Adherence to consensus-based diagnosis and treatment guidelines in adult soft-tissue sarcoma patients: a French prospective population-based study.

BACKGROUND: Soft-tissue sarcomas (STSs) are rare tumors with varied histological presentations. Management and treatment are thus complex, but crucial for patient outcomes. We assess adherence to adult STS management guidelines across two French regions (10% of the French population). We also report standardized incidence. PATIENTS AND METHODS: STS patients diagnosed from 1 November 2006 to 31 December 2007 were identified from pathology reports, medical hospital records, and cancer registries. Guideline adherence was assessed by 23 criteria (validated by Delphi consensus method), and age and sex-standardized incidence rates estimated. Associations between patient, treatment, and institutional factors and adherence with three major composite criteria relating to diagnostic imaging and biopsy as well as multidisciplinary team (MDT) case-review are reported. RESULTS: Two hundred and seventy-four patients were included (57.7% male, mean age 60.8 years). Practices were relatively compliant overall, with over 70% adherence for 10 criteria. Three criteria with perfect Delphi consensus had low adherence: receiving histological diagnosis before surgery, adequacy of histological diagnosis (adherence around 50% for both), and MDT discussion before surgery (adherence <30%). Treatment outside of specialized centers was associated with lower adherence for all three composite criteria, and specific tumor sites and/or features were associated with lower adherence for diagnostic imaging, methods, and MDT meetings. STS standardized incidence rates were 4.09 (European population) and 3.33 (World) /100 000 inhabitants. CONCLUSIONS: Initial STS diagnosis and treatment across all stages (imaging, biopsy, and MDT meetings) need improving, particularly outside specialized centers. Educational interventions to increase surgeon's sarcoma awareness and knowledge and to raise patients' awareness of the importance of seeking expert care are necessary.

[The role of a hospital-based registry of a regional cancer center for a population-based cancer registry]. / Intérêt des données du registre hospitalier (Enquête permanente cancer) d'un centre régional de lutte contre le cancer pour un registre de cancer en population.

BACKGROUND: Hospital-based cancer registries (HBR) of Comprehensive cancer centers (CCC) named "Enquête permanente cancer (EPC)" could represent an important information source of data for a population-based cancer registry (PBR). The main purpose of this study was to evaluate the concordance between data from HBR of the CCC for regions of Bordeaux and South-Western France and data from PBR of the General cancer registry of Gironde and the completeness for the year 2005, in order to explore the possibility for immediate integration of data collected by the HBR in the database of the PBR and to reduce the systematic consultation of medical records for cancer cases notified by the HBR. METHODS: We estimated the proportion of concordant cases between the HBR and the PBR and the unweighted and weighted Cohen's Kappa coefficient for certain variables. RESULTS: Among 1151 cases notified by the HBR, 1095 (positive predictive value of HBR: 95%) were included in the PBR database. For these admissible cases, sex, birth date and place for residence postal code at diagnosis were concordant in more than 94%. Concordance of cancer incidence date was 50% but difference between two dates was lower than 1 month in 91% of cases. Concordance of cancer topography and morphology was respectively 72% and 78%. Cancer progression, estimated by TNM classification was concordant in 96% of cases. The Kappa coefficient was 0.95 for pT, and respectively 0.92 for pN and M. CONCLUSION: Automatic data integration from the HBR database to the PBR database without consulting medical record will be possible in Gironde. But, topography and morphology will be systematically recoded using pathologist records. And, if cancer progression (coded by TNM classification) is missing in the HBR database, medical records will be consulted in order to complete this data in the PBR database.

[Statistical and epidemiological methods used in biomedical research: implications for initial medical education]. / Méthodes biostatistiques et épidémiologiques employées pour la recherche biomédicale : implications pour la formation médicale initiale.

