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Original research
Genetic diversity of HIV in seminal plasma remains higher than in blood after short-term antiretroviral therapy
  1. Miguel Ángel López Zúñiga1,
  2. Natalia Chueca2,3,
  3. Adolfo de Salazar2,
  4. José Angel Fernández Caballero2,
  5. Alicia Gutierrez Valencia4,
  6. David Vinuesa García5,
  7. Mohamed Omar Mohamed Balgahata6,
  8. Carmen Hidalgo Tenorio7,
  9. Miguel Angel Lopez-Ruz3,7,
  10. Federico Garcia2,3
  1. 1 Internal Medicine Service, Jaen University Hospital, Jaen, Andalucía, Spain
  2. 2 Microbiology Department, San Cecilio University Hospital, Granada, Spain
  3. 3 Instituto de Investigación Biosanitaria Ibs.Granada, Granada, Spain
  4. 4 Infection Disease Service, Virgen del Rocio University Hospital, Sevilla, Andalucía, Spain
  5. 5 Infectious Disease Service, San Cecilio University Hospital, Granada, Spain
  6. 6 Infectious Disease Department, Jaen University Hospital, Jaen, Spain
  7. 7 Infectious Disease Service, University Hospital Virgen de las Nieves, Granada, Spain
  1. Correspondence to Dr Federico Garcia, Hospital Universitario San Cecilio, 18016 Granada, Spain; fegarcia{at}ugr.es

Abstract

Objective To provide insight on viral kinetics and genetic diversity of HIV in seminal plasma at baseline and 1 month after initiating antiretroviral therapy (ART).

Patients and methods Blood and seminal samples from patients with newly diagnosed HIV were obtained before ART initiation (T0) and 1 month after ART initiation (T1). HIV env genetic diversity was studied using deep sequencing Nextera and V3 chemistry in a MiSeq Illumina platform. The number of viral quasispecies (5% cut-off) and Shannon Index were used to analyse diversity.

Results Forty-seven ART-naive patients were recruited between September 2016 and November 2018. At enrolment, the number of quasispecies in blood (median 4 (IQR 2–5)) was lower than in the seminal compartment (median 6, (IQR 4–8)) (p<0.01); the Shannon Index was also higher (p<0.001) in the seminal compartment than in blood (1.77 vs 0.64). At T1, for the 13 patients with detectable HIV in both blood/seminal plasma, viral diversity remained higher (p=0.139) in seminal plasma (median 2 (IQR 1–4.5)) than in blood (median 1 (IQR 1–1.5)) Integrase inhibitors (INI)-based regimens achieved higher levels of undetectability and led more frequently to lower variability (p<0.001) than protease inhibitors (PI) or non-nucleoside reverse transcriptase inhibitors (NNRTI).

Conclusion We provide here further evidence of a larger genetic diversity in seminal plasma, both at diagnosis and short term after ART initiation. Our results strengthen previous findings on HIV diversity in seminal plasma. In addition, INIs decrease variability more rapidly than PI and NNRTI in both blood and seminal plasma.

  • antiretroviral therapy
  • DNA amplification
  • HIV
  • HIV therapeutics
  • virology
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Handling editor Anna Maria Geretti

  • Twitter @carmenhtenorio

  • MAL-R and FG contributed equally.

  • Contributors MALZ: investigation, methodology, supervision, writing—original draft, writing—review and editing. NC: microbiological analysis, investigation. AdS: microbiological analysis, investigation. JAFC: microbiological analysis, investigation. AGV: microbiological analysis, investigation. DVG: investigation. MOMB: investigation. CHT: investigation. MALR: investigation, methodology, supervision, writing—original draft, writing—review and editing. FG: funding acquisition, investigation, methodology, supervision, writing—original draft, writing—review and editing.

  • Funding This paper has been funded in part by grants from Fondo de Investigación Sanitaria (www.isciii.es) (PI18/ 00819), Plan Nacional de I+D+I and Fondo Europeo de Desarrollo Regional-FEDER (www.redes/redes/inicio) (RD16/0025/0040).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.