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Dominique Costagliola

Publications and source records attributed to Dominique Costagliola.

At least 37 records · Page 2Linked to original sources
PubMed2006

Comparison of dynamic treatment regimes via inverse probability weighting.

Appropriate analysis of observational data is our best chance to obtain answers to many questions that involve dynamic treatment regimes. This paper describes a simple method to compare dynamic treatment regimes by artificially censoring subjects and then using inverse probability weighting (IPW) to adjust for any selection bias introduced by the artificial censoring. The basic strategy can be summarized in four steps: 1) define two regimes of interest, 2) artificially censor individuals when they stop following one of the regimes of interest, 3) estimate inverse probability weights to adjust for the potential selection bias introduced by censoring in the previous step, 4) compare the survival of the uncensored individuals under each regime of interest by fitting an inverse probability weighted Cox proportional hazards model with the dichotomous regime indicator and the baseline confounders as covariates. In the absence of model misspecification, the method is valid provided data are available on all time-varying and baseline joint predictors of survival and regime discontinuation. We present an application of the method to compare the AIDS-free survival under two dynamic treatment regimes in a large prospective study of HIV-infected patients. The paper concludes by discussing the relative advantages and disadvantages of censoring/IPW versus g-estimation of nested structural models to compare dynamic regimes.

Acquired Immunodeficiency Syndrome↗
PubMed2006

[Non-AIDS-defining malignancies in HIV patients: clinical features and perspectives].

Eventhough the advent of highly active antiretroviral therapy (HAART) has dramatically improved patient outcome and provided a significant shrinking of the cases and severity of opportunistic infections, AIDS malignancies have become responsible of a new vexing challenge in HIV patient care and cure. Indeed, malignant tumors currently rank among the leading cause of morbidity and mortality in patients infected with HIV. In addition to the AIDS-malignancies, non-AIDS defining tumors have a higher incidence than the general population such as Hodgkin disease, lung cancer, cutaneaous cancer and anal cancer. These malignant tumors are generally characterized by a more aggressive behaviour at diagnosis and a poorer outcome compared with the same tumors in the general population. Although recent therapeutic advances have been made in chemotherapy, combinations with antiretroviral agents, for many of these malignancies the pronostic remains poor and there is a deeply lack of current therapeutic guidelines for these cancer patients care and cure. These recommendations might be the fruit of a new networking between HIV specialists and oncologists and of an improving knowledge of the pathogenesis and clinical features of these AIDS non-defining tumors.

Antiretroviral Therapy, Highly Active↗
PubMed2005

HIV infection in older patients in the HAART era.

An increasing number of patients over 50 years of age are now living with HIV, owing to highly active antiretroviral therapy (HAART) that prolongs survival on the one hand and to late diagnosis of patients living with occult HIV infection on the other hand. Most studies have shown that compared with younger patients, patients over 50 generally have a slower immunological response to HAART and experience more rapid clinical progression, despite a better virological response. Low thymic output probably plays a role in the poorer CD4 cell response in patients initiating HAART over 50 years. Management of HIV infection in older patients is particularly complex, mainly because they are more likely to have co-morbidities necessitating specific medications that may interact with antiretroviral drugs. More controlled studies of HAART efficacy and tolerability in such patients are needed to establish specific management guidelines. Information campaigns targeting older patients and their doctors are also needed to ensure timely diagnosis of HIV infection and antiretroviral treatment initiation.

Aging↗
PubMed2005

No benefit of a structured treatment interruption based on genotypic resistance in heavily pretreated HIV-infected patients.

