No evidence for decay of the latent reservoir in HIV-1-infected patients receiving intensive enfuvirtide-containing antiretroviral therapy

Abstract

Human immunodeficiency virus type 1 (HIV-1) persists in a latent reservoir of infected resting memory CD4 cells in patients receiving antiretroviral therapy. We assessed whether multitarget therapy with enfuvirtide, 2 reverse-transcriptase inhibitors, and a ritonavir-boosted protease inhibitor leads to decay of this reservoir. Nineteen treatment-naive patients initiated this regimen; 9 experienced virologic suppression and continued enfuvirtide-containing therapy for at least 48 weeks. In enfuvirtide-treated patients with virological suppression, there was no decay of the latent reservoir (95% confidence interval for half-life, 11 months to infinity). The stability of the latent reservoir despite intensive therapy suggests that new strategies are needed to eradicate HIV-1 from this reservoir. (ClinicalTrials.gov identifier: NCT00051831 .).

Conflict of interest statement

Potential conflicts of interest: M.A. has served as a consultant to Pfizer. L.M.D. has a family member who is receiving royalties from Merck and GlaxoSmithKline for products not related to this study. J.J.E. has been an investigator for Merck, Panacos, GlaxoSmithKline, and Abbott on research grants to the University of North Carolina; has served as a paid consultant or speaker for Merck, Bristol-Myers Squibb, GlaxoSmithKline, Gilead, Tibotec, Roche, and Pfizer; and has been a consultant to Trimeris in the past. R.T.G. has received research grants or unrestricted educational grants from Tibotec, Abbott, and Gilead and has served as a paid speaker at an advisory board meeting for GlaxoSmithKline. All other authors report no potential conflicts.

Figures

Figure 1

Latent reservoir in human immunodeficiency virus type 1 (HIV-1)–infected patients receiving intensive enfuvirtide-containing anti-retroviral therapy (ART) who had sustained virologic suppression and remained on enfuvirtide for at least 48 weeks (solid lines). The 95% confidence interval for the half-life of the latent reservoir is 11 months to infinity. Dashed lines represent the mean decay slope and 95% confidence intervals from measurements of the latent reservoir in 62 patients who were on ART regimens that did not contain enfuvirtide (historical controls) [4]. IUPM, infectious units per million cells.

Figure 2

Inverse correlation between the mean latent-reservoir size and baseline CD4 cell count in human immunodeficiency virus type 1 (HIV-1)–infected patients in the analysis cohort. IUPM, infectious units per million cells.