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Raltegravir in women and reduced soluble CD14

Researchers are studying the impact of raltegravir (sold as Isentress) as part of combination therapy in HIV-positive women. In one Canadian-U.S. study, researchers enrolled women who were taking potent combination therapy for HIV (commonly called ART or HAART) and exchanged the protease inhibitor or non-nuke in their regimen for the integrase inhibitor raltegravir. Prior to this change in their regimens, all women had viral loads in their blood below the 50-copy/ml mark.

There were 36 women in total and their average age was about 43 years; most were overweight and had about 560 CD4+ cells.

For this 48-week study, half the women immediately changed their regimens and the other half delayed this change for 24 weeks.

Overall, after 24 weeks, levels of sCD14 in the women decreased significantly—by 21% among women who made the regimen change immediately. Among women who made the regimen change later, sCD14 levels fell by 10%. 

Assessing inflammation

There are many potential blood tests that doctors can use to try to assess inflammation, such as the following:

  • high-sensitivity C-reactive protein (written as hsCRP)
  • interleukin-6 (IL-6)
  • tumour necrosis factor (TNF)
  • D-dimer
  • soluble CD163 (sCD163)
  • soluble CD14 (sCD14)

Many of these proteins and others are being studied in research laboratories and testing for them may not always be available from local labs routinely used by clinics. The ideal protein, or group of proteins, to use to assess inflammation in HIV-positive people is not known.

Back to raltegravir

What is important about the raltegravir study in women mentioned earlier is that it reported on one measure of inflammation—sCD14—and how this decreased once raltegravir was used in treatment. Future studies need to be done to confirm this effect of raltegravir in HIV-positive women.

Another study found that HIV treatment regimens that used other classes of drugs, such as protease inhibitors and non-nukes, did not significantly reduce levels of sCD14 over the long-term.

Researchers are not certain why raltegravir was associated with a reduction in sCD14, but this may arise because of its generally neutral effect on cholesterol or perhaps because of its potent anti-HIV activity.

Raltegravir belongs to a class of drugs called integrase inhibitors. Other licensed members of this class include the following:

  • elvitegravir (in Stribild)
  • dolutegravir (in Tivicay)

Clinical trials with these two other integrase inhibitors are underway in HIV-positive women and hopefully will also demonstrate decreases in sCD14.

—Sean R. Hosein

REFERENCES:

  1. Lake J, McComsey G, Hulgan T, et al. Switch to raltegravir decreases soluble CD14 in virologically suppressed overweight women: the Women, Integrase and Fat Accumulation Trial. HIV Medicine. 2014; in press.
  2. Gupta SK, Mi D, Moe SM, et al. Effects of switching from efavirenz to raltegravir on endothelial function, bone mineral metabolism, inflammation, and renal function: a randomized, controlled trial. Journal of Acquired Immune Deficiency Syndromes. 2013 Nov 1;64(3):279-83.
  3. Asmuth DM, Ma ZM, Mann S, et al. Gastrointestinal-associated lymphoid tissue immune reconstitution in a randomized clinical trial of raltegravir versus non-nucleoside reverse transcriptase inhibitor-based regimens. AIDS. 2012 Aug 24;26(13):1625-34.