BACKGROUND: The main source of key medical information consists in original articles published in peer-reviewed biomedical journals. Reported studies use increasingly sophisticated statistical and epidemiological approaches that first require a solid understanding of core methods. However, such understanding is not widely shared among physicians. Our aim was to assess whether the basic statistical and epidemiological methods used in original articles published in general biomedical journals are taught during the first years of the medical curriculum in France. METHODS: We selected original articles published in The New England Journal of Medicine, The Lancet, and The Journal of the American Medical Association, over a period of six months in 2007 and in 2008. A standardized statistical content checklist was used to extract the necessary information in the "Abstract", "Methods", "Results", footnotes of tables, and legends of figures. The methods used in the selected articles were compared to the national program and the public health program of biostatistics and epidemiology taught during the first six years of medical school. RESULTS: The 237 analyzed original articles all used at least one statistical or epidemiological method. Descriptive statistics, confidence interval and Chi(2) or Fisher tests, methods used in more than 50% of articles, were repeatedly taught throughout the medicine curriculum. Measures of association, sample size, fit and Kaplan-Meier method, used in 40 to 50% of articles, were specifically taught during training sessions on critical reading methods. Cox model (41% of articles) and logistic regression (24% of articles) were never taught. The most widely used illustrations, contingency tables (92%) and flowcharts (48%), were not included in the national program. CONCLUSION: More teaching of the core methods underlying the understanding of sophisticated methods and illustrations should be included in the early medical curriculum so that physicians can read the scientific literature critically for their medical education.

[Performance evaluation of hospital claims database for the identification of incident central nervous system tumors compared with a cancer registry in Gironde, France, 2004]. / Évaluation des performances du PMSI pour l'identification des tumeurs incidentes du système nerveux central par rapport à un registre spécialisé en Gironde, France, en 2004.

BACKGROUND: Cancer registries cover 18% of the French population. A national surveillance might be warranted for some potentially environment-related cancers such as tumors of the central nervous system (CNS) to detect abnormal incidence variations. The PMSI database provides an interesting source of comprehensive, standardized and mandatory data collected from all health facilities. The aim of this work was to develop methods to identify incident CNS tumors using the PMSI database. METHODS: A selection of patients living in Gironde was made in the 2004 PMSI database of the hospital of Bordeaux, using the CNS tumors codification. Cases were validated via the CNS primary tumor registry of Gironde taken as the reference, or medical records. Various combinations of criteria were defined and tested. RESULTS: The first selection based on diagnoses identified patients with a sensitivity of 84% and a positive predictive value (PPV) of 34%. Patients wrongly identified by the PMSI were non-incident cases (49%) or patients without a CNS tumor (45%). Patients with a tumor not identified by the PMSI had been hospitalized in 2005 (44%) or had no code for CNS tumor (42%). According to the algorithms, the sensitivity ranged from 64% to 84%, and the PPV from 34% to 69%. The best combination had a sensitivity of 67% and a PPV of 69% and was obtained with codes for CNS tumor in 2004 associated with a diagnostic or therapeutic code for persons under 70 years without code for CNS tumor in previous years or code for metastasis in 2004. CONCLUSION: According to these results, the PMSI database cannot be used alone to calculate the incidence of these complex tumors. However the PMSI database plays an important role in cancer surveillance, in combination with other information sources and the expertise of cancer registries. This role could increase with further reflection and improvement of data quality.

The French National Mesothelioma Surveillance Program.

