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

TitleResidual plasma viraemia and infectious HIV-1 recovery from resting memory CD4 cells in patients on antiretroviral therapy: results from ACTG A5173.
Publication TypeJournal Article
Year of Publication2013
AuthorsGandhi RT, Bosch RJ, Aga E, Bedison MA, Bastow B, Schmitz JL, Siliciano JD, Siliciano RF, Eron JJ, Mellors JW
Corporate AuthorsACTG A5173 team
JournalAntivir Ther
Volume18
Issue4
Pagination607-13
Date Published2013
ISSN2040-2058
KeywordsAnti-HIV Agents, Antigens, CD38, CD4-Positive T-Lymphocytes, Gene Expression, HIV Envelope Protein gp41, HIV Infections, HIV-1, Humans, Immunologic Memory, Peptide Fragments, RNA, Viral, Viral Load, Viremia
Abstract

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 log10 HIV-1 RNA copies/ml per 1 log10 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.

DOI10.3851/IMP2543
Alternate JournalAntivir. Ther. (Lond.)
PubMed ID23411421
PubMed Central IDPMC3887470
Grant List1U01AI068636 / AI / NIAID NIH HHS / United States
2P30 AI060354-06 / AI / NIAID NIH HHS / United States
5-U01-AI-069415-03 / AI / NIAID NIH HHS / United States
5-U01-AI-069423-03 / AI / NIAID NIH HHS / United States
AI 068634 / AI / NIAID NIH HHS / United States
AI-069474 / AI / NIAID NIH HHS / United States
AI-069532 / AI / NIAID NIH HHS / United States
AI-27665 / AI / NIAID NIH HHS / United States
AI-54907 / AI / NIAID NIH HHS / United States
AI-69450 / AI / NIAID NIH HHS / United States
G08LM008830-01 / LM / NLM NIH HHS / United States
N01-AI-38858 / AI / NIAID NIH HHS / United States
P20-RR-11126 / RR / NCRR NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
P30--AI-078498 / AI / NIAID NIH HHS / United States
R01 AI066992 / AI / NIAID NIH HHS / United States
R01 AI066992-04A1 / AI / NIAID NIH HHS / United States
RR-025780 / RR / NCRR NIH HHS / United States
RR025747 / RR / NCRR NIH HHS / United States
U01 AI027659 / AI / NIAID NIH HHS / United States
U01 AI038855 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI069423 / AI / NIAID NIH HHS / United States
U01 AI069472 / AI / NIAID NIH HHS / United States
U01 AI694722 / AI / NIAID NIH HHS / United States
U01-AI-0694722 / AI / NIAID NIH HHS / United States
U01-AI-069495 / AI / NIAID NIH HHS / United States
U01-AI-069511 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States