Dual drug therapy—impact on the HIV reservoir

As explained earlier in this issue of TreatmentUpdate, clinical trials with dual drug regimens based on the powerful integrase inhibitor dolutegravir are underway. One dual drug combination, Juluca (dolutegravir + rilpivirine), has already been approved for use in Canada and other high-income countries. Juluca is meant for use as simplification in place of more complex regimens among patients whose viral loads are less than 50 copies/mL and have been that way for some time. Another combination, dolutegravir + 3TC, is expected to be approved in 2019 in Canada and other high-income countries.

About the reservoir

After HIV infection has occurred, the virus becomes established in cells of the immune system—T-cells and a group of relatively long-lived cells called monocytes (in their mature form these are called macrophages). Monocytes/macrophages travel throughout the body, spending time in major organ-systems. As a result, HIV-infected cells are found in many parts of the body, including the following:

  • brain and spinal cord
  • the immune system: lymph nodes and lymphoid tissues as well as organs such as the spleen, bone marrow and thymus gland
  • lungs
  • kidneys
  • fatty tissues

Although potent combination anti-HIV therapy (ART) greatly suppresses the production of HIV in the blood, some studies suggest that small amounts of HIV are still produced in lymph nodes.

Researchers refer to the burden of HIV-infected cells in the body as the reservoir. Studies are underway to try to reduce and possibly eliminate this burden.

An important question about dual drug therapy is its impact on the reservoir.

The Verona study

Researchers at the University of Verona in Italy conducted a pilot study to assess the impact of induction-maintenance therapy. All participants who were new to ART were initially treated with standard triple-drug therapy, in this case Triumeq (dolutegravir + 3TC + abacavir). After participants had achieved and maintained viral suppression for 12 consecutive months, their regimens were simplified to dolutegravir + 3TC.

In 14 participants who were able to undergo dual therapy for between one and eight months, researchers found no significant differences in the burden of infected cells in their blood samples compared to the level of these cells after 12 months of taking triple therapy.

Thus, data from this pilot study strongly suggest that induction-maintenance therapy does not increase the size of the HIV reservoir, at least over the short term. Longer and larger studies should be done to confirm this finding.

—Sean R. Hosein


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