OBJECTIVES: The French National Mesothelioma Surveillance Program (NMSP) was established in 1998 by the National Institute for Health Surveillance (InVS). Its objectives are to estimate the trends in mesothelioma incidence and the proportion attributable to occupational asbestos exposure, to help improve its pathology diagnosis, to assess its compensation as an occupational disease, and to contribute to research. METHODS: The NMSP records incident pleural tumours in 21 French districts that cover a population of approximately 16 million people (a quarter of the French population). A standardised procedure of pathological and clinical diagnosis ascertainment is used. Lifetime exposure to asbestos and to other factors (man made mineral fibres, ionising radiation, SV40 virus) is reconstructed, and a case-control study was also conducted. The proportion of mesothelioma compensated as an occupational disease was assessed. RESULTS: Depending on the hypothesis, the estimated number of incident cases in 1998 ranged from 660 to 761 (women: 127 to 146; men: 533 to 615). Among men, the industries with the highest risks of mesothelioma are construction and ship repair, asbestos industry, and manufacture of metal construction materials; the occupations at highest risk are plumbers, pipe-fitters, and sheet-metal workers. The attributable risk fraction for occupational asbestos exposure in men was 83.2% (95% CI 76.8 to 89.6). The initial pathologist's diagnosis was confirmed in 67% of cases, ruled out in 13%, and left uncertain in the others; for half of the latter, the clinical findings supported a mesothelioma diagnosis. In all, 62% applied for designation of an occupational disease, and 91% of these were receiving workers' compensation. CONCLUSIONS: The NMSP is a large scale epidemiological surveillance system with several original aspects, providing important information to improve the knowledge of malignant pleural mesothelioma, such as monitoring the evolution of its incidence, of high risk occupations and economic sectors, and improving pathology techniques.

[Health related quality of life and lipodystrophy syndrome among HIV-infected patients]. / Qualité de vie et syndrome lipodystrophique chez les patients infectés par le VIH.

AIM OF THE STUDY: The aim of this work is to show to what extent a psychosocial evaluation can lead bring to comprehension of the subjectivity of Quality of Life (QoL) among HIV-infected patients. Evaluation of QoL makes it possible to understand the link between the therapeutic effectiveness and the subjective evaluation of the treatment, but also to estimate more precisely how people live and take their treatment in the context of HIV infection. METHOD: This work confronts the variation of QoL with the variation of several social and psychosocial parameters identified as of the components of the system, which is the subjective evaluation, and more precisely to a specific side effect of Highly Active AntiRetroviral Therapies (HAART): lipodystrophy syndrome that consists in body fat redistribution. This side effect could consist in an accumulation of body fat, or a loss of body fat or a combination of both symptoms. The analysis was made on the data from APROCO-COPILOTE cohort composed of HIV-infected patients initiating HAART. RESULTS: Among a sample of 706 patients follow-up for three years and with available QoL data, we identified the variations of QoL according to the variation of this specific side effect and according to gender. Results show that lipodystrophy syndrome has a determinant impact on QoL different among male and female patients. Adjusted on clinical and socio-demographic characteristics, impaired women's QoL is associated with accumulation of body fat and impaired men's QoL is associated with loss of body fat. CONCLUSION: These results underline the role of body image on subjective evaluation of QoL. The analysis of empirical data made it possible to highlight the social implication of the evaluation of QoL from the role of the social support, patient-provider relationship and the social context.

Severe hepatic cytolysis: incidence and risk factors in patients treated by antiretroviral combinations. Aquitaine Cohort, France, 1996-1998. Groupe dEpidémiologie Clinique de Sida en Aquitaine (GECSA).

