combination of highly active antiretroviral therapy (HAART) and cytokines in early HIV-1 infection has been undertaken to test the hypothesis that HIV-1 remission can be reached with this strategy by flushing latently infected viral reservoirs. Ten previously antiretroviral naive patients have received a combination of zidovudine, lamivudine, didanosine, saquinavir, and ritonavir for 72 weeks. Between weeks 12 and 48, three courses of interleukin (IL)-2 (7.5 millions of international units [MUI] twice a day for 5 consecutive days) and 2 courses of gamma-interferon (IFN) (100 microg every other day during 2 weeks) were administered subcutaneously. All patients reached plasma HIV-1 RNA levels < 20 copies/ml within 12 +/- 4 weeks. Transient increases in plasma levels (< 120 copies/ml) were observed during administration of IL-2, but less frequently during gamma-IFN administration. HIV-1 RNA decreased in lymph node cells by approximately 4 log, then remained stable after week 24. A mean drop of -0.8 log in peripheral blood mononuclear cell (PBMC) proviral DNA was observed during the trial. Isolation of potentially infectious HIV-1 was successful in each case by coculture of CD4+ T cells taken at week 72. The 2 patients who stopped therapy at the end of the trial showed rebounding plasma HIV-1 RNA levels within a few weeks. No additional mutations were selected in comparison with those present at baseline in 8 patients. In addition, 2 patients developed new mutations in the reverse transcriptase or protease gene and in 1 case, resistance selection was found in lymphoid tissue HIV-1 RNA but not in latently infected cells. In all cases, a rapid increase in both naive and memory CD4+ T cells was observed, with a reduction in activation markers and preservation of the CD8+CD28+ subset. Consequently, an aggressive regimen of HAART and cytokines administered in early stage disease is associated with a positive effect in terms of proviral load reduction and immune reconstitution but is unable to induce HIV-1 remission, allowing low levels of viral replication to persist in lymphoid reservoirs.

Adult↗

Mitochondrial DNA sequence diversity in two groups of Italian Veneto speakers from Veneto.

Although frequencies of mitochondrial DNA (mtDNA) haplogroups in the different European populations are rather homogenous, there are a few European populations or linguistic isolates that show different mtDNA haplogroup distributions; examples are the Saami and Ladin speakers from the eastern Italian Alps. MtDNA sequence diversity was analysed from subjects from two villages in Veneto. The first, Posina, is situated in the Venetian Alps near Vicenza. The second, Barco di Pravisdomini is a village on the plains near Venice. In spite of their common Veneto dialect, the two group populations have not preserved a genetic homogeneity; particularly, they show differences in T and J haplogroups frequencies. MtDNA diversity in these two groups seems to depend more on their geographic situation.

Base Sequence↗

Impact of immune interventions on proviral HIV-1 DNA decay in patients receiving highly active antiretroviral therapy.

OBJECTIVE: To measure the evolution of proviral HIV-1 DNA levels in patients receiving highly active antiretroviral therapy (HAART) compared to those treated with HAART plus interleukin-2 (IL-2) and hydroxyurea. DESIGN: Prospective randomised trial. METHODS: Twenty-two HIV-1 infected patients were randomly assigned to a five-drug antiretroviral regimen for 72 weeks, with or without IL-2, followed by a three-drug regimen up to week 120 with additional hydroxyurea in patients having received IL-2. HIV-1 DNA levels in peripheral blood mononuclear cells (PBMC) were measured regularly using the Amplicor Monitor kit from Roche Diagnostics (Meylan, France). Potentially infectious HIV-1 was cultured in enhanced conditions from circulating CD4 T cells at week 120. RESULTS: During the study period of 120 weeks, HIV-1 DNA levels in PBMC decreased by -1.1 log in patients treated with HAART only compared with -1.8 log in patients with additional IL-2 and hydroxyurea. A two-phase decay rate was observed, with an inflexion point at 12 weeks. The second decay was slow, with mean half-lives of 130.1 +/- 21.3 weeks and 95.1 +/- 26.3 weeks for patients on HAART and those receiving additional IL-2 and hydroxyurea, respectively. At week 120, one out of 11 patients with HAART alone compared to six out of 11 in the group with IL-2 and hydroxyurea had undetectable proviral DNA levels and three of them had unsuccessful recovery of replication-competent HIV-1 from blood CD4 T cells. CONCLUSION: Therapeutic strategies combining HAART and immune interventions have higher potency to decrease the number of infected cells than HAART alone.

Adult↗

Phenotypic and genotypic resistance to nucleoside reverse transcriptase inhibitors in HIV-1 clinical isolates.

OBJECTIVE: To assess phenotypic and genotypic cross-resistance to nucleoside reverse transcriptase inhibitors in patients treated with a combination including zidovudine, who were switched to a combination including stavudine. METHODS: We analysed 24 clinical HIV-1 isolates from 12 patients before and several months after therapeutic switching. Plasma HIV-1 RNA was measured using quantitative polymerase chain reaction (Roche). Genotypic resistance was measured by sequencing the reverse transcriptase gene from plasma HIV-1 RNA. Phenotypic resistance was measured using a recombinant assay (Virco). RESULTS: Patients were treated with a combination including zidovudine for a mean (+/- SEM) period of 21.8 +/- 3.5 months and had a plasma viral load of 4.1 +/- 0.2 log HIV-1 RNA copies/mL (time 1). After a mean period of 19.3 +/- 1.6 months following the therapeutic change, the plasma viral load was 3.6 +/- 0.1 log copies/mL (time 2). At time 1, genotypic resistance to zidovudine was found in all cases (41L: four cases; 41L, 215Y: five cases; 41L, 210W, 215Y: two cases; K70R: one case) with a mean 6.6 +/- 1.6-fold increase in the median inhibitory concentration (IC50) to zidovudine and 1.7 +/- 0.4-fold to stavudine. At time 2, genotypic resistance to zidovudine was found in 11 out of 12 cases (41L: two cases; 41L, 215Y: six cases; 41L, 210W, 215Y: two cases; M41L, D67N, L210W, T215Y: one case) with a mean 18.9 +/- 8.8-fold increase in the IC50 to zidovudine and 1.4 +/- 0.4-fold to stavudine CONCLUSIONS: In this clinical series of patients with suboptimal control of plasma HIV-1 RNA using a combination including zidovudine, the presence of zidovudine-related mutations was associated with a decreased phenotypic sensitivity to this drug. Despite persistent HIV-1 replication, switching to stavudine was associated with a further decrease in phenotypic sensitivity to zidovudine but not to stavudine after 19 months. These data suggest that stavudine remains a possible option in zidovudine-experienced patients.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