[Adherence intervention for HIV-infected patients receiving antiretroviral treatment. Implementation and initial assessment]. / Consultation d'observance pour des malades infectés par le VIH et traités par antirétroviraux dans un service de maladies infectieuses et tropicales. Mise en place et première évaluation.

OBJECTIVE: To describe the implementation and initial results of a specific educational and counseling intervention to examine and improve adherence to antiretroviral therapy (ARV) in HIV-infected patients. METHOD: Four patient profiles were defined: 1) discontinuation and 2) failure: patients with virological failure (defined as two consecutive viral loads>200 copies/mL) at ARV discontinuation or under treatment, both seen after the fact; 3) preparation: naive patients seen before starting treatment, and 4) reinforcement: patients in treatment seen for counseling to prevent virological failure. A clinical psychologist, nurse and hospital pharmacist jointly conducted the session. Data collected include standardized information about the characteristics of HIV infection and ARV regimens, and demographic, behavioral, social and cultural indicators. CD4 cell counts and HIV viral loads were recorded at D0, M1, M3, M9 and M12. The effectiveness of the adherence intervention was defined separately for each patient profile based on some combination of taking or restarting an ARV regimen, virological response, and M12 follow-up. RESULTS: The study included 139 patients between November 1998 and April 2000. The intervention was defined as effective in 50% and 40% of the discontinuation (n=26) and failure (n=61) patients respectively, 84% of those with preparation profile (n=37) and 93% (14/15) of reinforcement patients. Only undetectable HIV viral load at M3 was significantly associated with the effectiveness of the adherence intervention for all 4 profiles. The preventive interventions (preparation and reinforcement) were less effective in patients from outside Europe (p=0.013). CONCLUSION: The adherence intervention was more effective in preventing virological failure than in restoring ARV effectiveness among patients who had already experienced virological failure. It should therefore be proposed primarily before starting ARV, to prevent failure in treatment-naive patients, especially those from outside Europe.

Use of efavirenz is not associated with a higher risk of depressive disorders: a substudy of the randomized clinical trial ALIZE-ANRS 099.

BACKGROUND: Efavirenz (EFV) is a highly active antiretroviral drug, use of which is associated with frequent (although transient) neurosensorial adverse reactions. Whether the use of EFV is associated with the risk of depression or suicide remains controversial. METHODS: ALIZE-ANRS (Agence Nationale de Recherches sur le SIDA et les Hepatites Virales) 099 was a 48-week randomized trial involving virologically suppressed, human immunodeficiency virus (HIV)-infected patients that compared the maintenance of a treatment regimen that contained protease inhibitors (177 subjects) with a switch to a once-daily combination of EFV, didanosine, and emtricitabine (178 subjects). We used the trial's adverse events reporting system and a self-administered Center for Epidemiologic Studies-Depression Scale questionnaire to assess depressive disorders. Determinants were studied using a multivariate proportional hazards model adjusted for antiretroviral treatment, sex, age, HIV risk factor, history of depression, hepatic disorder, alcohol abuse, and HIV-related or non-HIV-related events. RESULTS: Thirty cases of depressive disorder (26 cases of depression and 4 suicide attempts) occurred during treatment in 27 patients (12 patients [7%] and 15 patients [8%] in the protease inhibitor-based and EFV-based treatment arms, respectively; P = .56). In the proportional hazards model, only age (hazard ratio, 1.6 per 10 years younger; 95% confidence interval, 1.0-2.6) and a history of depressive disorder (hazard ratio, 5.0; 95% confidence interval, 2.1-12.0) were associated with a risk of depressive disorders. The proportion of depressive patients (24%), as determined on the basis of the Center for Epidemiologic Studies-Depression Scale data, was stable during the follow-up period, without difference between treatment groups. Patients with a history of depressive disorder were more frequently depressed (53%) than were those without such history (22%; P = .03). CONCLUSIONS: The frequency of depressive disorders was high in this population, but the disorders were not related to EFV treatment. Younger age and a history of depression are important determinants for depression and should be considered for early detection and case management.

[Antiretroviral therapy for HIV-infected patients with schizophrenia. Coordinated multidisciplinary management (7 cases)]. / Traitement antirétroviral chez des patients schizophrènes infectés par le VIH. Prise en charge multidisciplinaire coordonnée (7 cas).

