Does region of origin influence the timing and outcome of first-line antiretroviral therapy in France?

OBJECTIVES: The aim of the study was to assess whether the timing of combination antiretroviral therapy (cART) initiation, the choice of cART and virological response differ in migrants versus European natives in the north and east of Paris area, after dissemination of French recommendations for universal treatment. METHODS: Antiretroviral therapy-naïve HIV-1-infected adults with at least two follow-up visits at one of 15 participating centres between 1 January 2014 and 31 March 2015 were included in the study. Factors associated with cART initiation before 31 March 2015, with protease inhibitor (PI)-containing cART among individuals initiating cART, and with 1-year virological success after cART initiation were assessed using multivariable logistic regression models. Sex, age, region of origin [Western Europe, sub-Saharan Africa (SSA) or other], HIV transmission group, baseline AIDS status, CD4 cell count and plasma viral load (VL), and hepatitis B and/or C virus infection were considered in the analyses. RESULTS: Among 912 individuals, only 584 (64%) started cART during the study period. After adjustment, migrants from SSA were half as likely to initiate cART and to have a subsequent virological response compared with individuals from Western Europe [adjusted odds ratio (aOR) 0.54; 95% confidence interval (CI) 0.36-0.82; and aOR 0.52; 95% CI 0.28-0.98, respectively]. PI-containing cART was more frequently prescribed in migrants from SSA, in people with lower CD4 cell counts and in people with higher VL. CONCLUSIONS: Even in the context of universal cART recommendations and of free access to care, migrants from SSA still have delayed access to cART and a lower virological response. Efforts are still necessary to provide immediate cART to all people living with HIV.

[New strategies for antiretroviral treatment in HIV infected patients]. / Nouvelles stratégies de traitement antirétroviral chez les patients infectés par le VIH.

Medical care of HIV-infected patients has been greatly improved during the last four years with the combination of new highly active drugs and routine monitoring of plasma viral load. Three-drugs regimens including a protease inhibitor are the recommended treatments. The objective is the suppression of viral load below detectable levels and the correction of immune deficit. Non-nucleoside reverse transcriptase inhibitors can be used in new therapeutic regimens. To ameliorate efficacy of the antiretroviral treatment and to avoid viral resistance, the tolerance and the ability to adhere are an important challenge.

Resistant herpes simplex virus type 1 infection: an emerging concern after allogeneic stem cell transplantation.

Fourteen cases of severe acyclovir-resistant herpes simplex virus type 1 (HSV-1) infection, 7 of which showed resistance to foscarnet, were diagnosed among 196 allogeneic stem cell transplant recipients within a 29-month period. Recipients of unrelated stem cell transplants were at higher risk. All patients received foscarnet; 8 subsequently received cidofovir. Strains were initially foscarnet-resistant in 3 patients and secondarily so in 4 patients. In vitro resistance to acyclovir or foscarnet was associated with clinical failure of these drugs; however, in vitro susceptibility to foscarnet was associated with complete response in only 5 of 7 patients. No strain from any of the 7 patients was resistant in vitro to cidofovir; however, only 3 of 7 patients achieved complete response. Therefore, acyclovir- and/or foscarnet-resistant HSV-1 infections after allogeneic stem cell transplantation have become a concern; current strategies need to be reassessed and new strategies must be evaluated in this setting.

Usefulness of the cytomegalovirus (CMV) antigenemia assay for predicting the occurrence of CMV disease and death in patients with AIDS.