OBJECTIVE: To evaluate the potential benefits of a tailored antiretroviral treatment interruption with duration based on the observed reversion of resistance mutations. METHODS: In this open single-arm pilot study, 23 patients with multiple treatment failure interrupted therapy and underwent longitudinal genotypic resistance testing. Salvage gigatherapy was started when resistance mutations to at least two antiretroviral drug classes reverted. The primary endpoint was a fall in viral load by > 1 log10 copies/ml after 12 weeks of salvage therapy. RESULTS: Baseline median viral load was 5.14 log copies/ml and CD4 cell count 43 x 10 cells/l. Genotypic resistance testing showed a median of six, two and nine resistance mutations to nucleoside analogue reverse transcriptase inhibitors, non-nucleoside analogue reverse transcriptase inhibitors and protease inhibitors, respectively; viral strains were susceptible to no more than one drug in 17/23 patients. The median duration of treatment interruption was 24 weeks (range, 12-37), leading to median changes from baseline of + 0.54 log10 copies/ml and -30 x 10(6) cells/l. At the end of treatment interruption, plasma HIV was susceptible to at least three drugs in 16/23 patients. After 12 weeks of salvage multitherapy, only one patient had a decrease in viral load > 1 log copies/ml. All baseline resistance mutations recurred after treatment resumption. AIDS-defining events occurred in two-thirds of patients during the study period. CONCLUSION: In HIV-infected patients with multiple failures and no therapeutic options at baseline, significant reversion of resistance mutations after prolonged treatment interruption failed to restore antiviral efficacy of a salvage regimen and was clinically deleterious.

Anti-HIV Agents↗
PubMed2005

Evaluation of a peer support group therapy for HIV-infected adolescents.

OBJECTIVE: To assess the effects of a peer support group therapy on HIV-infected adolescents. DESIGN: A prospective study of a cohort of HIV-infected adolescents participating or not participating in a psychodynamic oriented, emotional support group. METHODS: From a group of 30 perinatally HIV-infected adolescents who attended an outpatient clinic, 10 agreed to participate in the peer support group (group 1), 10 declined (group 2) and 10 others who lived too far from the clinic were not invited to participate (group 3). The three groups were compared at baseline and 2 years later using the outcome measures: perceived illness experience scale, perceived treatment inventory, self-esteem inventory. RESULTS: At baseline, the three groups had similar characteristics overall. The adolescents' self-esteem was in the normal range. After 2 years, worries about illness had decreased in group 1, whereas the scores had increased or remained the same for the other adolescents (P = 0.026). The adolescents in group 1 had less negative perception of treatment at 2 years than those in groups 2 and 3 (P = 0.030). After intervention, the percentage of adolescents with an undetectable viral load had increased in group 1 from 30 to 80% (P = 0.063) but was unchanged in groups 2 and 3. Considering the three groups altogether, the decrease in the viral load correlated with improvement of the perceived treatment inventory (Spearman R = 0.482 P = 0.015). CONCLUSIONS: : This pilot study suggests that a peer support group intervention is associated with an improvement in adolescents' emotional well being, and that this can have a positive influence on medical outcomes.

Adolescent↗
PubMed2005

Prevalence of drug-resistant HIV-1 variants in untreated individuals in Europe: implications for clinical management.

BACKGROUND: Infection with drug-resistant human immunodeficiency virus type 1 (HIV-1) can impair the response to combination therapy. Widespread transmission of drug-resistant variants has the disturbing potential of limiting future therapy options and affecting the efficacy of postexposure prophylaxis. METHODS: We determined the baseline rate of drug resistance in 2208 therapy-naive patients recently and chronically infected with HIV-1 from 19 European countries during 1996-2002. RESULTS: In Europe, 1 of 10 antiretroviral-naive patients carried viruses with > or = 1 drug-resistance mutation. Recently infected patients harbored resistant variants more often than did chronically infected patients (13.5% vs. 8.7%; P=.006). Non-B viruses (30%) less frequently carried resistance mutations than did subtype B viruses (4.8% vs. 12.9%; P<.01). Baseline resistance increased over time in newly diagnosed cases of non-B infection: from 2.0% (1/49) in 1996-1998 to 8.2% (16/194) in 2000-2001. CONCLUSIONS: Drug-resistant variants are frequently present in both recently and chronically infected therapy-naive patients. Drug-resistant variants are most commonly seen in patients infected with subtype B virus, probably because of longer exposure of these viruses to drugs. However, an increase in baseline resistance in non-B viruses is observed. These data argue for testing all drug-naive patients and are of relevance when guidelines for management of postexposure prophylaxis and first-line therapy are updated.

Adult↗
PubMed2005

High rate of recurrence of cervical intraepithelial neoplasia after surgery in HIV-positive women.

