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Total HIV-1 DNA Dynamics and Influencing Factors in Long-Term ART-Treated Japanese Adults

A Retrospective Longitudinal Analysis

Stanoeva, Kamelia R., MD, MSc*; König, André, PhD; Fukuda, Asami, BSc; Kawanami, Yoko, BSc*; Kuwata, Takeo, PhD*; Satou, Yorifumi, MD, PhD; Matsushita, Shuzo, MD, PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: June 1, 2018 - Volume 78 - Issue 2 - p 239–247
doi: 10.1097/QAI.0000000000001662
Translational Science

Background: Understanding HIV persistence in treated patients is an important milestone toward drug-free control. We aimed at analyzing total HIV DNA dynamics and influencing factors in Japanese patients who received more than a decade of suppressive antiretroviral treatment (ART).

Methods: A retrospective study including clinical records and 840 peripheral blood mononuclear cells samples (mean 14 samples/patient) for 59 patients (92% male) was performed. Subjects were divided into 2 groups: with and without hematological comorbidity (mainly hemophilia) plus hepatitis C virus coinfection. Total HIV DNA was measured in peripheral blood mononuclear cells by quantitative polymerase chain reaction. The dynamics, regression over time, and influence of antiretrovirals by group were estimated using a novel regression model (R software v 3.2.3).

Results: Total HIV DNA decreased on ART initiation, and subsequently, its dynamics varied between groups with previously undescribed fluctuations. If calculated by on-treatment, the mean total HIV DNA levels were similar. The comorbidity group had unstable levels showing different regression over time (P = 0.088/0.094 in year 1/after year 8 of ART) and significantly different treatment responses as shown by antiretroviral group switching estimates. Furthermore, curing hepatitis C virus in hemophiliacs did not significantly alter total HIV DNA levels or regression.

Conclusions: Our data identified some effects of the long-term treatment on total HIV DNA levels and highlighted the partial influence of comorbidities and coinfections. Total HIV DNA monitoring contributed to therapy response estimates and HIV reservoir quantification. The results suggest that HIV DNA monitoring during ART might be useful as a persistence marker in both HIV-monoinfected patients and those with comorbidities and coinfections.

*Matsushita Project Laboratory, Center for AIDS Research, Kumamoto University, Kumamoto, Japan;

Faculty of Statistics, Technical University Dortmund, Dortmund, Germany; and

Satou Project Laboratory, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.

Correspondence to: Shuzo Matsushita, MD, PhD, Center for AIDS Research, 2-2-1 Honjo, Chuo, Kumamoto 860-0811, Japan (e-mail:

Supported in part by a Grant-in-Aid for scientific research (15H04870), Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan; by a grant (H24-AIDS-007) from the Ministry of Health, Labour and Welfare of Japan; and by a grant for the Research Program on HIV/AIDS (16fk0410102h001) from the Japan Agency for Medical Research and Development. MEXT scholarships (research and doctoral student 2014) were awarded to K.R.S. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Presented in part at the 7th International Workshop on HIV Persistence During Therapy; December 8–11, 2015; Miami, FL; the 2016 Towards an HIV Cure Symposium; July 16–17, 2016; Durban, South Africa; and the 30th Annual Meeting of the Japanese Society for AIDS Research; November 24–26, 2016; Kagoshima, Japan.

S.M. receives immunology research funding from Cured Ltd., Japan, unrelated to this work's topic. Although a current employee of Merck Ltd., A.K. contributed in his personal capacity and in affiliation with the TU Dortmund. The remaining authors have no funding or conflicts of interest to disclose.

K.R.S. and S.M. conceived and planned the study. S.M. was the attending physician and coordinated samples and clinical records collection, as well as ethical approval. K.R.S. and Y.K. processed the clinical records data and managed sample storage. Y.S. conceived the laboratory protocol and supervised the measurements. K.R.S. and A.F. performed the laboratory measurements. K.R.S. and A.K. analyzed the experimental and clinical records data. A.K. performed statistical analyses. K.R.S. and A.K. wrote the manuscript. T.K., Y.S., and S.M. reviewed the manuscript. All authors contributed to the revision and preparation of the final manuscript.

Y.S. and S.M. contributed equally to this work.

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Received October 02, 2017

Accepted February 12, 2018

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