OBJECTIVE: To study hepatic cytolysis in patients treated by highly active antiretroviral therapy (HAART) with protease inhibitor or with two nucleoside reverse transcriptase inhibitors (NRTIs). METHODS: We selected patients of the Aquitaine Cohort who initiated HAART or two NRTIs before 1 January 1998, had alanine amino-transferase (ALT) < or = 200 IU/I at baseline and at least one follow-up measure. Cox model was used to study the association between occurrence of severe hepatic cytolysis (ALT>200 IU/l) and age, gender, HIV transmission group, baseline CD4 and CD8 cell count, history of hepatic cytolysis, antiretroviral drug, baseline liver enzymes (WHO classification level 0: < or = 50 IU/l, level 1: 51 to 100, level 2: 101 to 200), hepatitis B and C co-infection. RESULTS: Sixty-four of 748 (8.5%) patients treated with HAART and 71 of 1249 (5.7%) treated with two NRTIs developed cytolysis. The probability of occurrence was 7.9% after 1 year [95% confidence interval (CI), 5.9-10.4] for patients treated with HAART and 4.8% (95% CI, 3.6-6.4) for patients treated with two NRTIs (log-rank test, P = 0.01). The median time to occurrence was 164 days for HAART-treated patients and 252 days for those treated with two NRTIs. In multivariate analysis, the history of cytolysis [hazard ratio (HR) = 2.3; 95% CI, 1.2-4.4], baseline value of ALT (HR = 2.4; 95% CI, 1.2-4.8 and HR = 3.3; 95% CI, 1.4-7.4 for levels 1 and 2, respectively), hepatitis B (HR = 3.0; 95% CI, 1.4-6.2) and C co-infections (HR = 3.2; 95% CI, 1.7-6.2) remained significantly associated with the occurrence of severe hepatic cytolysis among HAART-treated patients. History of cytolysis, hepatitis B and C were associated with cytolysis in patients treated with two NRTIs (HR = 14.8, 2.6 and 2.7, respectively). CONCLUSION: Hepatic cytolysis is more frequent among patients treated with HAART than with two NRTIs. Hepatitis B and C are the major risk factors after initiation of HAART or treatment with NRTIs. Co-infections with hepatitis B virus or hepatitis C virus may modify the management of HIV-infected patients treated by HAART.

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.

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.

Injuries in a problematic socioeconomic context: a population-based study in Réunion, Indian Ocean, 1993-1994. GEAR. Groupement d'Etude sur les Accidents à la Réunion.

BACKGROUND: This study was designed to estimate the incidence and describe the characteristics of injuries during a one-year period in the French island of Réunion, Indian Ocean, a defined geographic population with socioeconomic problems. METHODS: Cases were injuries from accidents (unintentional injuries), self-inflicted injuries (suicides and attempted suicides), or injuries purposely inflicted by other people, that resulted in hospital admission or death. Patients and injury characteristics were recorded prospectively, alternately every other week, in all emergency rooms on the island; all death certificates were studied. RESULTS: The overall annual incidence of injuries was 1578 per 100,000 residents. The three main causes of injury were (i) falls on the same level (23.6%), (ii) poisoning (23.0%) and (iii) traffic accidents (21.5%). Of the traffic accident cases, 44% were motorcyclists (mostly mopeds) and more than half of the cases were 15-25 years old. Suicides and attempted suicides accounted for 80.9% of poisonings, 35.5% of immediately fatal injuries, and 19.6% of non-fatal injuries. Homicides and assaults accounted for 8.3% of all injuries. The employment rate was lower for injured patients than in the total Réunion population (standardized ratio for males: 74; P < 0.001). Half of the injured hospitalized patients had an Injury Severity Score < 5 and 8 days after hospitalization, 83.5% of patients had returned home. CONCLUSION: Injury epidemiology may be affected by different demographic, socioeconomic, cultural and geographical factors. Targeted studies are therefore necessary to guide injury prevention measures.

[Feasibility of following up transfused patients]. / Faisabilité d'un suivi de patients transfusés.

The aim of this study was to assess the natural history of patients after transfusion and the acceptability of a standardized biological follow-up. In 1995, during 1 month, in 13 French hospitals, a follow-up at 3 and 6 months after blood transfusion was proposed to all blood recipients who had not received any blood transfusion within the past 6 months (eligible patients): screening for red cell antibodies, alanine aminotransferase (ALT) activity and specific viral markers of hepatitis B (hepatitis B surface antigen and antibody to hepatitis virus core antigen), of hepatitis C (antibodies) and of Human Immunodeficiency Virus (antibodies). At the beginning of the study, 296 patients were followed for 6 months. A complete follow-up was available at 3 months for 183 patients (62%), at 6 months for 168 (57%) and after 6 months, 198 patients (67%) have been once followed. Of eligible patients, 76% were alive at six months. After transfusion, the incidence of red cell alloantibodies and elevated ALT concentration were respectively 4% and 17%. At 6 months, one patient had Hepatitis B surface antigen; the responsibility of blood transfusion was excluded. Within the first 24 hours, 68 patients (23%) required another blood transfusion and 42% of units were transfused to patients with malignant disease. Our study quantifies in real conditions the difficulty of a biological follow-up in a transfused population, mostly composed of patients that could not be followed in the hospital where they were transfused.