OBJECTIVE: Schizophrenia might appear to be an obstacle to the initiation of and especially compliance with antiretroviral therapy for HIV-infected patients. The aims of this study were to describe the clinical, immunologic and virologic course after initiation of antiretroviral therapy in 7 HIV patients with schizophrenia (according to DSM-IV-R criteria), and to analyse the possibilities of an adequate antiretroviral therapy for those patients. OBSERVATIONS: Multidisciplinary management by specialists in infectious diseases, addiction-related disorders, treatment adherence and compliance, and psychiatrists, as well as social workers, home care agencies, and patient advocacy and assistance groups, was organized with coordinated medical-psychiatric follow-up at least once a month. The patients, 6 men and 1 woman, were aged from 26 to 48 years; schizophrenia had been diagnosed in 5 patients 6 months to 20 years before the HIV infection was discovered; diagnoses of both diseases were essentially simultaneous for the other 2. All patients took long-term neuroleptics for their schizophrenia. Two were active drug addicts who received drug substitution treatment. Before antiretroviral treatment began, 6 patients had advanced infection: stage C with peak CD4 cell counts ranging from 6 to 70/mm3; they began treatment with protease inhibitors between May 1996 and August 1997. The seventh patient was first seen during primary HIV infection in July 1998, and treatment began then. Response to antiretroviral treatment with protease inhibitors was slow for all patients, but viral load became undetectable for 6 of the 7, after 5 months to 4 years; 3 had opportunistic infections. Follow-up ended in January 2002: 5 patients still had undetectable viral loads,, with CD4 cell counts ranging from 45 to 1 000/mm3. One patient died from mixed terminal cirrhosis (alcohol abuse and hepatitis C); the viral load in another was only partially controlled (10 000 copies/ml), because of poor treatment adherence. CONCLUSION: Individuals with schizophrenia can respond well to antiretroviral treatment, although response may appear slow; they can adhere to complex treatment regimens as long as they receive well coordinated and sustained multidisciplinary support.

[Myocardial localisation of tuberculosis: the diagnostic value of cardiac MRI]. / Localisation myocardique de la tuberculose: intérêt diagnostique de l'IRM cardiaque.

INTRODUCTION: Tuberculosis can be responsible for myocardial damage, the frequency of which is probably underestimated because of the difficulty in its diagnosis. We studied the contribution of cardiac magnetic resonance imaging (MRI) in three patients. OBSERVATIONS: Three patients were treated for disseminated tuberculosis. They had moderate cardiac abnormalities (tachycardia, dyspnoea on effort). The electrocardiogram was normal in 2 patients and the echocardiography showed localized hyperkinesias. Cardiac MRI revealed intra-myocardial nodular gadolinium enhancement and hyperkinesias. The clinical outcome in the 3 patients was favourable following anti-tuberculosis therapy; one patient was also administered corticosteroids. DISCUSSION: Cardiac MRI is a non-invasive examination that brought important arguments for the diagnosis of tubercular myocarditis in the 3 patients.

Determinants of immune reconstitution inflammatory syndrome in HIV type 1-infected patients with tuberculosis after initiation of antiretroviral therapy.

Immune reconstitution inflammatory syndrome (IRIS) occurred in 16 of 37 antiretroviral-naive patients who were treated subsequently for tuberculosis and human immunodeficiency virus (HIV) type 1 infection. IRIS was related to increases in the CD4 cell percentage and in the ratio of CD4 cells to CD8 cells after 1 month of antiretroviral therapy and to dissemination of tuberculosis. These results have implications for the diagnosis of IRIS and the understanding of its pathogenesis.

An example of nonrandom missing data for hepatitis C virus status in a prognostic study among HIV-infected patients.

