Stochastic processes strongly influence HIV-1 evolution during suboptimal protease-inhibitor therapy

It has long been assumed that HIV-1 evolution is best described by deterministic evolutionary models because of the large population size. Recently, however, it was suggested that the effective population size (Ne) may be rather small, thereby allowing chance to influence evolution, a situation best described by a stochastic evolutionary model. To gain experimental evidence supporting one of the evolutionary models, we investigated whether the development of resistance to the protease inhibitor ritonavir affected the evolution of the env gene. Sequential serum samples from five patients treated with ritonavir were used for analysis of the protease gene and the V3 domain of the env gene. Multiple reverse transcription–PCR products were cloned, sequenced, and used to construct phylogenetic trees and to calculate the genetic variation and Ne. Genotypic resistance to ritonavir developed in all five patients, but each patient displayed a unique combination of mutations, indicating a stochastic element in the development of ritonavir resistance. Furthermore, development of resistance induced clear bottleneck effects in the env gene. The mean intrasample genetic variation, which ranged from 1.2% to 5.7% before treatment, decreased significantly (P < 0.025) during treatment. In agreement with these findings, Ne was estimated to be very small (500–15,000) compared with the total HIV-1 RNA copy number. This study combines three independent observations, strong population bottlenecking, small Ne, and selection of different combinations of protease-resistance mutations, all of which indicate that HIV-1 evolution is best described by a stochastic evolutionary model.

Vie de Démosthène;

Preservation photocopy.

The Upper Pima of San Cayetano del Tumacacori; an archaeohistorical reconstruction of the Ootam of Pimeria Alta.

Bibliography: p. [571]-589.

The Sobaipuri Indians of the Upper San Pedro River Valley, southeastern Arizona,

Bibliography: p. 277-285.

An examination of the Shelley manuscripts in the Bodleian Library : being a collation therof with the printed texts, resulting in the publication of several long fragments hitherto unknown, and the introduction of many improved readings into Prometheus unbound, and other poems /

Mode of access: Internet.

Engravings from the works of Sir Joshua Reynolds, P.R.A. /

Mounted mezzotint engravings after portraits by Sir Joshua Reynolds, executed mainly by Samuel William Reynolds and by numerous other engravers: Richard Parkes Bonington, W.A. Rainger, Frederik Bromley, George H. Every, James Scott, George Sanders, A. Sanders, Joseph W. Edwards, John Richardson Jackson, R. José, H.C. Balding, Charles Tomkins, George Salisbury Shury, Richard Josey, Charles Algernon Tomkins, Arthur Turrell, William Henry Egleton, A.N. Sanders, William T. Hulland, T. Hunt, Stephen H. Gimber, H. Davis, Edwin Hunt, Thomas Lewis Atkinson, T. José, A. Scott.

Le prince royal : l'exil, le retour, le collège, les premières armes, la Révolution de 1830, Anvers, les fiançailles, les fètes du mariage de Fontainbleau, les fètes de Versailles et de Paris, l'Algérie, le 15 juillet, Neuilly, les funérailles, Notre-Dame de Paris, les tombeaux de l'église de Dreux /

Publishing date from BN, v. 76, p. 1266.

Farm inheritance laws in other countries : what we can learn from their effects on farms /

Cover title.

The Motor vehicle act and the Highway travel act /

Mode of access: Internet.

The ethics of the Greek philosophers, Socrates, Plato and Aristotle. A lecture given before the Brooklyn ethical association, season of 1896 1897,

Several of the plates are preceded by a leaf with descriptive letterpress.

An examination of the Shelley manuscripts in the Bodleian library. Being a collation thereof with the printed texts, resulting in the publication of several long fragments hitherto unknown, and the introduction of many improved readings into Prometheus unbound, and other poems,

Mode of access: Internet.