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Replication Capacity Affects CD4 Response to HAART
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"Reduced HIV replication capacity is associated with improved CD4 reconstitution following suppressive HAART"
ABSTRACT 62
Antiviral Therapy 2004; 9:S71.
C Hicks
Duke University Medical Center, Durham, NC, USA
BACKGROUND: Increases in CD4+ lymphocytes following initiation of HAART are associated with the magnitude of HIV RNA reduction. The impact ofother viral characteristics is less clear. We analysed viral, host and immune factors in patients initiating HAART who achieved viral suppression to identifycorrelates of differing CD4 regeneration.
METHODS: Patients initiating HAART who achieved viral suppression (HIV RNA <400 copies/ml) by 12 months were identified. All persons for whom pretreatment (baseline BL) serum samples were available were included. Specimens were analysed for virological (resistance, viral replication capacity [RC] by modified PhenoSense assay; CCR5/CXCR4 co-receptor tropismby PhenoSense Entry assay) and immunological (cytokine assays by Luminex-based 17-plex bead arrays) characteristics. The Spearman correlation coefficient was used to correlate continuous variables with CD4 increase and the Wilcoxon rank-sum test was used to examine associations between categorical variables and CD4 increase.
RESULTS: The study population consisted of 18 ARV-naive patients: median age was 31 years (range 19--49); seven had CDC stage B or C infection. Allpatients were treated with two nucleosides, and either a protease inhibitor or an NNRTI. Median BL CD4 count: 167 cells/mm3 (range 5--437); median BL VL: 53,329 copies RNA/ml (range 4,976 to >750,000). The median CD4 increase over 12 months was +189 cells (range --63 to +438). Resistance to NNRTI was present in one patient; no other resistance was identified.
Patients in the lowest RC quartile (median=63) had a median CD4 increase of +283 cells while those in the highest quartile (median RC=219) had a median CD4 increase of +111 cells. Overall, lesser CD4 increases were noted in older patients, and in patients with lower nadir CD4 counts and higher BL VL. Viral characteristics associated with diminished CD4 responses also included dual co-receptor tropism. Patterns of cytokines present prior to therapy were complex and predictive associations were not apparent.
CONCLUSION: These data suggest that pre-treatment patient and viral characteristics determine the magnitude of CD4 reconstitution following suppressive HAART. If confirmed in larger populations, these findingscould allow individualization of treatment initiation timing based on measurable parameters that predict CD4 reconstitution.
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