PURPOSE: To describe information bias due to missing data for hepatitis C (HCV) status in the analysis of factors associated with mortality in HIV-infected patients. METHOD: The prospective APROCO cohort enrolled 1,151 HIV-infected adults at the first initiation of highly active antiretroviral treatment in 1997-1998. Conversely to other characteristics, hepatitis B and C serologic status were recorded retrospectively. RESULTS: In a first dataset, HCV status was missing in 29%. HCV infection was associated with a higher hazard of death (Cox model, hazard ratio [HR]=4.1; 95% confidence interval [95% CI], 1.5-11.3). After more efforts to actively document HCV status, the information remained missing in only 10%. All deceased patients who were secondarily documented were recorded as being HCV negative. In fact, before systematic collection of HCV status, nonstructured additional documentation for all deaths led to spontaneous notification of HCV-positive serology at death and not HCV negative. HCV was no longer associated with the hazard of death (HR=1.2; 95% CI, 0.6-2.7). CONCLUSION: These results underline the need to minimize missing data and to investigate the impact of missing data on the results, although the mechanism of bias is difficult to identify. In addition, these results might shed light on the current debate about the association between HCV and progression of HIV infection.

[Non tuberculous mycobacterial diseases]. / Les mycobactéries non tuberculeuses.

Mycobacteria species other than members of Mycobacterium tuberculosis complex are called non tuberculous mycobacteria (NTM) or "atypical" mycobacteria. To date, about 80 mycobacterial species have been described. They are usually opportunistic pathogens with variable degrees of virulence. Tuberculosis is the commonest mycobacterial disease in the world, followed by leprosy and Buruli ulcer. Before the AIDS epidemic, NTM diseases were confined to the lungs (M. kansasii, M. intracellulare and M. avium), the skin (M. marinum) or cervical lymph nodes (M. scrofulaceum). The outbreak of AIDS epidemic has dramatically changed the epidemiology of NTM diseases. Between 25 to 50% of AIDS patients in Europe and USA are infected with NTM. NTM infections are usually disseminated in patients with profound immunodeficiency. The inflammatory response and the prognosis of NTM diseases depend on the immunological status and the NTM species. Diagnosis may be difficult, especially in AIDS patients in whom numerous diseases are often associated. Diagnostic criteria involve clinical, radiological, microbiological and pathological findings. Identification of Mycobacterium species in cultures is the gold standard. Pathological examination has several interests: it may reveal an NTM disease, it provides a more rapid assessment of the infection than cultures, and helps to evaluate the virulence of NTM species identified by cultures.

Influence of HIV infection on the response to interferon therapy and the long-term outcome of chronic hepatitis B.

BACKGROUND & AIMS: The outcome of chronic hepatitis B and the efficacy of interferon alfa (IFN-alpha) remain controversial in human immunodeficiency virus (HIV)-positive patients. We analyzed the influence of HIV coinfection on the response to IFN-alpha therapy, long-term virologic status, progression to cirrhosis, and mortality. METHODS: This was a retrospective follow-up cohort study of 141 consecutive hepatitis B e antigen-positive patients (69 HIV positive) followed up for 45 months. RESULTS: The short-term response to IFN-alpha therapy was not significantly different in HIV-positive and HIV-negative patients (28% vs. 51%; P = 0.06) but was poorer in cases of low CD4 cell count (P = 0.038). The hepatitis B virus (HBV) reactivation rate was higher in HIV-positive patients (P = 0.033) and was associated with low CD4 cell count. The risk of cirrhosis was higher in HIV-positive patients with a CD4 cell count <200/mm(3) (relative risk [RR], 4.57; P = 0.007), in IFN-alpha-untreated patients (RR, 2.63; P = 0.041), in patients older than 33 years (RR, 4.59; P = 0.008), and in cases of high necroinflammatory score at baseline (RR, 1.27; P = 0.010). Cirrhosis-related death was more frequent in HIV-positive patients with low CD4 cell count at baseline (P = 0.041), in alcohol consumers (P = 0.001), in IFN-alpha-untreated patients (P = 0.052), and in patients with high histology activity index at baseline (P = 0.005). CONCLUSIONS: HIV coinfection was associated with poorer response to IFN-alpha therapy, more frequent HBV reactivations, and increased incidence of cirrhosis and cirrhosis-related death in cases of low CD4 count. IFN-alpha therapy decreased the incidence of HBV cirrhosis regardless of HIV status or serologic response.

Relationship between levels of indinavir in hair and virologic response to highly active antiretroviral therapy.

