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Biomedical subjects

R Tubiana

Publications and source records attributed to R Tubiana.

At least 19 recordsLinked to original sources
PubMed2006

[Early detection of hepatitis C virus infection using a new combined antigen-antibody detection assay: potential use in HIV co-infected individuals].

BACKGROUND: The aim of this study was to determine the clinical benefit of a new combined antigen-antibody immunoenzymatic assay (Monolisa HCV Ag-Ab Ultra, Biorad) in the setting of acute HCV infection in HIV infected patients. PATIENTS AND METHODS: The performance of this assay was first evaluated in 160 HIV positive samples from uninfected and chronically HCV infected patients. To assess the performance of the Ag-Ab assay in the context of acute hepatitis C, 94 stored frozen serums from 20 recently diagnosed cases were retrospectively tested for HCV-RNA and presence of anti-HCV antibodies, in parallel with the new assay. RESULTS: In HIV infected patients, the sensitivity and specificity of the Ultra assay was 100% with a strong discrimination between positive and negative samples. In HCV acutely infected patients, the Ag-Ab assay significantly reduced the seronegative period, allowing an earlier diagnosis compared to a 3rd generation ELISA in 65% of the cases. The combined assay became positive on the same bleed as the first HCV-RNA detection for 13 patients out of 20. Nevertheless, in one case, characterized by an absence of seroconversion over one year but a continuous viral replication above 1 million IU/ml, the combined assay did not improve HCV infection diagnosis. CONCLUSION: Use of this new assay as a first line screening would significantly reduce the long seronegative window period seen in HCV infection allowing earlier HCV diagnosis and rapid clinical management. However, in case of clinical acute hepatitis C, sensitive HCV-RNA detection should remain the gold standard.

Antigen-Antibody Complex↗
PubMed2006

Early detection of hepatitis C virus infection by use of a new combined antigen-antibody detection assay: potential use for high-risk individuals.

The performance of a new combined antigen-antibody assay (Monolisa HCV Ag-Ab Ultra; Bio-Rad Laboratories) was evaluated in the context of acute hepatitis C in human immunodeficiency virus-infected patients. The combined assay became positive as early as the first PCR and earlier than a third-generation enzyme-linked immunosorbent assay in 65% of the cases. Reduction of the long period of HCV seronegativity should improve the diagnosis of hepatitis C infection, especially in high-risk populations.

Adult↗
PubMed2005

[HIV management in Africa].

Africa is the continent hardest hit by the HIV pandemic with, according to the WHO for 2004, more than 25 million people infected. Although the mortality and socioeconomic consequences of HIV infection have been visible and predictable, only since 2000 has the catastrophic situation in Africa and other developing areas mobilized international political and medical attention, in view of the impressive results from antiretroviral treatments where they are accessible. The intolerable lack of access to medical care and effective treatments has engendered a fusion of energy and will - political and scientific, local and international - to make HIV treatment available in Africa. Access to treatment must be accompanied by creation of national public health programs and establishment of infrastructures and trained teams. Necessary steps including anticipation and prevention of pitfalls in the large-scale use of antiretrovirals, long-term planning, organization of supplies and distribution, ensuring the permanence of financial support, and making appropriate strategic choices. These steps are required to guarantee the future and to prevent an epidemic rebound due to drug-resistant HIV strains. The conditions of international economic and medical aid have been clarified and are now better adapted to real needs. Nonetheless large disparities still exist according to country and region. The initial results of cohorts of treated patients show results similar to those in the industrialized countries and provide encouragement about the future. Results in countries such as Uganda and Senegal show that local political involvement is primordial for long-term success. Access to antiretroviral drugs is an urgent and essential marker of comprehensive management, but the conditions of their use must be taken into account in assessing future projects if we want to change the course of HIV in Africa.

Africa↗
PubMed2004

Acute hepatitis C in HIV-infected men who have sex with men.

BACKGROUND: Hepatitis C virus (HCV) is usually transmitted via the parenteral route, but there are widely discrepant findings on its possible sexual transmission. Thus there are no recommendations concerning protected sex for couples in which only one partner is HCV-infected. Whether HIV or other sexually transmitted diseases could favour HCV transmission remains unclear, but recent data suggesting an increasing incidence of acute HCV in HIV-infected men underline the major public health implications of this issue. CASE REPORTS: Between June 2002 and July 2003, five HIV-infected homosexually active men presented with primary (n=4) and secondary (n=1) syphilis and concomitant abnormal liver function tests revealing acute asymptomatic HCV seroconversion. Other causes of acute viral hepatitis were inquired into and excluded. Highly at-risk sexual behaviour, including unprotected anal intercourse and unsafe oral sex, with concomitant syphilis, was found to be the only identifiable important risk factor for transmission of HCV. CONCLUSIONS: Sexual transmission may be fuelling a significant increase in HCV seroconversions among HIV-infected men who have highly risky sexual behaviours. Given the recent data suggesting the spread of sexually transmitted infections among HIV-infected gay men, specific recommendations concerning safe sex are urgently needed.

