Jean-Paul Moatti

Randomized Trial of Bone Marrow Versus Lenograstim-Primed Blood Cell Allogeneic Transplantation in Patients With Early-Stage Leukemia: A Report From the Société Française de Greffe de Moelle

PURPOSE To compare hematologic recovery in patients receiving allogeneic blood cell transplantation (BCT) with those receiving allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS One hundred eleven patients with leukemia in the early stages and with HLA-matched sibling donors were randomized in this study. One hundred one underwent transplantation. Standard procedures for collection and transplantation were used. Patients did not receive prophylactic granulocyte colony-stimulating factor after undergoing transplantation. In addition to clinical end points being established, a prospective and comparative economic evaluation of the first 6 months after transplantation was performed. RESULTS Groups were balanced for patient, donor, and transplant characteristics. Blood cell collection led to the collection of a higher number of CD34(+) and CD3(+) cells than did bone marrow collection (P < 10(-6)) without reported side effects for the donor. Patients in the BCT group reached platelet counts of 25 and 50 x 10(9) platelets/L 8 and 11 days earlier than did the BMT group (P < 10(-4) and P < 10(-5)), respectively. This resulted in fewer platelet transfusions during the first 180 days after transplantation (P =.002) for the former group. The time to reach neutrophil counts of 0.5 and 1 x 10(9) neutrophils/L was 6 and 7 days shorter, respectively, in the BCT group than in the BMT group (P < 10(-5)). This quicker hematologic recovery was associated with a shorter length of hospitalization and a decrease in total cost of procedure during the first 6 months. CONCLUSION This study establishes that allogeneic BCT results in quicker hematologic recovery but is associated with a higher occurrence of chronic graft-versus-host disease.

Failure to maintain long-term adherence to highly active antiretroviral therapy: the role of lipodystrophy

In a sample of 277 patients included in the French APROCO cohort study who were initially adherent at follow-up visit 4 months after initiation of a protease inhibitor-containing regimen, 76.4% self-reported at least one lipodystrophy-related symptom and 30.0% failed to maintain adherence behaviour 20 months after enrolment. After multiple adjustment for other related factors, such as younger age, alcohol consumption and poor housing conditions, the number of self-reported lipodystrophy symptoms was independently associated with adherence failure.

Adherence to HAART in French HIV-infected injecting drug users : The contribution of buprenorphine drug maintenance treatment

ObjectivesTo assess adherence to highly active antiretroviral therapies (HAART) in a cohort of French patients infected by HIV through injection drug use (IDU), and the impact on adherence of buprenorphine ambulatory drug maintenance treatment (DMT) which has been widely introduced since 1996. DesignAdherence assessment at first visit after initiation of HAART in the MANIF2000 cohort study. MethodsPatients face-to-face and self-administered questionnaires. Univariate and logistic regression adjusted odds ratios (OR) to compare characteristics of non-adherent versus adherent patients. ResultsOf the 164 patients, 34.8% took less than 80% of the prescribed HAART doses during the previous week. Decrease in viral load titres after initiation of HAART was significantly lower among non-adherent patients. After adjustment by logistic regression, non-adherence was associated with younger age, alcohol consumption, frequency of negative life-events during the prior 6 months and active drug use. However, IDU in buprenorphine DMT reached higher levels of adherence (78.1%) than ex-IDU (65.5%), although this difference did not reach statistical significance. ConclusionPrescription of buprenorphine DMT may increase adherence to HAART among HIV-infected opiate-dependent patients. Reducing the negative impact of stressful life-events through psychosocial interventions should be considered, even for those who have stopped using drugs.

Self-Reported Symptoms After Initiation of a Protease Inhibitor in HIV-Infected Patients and Their Impact on Adherence to HAART

Abstract Purpose: The purpose of our study was to assess short-term self-reported symptoms in patients who were started on two nucleoside reverse transcriptase inhibitors and one protease inhibitor (PI) in the multicenter APROCO cohort (N = 336) and to assess the influence of these symptoms on adherence. Method: Adherence and patient’s reported symptoms were measured at 1 and 4 months (M) after initiation of highly active antiretroviral therapy (HAART) through self-administered questionnaires. Results: Most patients reported at least one symptom (94.0% at M1; 88.0% at M4); fatigue and diarrhea were the most often reported symptoms. Respectively, 81.3% and 75.0% of patients were strictly adherent to HAART during the 4 days prior to M1 and M4 visits. After adjustment for younger age, history of antiretroviral treatment, unstable housing, poor social support, and alcohol consumption, patients who reported a high number of symptoms at M1 were more likely to be nonadherent at M4 (odds ratio per symptom = 1.13; 95% CI = 1.03-1.24). Conclusion: Patients reporting a high number of symptoms soon after HAART initiation are at higher risk of future nonadherence and could be targeted for interventions to achieve good levels of adherence and to improve treatment outcome.

