Helen Sambatakou

Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: case series, proposed nomenclature change, and review.

We describe 18 nonimmunocompromised patients with chronic pulmonary aspergillosis. Duration of the disease ranged from several months to >12 years. All 18 patients had prior pulmonary disease. Weight loss, chronic cough (often with hemoptysis and shortness of breath), fatigue, and chest pain were the most common symptoms. All 18 patients had cavities, usually multiple and in 1 or both upper lobes of the lung, that expanded over time, with or without intraluminal fungal balls. All had detectable Aspergillus precipitins and inflammatory markers. Elevated levels of total immunoglobulin E were seen in 78% of patients and of Aspergillus-specific immunoglobulin E in 64%. Directed lung biopsies showed chronic inflammation, necrosis, or granulomas without hyphal invasion. Antifungal therapy with itraconazole resulted in 71% of patients improved or stabilized, with relapse common. Interferon-gamma treatment was useful in 3 patients. In azole nonresponders, modest responses to intravenous amphotericin B (80%) followed by itraconazole were seen. Surgery removed disease but postoperative pleural aspergillosis was inevitable. Indicators of good long-term medical outcomes were mild symptoms, thin-walled quiescent cavities, residual pleural fibrosis, and normal inflammatory markers.

Assessment, Diagnosis, and Treatment of HIV-Associated Neurocognitive Disorder: A Consensus Report of the Mind Exchange Program

Many practical clinical questions regarding the management of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remain unanswered. We sought to identify and develop practical answers to key clinical questions in HAND management. Sixty-six specialists from 30 countries provided input into the program, which was overseen by a steering committee. Fourteen questions were rated as being of greatest clinical importance. Answers were drafted by an expert group based on a comprehensive literature review. Sixty-three experts convened to determine consensus and level of evidence for the answers. Consensus was reached on all answers. For instance, good practice suggests that all HIV patients should be screened for HAND early in disease using standardized tools. Follow-up frequency depends on whether HAND is already present or whether clinical data suggest risk for developing HAND. Worsening neurocognitive impairment may trigger consideration of antiretroviral modification when other causes have been excluded. The Mind Exchange program provides practical guidance in the diagnosis, monitoring, and treatment of HAND.

Distinct alleles of mannose-binding lectin (MBL) and surfactant proteins A (SP-A) in patients with chronic cavitary pulmonary aspergillosis and allergic bronchopulmonary aspergillosis.

Abstract Background: Distinct host immune status predisposes to different forms of pulmonary aspergillosis. Methods: Patients with chronic cavitary pulmonary aspergillosis (CCPA; n=15) or allergic bronchopulmonary aspergillosis (ABPA; n=7) of Caucasian origin were screened for single nucleotide polymorphisms (SNPs) in the collagen region of surfactant proteins A1 (SP-A1) and A2 (SP-A2) and mannose binding lectin (MBL). Results: The T allele at T1492C and G allele at G1649C of SP-A2 were observed at slightly higher frequencies in ABPA patients (86% and 93%) than in controls (63% and 83%), and the C alleles at position 1492 and 1649 were found in higher frequencies in CCPA patients (33% and 25%) than in ABPA patients (14% and 7%) (all p>0.05). However, the CC genotype at position 1649 of SP-A2 was significantly associated with CCPA (χ2=7.94; pcorr≤0.05). Similarly, ABPA patients showed a higher frequency of the TT genotype (71%) at 1492 of SP-A2 than controls (43%) and CCPA patients (41%) (p>0.05). In the case of MBL, the T allele (OR=3.1, range 1.2–8.9; p≤0.02) and CT genotype (χ2=6.54; pcorr≤0.05) at position 868 (codon 52) were significantly associated with CCPA, but not with ABPA. Further analysis of genotype combinations at position 1649 of SP-A2 and at 868 of MBL between patient groups showed that both CC/CC and CC/CT SP-A2/MBL were found only in CCPA patients, while GG/CT SP-A2/MBL was significantly higher in CCPA patients in comparison to ABPA patients (p≤0.05). SNPs analysed in SP-A1 did not differ between cases and controls. Conclusions: Distinct alleles, genotypes and genotype combinations of SP-A2 and MBL may contribute to differential susceptibility of the host to CCPA or ABPA. Clin Chem Lab Med 2007;45:183–6.

Increasing Prevalence of HIV-1 Subtype A in Greece: Estimating Epidemic History and Origin

BACKGROUND In North America and Europe, human immunodeficiency virus (HIV)-1 infection has typically been dominated by subtype B transmission. More recently, however, non-B subtypes have been increasingly reported in Europe. METHODS We analyzed 1158 HIV-1-infected individuals in Greece by DNA sequencing and phylogenetic analyses of protease and partial reverse-transcriptase regions. RESULTS We found that the prevalence of non-B subtypes has increased over time and that this significant trend can be mainly attributed to subtype A, which eventually surpassed subtype B in prevalence in 2004 (42% and 33%, respectively). Multivariate analysis revealed that the year of HIV diagnosis was independently associated with subtype A infection (odds ratio for being infected with subtype A for a 10-year increase in the time period of diagnosis, 2.09 [95% confidence interval, 1.36-3.24]; P<.001). Phylogenetic analysis revealed that the subtype A epidemic in Greece is the result of a single founder event. The date of the most recent common ancestor of the subtype A in Greece was estimated to be 1977.9 (95% highest posterior density interval, 1973.7-1981.9). CONCLUSIONS Subtype A circulates among the long-term residents of Greece. This is in contrast to the situation in most European countries, in which infection with non-B genetic forms is associated either with being an immigrant or heterosexual or with intravenous drug use.

Cytokine profiling of pulmonary aspergillosis.