Acute Disease↗
PubMed2003

[Lymph-node tuberculosis in patients infected or not with HIV: general characteristics, clinical presentation, microbiological diagnosis and treatment].

Lymph node tuberculosis is the most frequent form of extrapulmonary tuberculosis, especially in immunocompromised patients. We have studied patients with proven lymph node tuberculosis in the Department of Infectious Diseases at Pitié-Salpêtrière Hospital, Paris, between January 1997 and January 2002. Clinical presentation, microbiological diagnosis and treatment were analyzed in 13 HIV infected and 19 non-HIV infected patients. A risk factor for tuberculosis was present in all cases (HIV infection, immigration, life in community, poverty, past history of tuberculosis and IVDU). The median duration between the onset of symptoms and diagnosis was longer for HIV infected (2 months) compared with non-HIV infected patients (1 month). At the time of the diagnosis, general symptoms were present in >50% of patients of both groups. In HIV infected patients, abdominal lymph node involvement was more frequent (P < 0.05). All the non-HIV infected and 85% of HIV infected patients had peripheral adenopathies. A pulmonary tuberculosis was noted in more than half of the cases (53% non-HIV and 69% HIV patients). Inflammatory parameters and liver function tests were frequently abnormal in both groups. Hyponatremia was more frequent in HIV patients (P < 0.05). TB skin testing was more frequently positive and phlyctenular in non-HIV infected patients (P < 0.05). In this study, direct examination of the needle aspirate from infected lymph nodes was rarely positive; cultures were more frequently positive after biopsy compared to needle-aspiration. The median duration of treatment was 9 months for the two groups (6-24 months). Three HIV infected patients were infected by mycobacteria resistant to at least one antibiotic (isoniazid, 1; rifampicin, 1; isoniazid, streptomycin, etambutool, 1). All the patients recovered.

AIDS-Related Opportunistic Infections↗
PubMed2001

Re-occurrence of HIV-1 drug mutations after treatment re-initiation following interruption in patients with multiple treatment failure.

Antiretroviral treatment interruption in 20 extensively pre-treated HIV-1 patients with treatment failure led to genotype viral reversion of at least one class of drug-mutation resistance in half of the patients. The only predictive factor of reversion was found to be the duration of interruption. The outgrowth of residual wild-type virus seems not to be a true genetic reversion because drug mutations are detected rapidly at salvage therapy re-initiation.

Antiretroviral Therapy, Highly Active↗
PubMed2001

[Management of therapeutic failure in HIV-infected patients].

A COMMON SITUATION: Among HIV-infected patients treated with antiretroviral regimens, 20% to 50% escape therapeutic control. The principal factors predictive of treatment failure are low CD4 counts and high viral load prior to institution of the antiretroviral treatment. Several virological and pharmacological mechanisms are implicated. GENOTYPING AND PHENOTYPING: Genotyping is particularly useful to optimize treatment in HIV-infected patients who escape therapeutic control, irrespective of the therapeutic strategy. A committee of experts has developed a scheme for adapting treatment to the very complex results of genotyping tests. The benefit of phenotyping remains to be established. MANAGEMENT: Serum concentrations of antiretroviral agents should be determined and adapted in order to maximize the treatment effect. However, to manage therapeutic escape, the only method with a proven impact is genotyping. The possible usefulness of regular drug assays for adjusting treatment doses in case of therapeutic escape remains to be assessed in prospective trials.

Algorithms↗
PubMed2001

Discontinuation of maintenance therapy for cytomegalovirus retinitis in HIV-infected patients receiving highly active antiretroviral therapy.