The dynamic of Adherence to highly active antiretroviral therapy : Results from the French National APROCO cohort

Objectives: Our objective was to describe the evolution of adherence to highly active antiretroviral therapy (HAART) over a 20‐month period and its relationship with virologic success. Methods: Self‐reported adherence, clinical, and virologic data were collected 4 (M4), 12 (M12), and 20 (M20) months after initiation of a protease inhibitorcontaining regimen in the French APROCO cohort. At each visit, patients were classified as nonadherent, moderately, or highly adherent, and HIV plasma RNA was determined. Results: Among the 762 patients who were regularly followed until M20, the 436 patients who answered to all questionnaires, including adherence measurement, were selected for the analysis. The proportion of highly adherent patients was 55.7%, 62.2%, and 60.3% at M4, M12, and M20, respectively. A total of 137 patients (31.4%) was “always,” 225 (51.6%) “sometimes,” and 74 (17.0%) “never” “highly adherent” during follow‐up. After multiple adjustment for known baseline predictors, virologic success after 20 months of HAART was more likely achieved in patients who were always (odds ratio [OR] 95% confidence interval [CI], 3.02 [1.64‐5.58]) or sometimes (OR [95% CI], 2.15 [1.24‐3.74]) “highly adherent.” Conclusion: Adherence behavior is a dynamic process. Continued adherence was associated with better response to therapy and should be encouraged to reduce the risk of virologic failure.

Predictors of virological rebound in HIV-1-infected patients initiating a protease inhibitor-containing regimen.

Objective To study the predictors of virological rebound in patients having early virological response to protease inhibitor (PI)-containing regimen. Design and methods APROCO cohort study prospectively enrolled 1283 HIV-infected patients starting a PI-containing regimen in 1997–1999. Adherence to therapy was measured with self-administered questionnaires after 4 months of therapy (M4). Virological rebound was defined as a viral load (VL) > 500 copies/ml in patients having early virological response, defined as a VL < 500 copies/ml at M4. Predictors of time to virological rebound were studied with multivariate proportional hazards model. Results During a median follow-up of 20 months, virological rebound was observed in 32% of the 830 patients with early virological response. Virological rebound was more frequent when patients had received previous antiretroviral treatment [adjusted hazards ratio (HR) = 2.4;P < 0.0001], were younger (HR = 1.4 per each 10 years younger;P < 0.0001), had baseline CD4 cell count < 500 × 106/l (HR = 2.3;P < 0.001), had higher baseline VL (HR = 1.4 per each log10 copies/ml higher;P < 0.001), reported low adherence to therapy at M4 (HR = 2.1;P < 0.001) or had stopped PI at M4 (HR = 1.7;P = 0.04). Conclusion Initiation of treatment at a stage of preserved immunity is associated with a more durable virological response under protease inhibitor. Every effort should be made to monitor and strengthen adherence to therapy, even in patients having early virological response.

Low acceptability of A/H1N1 pandemic vaccination in French adult population: did public health policy fuel public dissonance?

Background In July 2009, French public health authorities embarked in a mass vaccination campaign against A/H1N1 2009 pandemic-influenza. We explored the attitudes and behaviors of the general population toward pandemic vaccination. Methodology/Principal Findings We conducted a cross-sectional online survey among 2,253 French representative adults aged 18 to 64 from November 17 to 25, 2009 (completion rate: 93.8%). The main outcome was the acceptability of A/H1N1 vaccination as defined by previous receipt or intention to get vaccinated (“Yes, certainly”, “Yes, probably”). Overall 17.0% (CI 95%, 15.5% to 18.7%) of respondents accepted A/H1N1 vaccination. Independent factors associated with acceptability included: male sex (p = .0001); older age (p = .002); highest or lowest level of education (p = .016); non-clerical occupation (p = .011); having only one child (p = .008); and having received seasonal flu vaccination in prior 3 years (p<.0001). Acceptability was also significantly higher among pregnant women (37.9%) and other at risk groups with chronic diseases (34.8%) (p = .002). Only 35.5% of respondents perceived A/H1N1 influenza illness as a severe disease and 12.7% had experienced A/H1N1 cases in their close relationships with higher acceptability (p<.0001 and p = .006, respectively). In comparison to 26.0% respondents who did not consult their primary care physician, acceptability was significantly higher among 8.0% respondents who were formally advised to get vaccinated, and lower among 63.7% respondents who were not advised to get vaccinated (respectively: 15.8%, 59.5% and 11.7%- p<.0001). Among respondents who refused vaccination, 71.2% expressed concerns about vaccine safety. Conclusions/Significance Our survey occurred one week before the peak of the pandemic in France. We found that alarming public health messages aiming at increasing the perception of risk severity were counteracted by daily personal experience which did not confirm the threat, while vaccine safety was a major issue. This dissonance may have been amplified by having not involved primary care physicians in the mass vaccination campaign.

