Dynamics of the resting CD4(+) T-cell latent HIV reservoir in infants initiating HAART less than 6 months of age

Abstract

Objectives: Identification of HIV infection in exposed infants facilitates early therapy, which may limit viral reservoirs that maintain HIV infection under HAART.

Methods: The dynamics of the resting CD4 T-cell latent HIV reservoir was determined over the first 2 years of life in 17 HIV-infected infants initiating lopinavir/ritonavir-based HAART at a median age of 8.1 weeks and achieving adequate suppression of plasma viral load by 24 weeks.

Results: The resting CD4 T-cell latent HIV reservoir was detected in 12 of 14 (86%) infants tested at 24 weeks of HAART [median frequency 1.88 infectious units per million (IUPM); range <0.22 to 81.7), and remained measurable (median IUPM = 0.32; range <0.22 to 3.25) in six of 10 (60%) children retested at 96 weeks. The reservoir declined, from 24 to 96 weeks of HAART, at an estimated mean rate of 0.028 log10 IUPM/month, corresponding to a half-life of 11 months (95% confidence interval 6-30 months]. A strong relationship was found between the frequency of latently infected CD4 T cells at 96 weeks of HAART and time to first undetectable plasma viral load (Spearman r = 0.91, P < 0.001).

Conclusion: Although the resting CD4 T-cell latent reservoir remains detectable over the first 2 years of HAART in a substantial proportion of infants, its size is associated with time to first undetectable viral load. To minimize HIV reservoirs in infants, rapid curtailment of viremia may limit HIV reservoirs and should be a therapeutic goal of early HAART in infants.

Trial registration: ClinicalTrials.gov NCT00038480.

Conflict of interest statement

Conflicts of interest

E.V.C. has served as a consultant to GlaxoSmithKline Bristol-Meyers Squibb and Johnson & Johnson. E.G.C. has had consultancies with Pfizer and Bristol-Meyers Squibb, and has owned stock+/− stock options in Abbott Labs, GlaxoSmithKline, Merck Inc., Bristol-Meyers Squibb and Johnsonn & Johnson, Novartis, Roche, and Sanofi. M.D.H. received grant support from Roche, honoraria or consultancies with Abbott Labs, Boehringer Ingelheim, Bristol-Meyers Squibb, Chiron, Medicines Development, Roche, Pfizer, Tibotec and Vironyx. K.L. has served as a consultant to Tibotec and Johnson and Johnson. D.P. has served as a consultant to Glaxo-SmithKlein. R.Y. has served on the Speaker’s Bureau for Merck Inc. and GlaxoSmithKline.

All other authors have no conflicts

Figures

Fig. 1. Frequencies of latently infected resting CD4+ T cells in infectious units per million (IUPM) at 24, 48 and 96 weeks of study treatment in infants initiating lopinavir/ritonavir HAART at less than 6 months of age

Each circle represents a single measurement per participant. At week 24, all infants with plasma HIV-1 RNA 2-log drop in plasma viral load below pretreatment levels were included. Measurements on infants initiating HAART at less than or greater than 6 weeks of age [12,13] are shown in red and blue, respectively. Latent reservoir measurements at weeks 48 and 96 are restricted to those infants who maintained suppression (apart from blips) through to week 96 of HAART. IUPM measurements that were below the limit of detection of the assay (IUPM

Fig. 2. Correlation between frequency of latently infected resting CD4+ T cells (log-scale) and HIV RNA level at week 24

Measurements on infants initiating HAART at less than or greater than 6 weeks of age [12,13] are shown in red and blue, respectively. Measurements that were below the limit of detection of the assay (IUPM

Fig. 3. Correlation between frequency of latently infected resting CD4+ T cells at 96 weeks of HAART (log-scale) and time to reach undetectable plasma viral load of less than 400 copies/ml

Measurements on infants initiating HAART at less than or greater than 6 weeks of age [12,13] are shown in red and blue, respectively. Measurements that were below the limit of detection of the assay (IUPM