The evolution of drug resistance within a HIV population

January 23, 2014, Public Library of Science

Drug resistance mutations in HIV reduce the genetic diversity in the rest of the virus genome when they spread within an infected patient, but they do so to a different extent in different patients. A new study published in PLOS Genetics, by Dr Pleuni Pennings and colleagues, found that in some patients a resistance mutation to a particular drug appeared in a single virus particle, which then rapidly proliferated until the entire viral population within the patient consisted of its progeny and was also resistant to the drug. In other patients the same resistance mutation occurred in multiple viral particles within a short window of time, which led to a more heterogeneous, but still drug-resistant, viral population.

One of the big questions that has concerned biologists working on HIV for two decades now is that of the "effective population size" of the virus within a patient. The effective population size is a mathematical quantity that determines, among other things, how quickly drug resistance may evolve. Estimates of this quantity for HIV based on different methods range widely, from 1,000 to 100,000,000, leaving researchers puzzled. Dr Pennings and colleagues observed that drug resistance in HIV evolves by means of so called hard and soft selective sweeps. In a hard sweep, the entire resistant population consists of progeny of a single virus particle; in a soft sweep, it consists of progeny of different virus particles. These two types of sweeps leave distinct signatures in the viral genome: hard sweeps wipe out , while soft sweeps do not. Pennings and colleagues realized that they could use the fraction of soft and hard sweeps for a particular mutation called K103N to estimate the effective population size of HIV within a patient. They estimate this quantity to be around 150,000.

For the current study, Dr Pennings and colleagues re-analyzed an old dataset from a clinical trial in the late 1990s. The data were very rich, with multiple sequences at multiple time points for more than one hundred patients. The authors focused on a subset of patients where the evolution of resistance could be best observed. In this subset of patients, the current study shows convincingly that soft sweeps and hard sweeps occur in HIV.

In the future, Dr Pennings plans to study treated with other drugs to understand how these drugs affect the HIV effective . This research may help understand which drugs are more effective in preventing evolution of resistance.

Explore further: Researchers find that pre-existing mutations can lead to drug resistance in HIV virus

Related Stories

Researchers find that pre-existing mutations can lead to drug resistance in HIV virus

June 7, 2012
In a critical step that may lead to more effective HIV treatments, Harvard scientists have found that, in a small number of HIV patients, pre-existing mutations in the virus can cause it to develop resistance to the drugs ...

Protease inhibitor resistance involves multiple stages of the HIV-1 life cycle

August 27, 2013
HIV-1 protease inhibitors are very effective antiviral drugs. These drugs target HIV-1 proteases, which are required for viral replication. Despite the success of protease inhibitors for suppressing HIV-1, some patients do ...

The genetics of HIV-1 resistance

October 2, 2012
Drug resistance is a major problem when treating infections. This problem is multiplied when the infection, like HIV-1, is chronic. New research published in BioMed Central's open access journal Retrovirology has examined ...

Geneticists map human resistance to HIV

October 29, 2013
The key to future HIV treatment could be hidden right in our own genes. Everyone who becomes infected deploys defense strategies, and some even manage to hold the virus at bay without any therapy at all. This immune system ...

New anti-HIV drug target identified

December 18, 2013
University of Minnesota researchers have discovered a first-of-its-kind series of compounds possessing anti-human immunodeficiency virus (HIV) activity. The compounds present a new target for potential HIV drug development ...

Recommended for you

HIV-1 genetic diversity is higher in vaginal tract than in blood during early infection

January 18, 2018
A first-of-its-kind study has found that the genetic diversity of human immunodeficiency virus type 1 (HIV-1) is higher in the vaginal tract than in the blood stream during early infection. This finding, published in PLOS ...

War in Ukraine has escalated HIV spread in the country: study

January 15, 2018
Conflict in Ukraine has increased the risk of HIV outbreaks throughout the country as displaced HIV-infected people move from war-affected regions to areas with higher risk of transmission, according to analysis by scientists.

Researchers offer new model for uncovering true HIV mortality rates in Zambia

January 12, 2018
A new study that seeks to better ascertain HIV mortality rates in Zambia could provide a model for improved national and regional surveillance approaches, and ultimately, more effective HIV treatment strategies.

New drug capsule may allow weekly HIV treatment

January 9, 2018
Researchers at MIT and Brigham and Women's Hospital have developed a capsule that can deliver a week's worth of HIV drugs in a single dose. This advance could make it much easier for patients to adhere to the strict schedule ...

New long-acting, less-toxic HIV drug suppresses virus in humanized mice

January 8, 2018
A team of Yale researchers tested a new chemical compound that suppresses HIV, protects immune cells, and remains effective for weeks with a single dose. In animal experiments, the compound proved to be a promising new candidate ...

Usage remains low for pill that can prevent HIV infection

January 8, 2018
From gritty neighborhoods in New York and Los Angeles to clinics in Kenya and Brazil, health workers are trying to popularize a pill that has proven highly effective in preventing HIV but which—in their view—remains woefully ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.