OBJECTIVE: Our study investigated the rate of recurrence of cervical intraepithelial neoplasia (CIN) in HIV-positive women after surgery in the era of highly active antiretroviral therapy (HAART). METHODS: One hundred twenty-one HIV-positive women were followed-up with cytology, colposcopy, and histology after surgery for CIN. We conducted univariate and multivariate analyses to determine the relation between recurrence of CIN and risk factors using Cox proportional hazard models with left truncation. RESULTS: The rate of recurrence of any CIN was 22.3 per 100 patient-years and the rate of high-grade CIN was 8.6 per 100 patient-years during 166 and 279 patient-years of follow-up, respectively. In multivariate analysis, a positive margin was associated with a risk of recurrence of any CIN (relative risk [RR] = 3.5, 95% confidence interval [CI]: 1.2-9.8) and a risk of recurrence of high-grade CIN (RR = 9.0, 95% CI: 2.2-36.5). CD4 counts <200 cells/mm were associated with a risk of recurrence of any CIN (RR = 9.4, 95% CI: 2.7-32.7) but not with a risk of recurrence of high-grade CIN. HAART exhibited a protective effect on the recurrence of any CIN (RR = 0.3, 95% CI: 0.1-0.7) and of high-grade CIN (RR = 0.2, 95% CI: 0.1-0.7). CONCLUSION: CD4 cell counts <200/mm(3) and a positive margin were predictors of recurrence, whereas HAART had a strong protective effect. Although surgery is highly effective in immunocompetent patients, it seems to be effective only in preventing progression to cancer in HIV-infected women.

Adult↗
PubMed2005

Therapeutic immunization with a human immunodeficiency virus (HIV) type 1-recombinant canarypox vaccine in chronically HIV-infected patients: The Vacciter Study (ANRS 094).

This open single-arm study evaluated whether the administration of an HIV-recombinant canarypox vaccine (vCP1433) in highly active antiretroviral therapy (HAART)-treated patients chronically infected with HIV was safe, immunogenic and associated with prolongation of treatment discontinuation: 48 patients received four monthly vCP1433 injections and stopped HAART. Immunization was safe. HIV-p24-specific lymphoproliferative responses (LPR), significantly increased in the whole group after two injections but decreased thereafter, HIV-gag-specific CD8 T cells were boosted in 55% patients tested. Altogether, 11% patients with at least one HIV-specific LPR during immunization remained off therapy after 44 weeks of interruption. Detection of such LPR response at the time of treatment interruption was significantly associated with the probability of remaining off therapy. These results provide rationale for future randomized trials exploring this strategy.

AIDS Vaccines↗
PubMed2005

Response to highly active antiretroviral therapy at 6 months and long-term disease progression in HIV-1 infection.

OBJECTIVE: To compare the long-term prognostic significance of different definitions of immunologic and virologic responses to highly active antiretroviral therapy (HAART) at 6 months. METHODS: This was a prospective study conducted in 68 French hospitals. HAART was initiated in 2236 protease inhibitor-naive patients included in the French Hospital Database on HIV. Multivariate Cox proportional hazard models measuring time from 6 months after starting HAART were used to compare the strength of the association between different definitions of immunologic and virologic responses at 6 months and subsequent progression to AIDS or death. The Akaike's Information Criteria were used to identify the most appropriate model. RESULTS: During a median follow-up of 58 months, 325 patients experienced an AIDS-defining event or died. The model that fitted best was the model in which the CD4 cell count and plasma HIV-1 RNA values attained at 6 months were considered. The risk of clinical progression at 5 years ranged from 7% (95% confidence interval [CI]: 4-10) in patients whose CD4 cell count at 6 months was >or=350 cells/microL and whose HIV-1 RNA concentration was <3 log10 copies/mL to 63% (95% CI: 52-75) in patients whose CD4 cell count at 6 months was <100 cells/microL and whose HIV-1 RNA concentration was >or=5 log10. CONCLUSIONS: Plasma HIV-1 RNA concentration and CD4 cell count should be taken into account independently when evaluating early response to treatment. The persistent impact of early response on clinical progression at 5 years emphasizes the major importance of the success of first-line HAART.

Antiretroviral Therapy, Highly Active↗
PubMed2005

Repertoire, diversity, and differentiation of specific CD8 T cells are associated with immune protection against human cytomegalovirus disease.

