Journal article
Low-Abundance Drug-Resistant HIV-1 Variants in Antiretroviral Drug-Naive Individuals: A Systematic Review of Detection Methods, Prevalence, and Clinical Impact.
- Mbunkah HA Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zürich, Switzerland.
- Bertagnolio S HIV Department, World Health Organization, Geneva, Switzerland.
- Hamers RL Amsterdam Institute for Global Health and Development, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
- Hunt G National Institute for Communicable Diseases, Johannesburg, South Africa.
- Inzaule S Amsterdam Institute for Global Health and Development, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
- Rinke De Wit TF Amsterdam Institute for Global Health and Development, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
- Paredes R Infectious Diseases Service and IrsiCaixa AIDS Research Institute for AIDS Research, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain.
- Parkin NT Data First Consulting, Sebastopol, California, USA.
- Jordan MR Division of Geographic Medicine and Infectious Disease, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts, USA.
- Metzner KJ Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zürich, Switzerland.
- 2019-12-07
Published in:
- The Journal of infectious diseases. - 2020
HIV-1
HIV-1 drug resistance
antiretroviral therapy
antitretroviral drug-naive individuals
low-abundance drug-resistant HIV-1 variants
minority variants
next-generation sequencing
English
BACKGROUND
The presence of high-abundance drug-resistant HIV-1 jeopardizes success of antiretroviral therapy (ART). Despite numerous investigations, the clinical impact of low-abundance drug-resistant HIV-1 variants (LA-DRVs) at levels <15%-25% of the virus population in antiretroviral (ARV) drug-naive individuals remains controversial.
METHODS
We systematically reviewed 103 studies assessing prevalence, detection methods, technical and clinical detection cutoffs, and clinical significance of LA-DRVs in antiretroviral drug-naive adults.
RESULTS
In total, 14 919 ARV drug-naive individuals were included. Prevalence of LA-DRVs (ie, proportion of individuals harboring LA-DRVs) was 0%-100%. Technical detection cutoffs showed a 4 log range (0.001%-10%); 42/103 (40.8%) studies investigating the impact of LA-DRVs on ART; 25 studies included only individuals on first-line nonnucleoside reverse transcriptase inhibitor-based ART regimens. Eleven of those 25 studies (44.0%) reported a significantly association between preexisting LA-DRVs and risk of virological failure whereas 14/25 (56.0%) did not.
CONCLUSIONS
Comparability of the 103 studies is hampered by high heterogeneity of the studies' designs and use of different methods to detect LA-DRVs. Thus, evaluating clinical impact of LA-DRVs on first-line ART remains challenging. We, the WHO HIVResNet working group, defined central areas of future investigations to guide further efforts to implement ultrasensitive resistance testing in routine settings.
The presence of high-abundance drug-resistant HIV-1 jeopardizes success of antiretroviral therapy (ART). Despite numerous investigations, the clinical impact of low-abundance drug-resistant HIV-1 variants (LA-DRVs) at levels <15%-25% of the virus population in antiretroviral (ARV) drug-naive individuals remains controversial.
METHODS
We systematically reviewed 103 studies assessing prevalence, detection methods, technical and clinical detection cutoffs, and clinical significance of LA-DRVs in antiretroviral drug-naive adults.
RESULTS
In total, 14 919 ARV drug-naive individuals were included. Prevalence of LA-DRVs (ie, proportion of individuals harboring LA-DRVs) was 0%-100%. Technical detection cutoffs showed a 4 log range (0.001%-10%); 42/103 (40.8%) studies investigating the impact of LA-DRVs on ART; 25 studies included only individuals on first-line nonnucleoside reverse transcriptase inhibitor-based ART regimens. Eleven of those 25 studies (44.0%) reported a significantly association between preexisting LA-DRVs and risk of virological failure whereas 14/25 (56.0%) did not.
CONCLUSIONS
Comparability of the 103 studies is hampered by high heterogeneity of the studies' designs and use of different methods to detect LA-DRVs. Thus, evaluating clinical impact of LA-DRVs on first-line ART remains challenging. We, the WHO HIVResNet working group, defined central areas of future investigations to guide further efforts to implement ultrasensitive resistance testing in routine settings.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1093/infdis/jiz650
- PMID 31809534
- Persistent URL
- https://sonar.ch/global/documents/152880
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