Tag Archives: ART

Manuscript on HIV sweeps and clonal interference posted on BioRxiv

13 Feb

Kadie-Ann Williams and I posted a new manuscript on the BioRiv. It is 30 pages with 28 figures and a supplement of 118 figures! I guess we could call it an HIV drug resistance evolution picture book!

P00089Muller

Muller plot showing clonal interference in patient 89.

Nowadays, drug resistance evolution is quite rare, but in the late 1990s, HIV populations within patients on treatment were undergoing soft sweeps, hard sweeps, clonal interference and other things. If you like sequence data, you’ll enjoy looking at our pictures!

Title: Drug resistance evolution in HIV in the late 1990s: hard sweeps, soft sweeps, clonal interference and the accumulation of drug resistance mutations

https://www.biorxiv.org/content/10.1101/548198v1

Abtract

The goal of this paper is to provide examples of evolutionary dynamics of HIV within patients who are treated with antiretrovirals. We hope that the figures in this paper will be used in evolution and population genetics classes. We show a wide variety of patterns, specifically: soft sweeps, hard sweeps, softening sweeps and hardening sweeps, simultaneous sweeps, accumulation of mutations and clonal interference.

Kadie

Kadie-Ann Williams, SFSU BSc 2014, MSc 2017

Download the paper 2019WilliamsPennings2019_Feb

Download the supplemental figures 2019WilliamsPennings2019_Supplement118Patients

 

Essay on HIV drug resistance published on the arXiv

26 Nov

A few days ago, I submitted a review paper to Infectious Disease Reports. The review is an invited essay for the special issue they are planning around the World AIDS Day (December 1st).

I was pleasantly surprised to see that the author guidelines of Infectious Disease Reports said: “Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.” So, I decided to upload the manuscript to the arXiv.

The essay describes the current situation of drug resistance in HIV. The main conclusion is that, overall, drug resistance is not as big a problem as one may think. Treatments have become very good, which means that the rate of evolution of drug resistance is low. At the same time, many new drugs have become available so that when drug resistance evolves, the patient can be switched to another set of drugs. However, in poor countries, where viral genotyping, viral load monitoring and many new drugs are not available, drug resistance still poses a serious threat to people’s health.

In the essay, I explain that transmitted drug resistance occurs, but at a level that is lower than many would have expected. Roughly 10% of newly infected patients are infected with an HIV strain with at least one major drug-resistance mutation. If the virus is genotyped before treatment is started (as is standard in rich, but not in poor, countries), then treatment success is very high for these patients.

Acquired drug resistance (when resistance evolves during treatment) is more common than transmitted drug resistance, and resistance can evolve even after many years of successful treatment. It can also happen that the virus becomes resistant against multiple drugs. Nowadays, there are many different drugs available, so that even patients with multi-class drug resistance can often be treated successfully, although this is not the case in poor countries, simply because the newer drugs are expensive.

I also describe what is known about resistance due to treatment for the prevention of mother-to-child-transmission (which is a big problem) and resistance due to pre-exposure prophylaxis (which occurs, but is uncommon). I also discuss the issue of low-frequency resistance mutations and their clinical relevance. Throughout the essay, I explain how certain effects are expected or surprising from an evolutionary perspective.

I thank my collaborators Daniel Rosenbloom and Alison Hill (both at Harvard) for useful comments on an earlier version of the manuscript.

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