Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection

BACKGROUND: For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are 500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.)

Delayed diagnosis of colorectal sexually transmitted diseases due to their resemblance to inflammatory bowel diseases

Objective: Sexually transmitted diseases (STDs), mainly lymphogranuloma venereum (LGV), induce colorectal symptoms that may be misdiagnosed as inflammatory bowel disease (IBD). This study describes patients who presented with STDs masquerading as IBD in order to improve understanding of missed diagnosis of colorectal STDs and their association with LGV in Israel. Methods: This retrospective, descriptive study characterized the clinical, endoscopic, and pathological findings of 16 patients who were diagnosed with a colorectal STD after erroneously being diagnosed with IBD. Molecular genotyping was used to characterize some of the Chlamydia trachomatis isolates. Results: All patients were men who have sex with men (MSM), mostly HIV-1-positive, and had clinical and endoscopic findings compatible with IBD. The STD was diagnosed 1–36 months after the initial diagnosis: 14 were positive for Chlamydia trachomatis, of which three were of the LGV2b (ST58) serotype and one was ST 108 serotype. Five were positive for gonorrhea and four were positive for syphilis. Several pathogens were diagnosed in six episodes. Conclusions: Colorectal STDs may resemble IBD and therefore their diagnosis may be delayed. IBD symptoms in MSM who engage in non-protected anal sex should prompt at least syphilis and anal PCR for STD testing. If C. trachomatis is diagnosed but LGV subtyping cannot be done, doxycycline 100 mg twice daily for 21 days should be recommended. Keywords: Chlamydia infection, Lymphogranuloma venereum, Neisseria gonorrhoeae, Syphilis, Proctitis, Men who have sex with me

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

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

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

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

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