Incidence, clinical presentation, and outcome of HIV-1-associated cryptococcal meningitis during the highly active antiretroviral therapy era: a nationwide cohort study

Madeleine Touma,1 Line D Rasmussen,2 Raquel Martin-Iguacel,2 Frederik Neess Engsig,3 Nina Breinholt Stærke,4 Mette Stærkind,5 Niels Obel,1 Magnus Glindvad Ahlström1 1Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, 2Department of Infectious Diseases, Odense University Hospital, Odense, 3Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, 4Department of Infectious Diseases, Aarhus University Hospital, Aarhus, 5Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark Background: Human immunodeficiency virus (HIV) infection with advanced immunosuppression predisposes to cryptococcal meningitis (CM). We describe the incidence, clinical presentation, and outcome of CM in HIV-infected individuals during the highly active antiretroviral therapy (HAART) era.Methods: A nationwide, population-based cohort of HIV-infected individuals was used to estimate incidence and mortality of CM including risk factors. A description of neurological symptoms of CM at presentation and follow-up in the study period 1995–2014 was included in this study.Results: Among 6,351 HIV-infected individuals, 40 were diagnosed with CM. The incidence rates were 3.7, 1.8, and 0.3 per 1000 person-years at risk in 1995–1996, 1997–1999, and 2000–2014, respectively. Initiation of HAART was associated with decreased risk of acquiring CM [incidence rate ratio (IRR), 0.1 (95% CI, 0.05–0.22)]. African origin was associated with increased risk of CM [IRR, 2.05 (95% CI, 1.00–4.20)]. The main signs and symptoms at presentation were headache, cognitive deficits, fever, neck stiffness, nausea, and vomiting. All individuals diagnosed with CM had a CD4+ cell count <200 cells/µl [median 26; interquartile range (IQR), 10–50)]. Overall, mortality following CM was high and mortality in the first 4 months has not changed substantially over time. However, individuals who survived generally had a favorable prognosis, with 86% (18/21) returning to the pre-CM level of activity.Conclusion: The incidence of HIV-associated CM has decreased substantially after the introduction of HAART. To further decrease CM incidence and associated mortality, early HIV diagnosis and HAART initiation seems crucial. Keywords: cryptococcal meningitis, highly active antiretroviral therapy, HIV&nbsp

Time to virological failure and treatment failure through the long term follow-up.

<p>Virological failure was defined as two consecutive measurements of pVL >50 copies/mL. Treatment failure included subjects with virological failure, treatment discontinuations due to drug toxicity, and death.</p

Mutations shown at failure in the reverse transcriptase and protease, and NRTI included in the regimen together with NVP and TDF (3TC vs FTC).

<p>Mutations shown at failure in the reverse transcriptase and protease, and NRTI included in the regimen together with NVP and TDF (3TC vs FTC).</p

Factors associated with virologic failure to a switch regimen composed of NVP plus TDF plus FTC (or 3TC) (n = 341).

<p>* Some individuals in early calendar years had an undetectable viral load at baseline, but with tests using a threshold of 80 or 200 copies/mL.</p><p>VL: viral load; VF: virologic failures; NNRTI: non-nucleoside reverse transcriptase inhibitor; NRTI: nucleoside analogue reverse transcriptase inhibitor; PI: protease inhibitor.</p><p>Factors associated with virologic failure to a switch regimen composed of NVP plus TDF plus FTC (or 3TC) (n = 341).</p

Patient characteristics at the initiation of NVP plus TDF plus FTC (or 3TC) as a switch strategy (n = 341).

<p>Data are median (IQR) or n (%).</p><p>* Some individuals in the early calendar years had an undetectable viral load at baseline, but with tests using at that moment a threshold of 80 or 200 copies/mL.</p><p>MSM: Men having sex with men; NRTI: Nucleos(t)ide reverse transcriptase inhibitor; NNRTI: non-nucleoside reverse transcriptase inhibitor; PI: Protease inhibitor.</p><p>Patient characteristics at the initiation of NVP plus TDF plus FTC (or 3TC) as a switch strategy (n = 341).</p

Infectious Proctitis: When to Suspect It Is Not Inflammatory Bowel Disease

Item does not contain fulltextBACKGROUND: Proctitis is a common problem and is most frequently associated with inflammatory bowel diseases. However, the incidence of infectious proctitis appears to be rising, especially in men who have sex with men. This may be due to the rise of people participating in receptive anal sex as well as the increase in sexually transmitted infections. The most frequently reported pathogens include Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, and herpes simplex. DIAGNOSIS: Symptoms of infectious proctitis can include rectal blood and mucous discharge, anorectal pain, ulcers, and occasionally lymphadenopathy and fever. History and physical examination are crucial in establishing a diagnosis, supported by endoscopy, histology, serology, culture and PCR. TREATMENT: Treatment with antibiotics or antivirals is usually initiated, either empirically or after establishing a diagnosis. Co-infections, HIV testing, and treatment of sexual partners should always be considered.1 februari 201