These data were presented in part at the 20th Conference on Retroviruses and Opportunistic Infections (Atlanta, GA, USA, 3–6 March 2013).
Switch to raltegravir decreases soluble CD14 in virologically suppressed overweight women: the Women, Integrase and Fat Accumulation Trial†
Article first published online: 10 FEB 2014
© 2014 British HIV Association
Volume 15, Issue 7, pages 431–441, August 2014
How to Cite
Lake, J., McComsey, G., Hulgan, T., Wanke, C., Mangili, A., Walmsley, S., Stramotas, S., Tracy, R. and Currier, J. (2014), Switch to raltegravir decreases soluble CD14 in virologically suppressed overweight women: the Women, Integrase and Fat Accumulation Trial. HIV Medicine, 15: 431–441. doi: 10.1111/hiv.12128
- Issue published online: 9 JUL 2014
- Article first published online: 10 FEB 2014
- Manuscript Accepted: 30 DEC 2013
- Merck and Co. Investigator-Initiated Studies Program
- Merck Canada
- Ontario HIV Treatment Network
- National Institutes of Health. Grant Numbers: M01-RR000865, K24 AI56933, P30-AG028748, T32 MH080634
- monocyte activation;
Soluble CD14 (sCD14) is a monocyte activation marker associated with increased mortality in HIV infection. We assessed 48-week changes in sCD14 and other inflammatory biomarkers in virologically suppressed, HIV-infected women switching to raltegravir (RAL) from a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI).
HIV-infected women with central adiposity and HIV-1 RNA < 50 HIV-1 RNA copies/mL continued their thymidine-sparing nucleoside reverse transcriptase inhibitor (NRTI) backbone and were randomized to switch to open-label RAL at week 0 (immediate) or 24 (delayed). In an exploratory analysis, inflammatory biomarkers were measured on stored fasting plasma.
Of the 37 evaluable subjects, 78% were non-White; the median age was 43 years, the median body mass index (BMI) was 32 kg/m2 and the median CD4 count was 558 cells/μL. At baseline, biomarker values were similar between groups. After 24 weeks, median sCD14 significantly declined in subjects switching to RAL [−21% (P < 0.001) vs. PI/NNRTI −5% (P = 0.49); between-group P < 0.01]. After 48 weeks, immediate-switch subjects maintained this decline and delayed-switch subjects experienced a similar decline following the switch to RAL (−10%; within-group P < 0.01). Immediate-switch subjects also experienced an initial increase in tumour necrosis factor (TNF)-α that was neither maintained after 48 weeks nor seen in delayed-switch subjects. After adjustment for multiple testing, only declines in sCD14 remained significant.
In this randomized trial of women with central adiposity, a switch to RAL from a PI or NNRTI was associated with a statistically significant decline in sCD14. Further studies are needed to determine whether integrase inhibitors have improved monocyte activation profiles compared with PIs and/or NNRTIs, and whether measured differences between antiretroviral agents translate to demonstrable clinical benefit.