Dan Turner

Anti-heart antibodies in postpericardiotomy syndrome: cause or epiphenomenon? A prospective, longitudinal pilot study.

Objectives : To assess the role of anti-heart antibodies (AHA) in postpericardiotomy syndrome (PPS) and the timing of their appearance in relation to the initial manifestations of PPS. Design and subjects : Twenty patients who were scheduled to undergo elective coronary artery bypass grafting (CABG) were enrolled in a prospective, longitudinal pilot study. Methods : Serum was sampled for AHA on the day prior to surgery and at regular intervals following surgery in all patients. In those who developed PPS, the serum AHA was determined on the day that typical clinical manifestations of PPS appeared and at regular intervals following the onset of PPS. Results : All patients were negative for AHA on the day preceding surgery. Three (15%) patients developed PPS. Their sera were negative for AHA on the day they were diagnosed as suffering from PPS and the sera became positive for AHA within 14 days from the time of diagnosis. The intensity of immunofluorescence decreased markedly 30 days afterwards and AHA had disappeared within 90 days after diagnosis of PPS. The other 17 (85%) patients were negative for AHA prior to surgery and remained so during the six-month postoperative follow-up period. Conclusion : The findings of this study suggest that serum AHA may not play a causal role in the pathogenesis of PPS, but may rather be an epiphenomenon, reflecting an immune response to pericardial and/or myocardial injury.

Boosted protease inhibitor monotherapy in HIV- infected adults: outputs from a pan-European expert panel meeting

While the introduction of combination highly active antiretroviral therapy (HAART) regimens represents an important advance in the management of human immunodeficiency virus (HIV)-infected patients, tolerability can be an issue and the use of several different agents may produce problems. The switch of combination HAART to ritonavir-boosted protease inhibitor (PI) monotherapy may offer the opportunity to maintain antiviral efficacy while reducing treatment complexity and the risks of toxicity. Current European AIDS Clinical Society (EACS) guidelines recognise ritonavir-boosted PI monotherapy with twice-daily lopinavir/ritonavir or once-daily darunavir/ritonavir as a possible option in patients who have intolerance to nucleoside reverse transcriptase inhibitors, or for treatment simplification. Clinical trials data for PI boosted monotherapy are encouraging, showing substantial efficacy in the majority of patients; however, further data are required before this approach can be recommended as a routine treatment. Available data indicate that the most suitable candidates for the use of boosted PI monotherapy are long-term virologically suppressed patients who have demonstrated good adherence to antiretroviral therapy, who do not have chronic hepatitis B, have no history of treatment failure on PIs and are able to tolerate low-dose ritonavir.

Pulmonary Adiaspiromycosis in a patient with acquired immunodeficiency syndrome

Abstract Adiaspiromycosis is a noninfectious, nonarthropod-transmitted fungal infection that occurs worldwide in lower vertebrates, especially rodents. However, humans may become accidental hosts. Reported here is a case of adiaspiromycosis of the lung in an HIV-positive, 40-year-old, bisexual man who first presented with cough and dyspnea. Cultures of a bronchoalveolar lavage and protected brush specimen revealed the presence of fungal elements that were identified as Emmonsia parva var. parva. The patient was successfully treated with amphotericin B and thereafter with fluconazole. This organism should be added to the list of pathogens that cause pulmonary infection in AIDS patients.

Prevalence of the K65R resistance reverse transcriptase mutation in different HIV‐1 subtypes in Israel

