Abstract

TUPDB0204 - Poster Discussion Session

Very early initiation of combination antiviral therapy results in normal levels of markers of immune activation

Presented by Martin Markowitz (United States).

M. Markowitz, T. Evering, A. Figueroa, K. Rodriguez, M. La Mar, D. Garmon, V. Sahi, H. Mohri

Aaron Diamond AIDS Research Center, New York, United States

Background: The use of combination antiretroviral therapy (cART) has resulted in dramatic reductions in HIV-related mortality and morbidity. Nevertheless, despite sustained suppression of viral replication there remains evidence of increased levels of immune activation, particularly in patients initiating treatment during late-stage infection. We asked whether early initiation of therapy could potentially ameliorate this apparent limitation of cART.
Methods: 40 subjects identified as acutely or early HIV-1 infected were treated with either 3-drug cART (N=14) which included TDF/FTC, a ritonavir-boosted protease inhibitor (atazanavir or darunavir) or 5-drugs (N=26) cART as above with raltegravir and maraviroc. CD38 and HLA-DR expression on CD8+ T cells were determined by flow cytometry at baseline and weeks 48 and 96. Levels of sCD14 by ELISA were measured at weeks 48 and 96. These results were compared to values in 13 healthy, HIV-1 uninfected volunteers.
Results: A total of 29 subjects, 11 on 3-drugs and 18 on 5-drugs remained on therapy, suppressed and were available for analysis at 48 weeks. After 96-weeks 25 subjects, 9 on 3-drugs and 16 on 5-drugs were similarly analyzed. There are no statistically significant differences (Mann-Whitney, p< 0.05) in markers of cellular or systemic immune activation between the 3-drug and 5-drug groups at baseline or after 48 and 96 weeks of therapy. Importantly, the early treated HIV-infected subjects display comparable levels of markers of cellular and systemic immune activation when compared to the healthy HIV-uninfected controls . Markers of Immu...

Group	Baseline %CD8+CD38+HLA-DR+ T cells	week 48 %CD8+CD38+HLA-DR+ T cells	week 96 %CD8+CD38+HLA-DR+ T cells	week 48 Mean sCD14 (ng/mL)	week 96 Mean sCD14 (ng/mL)
3-drug	49.4	7.4	3.8	1681	1493
5-drug	36.6	7.5	5.2	1558	1449
HIV-uninfected, healthy controls	7.3	-	-	1416	-

[Markers of Immune Activation]


Conclusions: These data suggest that the early initiation of cART may result in normalization of markers of immune activation that may provide clinical benefit. These results support well-designed prospective trials to confirm these findings.