Rituximab identified as an independent risk factor for severe PJP: A case-control study.

ObjectivePneumocystis jirovecii pneumonia (PJP) was reported among immunosuppressed patients with deficits in cell-mediated immunity and in patients treated with immunomodulatory drugs. The aim of this study was to identify risk-factors for PJP in noninfected HIV patients.MethodsThis retrospective, test negative, case-control study was conducted in six hospitals in Israel, 2006-2016. Cases were hospitalized HIV-negative patients with pneumonia diagnosed as PJP by bronchoalveolar lavage. Controls were similar patients negative for PJP.ResultsSeventy-six cases and 159 controls were identified. Median age was 63.7 years, 65% males, 34% had hematological malignancies, 11% inflammatory diseases, 47% used steroids and 9% received antilymphocyte monoclonal antibodies. PJP was independently associated with antilymphocyte monoclonal antibodies (OR 11.47, CI 1.50-87.74), high-dose steroid treatment (OR 4.39, CI 1.52-12.63), lymphopenia (OR 8.13, CI 2.48-26.60), low albumin (OR 0.15, CI 0.40-0.54) and low BMI (OR 0.80, CI 0.68-0.93).ConclusionIn conclusion, rituximab, which is prescribed for a wide variety of malignant and inflammatory disorders, was found to be significant risk-factor for PJP. Increased awareness of possible PJP infection in this patient population is warranted

A Population-Structured HIV Epidemic in Israel: Roles of Risk and Ethnicity

<div><p>Background</p><p>HIV in Israel started with a subtype-B epidemic among men who have sex with men, followed in the 1980s and 1990s by introductions of subtype C from Ethiopia (predominantly acquired by heterosexual transmission) and subtype A from the former Soviet Union (FSU, most often acquired by intravenous drug use). The epidemic matured over the last 15 years without additional large influx of exogenous infections. Between 2005 and 2013 the number of infected men who have sex with men (MSM) increased 2.9-fold, compared to 1.6-fold and 1.3-fold for intravenous drug users (IVDU) and Ethiopian-origin residents. Understanding contemporary spread is essential for effective public health planning.</p><p>Methods</p><p>We analyzed demographic and virologic data from 1,427 HIV-infected individuals diagnosed with HIV-I during 1998–2012. HIV phylogenies were reconstructed with maximum-likelihood and Bayesian methods.</p><p>Results</p><p>Subtype-B viruses, but not A or C, demonstrated a striking number of large clusters with common ancestors having posterior probability ≥0.95, including some suggesting presence of transmission networks. Transmitted drug resistance was highest in subtype B (13%). MSM represented a frequent risk factor in cross-ethnic transmission, demonstrated by the presence of Israeli-born with non-B virus infections and FSU immigrants with non-A subtypes.</p><p>Conclusions</p><p>Reconstructed phylogenetic trees demonstrated substantial grouping in subtype B, but not in non-MSM subtype-A or in subtype-C, reflecting differences in transmission dynamics linked to HIV transmission categories. Cross-ethnic spread occurred through multiple independent introductions, with MSM playing a prevalent role in the transmission of the virus. Such data provide a baseline to track epidemic trends and will be useful in informing and quantifying efforts to reduce HIV transmission.</p></div

BEAST of subtype A.

<p>Analysis of sequences from patients infected with subtype A (Including 61 reference sequences). Notations as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135061#pone.0135061.g002" target="_blank">Fig 2</a>.</p

Cluster # 48.

<p>The first of three examples of large subtype-B clusters embedded in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135061#pone.0135061.g004" target="_blank">Fig 4</a>. Cluster 48 is composed of 25 males, 24 of them MSM, diagnosed and genotyped between 2008 and 2013. All but one harbored the protease mutations L90M and L10V; the remaining one had only L10V. The group contains one seroconverter who was diagnosed in 2008. 20 members had a posterior probability of recent common ancestor >0.99 and had short branches. Year of genotyping is indicated as well as branch lengths in years and selected resistance related mutations. Posterior probabilities ≥0.99 are indicated in red. Blue asterisk–seroconverters; green triangles–heterosexual males; green circles–heterosexual females; white triangles–male, risk group unknown; yellow triangles–IVDU males; yellow circles–IVDU females; FSU, Former Soviet Union; Hetero, heterosexuals; IVDU, intravenous drug users; MSM, men who have sex with men.</p

BEAST of subtype B.

<p>Analysis of sequences from patients infected with subtype B (Including 30 reference sequences). Notations as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135061#pone.0135061.g002" target="_blank">Fig 2</a>.</p

Bayesian evolutionary analysis sampling trees (BEAST) of subtype C.

<p>Sequences from patients infected with subtype C viruses were subjected to Monte-Carlo Markov Chain (MCMC) analyses using BEAST to construct phylogenies and investigate ancestral relationships. 47 reference subtype C sequences (<a href="http://www.hiv.lanl.gov/" target="_blank">http://www.hiv.lanl.gov/</a>) were included. The MCMC length (burn in 10%) was of 400–600 million states to achieve posterior effective sample size (ESS) >200 as described [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135061#pone.0135061.ref026" target="_blank">26</a>]. Red lines represent branches with posterior probability of recent common ancestor ≥0.95. Red-circled nodes represent posterior probability ≥0.95. The largest clusters are marked. Insets describe the number and size of clusters. Israeli-born and FSU-born infected with subtype C are marked with thin blue and red arrows, respectively. Dashed arrows indicate calculated year of selected nodes. FSU, Former Soviet Union; Hetero, heterosexuals; IVDU, intravenous drug users; MSM, men who have sex with men.</p

Cluster # 52.

<p>Cluster 52 is composed of 48 males, diagnosed and genotyped between 2007 and 2013. 26 harbored K103N, one K103E, and 4 had T215S. The group contains 3 seroconverters who were diagnosed 3 years apart (in 2007 and 2009). A transmission network of 7 members is noted (arrow). Notations as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135061#pone.0135061.g005" target="_blank">Fig 5</a>.</p