Residual plasma viraemia and infectious HIV-1 recovery from resting memory CD4 cells in patients on antiretroviral therapy: results from ACTG A5173.

Background: In HIV-1-infected patients receiving antiretroviral therapy (ART), the relationship between residual viraemia and ex vivo recovery of infectious virus from latently infected CD4 cells is uncertain. Methods: We measured residual viraemia (HIV-1 RNA copies/ml) by single-copy assay (SCA) and the latent reservoir by infectious virus recovery from resting memory CD4 cells (infectious units per million cells [IUPM]) in patients who initiated ART. We assessed immune activation by measuring CD38 expression on T-cells. Results: Ten patients who initiated ART and maintained a plasma HIV-1 RNA level < 200 copies/ml had residual viraemia and IUPM measured every 24 weeks. Five of 10 patients had longitudinal IUPM measured at weeks 24-96; the remainder had IUPM measured 1-3 times over 24-72 weeks. Analyses of 29 paired measurements revealed a positive association between level of residual viraemia and IUPM (0.56 higher log(10) HIV-1 RNA copies/ml per 1 log(10) higher IUPM; P=0.005). Residual viraemia level was positively associated with CD38 density and percentage on CD8(+) T-cells in concurrent samples and with pre-ART HIV-1 RNA levels. Conclusions: In patients with HIV-1 RNA levels < 200 copies/ml 24-96 weeks after initiating ART, the level of viraemia is positively associated with infectious virus recovery from resting memory CD4 cells. Whether this association persists after longer-term suppressive ART needs to be determined. If additional studies show that residual viraemia measured by SCA reflects the size of the latent reservoir in patients who have had virological suppression for longer periods of time, this could facilitate testing of potentially curative strategies to reduce this important reservoir.