Long-term follow-up of 11 protease inhibitor (PI)-naïve and PI-treated HIV-infected patients harbouring virus with insertions in the HIV-1 protease gene.

OBJECTIVES: Amino acid insertions in the protease gene have been reported rarely, and mainly in patients receiving protease inhibitors (PIs). The aim of the study was to assess the long-term viro-immunological follow-up of HIV-infected patients harbouring virus with protease insertions. METHODS: Cases of virus exhibiting protease insertions were identified in routine resistance genotyping tests. Therapeutic, immunological and virological data were retrospectively collected. RESULTS: Eleven patients harbouring virus with a protease gene insertion were detected (prevalence 0.24%), including three PI-naïve patients. The insertions were mainly located between codons 33 and 39 and associated with surrounding mutations (M36I/L and R41K). The three PI-naïve patients were infected with an HIV-1 non-B subtype. Follow-up of these PI-naïve patients showed that the insert-containing virus persisted for several years, was archived in HIV DNA, and displayed a reduced viral replicative capacity with no impact on resistance level. Of the eight PI-experienced patients, 63% were infected with HIV-1 subtype B; one had been antiretroviral-free for 5 years and seven were heavily PI-experienced (median duration of follow-up 24 months; range 10-62 months). The protease insertion was selected under lopinavir in four patients and under darunavir in one, in the context of major PI-resistance mutations, and following long-term exposure to PIs. The insert-containing virus persisted for a median of 32 months (range 12-62 months) and displayed no specific impact on phenotypic resistance level or viral replicative capacity. CONCLUSION: Our data, obtained during long-term follow-up, show that insertions in the protease gene do not seem to have an impact on resistance level. This finding supports the recommendation of PI-based regimens, although further work is required to confirm it.

Bacterial chondritis complications following ear piercing.

BACKGROUND: Body piercing has become widespread and is associated with increased complications. Post-piercing chondritis may lead to severe residual deformity. We aimed to report case patients presenting with post-piercing chondritis in our department and to describe clinical features and treatment. PATIENTS AND METHODS: We conducted a retrospective study of patients presenting with post-piercing chondritis in the infectious disease department of Tenon Hospital, Paris, France. RESULTS: We included 21 patients. Fifteen bacteriological cultures were positive (7 Pseudomonas aeruginosa, 5 Staphylococcus aureus, and three other). Dual intravenous antibiotic therapy was administered to 13 patients for a median duration of six days [2-8], replaced by an oral antibiotic therapy for a median duration of 15 days [7-40]. Eight patients received oral antibiotic monotherapy for 10 days [7-30]. Median duration of antibiotic therapy was 16 days. Earring removal was performed for 18 patients. No ear deformity or general complication was reported. CONCLUSION: Transcartilaginous ear piercing may lead to infectious complications or deformity. In case of chondritis, early administration of an antibiotic therapy active against P. aeruginosa and S. aureus is recommended. Specific guidelines are needed.

[Viral failure in infants perinatally infected with HIV: A double punishment]. / Échec virologique chez les nourrissons infectés par le VIH par transmission périnatale : une double peine.

BACKGROUND: Considering the remarkable efficacy of the strategies for preventing mother-to-child transmission of HIV infection (PMTCT), failures are rare in high-resource countries and deserve further investigation. Moreover, infants have been found to be at increased risk of viral failure. We analyzed the factors related to the children's environment, including maternal psychological factors that may be associated with viral failure in children diagnosed before the age of 1 year. PATIENTS AND METHODS: Retrospective study of all HIV-infected infants, born in France between July 2003 and July 2013, diagnosed before the age of 1 year, cared for in a single reference center, comparing the group of children in viral success to the group of children presenting at least one episode of viral failure, using data available in their medical, psychological and social files. RESULTS: Out of 1061 infants included in the prospective PMTCT follow-up, eight infants were found HIV-positive and an additional six cases were referred from other centers before the age of 1 year, for a total of 14 children born to 13 mothers. Seven children presented durable optimal viral control (VL<50 c/mL) whereas seven others did not reach or maintain optimal viral control over time. The main difference between the two groups was the presence among the mothers of children with viral failure of severe psychological disorders, leading to treatment adherence problems in the mothers who were aware of their HIV status before pregnancy, and difficulties in giving their children's treatments correctly. CONCLUSIONS: Although seroconversion during pregnancy is responsible for a significant proportion of residual transmission in high-resource countries, severe psychological or psychiatric conditions in HIV-positive mothers play an important role on the risk of both MTC residual transmission and viral failure in their infants.

Intravenous methotrexate for primary central nervous system non-Hodgkin's lymphoma in AIDS.

