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Is Protease Inhibitor Monotherapy Sufficient to Keep HIV Under Control in the Brain?

November 1, 2012

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Shortly after HIV enters the body it infects cells of the immune system. As these infected cells are carried by the blood stream, HIV is spread throughout the body, including to the brain and spinal cord -- the Central Nervous System (CNS). HIV does not infect brain cells, but it does infect cells of the immune system that travel to or are permanent residents of the brain. These HIV-infected cells release proteins and chemical signals that cause inflammation and impair the functioning of brain cells. If left untreated, HIV infection can eventually result in serious neurological issues -- causing the brain to shrink, affecting clear thinking, bringing about difficulty controlling muscles and movement, degrading memory and key reflexes, and inciting changes to personality.

In high-income countries such as Canada, Australia and the United States and in regions such as Western Europe where potent combinations of anti-HIV therapy (commonly called ART or HAART) are widely available, severe HIV-related neurocognitive problems are no longer common compared to in the pre-HAART era. However, some research teams have reported that very mild neurocognitive impairment, detectable only with sophisticated and complex testing, appears to be relatively common among some ART users in the current era. The reasons for this are not clear but might be related to the following:

  • aging of HIV-positive people
  • possible impact of co-morbidities (such as cardiovascular disease, diabetes, hepatitis C co-infection) on the brain
  • low-grade persistent inflammation in the CNS
  • potential neurotoxicity of ART
  • the inability of some anti-HIV drugs to enter or remain within the CNS


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ART Today

At present, ART generally refers to at least the following combinations of drug classes:

  • two nukes + a non-nuke
  • two nukes + a ritonavir-boosted protease inhibitor
  • two nukes + an integrase inhibitor

When starting therapy for the first time, one of these combinations is usually prescribed. Among treatment-experienced patients, sometimes more complex regimens are used.


One Type of Simplification

Standard ART is expensive. Some doctors and their patients are also concerned about potential side effects from ART and would like to use fewer therapies. To try to find simpler regimens of anti-HIV drugs, researchers, mainly in Western Europe, have been conducting clinical trials of simplified therapy -- particularly based on a protease inhibitor boosted with a small dose of ritonavir (Norvir). This is generally called protease inhibitor monotherapy (PI monotherapy).

The drugs most commonly used for PI monotherapy are as follows:

  • darunavir (Prezista) and ritonavir
  • lopinavir (in Kaletra; a fixed-dose combination of lopinavir and ritonavir)

In general, most clinical trials of PI monotherapy have found that such combinations are not as effective as standard triple therapy, the cornerstone of ART. However, in such trials when virologic failure occurred among participants given PI monotherapy, adding two nukes to their regimen was able to return HIV viral load to less than 50 copies/ml in 93% of cases.


Small and Short

Based on published clinical trials so far, researchers estimate that the risk of PI monotherapy failing after one year is about 10%. However, it is important to bear in mind that most trials of PI monotherapy have had relatively small numbers of participants and did not last for more than one or two years. As a result, the overall long-term safety and effectiveness of PI monotherapy is not known.

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

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