Aspergillus fumigatus is ubiquitous and yet causes invasive, chronic and allergic disease of the lung. Chronic cavitary pulmonary aspergillosis (CCPA) is a slowly destructive form of pulmonary aspergillosis, without immunocompromise. We hypothesized that CCPA cytokine gene polymorphisms would differ from patients with allergic bronchopulmonary aspergillosis (ABPA) and uninfected controls.

Low-Dose IFN-α Monotherapy in Treatment-Naive Individuals with HIV-1 Infection: Evidence of Potent Suppression of Viral Replication

To evaluate the safety and antiviral action of interferon-alpha (IFN-alpha) in HIV-1 infection, we undertook a proof of concept study in 27 treatment-naive patients. Eligible patients comprised two groups: the IFN-alphaT group (n = 17), which received 5 MIU IFN-alpha s.c. daily for 32 consecutive days, and the IFN-alphaNT group (n = 10), which did not receive IFN-alpha prior to highly active antiretroviral therapy (HAART), which was commenced on day 28 in both groups. IFN-alphaTreatment was well tolerated in 14 of the 17 patients of the IFN-alphaT group who completed the study. The mean HIV RNA reduction in the IFN-alphaT group on day 14 was 1.1 log(10). Viral load suppression was inversely associated with baseline viral load (p = 0.031). Four weeks after initiation of HAART, IFN-alphaT and IFN-alphaNT group patients had 2.40 and 1.82 log(10) HIV RNA reduction from baseline, respectively (p < 0.001). There was no evidence of cross-resistance with existing antiretrovirals in patients with HIV-RNA rebound after initial plasma viral load decline > or = 1 log(10) during IFN-alpha monotherapy. Thus, low daily IFN-alpha exhibits potent anti-HIV-1 activity in vivo without serious adverse effects. These properties render IFN-alpha an attractive candidate for further assessment as a constituent of HAART.

Changes in hospital admissions across Europe: 1995-2003. Results from the EuroSIDA study

To describe changes in the proportions of patients admitted to hospital and the duration of admission during the month of March between 1995 and 2003 and to describe the factors related to admission for 9802 patients from EuroSIDA, a pan‐European, observational cohort study.

A standardized algorithm for determining the underlying cause of death in HIV infection as AIDS or non-AIDS related: results from the EuroSIDA study.

Abstract Objectives: Analyzing changes in causes of death over time is essential for understanding the emerging trends in HIV population mortality, yet data on cause of death are often missing. This poses analytic limitations, as does the changing approach in data collection by longitudinal studies, which are a natural consequence of an increased awareness and knowledge in the field. To monitor and analyze changes in mortality over time, we have explored this issue within the EuroSIDA study and propose a standardized protocol unifying data collected and allowing for classification of all deaths as AIDS or non-AIDS related, including events with missing cause of death. Methods: Several classifications of the underlying cause of death as AIDS or non-AIDS related within the EuroSIDA study were compared: central classification (CC-reference group) based on an externally standardised method (the CoDe procedures), local cohort classification (LCC) as reported by the site investigator, and 4 algorithms (ALG) created based on survival times after specific AIDS events. Results: A total of 2,783 deaths occurred, 540 CoDe forms were collected, and 488 were used to evaluate agreements. The agreement between CC and LCC was substantial (κ = 0.7) and the agreement between CC and ALG was moderate (κ < 0.6). Consequently, a stepwise algorithm was derived prioritizing CC over LCC and, in patients with no information available, best-fit ALG. Using this algorithm, 1,332 (47.9%) deaths were classified as AIDS and 1,451 (52.1%) as non-AIDS related. Conclusions: Our proposed stepwise algorithm for classifying deaths provides a valuable tool for future research, however validation in another setting is warranted.

Invasive pulmonary aspergillosis transformed into fatal mucous impaction by immune reconstitution in an AIDS patient

Reported here is the case of a newly diagnosed AIDS patient with end-stage HIV infection and biopsy-proven invasive pulmonary aspergillosis who responded to antifungal therapy but developed severe mucous impaction in association with rapid immune restoration that was ultimately fatal. Invasive pulmonary aspergillosis complicates about 4% of AIDS infections. A search of the medical literature revealed no previous report of this organisms involvement in immune restoration syndrome.

Virological and Immunological Response to HAART Therapy in a Community-Based Cohort of HIV-1-Positive Individuals

Abstract Purpose: To determine virological and immunological response to highly active antiretroviral therapy (HAART) and to investigate factors influencing response in a community-based setting. Method: Plasma HIV RNA levels and CD4 cell counts were studied in 168 unselected individuals starting HAART including indinavir or ritonavir or hard-gel saquinavir-containing regimens. Results: Overall, 60% of the patients reduced their HIV RNA to below 500 Eq/mL, but half of them experienced a subsequent virologic rebound. Patients with higher baseline HIV RNA, higher baseline CD4 cell count, and simultaneous initiation of combination therapy and patients on indinavir or ritonavir regimen were more likely to have virologic response within 6 months since HAART initiation. Patients with lower baseline CD4 cell count and with lower rates of viral clearance had a higher probability of a subsequent virologic rebound. Forty percent of the patients had increased their CD4 cell counts by more than 100 cells/μL (immunologic response). The probability of immunologic response was independent of baseline HIV RNA levels and CD4 cell count; however, the more complete the virologic suppression, the higher the probability of immunologic response. Thirty percent of the patients had discordance between virologic and immunologic responses. Conclusion: The rate of virologic failure in this unselected group of patients was higher than that observed in randomized clinical trials, but only a minority (11%) of the patients were treatment naïve. Starting combination therapy simultaneously and initiating antiretroviral therapy before advanced HIV disease has developed predict virologic response, whereas the magnitude of viral suppression predicts mid to long immunological response.