A cohort study of 214 human immunodeficiency virus (HIV)-infected patients was performed to assess the usefulness of the cytomegalovirus (CMV) antigenemia assay for predicting the occurrence of CMV disease and death. Multivariate analysis revealed that only positive baseline CMV antigenemia assays (relative risk [RR], 7.2; 95% confidence interval [CI], 3.7-14.2; P = .0001) and CD4 cell counts (RR, 0.98; 95% CI, 0.97-0.99; P = .009) were associated with CMV disease. A positive baseline CMV antigenemia assay was also associated with death by multivariate analysis (RR, 2.2; 95% CI, 1.5-3.4; P = .0003). Increasing levels of CMV antigenemia during follow-up were associated with increased risks of CMV disease and death. A positive CMV antigenemia assay that showed > 10 cells per 2 x 10(5) polymorphonuclear leukocytes during follow-up was 91% sensitive and 84% specific for predicting a diagnosis of CMV disease; the negative predictive value for this positive test was high (97%). Therefore, the CMV antigenemia assay appears to be a simple, rapid, and inexpensive test for predicting the occurrence of CMV disease and death in patients with advanced HIV infection.

Tuberculosis generates a microenvironment enhancing the productive infection of local lymphocytes by HIV.

Tuberculosis (TB) contributes to the progression of HIV disease but, so far, the mechanism involved is not clear. Several cytokines accumulating in vivo at the site of mycobacterial infection up-regulate HIV expression in vitro. In this study, we assessed the role of pleural fluids recovered from seronegative patients with TB on HIV replication in acutely infected blast cells. Pleural fluids from subjects with congestive heart failure served as controls. In all cases, TB pleural fluids stimulated HIV replication in vitro. TNF-alpha, IL-6, IFN-gamma, and granulocyte/macrophage (GM)-CSF, as well as very low levels of IL-2, were detected in TB pleural fluids. An anti-IL-2 Ab preincubated with TB pleural fluids exhibited no blocking effect on HIV replication similarly to anti-IFN-gamma and anti-GM-CSF Abs. In contrast, anti-TNF-alpha and anti-IL-6 Abs decreased HIV replication by 60 and 90%, respectively. Recombinant TNF-alpha and IL-6 stimulated HIV replication, while IFN-gamma and GM-CSF had a more ambiguous role. The capacity of pleural fluids to stimulate HIV replication was specific for TB, since the capacity of control fluids was significantly lower. Finally, in contrast to PBL, which require in vitro activation for their productive infection by HIV, unstimulated tuberculous pleural lymphocytes were productively infectable by HIV. Taken together, our data suggest that the microenvironment generated by TB might increase the HIV burden in infected subjects, partly through cytokines other than IL-2, namely TNF-alpha and IL-6.

[Primary cerebral lymphoma in AIDS. Retrospective study of 20 patients]. / Lymphome cérébral primitif au cours du SIDA. Etude rétrospective de 20 patients.

OBJECTIVES: Analyze the epidemiological pattern of primary central nervous system lymphoma in AIDS patients together with the clinical expression and course under treatment. METHODS: We retrospectively reviewed 20 patients with AIDS-associated primary central nervous system lymphoma hospitalized in our unit between April 1992 and July 1996. Diagnosis was considered probable when an expansive intracranial process was associated with CT-scan enhancement and antitoxoplasma therapy failure in patients with extraneurological localization. Diagnosis was considered to be certain after histological confirmation. RESULTS: Most-patients were male (19/20), with a median CD4 cell count of 9/mm3 (range 0-138). Ninety percent had AIDS before diagnosis. The presenting symptoms were mental status changes (70%), neurologic deficits (55%), fever without another cause (30%), increased intracranial pressure (25%) or seizures (25%). Opportunistic diseases were usually associated (60%). CT-scan (18/20) showed spontaneous iso or hyperdense lesions, most often solitary (67%), with nodular contrast enhancement (72%). When performed (7/20), magnetic resonance imaging showed hypointense lesions on T1-weighted images with marked contrast enhancement. Diagnosis of primary central nervous system lymphoma was suspected in 19 patients because of the failure of antitoxoplasma treatment; 4 patients had stereotactic biopsy which confirmed the diagnosis. Patients were treated with either total brain radiation therapy (10%), corticosteroids (30%), or both (60%). The median survival time after onset of symptoms was better with combined therapy or radiation therapy alone than with steroids alone (6 vs. 2 months). Interestingly, most of the patients died from neurological complications of lymphoma (85%). DISCUSSION: The frequency of lymphoma-related death is probably due to better management of opportunistic infections and the effect of antiretroviral therapy. Further studies combining antiretroviral therapy, radiation and chemotherapy in patients with good performance status should be considered to improve the poor prognosis of AIDS-associated primary central nervous system lymphoma.