OBJECTIVE: To evaluate high-dose intravenous methotrexate in primary central nervous system (CNS) lymphoma in HIV-infected patients. DESIGN: An uncontrolled pilot trial. SETTING: An infectious diseases department in Paris, France. PATIENTS: All consecutive AIDS patients with primary CNS lymphoma attending the same unit from August 1994 to March 1996. INTERVENTIONS: Methotrexate was intravenously administered at a dose of 3 g/m2 every 14 days with leucovorin rescue. A maximum of six cycles was planned. Steroids were given to all patients and haematological growth factors were administered as required. MAIN OUTCOME MEASURES: Rate of response, time to response and survival. RESULTS: Fifteen patients (10 with histological documentation) were recruited. The median time since clinical onset was 27 days (range, 7-69 days), median Karnofsky score was 51 (range, 30-70), and mean CD4+ cell count was 30 +/- 19 x 10(6)/l (range, 7-69 x 10(6)/l). Complete responses, defined as clinical improvement and disappearance of contrast-enhancing brain abnormalities on computed tomography or magnetic resonance imaging, were obtained in seven out of 15 patients (three out of 10 patients with histological diagnosis and four out of five patients without histological confirmation). The Karnofsky score of these seven patients improved to 80 +/- 10 (range, 70-100). The mean time taken to respond was 62 +/- 20 days (range, 45-90 days). One patient relapsed at 6 months. Six patients failed to respond, and two died of severe sepsis on days 15 and 45. The median survival time was 290 days (range, 11-570 days): 73 days (range, 11-570 days) in the 10 patients with histological diagnosis, and 347 days (range, 286-409 days) in the five patients without histological confirmation. Side-effects occurred in 10 patients, with gastrointestinal disorders in five, mucositis and skin rash in two, and fever in three patients; however, these events were mild and did not require cycle postponement or dose changes. No cognitive dysfunction occurred. CONCLUSION: Methotrexate appears to be an attractive alternative to radiation therapy for primary CNS lymphoma and is associated with a far greater improvement in quality of life relative to historical series of radiation therapy.

[Piercing and its infectious complications. A public health issue in France]. / Le piercing et ses complications infectieuses. Un enjeu de santé publique en France.

CHARACTERISTIC FEATURES: Piercing, an act that modifies the body, has progressed considerably in France over the last few years. The population involved has grown and become more diversified. Performed with a solid needle or a catheter, a wide variety of anatomic localizations are concerned, particularly the nose, ears, and navel. The shape of the "rings", generally made of surgical steel, niobium or titanium, varies greatly. Wound healing by epithelialisation can take up to several months. INFECTIOUS RISK: Between 10% and 20% of all piercings lead to a local infection. The most commonly found causal agests are Staphylococcus aureus, group A Streptococcus and Pseudomonas sp. These germs can cause severe life-threatening complications even in common localizations (earlobe). Viral transmission is another risk (hepatitis B, hepatitis C, hepatitis delta, HIV). A few cases of fatal fulminant hepatitis have been described immediately after piercing. SAFETY MEASURES: Generally performed under less than desirable sanitary conditions, safety measures are needed for piercing. Among professional "piercers", a certain number have emphasized the need for providing their clients with safer services. The prevention of infection risk should be a priority for all. Work along this line has been done in the United States and Canada. In light of the impact on public health, it is important to rapidly develop guidelines and regulations for piercing in France. Both professional piercers and health care workers should participate in developing these safety measures in order to assure their implementation.

[Lesions of the conus medullaris and the cauda equina caused by cytomegalovirus in HIV infection. 7 cases]. / Atteintes du cône terminal et de la queue de cheval dues au cytomégalovirus au cours de l'infection à VIH. 7 observations.

OBJECTIVES: Neurologic infections caused by cytomegalovirus are common in patients with acquired immunodeficiency syndrome (AIDS). The prognosis is particularly severe when the infection is localized in the conus medullaris and/or the cauda equina. METHODS: Among the 861 patients with AIDS treated in our unit from 1991 to 1993, 7 cases involving cytomegalovirus infection of the conus medullaris and/or the cauda equina were studied retrospectively. RESULTS OF THE CASE REPORTS: Clinical manifestations were nearly always the same: low back pain, motor deficiency in the lower limbs progressing to flaccid paraplegia and sphincter failure. The cerebrospinal fluid contained a high cell count with unaltered polynuclears and increased protein levels. In 6/7 patients virus cultures and search for the viral genome in the cerebrospinal fluid were positive. The clinical course was favourable in 6 patients after 3 weeks treatment with ganciclovir and/or foscarnet. Virology tests became negative in three-fourths of the patients. Nevertheless, relapse occurred after 4.2 weeks despite long-term therapy. CONCLUSION: The severe clinical course of this disease and the gravity of constantly fatal relapse requires highly adapted treatment and overall health care.

