Caution Needed When Interpreting the Results of Simplification Studies

January 2016

There is much excitement from researchers about finding new ways to use dolutegravir (Tivicay and in Triumeq). In this issue of TreatmentUpdate we present some results from small and generally short simplification trials with dolutegravir (and other drugs). However, because of their design, these studies raise many issues, which have yet to be addressed. Here are some examples:

  • What is the long-term effectiveness of dolutegravir monotherapy?
  • In people who use potent combination anti-HIV therapy (ART), HIV continues to infect cells and replicate at low levels in lymph nodes and lymphatic tissue. Some researchers think that this continued replication in lymphatic tissues is one of the reasons ART is unable to cure HIV. What happens in these locations with simplified therapy?
  • HIV affects the brain. Is simplified therapy with dolutegravir sufficient to maintain a person's neurocognitive abilities?
  • HIV-positive people who use ART and maintain an undetectable viral load in the blood and who do not have sexually transmitted infections are highly unlikely to sexually spread HIV. Is simplified therapy with dolutegravir able to suppress levels of HIV in the genital tract?
  • Is simplified therapy with two drugs, such as dolutegravir + 3TC, equivalent in potency to therapy with dolutegravir + two other drugs?
  • Does the reservoir, or burden, of HIV-infected cells increase, decrease or stay the same with simplification therapy?
  • HIV is associated with inflammation and activation of the immune system, even in people who take ART. This inflammation/activation may increase the risk for complications over the long term. What effect does simplification therapy have on inflammation/activation of the immune system?

Until robustly designed clinical trials can provide clear answers to these and other related questions, we urge our readers to be cautious about interpreting the preliminary results from simplification therapy that they may hear or read about. Furthermore, treatment guidelines in Canada and the U.S. do not recommend the use of such simplified therapy with dolutegravir.


  1. Herbeuval JP, Nilsson J, Boasso A, et al. HAART reduces death ligand but not death receptors in lymphoid tissue of HIV-infected patients and simian immunodeficiency virus-infected macaques. AIDS. 2009 Jan 2;23(1):35-40.
  2. Fletcher CV, Staskus K, Wietgrefe SW, et al. Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proceedings of the National Academy of Sciences USA. 2014 Feb 11;111(6):2307-12.
  3. Rothenberger MK, Keele BF, Wietgrefe SW, et al. Large number of rebounding/founder HIV variants emerge from multifocal infection in lymphatic tissues after treatment interruption. Proceedings of the National Academy of Sciences USA. 2015 Mar 10;112(10):E1126-34.
  4. Lederman MM, Funderburg NT, Sekaly RP, et al. Residual immune dysregulation syndrome in treated HIV infection. Advances in Immunology. 2013;119:51-83.
  5. Antinori A, Clarke A, Svedhem-Johansson V, et al. Week 48 efficacy and central nervous system analysis of darunavir/ritonavir monotherapy versus darunavir/ritonavir with two nucleoside analogues. AIDS. 2015 Sep 10;29(14):1811-20.
  6. Letendre SL. Editorial commentary: Protease inhibitor monotherapy: safe for the CNS in durably suppressed patients? Clinical Infectious Diseases. 2014 Dec 1;59(11):1635-7.

Related Stories

Is Dolutegravir Alone Enough to Control HIV?
Why Dolutegravir Might Get Us Closer to Ending AIDS: Next Step, Further Research
Dolutegravir Minimalism: A Top HIV Clinical Development of 2015
Dolutegravir: A Powerful Drug Entering Different Research Paths

This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication TreatmentUpdate. Visit CATIE's Web site to find out more about their activities, publications and services.

No comments have been made.

Add Your Comment:
(Please note: Your name and comment will be public, and may even show up in
Internet search results. Be careful when providing personal information! Before
adding your comment, please read's Comment Policy.)

Your Name:

Your Location:

(ex: San Francisco, CA)

Your Comment:

Characters remaining:


The content on this page is free of advertiser influence and was produced by our editorial team. See our content and advertising policies.