Genetic complexity in the replication-competent latent HIV reservoir increases with untreated infection duration in infected youth

Citation: Brumme ZL, Sudderuddin H, Ziemniak C, Luzuriaga K, Jones BR, Joy JB, Cunningham CK, Greenough T, Persaud D. Genetic complexity in the replication-competent latent HIV reservoir increases with untreated infection duration in infected youth. AIDS. 2019 Feb 1;33(2):211-218. PMID: 30325763; PMCID: PMC6298800

Access full article:

https://www.ncbi.nlm.nih.gov/pubmed/30325763

OBJECTIVE:
Timely initiation of combination antiretroviral therapy (ART) limits latent HIV reservoir size and should also limit reservoir genetic complexity. However, the relationship between these two factors remains unclear, particularly among HIV-infected youth.

DESIGN:
Retrospective analysis of replication-competent latent HIV clones serially isolated by limiting-dilution culture from resting CD4 T-cell reservoirs from ART-suppressed, young adult participants of a historic phase I therapeutic vaccine trial (PACTG/IMPAACT-P1059).

METHODS:
Replication-competent latent HIV clones isolated from resting CD4 T cells of four perinatally and 10 nonperinatally infected young adults (average 22 versus 6 years uncontrolled infection, respectively) were sequenced in Pol and Nef. Within-host HIV sequence datasets were characterized with respect to their genetic diversity and inferred immune escape mutation burden.

RESULTS:
Although participants were comparable in terms of sociodemographic and HIV sampling characteristics (e.g. on average, a mean 17 Pol sequences were recovered at five timepoints over up to 70 weeks) and the length of ART suppression at study entry (average 3 years), replication-competent HIV reservoir size, genetic diversity, immune escape mutation burden and variant complexity were significantly higher among the perinatally infected participants who experienced longer durations of uncontrolled viremia. Nevertheless, viral sequences inferred to retain susceptibility to host cellular immune responses were detected in all participants, irrespective of uncontrolled viremia duration.

CONCLUSION:
HIV elimination in late-suppressed youth may be doubly challenged by larger and more genetically complex reservoirs. Strategies that integrate host and viral genetic complexity to achieve HIV remission or cure may merit consideration in such cases.

Categories

CRS
Topics

Clinical Trials

A5342: Evaluating the Safety, Tolerability, and Effect of a...

The purpose of this study is to evaluate the safety, tolerability, and effect of an experimental human monoclonal antibody...

Read More

A5349: Rifapentine-containing treatment shortening regimens...

The purpose of this study is to determine whether one or two four-month regimens of tuberculosis treatment are as effective as a...

Read More

A5314: Effect of LDMTX on Inflammation in HIV-infected...

A5314 is a phase II randomized, double-blind, placebo-controlled 36-week trial that will examine the safety and efficacy of...

Read More

A5300B/I2003B/PHOENIX, Protecting Households On Exposure to...

This study will compare the efficacy and safety of 26 weeks of delamanid (DLM) versus 26 weeks of isoniazid (INH) for preventing...

Read More

P2010: Phase III Study of the Virologic Efficacy and Safety...

IMPAACT 2010 is a Phase III, three-arm, randomized, open-label study of HIV-1-infected pregnant women initiating either a...

Read More