BACKGROUND: Suboptimal levels of antiretroviral drugs result in virologic failure in HIV-infected patients treated with highly active antiretroviral therapy (HAART). OBJECTIVE: To assess the relationship between levels of indinavir in hair and virologic outcome. DESIGN: Cross-sectional study. SETTING: 7 AIDS clinics in France. PATIENTS: 89 HIV-infected patients who received HAART that included indinavir. MEASUREMENTS: Patients were classified as responders or nonresponders on the basis of viremia at the time of hair collection. In nonresponders, levels of indinavir in hair and resistance mutations in the protease gene were assessed at baseline and at the time of indinavir measurement. RESULTS: Mean indinavir levels (+/-SD) were significantly higher in the 65 responders than in the 24 nonresponders (24.4 +/- 16 microg/g vs. 12.9 +/- 8.6 microg/g) (P < 0.001). Nonresponders with intermediate levels of indinavir in hair had more mutations in the protease gene than did nonresponders with low levels of indinavir in hair. CONCLUSION: Indinavir levels in hair are associated with virologic outcome in patients receiving HAART.

Factors associated with mortality in human immunodeficiency virus type 1-infected adults initiating protease inhibitor-containing therapy: role of education level and of early transaminase level elevation (APROCO-ANRS EP11 study). The Antiprotéases Cohorte Agence Nationale de Recherches sur le SIDA EP 11 study.

This study attempted to identify factors associated with mortality among human immunodeficiency virus (HIV)-infected adults starting a protease inhibitor (PI)-containing therapy. Among 1155 patients consecutively enrolled in the APROCO study between May 1997 and June 1998, clinical characteristics were as follows: median age, 36 years; median baseline CD4 cell count, 288 cells/mm(3); and median baseline plasma HIV RNA load, 4.4 log(10) copies/mL. After a median follow-up of 27 months, 48 deaths had occurred, of which 44% were related to acquired immune deficiency syndrome. The mortality rate was 2.9% at 12 months. When both data at baseline and data at 4 months after the start of PI therapy were considered, factors independently associated with mortality were (Cox model) low baseline plasma creatinine level, low school education level, low CD4 cell count at 4 months, low hemoglobin level, and elevated hepatic transaminase levels. Thus, social context plus clinical and biologic data, including the 4-month response to treatment, must be considered in treatment of HIV-infected patients.

Randomized phase II trial of atovaquone with pyrimethamine or sulfadiazine for treatment of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome: ACTG 237/ANRS 039 Study. AIDS Clinical Trials Group 237/Agence Nationale de Recherche sur le SIDA, Essai 039.

In this international, noncomparative, randomized phase II trial, we evaluated the effectiveness and tolerance of atovaquone suspension (1500 mg orally twice daily) plus either pyrimethamine (75 mg per day after a 200-mg loading dose) or sulfadiazine (1500 mg 4 times daily) as treatment for acute disease (for 6 weeks) and as maintenance therapy (for 42 weeks) for toxoplasmic encephalitis (TE) in patients infected with human immunodeficiency virus. Twenty-one (75%) of 28 patients receiving pyrimethamine (95% lower confidence interval [CI], 58%) and 9 (82%) of 11 patients receiving sulfadiazine (95% lower CI, 53%) responded to treatment for acute disease. Of 20 patients in the maintenance phase, only 1 experienced relapse. Eleven (28%) of 40 eligible patients discontinued treatment as a result of adverse events, 9 because of nausea and vomiting or intolerance of the taste of the atovaquone suspension. Although gastrointestinal side effects were frequent, atovaquone-containing regimens are otherwise well tolerated and safe and may be useful for patients intolerant of standard regimens for toxoplasmic encephalitis.

Amprenavir inhibitory quotient and virological response in human immunodeficiency virus-infected patients on an amprenavir-containing salvage regimen without or with ritonavir.

The efficacy of an amprenavir (APV)-containing therapy without (group A) or with (group B) ritonavir was assessed in patients with failure of previous protease inhibitor therapy for human immunodeficiency virus (HIV) infection. The mean minimal plasma APV concentrations in groups A and B were 58 and 1,320 ng/ml, respectively, corresponding to APV inhibitory quotients of 0.2 (range, 0.03 to 0.70) and 7.0 (range, 1.4 to 145), respectively. At week 24, 2 of 8 and 13 of 14 patients in groups A and B, respectively, had <200 HIV RNA copies/ml of plasma, including 4 of 5 patients infected with APV-resistant viruses.