To determine the correlates of immune recovery from active human CMV (HCMV) disease, we compared the antigenic repertoire, diversity, magnitude, and differentiation of HCMV-specific CD8+ T cells in HIV-HCMV coinfected subjects with no, cured, or active HCMV disease and in healthy HIV-negative HCMV-positive controls. ELISPOT-IFN-gamma assays using peptide pools spanning the pp65 and immediate early 1 (IE1) HCMV proteins showed that HCMV-specific CD8+ T cells had a significantly broader antigenic repertoire and greater diversity in HIV-positive patients controlling HCMV replication than in those with active HCMV disease, but the magnitude of the CD8 T cell response did not differ between the different groups. HCMV-specific T cells mainly were focused against IE1 during the short-term recovery from retinitis, and switched toward pp65 during long-term recovery. HCMV-specific T cells displaying an "early" (CD8+CD27+CD28+) and "intermediate" (CD8+CD27-CD28+) differentiation phenotype were increased significantly during long-term recovery compared with other HIV-positive patients and were nearly undetectable during active HCMV disease. HCMV-specific T cells with a "late" (CD8+CD27-28-) differentiation phenotype predominated in all cases. Therefore, restoration of immune protection against HCMV after active HCMV disease in immunodeficient individuals is associated with enlarged repertoire and diversity, and with early differentiation of virus-specific CD8+ T cells, thus defining immune correlates of protection against diseases caused by persistent viruses.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Combination of HIV-1-specific CD4 Th1 cell responses and IgG2 antibodies is the best predictor for persistence of long-term nonprogression.

BACKGROUND: Strong T cell and antibody responses to human immunodeficiency virus (HIV), low virus production, and some genetic traits have been individually associated with nonprogression of HIV infection, but the best correlate with protection against disease progression remains unknown. METHODS: We prospectively followed 66 untreated long-term nonprogressors and analyzed relationships between HIV-1-specific CD4 T helper (Th) 1 and CD8 T cell responses and HIV-1-specific antibodies, HIV-1 RNA and proviral DNA loads, host genes, and CD4 Th1 cell counts at entry into the study and 4 years later. RESULTS: HIV-1 p24-specific CD4 Th1 cell proliferation, interferon (IFN)- gamma production, and IFN- gamma -producing cell frequencies at entry significantly and negatively correlated with HIV-1 RNA and proviral DNA loads and were independent of CD4 Th1 cell counts and host genes. HIV-1 Gag-specific IFN- gamma -producing CD8 T cell frequencies correlated with HIV-1 proviral DNA loads but not with RNA loads. Only high frequencies of HIV-1 p24-specific CD4 Th1 cells combined with HIV-1 gp41-specific IgG2 antibodies significantly predicted persistence of high CD4 Th1 cell counts. CONCLUSION: HIV-1-specific CD4 Th1 responses combined with IgG2 antibodies and IFN- gamma -producing CD4 Th1 cells are better predictors of long-term nonprogression than are virus parameters, host genes, or HIV-1-specific CD4 Th1 or CD8 T cell proliferation.

Adult↗
PubMed2005

French national sentinel survey of antiretroviral drug resistance in patients with HIV-1 primary infection and in antiretroviral-naive chronically infected patients in 2001-2002.

OBJECTIVE: To survey the frequency of genotypic antiretroviral resistance and the spread of non-B subtypes in patients with primary HIV-1 infection (2001-2002) and in treatment-naive chronically HIV-1-infected patients (2001). METHODS: Plasma samples from 303 patients with acute HIV-1 infection (Primo study) and 363 treatment-naive patients with chronic HIV-1 infection (Odyssee study) were tested for genotypic resistance. Resistance mutations were identified from the International AIDS Society Resistance Testing-USA panel and resistant viruses were defined according to the French Agence Nationale de Recherches sur le SIDA (ANRS) resistance algorithm. RESULTS: In the Primo study, 14% of the patients had viruses with resistance mutations and 12% of patients had viruses with mutations conferring resistance to least 1 antiretroviral drug. Thirty patients had viruses with mutations to at least 1 antiretroviral drug in a single pharmacologic class. Six patients were infected by viruses resistant to 2 or 3 classes of drugs. In the Odyssee study, the prevalence of reverse transcript (RT) associated and major protease inhibitor-associated mutations was 6.1% (95% CI: 3.6-8.6). Six patients had viruses resistant to at least 1 antiretroviral drug and 3 patients had viruses resistant to 2 classes of antiretroviral drugs. Twenty-four percent of acutely infected patients harbored non-B subtype strains (19% in 1999-2000) and 33.2% of chronically infected patients (10% in 1998; P < 0.0001). CONCLUSION: In France, the frequency of HIV-1 resistance in untreated patients was not significantly higher in 2001-2002 than in previous surveys while the prevalence of non-B subtypes is increasing.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Alterations of self-reactive antibody repertoires in HIV disease: an insight into the role of T cells in the selection of autoreactive B cells.