OBJECTIVE: To study the safety of discontinuing cytomegalovirus (CMV) maintenance therapy among patients with cured CMV retinitis receiving highly active antiretroviral therapy (HAART). METHODS: Patients with a history of CMV retinitis who were receiving anti-CMV maintenance therapy and who had a CD4 cell count > 75 x 10(6) cells/l and a plasma HIV RNA level < 30000 copies/ml while on HAART were included in a multicentre prospective study. Maintenance therapy for CMV retinitis was discontinued at enrolment and all the patients were monitored for 48 weeks by ophthalmological examinations and by determination of CMV markers, CD4 cell counts and plasma HIV RNA levels. T helper-1 anti-CMV responses were assessed in a subgroup of patients. The primary study endpoint was recurrence of CMV disease. RESULTS: At entry, the 48 assessable patients had been taking HAART for a median of 18 months. The median CD4 cell count was 239 x 10(6) cells/l and the median HIV RNA load was 213 copies/ml. Over the 48 weeks, 2 of the 48 patients had a recurrence of CMV disease. The cumulative probability of CMV retinitis relapse was 2.2% at week 48 (95% confidence interval, 0.4-11.3) and that of all forms of CMV disease 4.2%. CMV blood markers remained negative throughout follow-up. The proportion of patients with CMV-specific CD4 T cell reactivity was 46% at baseline and 64% at week 48. CONCLUSIONS: CMV retinitis maintenance therapy may be safely discontinued in patients with CD4 cell counts above 75 x 10(6) cells/l who have been taking HAART for at least 18 months.

AIDS-Related Opportunistic Infections↗
PubMed2001

Transient mobilization of human immunodeficiency virus (HIV)-specific CD4 T-helper cells fails to control virus rebounds during intermittent antiretroviral therapy in chronic HIV type 1 infection.

Immune control of human immunodeficiency virus (HIV) is not restored by highly active antiretroviral therapies (HAART) during chronic infection. We examined the capacity of repeated structured therapeutic interruptions (STI) to restore HIV-specific CD4 and CD8 T-cell responses that controlled virus production. Eleven STI (median duration, 7 days; ranges, 4 to 24 days) were performed in three chronically HIV-infected patients with CD4 counts above 400/mm(3) and less than 200 HIV RNA copies/ml after 18 to 21 months of HAART; treatment resumed after 1 week or when virus became detectable. HIV-specific T-cell responses were analyzed by proliferation, gamma interferon (IFN-gamma) production, and enzyme-linked immunospot assays. Seven virus rebounds were observed (median, 4,712 HIV-1 RNA copies/ml) with a median of 7 days during which CD4 and CD8 counts did not significantly change. After treatment resumed, the viral load returned below 200 copies/ml within 3 weeks. Significant CD4 T-cell proliferation and IFN-gamma production against HIV p24 appeared simultaneously with or even before the virus rebounds in all patients. These CD4 responses lasted for less than 3 weeks and disappeared before therapeutic control of the virus had occurred. Increases in the numbers of HIV-specific CD8 T cells were delayed compared to changes in HIV-specific CD4 T-cell responses. No delay or increase in virus doubling time was observed after repeated STI. Iterative reexposure to HIV during short STI in chronically infected patients only transiently mobilized HIV-specific CD4 T1-helper cells, which might be rapidly altered by virus replication. Such kinetics might explain the failure at delaying subsequent virus rebounds and raises concerns about strategies based on STI to restore durable HIV-specific T-cell responses in chronic HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Dynamics of HIV-specific CD8+ T lymphocytes with changes in viral load.The RESTIM and COMET Study Groups.

The influence of HIV burden variations on the frequencies of Ag-specific CD8+ T cell responses was evaluated before and during highly active antiretroviral therapy by analyzing the number, diversity, and function of these cells. The frequencies of HLA-A2-restricted CD8+ PBL binding HLA-A2/HIV-epitope tetramers or producing IFN-gamma were below 1%. A panel of 16 CTL epitopes covering 15 HLA class I molecules in 14 patients allowed us to test 3.8 epitopes/patient and to detect 2.2 +/- 1.8 HIV epitope-specific CD8+ subsets per patient with a median frequency of 0.24% (0.11-4. 79%). During the first month of treatment, viral load rapidly decreased and frequencies of HIV-specific CD8 PBL tripled, eight new HIV specificities appeared of 11 undetectable at entry, while CMV-specific CD8+ PBL also appeared. With efficient HIV load control, all HIV specificities decayed involving a reduction of the CD8+CD27+CD11ahigh HIV-specific effector subset. Virus rebounds triggered by scheduled drug interruptions or transient therapeutic failures induced four patterns of epitope-specific CD8+ lymphocyte dynamics, i.e., peaks or disappearance of preexisting specificities, emergence of new specificities, or lack of changes. The HIV load rebounds mobilized both effector/memory HIV- and CMV-specific CD8+ lymphocytes. Therefore, frequencies of virus-specific CD8 T cells appear to be positively correlated to HIV production in most cases during highly active antiretroviral therapy, but an inverse correlation can also be observed with rapid virus changes that might involve redistribution, sequestration, or expansion of these Ag-specific CD8 T cells. Future strategies of therapeutic interruptions should take into account these various HIV-specific cell dynamics during HIV rebounds.

