Human Immunodeficiency Virus (HIV) Genetic Diversity Informs Stage of HIV-1 Infection Among Patients Receiving Antiretroviral Therapy in Botswana

J Infect Dis. 2022 Apr 19;225(8):1330-1338. doi: 10.1093/infdis/jiab293.

Abstract

Background: Human immunodeficiency virus (HIV)-1 genetic diversity increases during infection and can help infer the time elapsed since infection. However, the effect of antiretroviral treatment (ART) on the inference remains unknown.

Methods: Participants with estimated duration of HIV-1 infection based on repeated testing were sourced from cohorts in Botswana (n = 1944). Full-length HIV genome sequencing was performed from proviral deoxyribonucleic acid. We optimized a machine learning model to classify infections as < or >1 year based on viral genetic diversity, demographic, and clinical data.

Results: The best predictive model included variables for genetic diversity of HIV-1 gag, pol, and env, viral load, age, sex, and ART status. Most participants were on ART. Balanced accuracy was 90.6% (95% confidence interval, 86.7%-94.1%). We tested the algorithm among newly diagnosed participants with or without documented negative HIV tests. Among those without records, those who self-reported a negative HIV test within <1 year were more frequently classified as recent than those who reported a test >1 year previously. There was no difference in classification between those self-reporting a negative HIV test <1 year, whether or not they had a record.

Conclusions: These results indicate that recency of HIV-1 infection can be inferred from viral sequence diversity even among patients on suppressive ART.

Keywords: ART; HIV; HIV treatment; NGS; early HIV infection.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Retroviral Agents / pharmacology
  • Anti-Retroviral Agents / therapeutic use
  • Botswana / epidemiology
  • Genetic Variation
  • HIV Infections* / drug therapy
  • HIV-1* / genetics
  • Humans
  • Viral Load

Substances

  • Anti-Retroviral Agents