Nonadherence among HIV-infected injecting drug users: the impact of social instability.

Summary: The authors tested the impact of social instability on adherence to highly active antiretroviral therapy (HAART) among patients infected with HIV through injection drug use (IDU; MANIF2000 cohort). In the study, they analyzed sociodemographic baseline characteristics to develop an indicator of social instability. Information concerning adherence to HAART was collected through questionnaires during a 2‐year follow‐up period. Factors associated with nonadherence were studied in two different groups: 1) patients who had stopped injection drug use (ex‐IDUs) and who were not in drug maintenance programs (DMT) during the entire follow‐up period, and 2) those who were still opiate dependent. Among the 210 eligible patients, 114 were classified as ex‐IDUs and 96 as opiate dependent. Ex‐IDUs reported nonadherence behaviors in 96 of 384 visits (25.0%), while opiate‐dependent patients were nonadherent in 111 of 308 visits (36.0%; p = .02). Among ex‐IDUs, the only factor associated with nonadherence was social instability, while among opiate‐dependent patients, injection behavior was the only determinant of nonadherence behavior. For opiate‐dependent patients, DMT may enhance adherence to HAART, but only if it is successful in reducing abuse of injection practices. For ex‐IDUs, it is very important that the management of social difficulties be taken into account to increase adherence to HAART.

Health-related quality of life after 1 year of highly active antiretroviral therapy.

Objective: We investigated the impact of the first year of highly active antiretroviral therapy (HAART) on health‐related quality of life (HRQL). Methods: Medical data for patients in the French APROCO cohort were collected at enrollment (MO) and month 12 (Ml2). A self‐administered questionnaire gathered information about HRQL (Medical Outcome Study 36‐Item Short Form Health Survey) and toxicity‐related symptoms. Using the twenty‐fifth percentile of HRQL scales in the French population as a threshold, patients with normal values in at least three mental and three physical scales were considered to have a “normal HRQL.” Results: Of the 1053 patients followed through M12, HRQL data at M0 and M12 were available for 654. Among the 233 patients with a normal baseline HRQL, 63 (27.0%) experienced a deterioration of HRQL at M12. Among the 421 patients with a low baseline HRQL, 121 achieved a normal HRQL at M12. Logistic regression showed that factors independently associated with a normal HRQL at M12 were normal baseline HRQL, baseline CD4 count <500 cells/mm3, time since HIV diagnosis <8 years, undetectable HIV‐RNA at M12, and lower number of self‐reported symptoms at M12. Conclusion: An assessment of HRQL should be integrated to efficacy outcomes to evaluate and compare long‐term strategies properly and to optimize the durability of response to antiretroviral therapy.

Failure to maintain adherence to HAART in a cohort of French HIV-positive injecting drug users.

The study, carriedoutintheFrench MANIF2000 cohortofHIVpositive patients contaminated through injecting drug use, assessed the impact of patients’ sociodemographic and psychological characteristics, behaviors toward drug abuse, and antiretroviral treatment characteristics on the maintenance of adherence to HAART (highly active antiretroviral therapies). A total of 96 patients (30 men and 66 women), who were initially adherent at their first visit after HAART prescription, were considered for analysis. Among these 96 patients, 22 (22.9%) experienced adherence failure defined as a self-reported, non-adherence behavior at any visit before the 18th month of treatment. Logistic regression showed that lack of a stable relationship, active drug injection, and depression were independently associated with adherence failure. Patients’ counseling for facilitating maintenance of adherence to HAART over time should focusonpreventionofdrug use, provisionofsocial support and consider the potential impact of difficulties with treatment on psychological well-being.