Abstract | BACKGROUND: HIV-infected patients who fail to reconstitute their CD4 T-cell counts during suppressive antiretroviral therapy (ART) have increased risk of both AIDS-related and non- AIDS-related morbidity and mortality. Improved understanding of immunological nonresponse (INR) is necessary to enable earlier clinical intervention. METHODS: In a cohort of 112 HIV-infected patients starting ART, we performed a serial analysis of 32 plasma-soluble markers, assessed by multiplex cytokine and enzyme immunoassay. Samples were drawn pre-ART and during the first 3 years of treatment, with a final observation time of 8.4 years (interquartile range, 7.0-10.7 years) on ART. Long-term INR (LT-INR) was defined as failure to reach a CD4 T-cell count >350 cells per microliter. Marker stability was evaluated by parallel analysis of samples from ART-naïve and HIV-seronegative controls. RESULTS: Baseline CD4 T-cell counts predicted subsequent LT-INR (n = 15) [odds ratio, 1.10 (95% confidence interval: 1.01 to 1.19) pr. 10 cells/μL reduction in CD4 count, P = 0.030] in the cohort as a whole, but not in patients with baseline CD4 counts <200 cells per microliter (n = 78). LT-INR was best characterized by elevated plasma levels of the CC chemokine macrophage inflammatory protein 1β (MIP-1β), both at baseline (pre-ART) and during ART. In patients with baseline CD4 counts <200 cells per microliter, baseline MIP-1β predicted LT-INR [odds ratio 1.23 (95% confidence interval: 1.02 to 1.47) per 10 pg/mL increase in MIP-1β, P = 0.029]. CONCLUSIONS: Elevated pre-ART levels of MIP-1β identified LT-INR patients who started ART at CD4 counts <200. INR was characterized by persistently high MIP-1β during suppressive ART. Thus, MIP-1β may be of use for early identification of LT-INR.
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Authors | Christian Prebensen, Thor Ueland, Annika E Michelsen, Andreas Lind, Frank O Pettersen, Tom Eirik Mollnes, Pål Aukrust, Anne Ma Dyrhol-Riise, Dag Kvale |
Journal | Journal of acquired immune deficiency syndromes (1999)
(J Acquir Immune Defic Syndr)
Vol. 69
Issue 4
Pg. 395-402
(Aug 01 2015)
ISSN: 1944-7884 [Electronic] United States |
PMID | 26115437
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-HIV Agents
- Biomarkers
- CCL4 protein, human
- Chemokine CCL4
- RNA, Viral
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Topics |
- Adult
- Anti-HIV Agents
(therapeutic use)
- Biomarkers
- CD4 Lymphocyte Count
- Chemokine CCL4
(blood, genetics, metabolism)
- Female
- HIV Infections
(drug therapy, virology)
- Humans
- Male
- Middle Aged
- RNA, Viral
- Treatment Failure
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