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Study Finds Durable Drug-Free Control of HIV Is Uncommon When Treatment Is Interrupted

January 27, 2016

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By strengthening the immune system and reducing the amount of HIV in the blood below the threshold of detection -- a level commonly called "undetectable" -- potent combination anti-HIV therapy (commonly called ART) can have several benefits, including the following:

  • It can tremendously reduce the risk of developing AIDS-related infections.
  • It can increase the life expectancy of some people to near normal.
  • It can significantly reduce the risk of sexually spreading HIV.

However, ART does have some drawbacks, including the following:

  • It cannot cure HIV infection.
  • It needs to be taken at least once daily for life.
  • Some regimens can have side effects.


Caution Needed

Studies have found that interrupting ART is fraught with risk. HIV levels can quickly rise and the immune system can again decline once treatment is interrupted. A large, well-designed clinical trial called SMART found that interrupting treatment increases the risk for some inflammation-related complications, infections and death.


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Is ART-Free Control of HIV Possible?

Researchers have found that drug-free control of HIV can occur in certain populations, including the following:

  • so-called Elite controllers -- Researchers have defined this group of people as those with an undetectable viral load in the blood (less than 50 copies/ml) without the use of ART. Such people are rare, accounting for less than 1% of all HIV-positive people.
  • post-treatment controllers -- People in this group initiated ART very shortly after infection and therapy was later interrupted. Despite this interruption, their immune systems are apparently able to control HIV. Post-treatment controllers are uncommon.
  • There are also reports of temporary drug-free control of HIV in the blood in a few other cases -- for example, a couple of adults who had bone marrow transplants as part of attempts to cure HIV infection and a baby treated shortly after infection (the "Mississippi baby").

Researchers who have extensively reviewed the above groups and cases have been at a loss to know why virological control unexpectedly occurred and why and when such control might subsequently fail. However, what the groups and cases have in common is that tests in research labs suggest that they have a relatively low amount of HIV-infected cells in their body compared to the average HIV-positive person who uses ART. Scientists refer to this burden of infected cells in the body as the reservoir.


Multiple and Simultaneously Applied Approaches Will Be Needed

In an attempt to induce a period of ART-free remission, teams of researchers are planning experiments with HIV-positive people who are taking ART and who have a relatively small reservoir of HIV-infected cells. Such experiments will likely involve the use of combinations of agents that try to enhance the ability of the immune system to kill HIV-infected cells and to hopefully decrease the size of the reservoir. There are many potential options that could be used in such experiments, including vaccines to stimulate immunity against HIV, drugs that enhance the immune system's ability to recognize and kill HIV-infected cells, bone marrow transplants, and gene therapy. In the future, only after implementing such options might researchers feel it useful to attempt treatment interruptions to assess the ability of the immune system to control HIV.


Ultrastop

Researchers in France conducted an experiment with a limited number of very carefully selected HIV-positive people in the absence of the many potential interventions mentioned above. All participants had begun ART relatively early in the course of HIV infection and had a viral load in the blood less than 50 copies/ml and a CD4+ count greater than 500 cells/mm3. Furthermore, the amount of HIV-infected cells in their reservoirs was unusually low.

After an interruption of treatment, viral loads resurged in most participants within four weeks. However, one participant continued to have a low viral load -- less than 400 copies/ml -- for about one year after interruption of ART. Despite conducting extensive tests on samples of his HIV and immune system, French researchers remain mystified as to how he is able to control HIV in his blood.

An important finding from Ultrastop is that despite very careful selection of participants (based on many factors, including immunological, virological and treatment history and assessment of their HIV reservoir) interruption of ART led to a limited period of virological control for 90% of them. The findings from Ultrastop suggest that, by itself, treatment interruption may not be a useful way to try to help HIV-positive people control HIV.


Study Details

Researchers carefully selected potential participants for this study. In addition to performing complex analyses of participants' blood, researchers reviewed their medical history and had them undergo psychological evaluation to be sure that they were capable of engaging in a study of this nature where frequent laboratory visits would be needed.

Researchers reported results from 10 participants, whose average profile at the start of the study was as follows:

  • age -- 42 years
  • seven men, three women
  • time since HIV diagnosis -- six years
  • duration of HIV infection with a viral load less than 50 copies/ml -- five years
  • lowest-ever CD4+ count -- 495 cells/mm3
  • CD4+ count -- 1,118 cells/mm3
  • CD8+ count -- 566 cells/mm3
  • CD4/CD8 ratio -- 2.1

Using an ultrasensitive assay, technicians found that one month prior to the study all participants had a viral load less than 20 copies/ml. Also, all participants had a very low level of HIV-infected cells in their blood, suggesting that their reservoir was unusually small.

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Related Stories

HIV Remission for More Than 12 Years After Very Early Treatment in French Teenager
Viral Rebound Is Significantly Delayed Among Some Who Interrupt HIV Treatment



This article was provided by Canadian AIDS Treatment Information Exchange. Visit CATIE's Web site to find out more about their activities, publications and services.
 

 

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