Emergence of HIV-1 drug resistance in previously untreated patients initiating combination antiretroviral treatment: a comparison of different regimen types

BACKGROUND: Standard first-line combination antiretroviral treatment (cART) against human immunodeficiency virus 1 (HIV-1) contains either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r). Differences between these regimen types in the extent of the emergence of drug resistance on virological failure and the implications for further treatment options have rarely been assessed. METHODS: We investigated virological outcomes in patients from the Swiss HIV Cohort Study initiating cART between January 1, 1999, and December 31, 2005, with an unboosted PI, a PI/r, or an NNRTI and compared genotypic drug resistance patterns among these groups at treatment failure. RESULTS: A total of 489 patients started cART with a PI, 518 with a PI/r, and 805 with an NNRTI. A total of 177 virological failures were observed (108 [22%] PI failures, 24 [5%] PI/r failures, and 45 [6%] NNRTI failures). The failure rate was highest in the PI group (10.3 per 100 person-years; 95% confidence interval [CI], 8.5-12.4). No difference was seen between patients taking a PI/r (2.7; 95% CI, 1.8-4.0) and those taking an NNRTI (2.4; 95% CI, 1.8-3.3). Genotypic test results were available for 142 (80%) of the patients with a virological treatment failure. Resistance mutations were found in 84% (95% CI, 75%-92%) of patients taking a PI, 30% (95% CI, 12%-54%) of patients taking a PI/r, and 66% (95% CI, 49%-80%) of patients taking an NNRTI (P < .001). Multidrug resistance occurred almost exclusively as resistance against lamivudine-emtricitabine and the group-specific third drug and was observed in 17% (95% CI, 9%-26%) of patients taking a PI, 10% (95% CI, 0.1%-32%) of patients taking a PI/r, and 50% (95% CI, 33%-67%) of patients taking an NNRTI (P < .001). CONCLUSIONS: Regimens that contained a PI/r or an NNRTI exhibited similar potency as first-line regimens. However, the use of a PI/r led to less resistance in case of virological failure, preserving more drug options for the future.

Localized amyloid light-chain amyloidosis and extramedullary plasmacytoma of the mitral valve

An unusual case of localized amyloid light-chain (AL) amyloidosis and extramedullary plasmacytoma of the mitral valve is described. The worsening of a mitral regurgitation led to investigations and surgery. The valve presented marked distortion and thickening by type AL amyloid associated with a monotypic CD138+ immunoglobulin lambda plasma cell proliferation. Systemic staging showed a normal bone marrow and no evidence of amyloid deposition in other localizations. The patient's outcome after mitral valve replacement was excellent. To our knowledge, this is the first description of a localized AL amyloidosis as well as of a primary extramedullary plasmacytoma of the mitral valve.

Anmerkungen zu der Schrift des Herrn Dohm, über die bürgerliche Verfassung der Juden

von J. C. U.

Rettung der Juden : Als ein Anhang zu des Hrn. Kriegsraths Dohm Abhandlung: Ueber die bürgerliche Verbesserung der Juden

Manasseh Ben Israel. Aus dem Engl. übers. Nebst einer Vorrede von Moses Mendelssohn

Worte der Wahrheit und des Friedens an die gesammte jüdische Nation : vorzüglich an diejenigen, so unter dem Schutze des glorreichen und großmächtigsten Kaysers Josephs II. wohnen

[Naphtali Herz Wessely.] Aus dem Hebr. [von David Friedländer]

Ueber die Unnütz- und Schädlichkeit der Juden im Königreiche Böheim, und Mähren

[Ignaz Klingler]

Discorso pronunziato : ... sovrana risoluzione 16. maggio 1781

da Elia Morpurgo

Das Forschen nach Licht und Recht in einem Schreiben an Herrn Moses Mendelssohn auf Veranlassung seiner merkwürdigen Vorrede zu Manasseh Ben Israel

[Daniel Ernst Mörschel]

Jüdische Religionsstütze oder: Grundsätze der jüdischen Religion aus den heiligen Büchern, Talmud und den vorzüglichsten Rabbinen

zusgetr. von Wolf Abraham Nathan

Harmonia juris naturae, canonici, civilis & publici Germaniae circa educationem liberorum in casu, quo uxor Hebraea, reluctante marito, ad christiana sacra transiit

Heidelberg, Univ., Diss., 1782

De Judaeo iurisiurandi suppletorii haud incapace

Wittemberg, Univ., Diss., 1782