Infection with human immunodeficiency virus (HIV) is characterized by a progressive depletion of CD4(+) T cells that parallels a dysfunction of the B cell compartment and a disturbed recognition of self-antigens. The relationship between T lymphocyte homeostasis and abnormalities in the selection of self-reactive B cells is not clear as yet. We have therefore compared repertoires of natural antibodies of healthy donors and of patients at various stages of HIV infection. The reactivity of IgM and IgG antibodies in plasma of healthy blood donors and of HIV-positive patients with high and low CD4(+) T cell counts was assessed by semi-quantitative immunoblotting using self-antigens extracted from normal human tissues. Repertoires of reactivites were compared between groups of individuals by means of multiparametric statistical analysis. We observed that repertoires of self-reactive IgM and IgG from HIV-seropositive patients exhibited significantly altered patterns of reactivity, as compared to those of healthy controls. Further, self-reactive repertoires of IgM and IgG of patients with high CD4(+) T cell counts differed significantly from those of patients with low CD4(+) T cell counts. A longitudinal analysis of self-reactive antibody repertoires of progressor and non-progressor patients suggested an influence of CD4(+) T cell counts on immunoglobulin reactivity toward self-antigens. These observations support the hypothesis that altered T cell/B cell interactions due to altered CD4(+) T cell help severely impact on the selection of self-reactive antibody repertoires and may contribute to the onset of pathological autoimmunity in HIV disease.

Autoantibodies↗
PubMed2005

Prevalence of complete resistance to at least two classes of antiretroviral drugs in treated HIV-1-infected patients: a French nationwide study.

The objective of the study was to estimate the prevalence of HIV-1 resistance to all drugs belonging to two or more antiretroviral drug (ARV) classes in treated patients in France. All genotyping assays performed in June 2001 and in November 2002 by the ANRS resistance laboratory network were analyzed by the ANRS algorithm. The 17 and 21 centers of the ANRS network participating in the study in 2001 and 2002, respectively, genotyped the viruses in plasma of 456 and 529 patients, respectively. In 2002, the proportions of patients harboring viruses fully resistant to one, two, and three ARV classes were 5.1%, 8.1%, and 2.5%, respectively. These results were similar to those obtained in 2001. In 2002, among the 56 patients with viruses completely resistant to at least two ARV classes, 98%, 96%, and 29% of patients had viruses with complete class resistance to NRTIs, NNRTIs, and PIs, respectively. Complete resistance to PIs was less frequent than full resistance to the other two ARV classes, and ritonavir-boosted amprenavir and lopinavir/r remained potentially active in respectively 71.4% and 42.9% of these 56 patients. In 2001 and 2002, respectively 30% of the 65 patients and 24% of the 56 patients with viruses completely resistant to at least two ARV classes were at an advanced stage of HIV disease, with CD4(+) cell counts below 200/microl and viral loads above 30 000 copies/ml. In France, the prevalence of HIV-1 viruses completely resistant to two or more ARV classes remained stable between 2001 and 2002. Resistance to RT inhibitors was more frequent than resistance to PIs in patients with viruses completely resistant to two or three classes of ARV.

Adolescent↗
PubMed2005

Virological and pharmacological factors associated with virological response to salvage therapy after an 8-week of treatment interruption in a context of very advanced HIV disease (GigHAART ANRS 097).