The K65R mutation in HIV‐1 reverse transcriptase (RT) can be selected by the RT inhibitors tenofovir (TDF), abacavir (ABC), and didanosine (DDI). Recently, in vitro studies have shown that K65R is selected in tissue culture more rapidly with subtype C than subtype B viruses. The prevalence of K65R in viruses sequenced at the Tel‐Aviv AIDS Center was evaluated. This study analyzed retrospectively sequences from 1999 to 2007 in patients treated with TDF, ABC, and/or DDI and compared rates of mutational prevalence between subtypes. Fishers exact test was used to determine statistical significance. Forty‐four sequences from patients treated with the three above‐cited drugs were analyzed. Subtypes A (n = 1), CRF01_AE (n = 4), CRF02_AG (n = 2), B (n = 21), C (n = 11), D (n = 1), F (n = 3), and G (n = 1) were represented. Seven non‐B viruses had the K65R mutation, which was only found in one subtype B virus. Of these seven samples four were subtype C, one was subtype CRF01_AE, and two were subtype CRF02_AG. None of the eight viruses with K65R harbored thymidine analogue mutations. In this study, non‐subtype B viruses possessed the K65R mutation at higher incidence than subtype B viruses. Subtype C viruses may be especially prone to develop this mutation. Larger studies are needed to confirm these data. Efforts should be intensified to understand better differences in drug resistance between various HIV subtypes. J. Med. Virol. 81:1509–1512, 2009.

Increased intracellular macrophage inflammatory protein-1β correlates with advanced HIV disease

The objective of this study was to correlate between macrophage inflammatory protein-1beta (MIP1beta) and viral loads in untreated, HIV-infected individuals. For that purpose, HIV-positive patients were tested for number of copies of HIV-RNA in plasma and for intracellular MIP1beta in freshly explanted CD8 and CD4 lymphocytes and monocytes. Results demonstrate that the levels of MIP1beta in the various cell populations were significantly higher in the HIV group than in age-matched healthy individuals. Moreover, patients with low CD4 cell counts (<500/microl) and relatively high viral loads exhibited much higher levels of intracellular MIP1beta than patients with lower viral loads and CD4 counts >500/microl. We conclude therefore that although MIP1beta is induced in the various cell populations as a result of HIV infection in vivo, a high intracellular level of MIP1beta appears to be linked to a deterioration in the immune status of the patients.

Transmission patterns of HIV-subtypes A/AE versus B: inferring risk-behavior trends and treatment-efficacy limitations from viral genotypic data obtained prior to and during antiretroviral therapy.

Background HIV subtypes A and CRF01_AE (A/AE) became prevalent in Israel, first through immigration of infected people, mostly intravenous-drug users (IVDU), from Former Soviet-Union (FSU) countries and then also by local spreading. We retrospectively studied virus-transmission patterns of these subtypes in comparison to the longer-established subtype B, evaluating in particular risk-group related differences. We also examined to what extent distinct drug-resistance patterns in subtypes A/AE versus B reflected differences in patient behavior and drug-treatment history. Methods Reverse-transcriptase (RT) and protease sequences were retrospectively analyzed along with clinical and epidemiological data. MEGA, ClusalX, and Beast programs were used in a phylogenetic analysis to identify transmission networks. Results 318 drug-naive individuals with A/AE or patients failing combination antiretroviral therapy (cART) were identified. 61% were IVDU. Compared to infected homosexuals, IVDU transmitted HIV infrequently and, typically, only to a single partner. 6.8% of drug-naive patients had drug resistance. Treatment-failing, regimen-stratified subtype-A/AE- and B-patients differed from each other significantly in the frequencies of the major resistance-conferring mutations T215FY, K219QE and several secondary mutations. Notably, failing boosted protease-inhibitors (PI) treatment was not significantly associated with protease or RT mutations in either subtype. Conclusions While sizable transmission networks occur in infected homosexuals, continued HIV transmission among IVDU in Israel is largely sporadic and the rate is relatively modest, as is that of drug-resistance transmission. Deviation of drug-naive A/AE sequences from subtype-B consensus sequence, documented here, may subtly affect drug-resistance pathways. Conspicuous differences in overall drug-resistance that are manifest before regimen stratification can be largely explained in terms of treatment history, by the different efficacy/adherence limitations of older versus newer regimens. The phenomenon of treatment failure in boosted-PI-including regimens in the apparent absence of drug-resistance to any of the drugs, and its relation to adherence, require further investigation.

