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Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy
- Source :
- J Infect Dis
- Publication Year :
- 2020
-
Abstract
- Background HIV-1 proviruses persist in people on antiretroviral therapy (ART) but most are defective and do not constitute a replication-competent reservoir. The decay of infected cells carrying intact compared with defective HIV-1 proviruses has not been well defined in people on ART. Methods We separately quantified intact and defective proviruses, residual plasma viremia, and markers of inflammation and activation in people on long-term ART. Results Among 40 participants tested longitudinally from a median of 7.1 years to 12 years after ART initiation, intact provirus levels declined significantly over time (median half-life, 7.1 years; 95% confidence interval [CI], 3.9–18), whereas defective provirus levels did not decrease. The median half-life of total HIV-1 DNA was 41.6 years (95% CI, 13.6–75). The proportion of all proviruses that were intact diminished over time on ART, from about 10% at the first on-ART time point to about 5% at the last. Intact provirus levels on ART correlated with total HIV-1 DNA and residual plasma viremia, but there was no evidence for associations between intact provirus levels and inflammation or immune activation. Conclusions Cells containing intact, replication-competent proviruses are selectively lost during suppressive ART. Defining the mechanisms involved should inform strategies to accelerate HIV-1 reservoir depletion.
- Subjects :
- 0301 basic medicine
Adult
CD4-Positive T-Lymphocytes
Male
Time Factors
Anti-HIV Agents
Art initiation
030106 microbiology
Human immunodeficiency virus (HIV)
Inflammation
Proviral dna
Viremia
HIV Infections
medicine.disease_cause
03 medical and health sciences
Major Articles and Brief Reports
Proviruses
Antiretroviral Therapy, Highly Active
medicine
Immunology and Allergy
Humans
business.industry
Provirus
Middle Aged
Viral Load
medicine.disease
Virology
Antiretroviral therapy
3. Good health
CD4 Lymphocyte Count
030104 developmental biology
Infectious Diseases
DNA, Viral
HIV-1
RNA, Viral
Female
medicine.symptom
business
Immune activation
Subjects
Details
- ISSN :
- 15376613
- Volume :
- 223
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- The Journal of infectious diseases
- Accession number :
- edsair.doi.dedup.....cb7fb912cce840879b3115b9e1f3e948