[Plurifocal alveolar pneumonia in a patient with AIDS: disseminated Mycobacterium avium intracellulare infection with difficult diagnosis]. / Pneumopathie alvéolaire plurifocale chez un patient atteint de SIDA: une infection disséminée à Mycobacterium avium intracellulare de diagnostic difficile.

In patients with the acquired immunodeficiency syndrome (AIDS), manifestations of generalized Mycobacterium avium intracellulare infection are non-specific and pneumopathy is rarely encountered. We report a case of a patient with AIDS who had clinical and radiological manifestations of multifocal alveolar pneumopathy which was found on autopsy to be due to disseminated Mycobacterium avium intracellulare.

Clinical and bacteriologic impact of rifabutin prophylaxis for Mycobacterium avium complex infection in patients with human immunodeficiency virus infection.

We conducted a prospective observational study to determine the feasibility and impact of rifabutin prophylaxis (300 mg daily) for human immunodeficiency virus-infected patients whose CD4 cell counts were <100/mm3. Three hundred seventy-one patients (65.2% of all patients with CD4 cell counts of <100/mm3 [mean +/- SD, 30 +/- 25/mm3]) received rifabutin prophylaxis for a mean duration +/- SD of 35.5 +/- 34.2 weeks; 198 patients (mean CD4 cell count +/- SD, 51.6 +/- 32/mm3) did not receive prophylaxis. Rifabutin prophylaxis for 8.4% of patients was interrupted because of adverse events. Mycobacterium avium complex (MAC) bacteremia developed in 17 (4.6%) of 371 patients receiving rifabutin prophylaxis and in 22 (11.1%) of 198 patients not receiving rifabutin prophylaxis. The mean CD4 cell count +/- SD at the diagnosis of MAC bacteremia was lower in patients receiving prophylaxis than in those not receiving prophylaxis (11.5 +/- 6.8/mm3 vs. 34.7 +/- 36/mm3, respectively; P < .01). MICs for MAC strains isolated from patients receiving prophylaxis were less than or equal to those for strains isolated from patients not receiving prophylaxis.

AIDS-related primary pulmonary lymphoma.

We describe 12 cases of AIDS-related primary pulmonary lymphoma occurring between 1986 and 1996 in a large French cohort of HIV-infected patients. Diagnostic criteria were: (1) histologically proven lymphomatous pulmonary involvement; (2) absence of mediastinal and/or hilar adenopathy on chest radiography; (3) absence of extrathoracic lymphoma extension. All patients were severely immunodeficient at the time of diagnosis. All but one patient presented with B and/or nonspecific respiratory symptoms. Chest radiography showed one or more marginated nodule(s) or large mass. CT scan showed a cavitary lesion in five patients. No lymph node enlargement or specific pleural effusion was detected. Transthoracic needle biopsies were performed in 10 patients and avoided open-lung biopsy for the diagnosis of lymphoma in five patients. All but one of the primary pulmonary lymphoma were high-grade B-cell non-Hodgkin's lymphomas. Using antilatent membrane protein-1 antibodies and an Epstein-Barr-Virus-encoded RNA transcript-specific probe, latent EBV infection of tumor cells was demonstrated in every case. All but one of the patients received chemotherapy. The median survival time was 4 mo, and no patient was still alive at the cut-off date for this analysis. Progessive pulmonary lymphoma was the main cause of death, but infections were also frequent.

Pneumocystis jirovecii dihydropteroate synthase genotypes in French patients with pneumocystosis: a 1998-2001 prospective study.

Dihydropteroate synthase gene (DHPS) mutations at codons 55 and 57 have been associated with sulfa/sulfone resistance in Pneumocystis jirovecii strains from patients who previously received prophylaxis. To evaluate the prevalence of these mutations, a portion of P. jirovecii DHPS gene was analysed using PCR combined with restriction fragment length polymorphism (RFLP) analysis in 92 bronchoalveolar fluid samples collected between January 1998 and September 2001 from French patients with pulmonary pneumocystosis (PCP). Seventy-six samples contained the wild-type DHPS genotype (82.6%) and 16 contained a mutant genotype (17.4%). Twelve out of the 16 isolates with a mutant DHPS genotype corresponded to patients who had never received sulfa or sulfone prophylaxis, suggesting that DHPS mutants may be acquired de novo. There was no significant difference in favourable or adverse outcome in PCP caused by the wild or mutant DHPS genotypes (P = 0.34).