Emergence of an HIV-1 cluster harbouring the major protease L90M mutation among treatment-naïve patients in Tel Aviv, Israel.

Drug resistance‐associated mutations (DRMs) among HIV‐1 treatment‐naïve patients have increased in recent years. Their incidence and prevalence in various exposure risk categories (ERCs) were evaluated.

An intracellular antigen that reacts with MO2, a monoclonal antibody to CD14, is expressed by human lymphocytes

CD14, a lipopolysaccharide (LPS) receptor, is present on the surface membrane of phagocytic leukocytes; it is also present in a soluble form in serum. Recently published results confer to this molecule novel functions that are linked to T-cell activation and to apoptosis. We report here that we have defined and characterized a novel lymphocyte population in human peripheral blood, a population that expresses an intracellular antigen detectable with MO2, a monoclonal antibody directed against the human CD14 molecule. This population is composed primarily of CD8-positive T-cells. We found surprisingly that this novel MO2-positive population of lymphocytes was greatly enhanced in asymptomatic, untreated HIV-positive individuals.

Validation of two commercial real-time PCR assays for rapid screening of the HLA-B*57:01 allele in the HIV clinical laboratory.

The pharmacogenetics approach to screen for the presence of the HLA-B*57:01 allele in HIV-1 infected patients is mandatory to prevent the potential development of hypersensitivity reaction to abacavir treatment. Given the limitations of current genotype methodologies, commercial real-time PCR assays were specifically developed for this purpose, but have not been sufficiently validated and are still not widely used. Here, in the context of the HIV laboratory, we assessed the ability of two commercial kits, the LightSNiP rs2395029 HPC5 assay (TIB Molbiol) and the DuplicαReal-TimeHLA-B*5701 Genotyping kit (Euroclone), to retrospectively detect HLA-B*57:01 positive and negative samples of Israeli HIV-1 infected patients. The LightSNiP rs2395029 HPC5 assay had false-positive results, whereas the DuplicαReal-Time HLA-B*5701 Genotyping kit was highly accurate and could be readily implemented into clinical practice. It is hoped that this study will facilitate the assessment of additional commercial kits for HLA-B*57:01 detection and expand their use in the clinical laboratory. Such studies can likely help the use of abacavir treatment in HIV-1 infected patients.

Evaluation of the virtues and pitfalls in an HIV screening algorithm based on two fourth generation assays – A step towards an improved national algorithm

BACKGROUND Fourth-generation immunoassays used for HIV screening, simultaneously detect anti-HIV antibodies and HIV-1 P24 antigen, but are prone to false-positive results. Usually, they are followed by highly specific third-generation assay, able to differentiate between HIV-1/2 infections. In Israel, screening algorithm is based on consecutive testing by two fourth-generation assays and confirmation by a third-generation test. OBJECTIVES To evaluate the performance of this algorithm. STUDY DESIGN Architect HIV1/2 Combo (Combo) reactive results were tested by Vidas HIV Duo Ultra (VD). Confirmation was by INNO-LIA HIV 1/2 or Geenius assays. Five-year results were retrospectively analyzed. HIV true positives (TPs), acute infected (AI), false-positives (FPs) and HIV negatives, were as defined by the algorithm. RESULTS 501,338 individuals were screened, of which 956 were TPs, 64 AI and 30 F Ps. Specificity was almost 100% and positive predictive value 97%. VD was negative in 94% of confirmed Combo false-reactive individuals. The Combo results in the first tested sample differed substantially between TPs, AI and FPs, enabling the determination of a cutoff value that distinguished 94% of TPs and AI from FPs. CONCLUSIONS An algorithm is suggested that will use a single sample collection. HIV negative diagnosis will be based on Combo unreactive or Combo reactive/VD negative results. HIV positive diagnosis will be based on Combo reactive/ VD positive results, given a Combo value above a designated cutoff. Below this cutoff samples will be tested by a molecular assay. Since HIV-2 rarely occurs in Israel, the use of a third-generation confirmation assay should be discussed.