Tag Archives: resistance

eLife paper and video on how HIV treatments affect selective sweeps

15 Feb

Very happy to announce that we have a new paper out and an accompanying video! The paper is about how effective treatments lead to (few) hard selective sweeps and bad treatments lead to soft selective sweeps.

The paper can be found here on the eLife website, but I suggest starting with the video that Alison Feder made.

 

Paper details

Title: More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1.

Authors: Alison F Feder, Soo-Yon Rhee, Susan P Holmes, Robert W Shafer, Dmitri A Petrov, Pleuni S Pennings

DOI: http://dx.doi.org/10.7554/eLife.10670

Abstract: In the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistance mutations. If many adaptive mutations arise simultaneously, then adaptation proceeds by soft selective sweeps in which multiple adaptive mutations spread concomitantly, but if adaptive mutations occur rarely in the population, then a single adaptive mutation should spread alone in a hard selective sweep. Here, we use 6717 HIV-1 consensus sequences from patients treated with first-line therapies between 1989 and 2013 to confirm that the transition from fast to slow evolution of drug resistance was indeed accompanied with the expected transition from soft to hard selective sweeps. This suggests more generally that evolution proceeds via hard sweeps if resistance is unlikely and via soft sweeps if it is likely.

 

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New paper, new videos!

31 Dec

With Ben Wilson, Nandita Garud, Alison Feder and Zoe Assaf, I wrote a review paper about population genetics and drug resistance. It was a lot of fun to write this paper and I feel like I learned a lot during the process.

We wrote about drug resistance in influenza, malaria, TB, MRSA and HIV. It turns out that each of these case studies have something unique to teach us about evolution.

The paper is now out in Molecular Ecology. You can also download it here: 2015Wilson_et_al-Molecular_Ecology.

We made five short movies about the paper. Have a look at the one you are most interested in!

Nandita Garud on using genome scans to find resistance loci in malaria

MolEcolNandita from Pleuni Pennings on Vimeo.

Ben Wilson on the role of epistasis in resistance in Influenza

BenMolEcol from Pleuni Pennings on Vimeo.

Pleuni Pennings on standing genetic variation in HIV

MolEcol from Pleuni Pennings on Vimeo.

Alison Feder on clonal interference in TB

MolEcolAlison from Pleuni Pennings on Vimeo.

Zoe Assaf on the origins of the SCCmec element that causes methicillin resistance

MolEcolZoe from Pleuni Pennings on Vimeo.

Review paper on HIV drug resistance is out

17 Jun

My review paper on HIV drug resistance for Infectious Disease Reports is out (see here). It is part of a special issue entitled “Current perspectives in HIV/AIDS“. You can download the paper here: Pennings2013IDR

Abstract: Access to combination antiretroviral treatment (ART) has improved greatly over recent years. At the end of 2011, more than eight million HIV-infected people were receiving ART in low-income and middle-income countries. ART generally works well in keeping the virus suppressed and the patient healthy. However, treatment only works as long as the virus is not resistant against the drugs used. In the last decades, HIV treatments have become better and better at slowing down the evolution of drug resistance, so that some patients are treated for many years without having any resistance problems. However, for some patients, especially in low-income countries, drug resistance is still a serious threat to their health. This essay will review what is known about transmitted and acquired drug resistance, multi-class drug resistance, resistance to newer drugs, resistance due to treatment for the prevention of mother-to-child transmission, the role of minority variants (low-frequency drug-resistance mutations), and resistance due to pre-exposure prophylaxis.

IDRpaper

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