[Pilot study of the characteristics of transfused patients and utilized labile blood products]. / Etude pilote des caractéristiques des patients transfusés et des produits sanguins labiles utilisés.

The aim of this study was to describe blood recipients and blood components transfused during the first 24 hours in 13 French hospitals. We included all blood recipients who had not had any blood transfusion within the past six months. Recipients were screened for red cell alloantibodies, the alanine aminotransferase activity and specific viral markers (hepatitis B and C, Human Immunodeficiency Virus). Eligible patients represented 47% of the all transfused. Among the 371 patients included, 57% were males and 71% were transfused in a surgical unit. Alloantibodies, non specific and specific viral markers were detected in 3%, 19% and 2% respectively. Among the patients included, 42 received 172 autologous units. In total, 1056 allogeneic units (an average of 3 units per patient) were transfused; blood products were leucocyte-depleted (49%) or leucocyte-poor (20%); 54% of red cell units were matched for antigens Rh and Kell. Neoplasms were the most frequently reported disease for which patients were transfused. This study provides baseline blood transfusion information on recipients and blood utilization for a specific period in French hospitals. Following this study, a national study will allow the clarification of the characteristics, for instance the surgical procedures requiring transfusion.

[Epidemiology of atherosclerotic cardiovascular risk in HIV-1 infected patients]. / Epidémiologie du risque vasculaire d'origine athéroscléreuse chez les patients infectés par le VIH-1.

OBVIOUS EFFICACY, BUT ALSO RISKS: The administration of combinations of highly active antiretroviral since 1996 has greatly decreased morbidity and mortality in HIV-1 infected patients. Side effects associated with these treatments were rapidly described. Other than abnormal distribution of fat, the dyslipidemia and insulin-resistance leads to a pro-atherogenic profile in these patients. Since 1998, the publication of several observations of acute cardio-vascular events in HIV-1 infected patients most often treated by antiretrovirals has raised the question of the increased risk of atherosclerosis in these patients. Today, some studies have been published and several are ongoing to evaluate the cardiovascular risk in HIV-1 infected patients. TWO FUNDAMENTAL QUESTIONS: The purpose of this review was to critically report the results of published studies in order to answer the two major questions: do HIV-1 infected patients have an increased cardiovascular risk compared to non infected subjects, and what are these cardiovascular risk factors? REPLY ELEMENTS: The review of available published results is in favour of an increased risk in HIV-1 infected patients compared to the general population. However, it is difficult to evaluate the importance of the absolute risk compared to the benefits of antiretroviral treatments and also the inherent effect of antiretroviral molecules. The main risk factors seem to be classical risk factors such as smoking habits, age and dyslipidemia that are partly due themselves to highly active antiretroviral treatments

Early evolution of plasma soluble TNF-alpha p75 receptor as a marker of progression in treated HIV-infected patients.

Abstract We evaluated the prognostic value of different mediators of inflammation: TNF-alpha and its soluble receptor p75, platelet-activating factor, and glutathione tripeptide in a case-control study nested within a cohort of 1281 patients infected by the human immunodeficiency virus (HIV) started on highly active antiretroviral treatment (HAART). During the first year of HAART, 16 cases experienced an AIDS-defining event and 6 experienced an evolution of T CD4(+) cell count <100/mm(3). Forty-four controls who did not progress during the same follow-up period were matched for age, baseline CD4(+), and HIV-RNA. In the control group, plasma levels of TNF-alpha and its soluble receptor p75 decreased significantly from baseline to month 4: from 11.0 to 8.7 pg/ml (p < 0.001) and from 27.3 to 22.8 pg/ml (p < 0.003), respectively. Furthermore the decrease of TNF-alpha soluble receptor p75 was larger in nonprogressors than in progressors (p = 0.003). Measurement of TNF-alpha soluble receptor p75 may be of interest as an additional marker of early antiretroviral effect.

