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 not respond to protease inhibitor therapy. For most patients, the lack of response is not due to mutation of the HIV-1 protease.

In this issue of the Journal of Clinical Investigation, Robert Silcano and colleagues at Johns Hopkins University identify the effects of protease inhibitors on different stages of viral replication. The authors found that protease inhibitors do not prevent virus release from infected cells, but do prevent viral entry into new cells, and have an effect on the reverse transcription and post-transcription stages of the HIV-1 life cycle.

Additionally, mutations in the viral , which is involved in cell entry, were associated with resistance to protease inhibitor treatment. In the accompanying Attending Physician article, John Bartlett of Duke University discusses how these findings may dictate testing for HIV-1 envelope mutations in patients that have not responded to treatment with .

Explore further: Drug designer: New tool reveals mutations that cause HIV-drug resistance

More information: Multi-step inhibition explains HIV-1 protease inhibitor pharmacodynamics and resistance, J Clin Invest. 2013;123(9):3848–3860. DOI: 10.1172/JCI67399
Lack of protease inhibitor resistance following treatment failure—too good to be true? J Clin Invest. 2013;123(9):3704–3705. DOI: 10.1172/JCI71784

Related Stories

Recommended for you

Targeting HIV in semen to shut down AIDS

August 18, 2015

There may be two new ways to fight AIDS—using a heat shock protein or a small molecule - to attack fibrils in semen associated with the human immunodeficiency virus (HIV) during the initial phases of infection, according ...

Vitamin D status related to immune response to HIV-1

June 15, 2015

Vitamin D plays an important part in the human immune response and deficiency can leave individuals less able to fight infections like HIV-1. Now an international team of researchers has found that high-dose vitamin D supplementation ...

HVTN 505 vaccine induced antibodies nonspecific for HIV

July 30, 2015

A study by researchers at the National Institute of Allergy and Infectious Diseases and Duke University helps explain why the candidate vaccine used in the HVTN 505 clinical trial was not protective against HIV infection ...

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.