Campylobacter infections in HIV-infected patients: clinical and bacteriological features.

OBJECTIVE: To study the clinical and bacteriological features of Campylobacter infections in HIV-infected patients. DESIGN: A retrospective analysis (1989-1992), followed by a prospective analysis (1992-1994). SETTING: Hospital HIV inpatient unit. PATIENTS AND METHODS: All patients with Campylobacter spp. identified by the laboratory of microbiology at Saint-Louis Hospital, Paris were studied, and their clinical features as well as their response to therapy recorded. RESULTS: During the study period, Campylobacter infection was documented in 38 HIV-infected patients, 76% of whom had AIDS. Campylobacter spp. was isolated from stools in 36 cases and from blood cultures in four cases. Species identification yielded C. jejuni (84%) and C. coli (16%). High-level resistance to quinolones was frequently observed (21%), but resistance to erythromycin (3%) and tetracycline (5%) was rare. Diarrhoea, fever and abdominal pain were the main clinical features of infection. Other intestinal pathogens were found in 42% of patients. Most patients had an acute illness with rapid resolution under appropriate antimicrobial therapy. However, eight patients (21%), experienced chronic diarrhoea with persistent isolation of Campylobacter and in vivo selection of resistant strains, requiring multiple courses of antibiotics. CONCLUSIONS: Campylobacter usually cause acute diarrhoea in patients with HIV infection. Antimicrobial therapy should be guided on in vitro susceptibility testing because of the prevalence of antibiotic resistance. Despite appropriate therapy, some patients will present with prolonged diarrhoea and in vivo selection of multiresistant isolates.

[Role of human immunodeficiency virus infection in 67 patients with tuberculosis]. / Rôle de l'infection par le virus de l'immunodéficience humaine chez 67 patients atteints de tuberculose.

This retrospective study compared the epidemiological, clinical and bacteriological characteristics of tuberculosis in HIV-infected (HIV+) and seronegative (HIV-) patients in France. It included 67 cases of tuberculosis observed in the hospital setting between 1985 and 1990. The 35 HIV+ patients (52.2%) were more frequently of European origin, while those of African origin were HIV-. Disseminated tuberculosis predominated in HIV+ patients, as opposed to pulmonary tuberculosis in HIV- patients. The tuberculin test was more often positive in HIV- patients than in HIV+ ones (65.6 versus 17.1%; p < 0.001). Direct bacteriological examination of the sputum was positive more frequently in HIV- than HIV+ patients (56.2 versus 22.8%; p < 0.01). A high percentage of the Mycobacterium tuberculosis strains isolated from HIV+ patients (20%) was resistant to anti-tuberculous drugs, primarily isoniazid, while no resistance was found in HIV- patients. The initial response to treatment and the therapy-associated side effects did not differ between the two groups. Four relapses (11.4%) occurred in HIV+ patients, raising the question of the indication of drug prophylaxis following tuberculosis in HIV-infected patients.

[Pneumococcal pneumonia resistant to penicillin]. / Pneumopathie à pneumocoque résistant à la pénicilline.

The authors report a case of community-acquired pneumonia in a patient with chronic obstructive lung disease. The initial antibiotic therapy consisted of an amoxicillin-clavulanic acid combination and intravenous macrolides. Twenty-four hours after admission, blood cultures were positive for pneumococcus. Pending the results of disc sensitivity tests, the antibiotic therapy was modified and amoxicillin alone was prescribed. Clinical deterioration then developed rapidly, as the pathogen was amoxicillin-resistant. Subsequently, the patient recovered under erythromycin therapy. As illustrated by this case, the emergence of pneumococci resistant, or showing low sensitivity to penicillins raises the problem of the antibiotic therapy to be used against community-acquired lung diseases.