Amino Acid Sequence↗
PubMed2000

Phase II placebo-controlled trial of fozivudine tidoxil for HIV infection: pharmacokinetics, tolerability, and efficacy.

Fozivudine tidoxil (FZD) is a thioether lipid-zidovudine (ZDV) conjugate with anti-HIV activity demonstrated in vitro and in pilot phase I studies. To assess its safety, efficacy and pharmacokinetics, we conducted a multicenter, randomized, double-blind, placebo-controlled trial of FZD monotherapy in 72 HIV-infected patients who had not previously received antiretroviral therapy. In each dosage group (200 mg daily, 400 mg daily, 200 mg twice daily, 800 mg daily, 400 mg twice daily, and 600 mg twice daily), 12 patients were randomized to receive in a 10:2 ratio either FZD or a placebo for 4 weeks. Overall, FZD was well tolerated in all dosage groups; only 1 patient discontinued the drug, because of a moderate rise in aminotransaminase activity. HIV viral load fell in all the patients who were receiving FZD, except in the 200 mg daily group. The largest decrease (-0.67 log10) was observed in the 600 mg twice daily group. The plasma half-life was significantly longer (approximately 3.8 hours) than that of the parent drug ZDV. Exposure to ZDV, as reflected by the area under the time-concentration curve, was much lower after FZD than after ZDV administration. FZD thus appears to be as effective as and potentially better tolerated than ZDV during short-term administration and has the advantage of once daily intake.

Adult↗
PubMed2000

CD4+Ki67+ lymphocytes in HIV-infected patients are effector T cells accumulated in the G1 phase of the cell cycle.

Entry into the cell cycle represents a fundamental step before generating an effector immune response. The relationship between the cell cycle and antigen-driven T cell response remains, however, poorly understood in virus infection, including HIV. We have identified a critical fraction of CD4+CD45RO+ memory T lymphocytes that express the Ki67 antigen in chronically HIV-infected patients. A high accumulation of Ki67 protein is detected in CD4+CD45RO+Ki67+ cells that are in the G1 phase of the cell cycle (92 ¿ 5 %) but not in S and G2 + M phases, in contrast to normal individuals. Of these cells, 20 - 60 % are spontaneously producing IL-2 and IFN-, unlike CD4+CD45RO+ that do not express Ki67. In addition, HIV-p24 antigen is detectable only in a small fraction CD4+Ki67+ cells. In conclusion, CD4+Ki67+ lymphocytes are circulating effector cells accumulated in the G1 phase of the cell cycle and may be involved in the immune surveillance during HIV infection.

Antiretroviral Therapy, Highly Active↗
PubMed2000

[Classification of finger deformities due to muscle-tendon imbalance].

We have developed a 4 stages classification comprising: purely dynamic imbalance (Stage 1); tenodesis effect (Stage 2); articular rigidity without cartilage lesion (Stage 3); articular rigidity with bone and cartilage destruction (Stage 4). This classification is easy to remember and general enough to be used for most deformities due to musculo-tendinous imbalance, whatever their type or etiology. We believe that this assessment will help to clarify the therapeutic indications and allow better interpretation of the results.

Biomechanical Phenomena↗
PubMed1999

Determinants of paradoxical CD4 cell reconstitution after protease inhibitor-containing antiretroviral regimen.

