Abstract
BackgroundTo determine if tropism for CXCR4 or CCR5 correlates with cellular HIV DNA load, residual viraemia and CD4 count in 219 successfully treated naive subjects with HIV infection enrolled in five infectious diseases units in Northeastern Italy.MethodsA subset of subjects, achieving plasma HIV RNA level <50 copies/ml after initiation of first-line therapy and maintaining it until follow-up time points, was retrospectively selected from a prospective cohort. Blood samples were collected before the beginning of therapy (T0), at the first follow-up time (T1) and, when available, at a second (T2) follow-up time.ResultsHIV DNA, CD4 count and plasma viraemia were available from all 219 patients at T0 and T1, and in 86 subjects at T2, while tropism determinations were available from 109 subjects at T0, 219 at T1, and from 86 subjects at T2. Achieving residual viraemia <2.5 copies/ml at T1 correlated with having the same condition at T2 (p = 0.0007). X4 tropism at T1 was negatively correlated with the possibility of achieving viraemia<2.5 copies/ml at T2 (p = 0.0076). T1-T2 tropism stability was significant (p <0.0001). T0 tropism correlated with T1 and T2 tropism (p < 0.001); therefore the stability of the tropism over the two follow-up periods was significant (p = 0.0003). An effective viremic suppression (viraemia<2.5 copies/ml) correlated with R5 coreceptor affinity (p= 0.047).ConclusionsThe tropism of archived virus was stable during an effective treatment, with 15-18% of subjects switching over time, despite a viraemia<50 copies/ml. R5 tropism and its stability were related to achieving and maintaining viraemia<2.5 copies/ml.
Highlights
To determine if tropism for CXCR4 or CCR5 correlates with cellular HIV DNA load, residual viraemia and CD4 count in 219 successfully treated naive subjects with HIV infection enrolled in five infectious diseases units in Northeastern Italy
The studies that have attempted to correlate viral tropism with the response to antiretroviral therapy (ARV) have generally demonstrated no differences in the response to treatment between patients harbouring an X4- or R5-tropic virus, a poor recovery in the number of CD4+ cells has been shown in patients with an X4-tropic virus before the beginning of treatment or in PBMCs after treatment [1,12,13]
The presence of an X4-tropic virus has been demonstrated to have a deleterious effect on CD4 cell count growth and the risk of clinical disease in patients undergoing the first line of HAART (Highly Active Antiretroviral Therapy) [7]
Summary
To determine if tropism for CXCR4 or CCR5 correlates with cellular HIV DNA load, residual viraemia and CD4 count in 219 successfully treated naive subjects with HIV infection enrolled in five infectious diseases units in Northeastern Italy. Studies aimed at assessing the influence and frequency of the switch of viral tropism during the course of therapy showed a low event rate in patients responding to HAART, and there have been conflicting results regarding the response to treatment, even if a direct correlation between the switch from an R5- to an X4tropic virus and a low CD4 + nadir was found in treated patients [14,15,16,17].A change in viral tropism has been shown to occur in patients during ARV interruption, and the switch from an R5-tropic to an X4-tropic virus is associated with a previous heavy treatment experience, a considerable decrease in the CD4 cell count and a shorter length of treatment interruption [18,19]
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