Both highly potent antiretroviral drug rescue multi therapy and treatment interruption (TI) have been suggested to be effective in HIV-1 infected-patients with multiple treatment failure. GigHAART-ANRS 097 was the only randomized trial during which an 8-week TI was beneficial in heavily pre-treated patients with multi-drug resistant virus on resuming a multiple-drug salvage regimen. The aim of this study was to analyze virological and pharmacological factors associated with a virological response. Clonal resistance analysis showed that although the viral population was highly mutated and nearly monoclonal at baseline, the 8-week interruption therapy allowed the re-emergence of more susceptible quasispecies to the subsequent salvage therapy, which were not detected by classical genotypic resistance testing. The fact that not every viral clone harbored all resistance viral mutations could explain a part of the virological response to a six to eight drug regimen for patients enrolled in the TI group. This phenomenon was associated with a transient virological response after the use of a GigHAART therapy, but was followed by the re-emergence of baseline resistance pattern and acquisition of additional mutations in patients failing this strategy. A combined factor of protease inhibitor (PI) concentration and genotypic score, expressed as a genotypic inhibitory quotient (GIQ), was used to assess the importance of genotypic resistance and plasma drug levels in the rate of response to multiple PI combination. The GIQ of each PI used in the regimen was not associated with virological success. However, the sum of PI GIQs was predictive of a virological response. These results suggest that pharmacological enhancement might overcome viral resistance and that there is some benefit in adding the activity of several boosted-PIs to improve the response to a salvage regimen.

Anti-HIV Agents↗
PubMed2005

Liver disease as a major cause of death among HIV infected patients: role of hepatitis C and B viruses and alcohol.

BACKGROUND/AIMS: We analyzed the characteristics of HIV infected patients who died from liver disease, focusing on hepatitis virus co-infection. METHODS: One-hundred and eighty-five French hospital departments involved in HIV/AIDS management prospectively notified all deaths occurring in 2000. Patients whose hepatitis C (HCV) and hepatitis B (HBV) serostatus was known were classified as being infected by HCV alone, HBV alone (HBsAg positive), both HCV and HBV, or neither HCB nor HBV. RESULTS: Among 822 HIV infected patients, 29% were infected by HCV alone, 8% by HBV alone, and 4% by both HCV and HBV. The most frequent causes of death were liver disease (31% of cases) and AIDS (29%) among HIV-HCV co-infected patients, and AIDS (38%) and liver disease (22%) among HIV-HBV co-infected patients. Liver disease was a more frequent cause of death among patients co-infected by both HCV and HBV (44% of cases). Hepatocellular carcinoma was present in 15% of patients who died from liver disease, and was associated with HBV co-infection. Nearly half the patients who died from liver disease had more than 200 CD4/mm3. CONCLUSIONS: Liver disease is now a leading cause of death among HIV-HCV co-infected patients and is becoming an important cause of death among HIV-HBV co-infected patients. The risk of death from liver disease is highest in patients co-infected by both HCV and HBV.

Adult↗
PubMed2005

Opportunistic infections as causes of death in HIV-infected patients in the HAART era in France.

The objective of the study was to describe the underlying causes of death of HIV-infected patients in the HAART era and to focus on those related to opportunistic infection (OI), in a national multicentre study ('Mortalité 2000'). A total of 964 deaths were recorded and 924 cases were available for analysis. Underlying cause of death were AIDS-related (47%), viral hepatitis (11%), non-AIDS cancers (11%), cardiovascular diseases (7%) and others (11%). Among patients who died of AIDS events, 262 (27%) died of at least one OI. OIs reported at the time of death were Cytomegalovirus infection 67 times, Pneumocystis jiroveci pneumonia 56, disseminated Mycobacterium avium intracellulare infection 53 and cerebral toxoplasmosis 48. Compared to patients who died of other causes, patients who died of OIs were younger and more likely to be infected through heterosexual contact, in poor socioeconomic conditions, migrants, more recently diagnosed for HIV infection, and naive of antiretroviral therapy and OI prophylaxis. OIs are still a major cause of death in HIV-infected patient in the HAART era, especially among patients recently diagnosed for HIV infection and who do not have access to care, as well as in long term infected patients where prophylaxis should be revisited.

AIDS-Related Opportunistic Infections↗