OBJECTIVES: We evaluated the parameters influencing CD4 cell reconstitution after the introduction of highly active antiretroviral therapies in real life, as well as the frequency and the determinants of the discrepancies occurring between virus and CD4 cell count evolution. DESIGN AND METHODS: A total of 317 pre-treated patients starting a protease inhibitor (PI)-containing regimen were prospectively followed for 2 years on an intent-to-treat basis for CD4 cell counts and viral loads. RESULTS: The CD4 cell counts rapidly increased from baseline (50/mm3) by a median of 50/mm3 at month 2 (+0.72 CD4 cells/mm3/day) and up to 137/mm3 at the last follow-up (second slope: +0.16 CD4 cells/mm3/day). Two independent major factors among five parameters tested significantly affected the first phase, which was negatively correlated to the slope of CD4 cell decline before PI initiation, and was positively correlated to baseline CD4 cell counts (P = 0.0001); the second phase was mostly affected by the mean viral load reduction over time (P = 0.0001). Paradoxical CD4 cell reconstitution (15% of cases) was defined by a rapid or slow CD4 cell increase contrasting with a minor or strong viral reduction, respectively. The role of previous CD4 cell decline and the low effect of viral load reduction during the first 2 months explain the early paradoxical CD4 cell responses. The major influence of viral load reduction on the long-term reconstitution, however, reduces such paradoxical responses at 2 years. CONCLUSIONS: Early paradoxical CD4 cell reconstitution after the introduction of a PI are explained by the major influence of previous disease progression on the early CD4 cell increase, whereas the magnitude of viral load reduction over time reduces such paradoxical evolutions in the long term.

Adult↗
PubMed1999

HIV-1 rebound during interruption of highly active antiretroviral therapy has no deleterious effect on reinitiated treatment. Comet Study Group.

BACKGROUND: Potent antiretroviral therapy (ART) with a protease inhibitor-based regimen is commonly used to treat HIV-1-infected patients. Transient treatment interruptions because of drug intolerance or other reasons are not uncommon. HIV-1 dynamics during therapy interruption and its consequences for the subsequent reinitiation of therapy have not been properly studied. METHODS: Ten antiretroviral-naive, HIV-1-infected subjects (mean baseline CD4 cell count of 414 cells/mm3 and plasma viral load of 4.8 log10 copies/ml) were treated with the triple drug ART regimen indinavir/zidovudine/lamivudine for 28 days. Therapy was then interrupted for 28 days, after which the same ART regimen was re-started. RESULTS: HIV-1 in plasma declined during the first 7 days of therapy with T1/2 of 1.5 days, and during days 7-28 with T1/2 of 8.9 days. Once therapy was interrupted, a delay of 4-7 days was observed in all subjects, preceding a rapid viral rebound with a mean doubling time of 1.6 days. Mean viral load after 28 days of interruption was 96% of baseline. Upon reinitiation of the same ART regimen, viral load declined at rates similar to those observed during the initial therapy (T1/2 of 1.6 and 8.0 days, respectively). No resistance-conferring mutations were observed in the HIV-1 reverse transcriptase (RT) and protease regions after the interruption of therapy. Plasma viral loads were maintained below 200 copies/ml in subjects continuing therapy for 4 (n = 9) to 12 (n = 5) months, with a mean CD4 cell count increase of 145 cells/mm3. CONCLUSIONS: The reintroduction of efficient ART therapy after a 1 month interruption shows viral kinetics similar to that of naive patients, and is not associated with the development of resistance. No deleterious effect on the reinitiated therapy was observed in patients who temporarily discontinued ART therapy. Nevertheless, because viral load rebounds back to baseline during treatment interruption, viral suppression is in effect put off by that period of time.

Anti-HIV Agents↗
PubMed1999

[Immunologic reconstruction after antiretroviral treatment].

DATA FAVORING IMMUNE RECONSTITUTION: Multiple drug therapies for HIV infection have enabled a major reduction in the viral load, higher CD4 counts, and a lower incidence of opportunistic infections and tumor formations, and subsequently lower hospitalization rates and mortality. TWO STAGES OF CD4 RECONSTITUTION: In HIV-positive patients with advanced stage disease treated with a protease inhibitor associated with 2 nucleoside analog reverse transcriptase inhibitors and followed prospectively, it has been observed that CD4 counts rise considerably, with a rapid increase during the first 2 months followed by a slower but still positive slope over a period of 18 months. Discordant results have however also been observed suggesting an ineffective anti-viral effect or a retarded immune reconstitution. SEVERAL MECHANISMS: The lymphocyte amplification observed during the early phase corresponds to re-circulation of CD4 and CD8 lymphocytes which had been sequestered in lymphoid organs; most of these CD4 lymphocytes are memory cells. A second phase corresponds to a more moderate and progressive rise in naive CD4 cells which originate from an unknown source. This biphasic reconstitution of CD4 lymphocytes is associated with a correction of the chronic lymphocyte overactivation. PARTIAL IMMUNE RECONSTITUTION: With treatment, the capacity to respond to known antigens reappears. This restored capacity is secondary to the amplification of CD4 memory cells and appears prior to the expansion phase of naive cells. The response remains moderate and is only observed against antigens from microorganisms highly prevalent during advanced stage infection.

Antiviral Agents↗