805. Emergence of Monotypic HIV-1 DNA During Antiretroviral Treatment (ART) Suggests Proliferation of Cells with Integrated HIV DNA Provirus May Sustain Infection
Session: Abstracts: Oral Abstract Session: HIV Complications and Pathogenesis
Friday, October 22, 2010: 2:45 PM
118-120
Background:

A cure for HIV requires better understanding of HIV persistence. During ART some individuals have multiple identical HIV DNA sequences and persistent clones have been noted in the plasma, suggesting that proliferation of cells with integrated provirus may help sustain HIV infection. If true, we hypothesize that cells with identical proviral sequences should increase over time on effective ART.

Methods:

Specimens from before and > 2 time-points during effective ART were studied. Sequences were generated from peripheral blood mononuclear cells (PBMC) and sputum cells by single genome amplification of env (C2-V5) and pol. The main outcomes were detection of monotypic sequences (group of identical sequences comprising ≥ 5% of sequences) and change over time in prevalence of monotypic sequences. P values were calculated by paired Wilcoxon two-sided ranked sign test.

Results:

A total of 1735 sequences (867 env and 868 RT) were amplified from six individuals. 18% of the sequences were from specimens collected before ART, the remainder were from specimens collected over a median of 9.5 (range 8 - 11) years of effective ART. 31% of the sequences were generated from sputum DNA, all from after the initiation of ART. All individuals had at least one RT and env monotypic cluster, comprised of sequences from multiple time-points and/or cell-types (PBMC or sputum cells). The monotypic clusters were distributed throughout associated phylogenetic trees. The prevalence of monotypic env sequences increased from a median of 0% (range 0 – 12.5%) pre-ART, to 9.8% (range 5.6 – 35.6%) during ART (p = 0.05), and reached 19.8% (range 5.62 – 42.3%) after 5 years of ART. The prevalence of monotypic RT sequences increased from a median of 0% (range 0 – 14.7%) pre-ART, to 14.7% (range 8.1 – 35.9%) during ART (p = 0.05), and reached 16.5% (range 8.1 – 51.1%) after 5 years of ART. Multiplexed first round PCR precludes independent statistical analysis of RT and env.

Conclusion:

Monotypic HIV DNA RT and env sequences became common during ART, comprising 22% of blood and sputum sequences after 5 years of effective ART. The persistence and growth of monotypic clusters suggests that proliferation of infected cells may help sustain infection when active replication is suppressed by ART.


Subject Category: H. HIV/AIDS and other retroviruses

Speakers:
Thor Wagner, MD , University of Washington & Seattle Children's, Seattle, WA
Jennifer McKernan , Seattle Children's Research Insitute, Seattle, WA
Nicole Tobin, MD , Santa Clara Valley Medical Center, Santa Clara, CA
Lisa Frenkel, MD , Seattle Children's Hospital Research, Seattle, WA

Disclosures:

T. Wagner, None

J. McKernan, None

N. Tobin, None

L. Frenkel, None


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