Modeling changes in CD4-positive T-lymphocyte counts after the start of highly active antiretroviral therapy and the relation with risk of opportunistic infections: the Aquitaine Cohort, 1996-1997.

After initiation of a treatment for human immunodeficiency virus type 1 infection containing a protease inhibitor, immune restoration associated with increases in CD4-positive (CD4+) T lymphocyte count may be delayed. In a sample of patients who had been prescribed protease inhibitors for the first time, the authors tested to see whether there was a minimal duration of CD4+ cell count increase before the increase had an impact on the occurrence of opportunistic infections. The evolution (difference between time t and baseline) of CD4+ cell count was modeled using a mixed effects linear model. Changes in CD4+ count estimated by this model were then included as time-dependent covariates in a proportional hazards model. Finally, the authors tested for the existence of a CD4+ change x time interaction. The authors used a sample of 553 French patients first prescribed protease inhibitors in 1996 and followed for a median of 16 months. During the first 120 days, there was no association between CD4+ change and the rate of opportunistic infections. After 120 days, each 50-cell/mm3 increase in CD4+ count was associated with a 60% (95% confidence interval: 45, 72) reduction in the incidence of opportunistic infections. These results, based on modeling of CD4+ cell response, at least indirectly reinforce the concept of a delayed but possible immune recovery with the use of protease inhibitors. The findings support the potential for interruption of certain types of prophylaxis against opportunistic infections under reasonable conditions of duration of antiretroviral therapy and sustained CD4+ cell response.

Viral load as a primary outcome in human immunodeficiency virus trials: a review of statistical analysis methods.

In Human Immunodeficiency Virus infection, several statistical methods are available to analyze viral load (HIV-1 RNA) used as a surrogate outcome in trials of antiretroviral treatments. We compared the most frequently used methods and applied them to one of these trials, where HIV-1 RNA was measured using two lower limits of detection. Methods were reviewed for different properties dealing with validity, interpretation, and handling. Compared to change of HIV-1 RNA at the end of follow-up or HIV-1 RNA area-under-the-curve during follow-up minus baseline, the most attractive methods appeared to be HIV-1 RNA undetectability, HIV-1 RNA reduction at the end of follow-up with censoring adjustment, and mixed linear model on HIV-1 RNA.

Correlations of soluble interleukin-2 and tumor necrosis factor type II receptors with immunologic and virologic responses under HAART.

We assessed the correlations between some plasma markers of immune activation (soluble receptors of interleukin 2 (sIL2-R) and TNFap75 (sTNFII-R) and usual markers of HIV infection in patients treated with protease-inhibitors (PI). Forty-six PI-naive HIV-1-infected adults were included in a 1-year prospective cohort from the initiation of a P1-containing regimen (M0). Measurements of CD4+cell count, plasma HIV-RNA, sIL2-R and sTNFII-R were performed at M0, M6, and M12. The evolution of sIL2-R from baseline to M12 was significantly different between immunological responders (IR) (CD4+count above 200/mm3 for subject having less than 200 CD4 +/mm3 at inclusion, or increase of at least 50 CD4+/mm3 for others) (58 UI/ml) and non-IR (+28 UI/ml) (P =0.01). The evolution of sTNFII-R between M0 and M12 was significantly different between virological responders (VR) (plasma HIV-1 RNA less than 500 copies/ml at M12) (-2.5 ng/ml) and non-VR (+0.2 ng/ml) (P = 0.02). Our study shows significative correlations between the evolutions of soluble interleukin-2 and TNFR-II receptors and those of CD4+T-lymphocytes or HIV-RNA responses in patients under HAART.