Antiretroviral Therapy, Drug Resistance, Microbial, HIV -1 Infection
Conditions
Keywords
antiretroviral therapy, regimen switch, archived resistance, low level viremia, proviral DNA, HIV infection
Brief summary
The study aims to determine the prevalence of drug resistance mutation (DRM) in virally suppressed HIV infection, and the impacts of regimen change and the presence of low level viremia. Adults living with HIV infection on antiretroviral therapy (ART) with full viral suppression would be recruited. Cases are patients planning for regimen switch, while controls are those with and without low level viraemia (LLV) not planned for switch. Blood samples would be collected before and after switch. Sequencing would be performed to identify DRM present in HIV-1 proviral DNA.
Detailed description
Aim/objectives: With the aim of determining the impact of antiretroviral regimen and switch on archived HIV-1 drug resistance mutation (DRM), the study's objectives are, to: (a) estimate the prevalence of DRM in virally suppressed HIV infection; (b) assess changes in archived resistance before and after switch; and (c) identify predictors of archived DRM after regimen switch. Design: A prospective observational study Setting: All HIV specialist clinic services in Hong Kong Methods: Adults living with HIV infection on antiretroviral therapy (ART) with full viral suppression who are planned for regimen switch would be recruited. Controls are patients with and without low level viraemia (LLV) not planned for switch, matched by antiretroviral regimen. Blood samples would be collected before switch, shortly and then 2-3 years after switch. Nanopore sequencing would be performed to identify DRM present in HIV-1 proviral DNA. Transcription of relevant clinical record data would be made to contribute to statistical and phylogenetic analyses Main outcome measures: Change in DRM frequency between baseline and followups at (a) short term and long term; (b) occurrence of virological failure and time to failure; (c) difference in DRM frequency between presence and absence of LLV, and switched and non-switched patients. Anticipated outcome: The study results would determine if archived resistance clearance would change following ART switch, identify factors associated with persistence of archived resistance, and inform management on the application of proviral DNA testing in clinical practice.
Interventions
None listed
Sponsors
Chinese University of Hong Kong
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients living with HIV who are (a) aged 18 or above, (b) on antiretroviral therapy, (c) has viral load \<20 copies/mL at 2 time points for ≥6 months, (d) planning regimen switch. * Patients for inclusion in the control group meet the same criteria (a) but they are not planned for switch. Controls include patients with low level viremia (LLV) as defined as ≥2 consecutive viral load level between 21 and 200 copies/mL in the preceding 2 years.
Exclusion criteria
* Patients living with HIV who (a) are pregnant, (b) have virologic failure, (c) are suffering from concurrent opportunistic infections, (d) are prisoners , (e) are unable to give consent, and (f) have mental illnesses.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportional difference of drug resistance mutation at short term after regimen switch | from enrolment to 3-6 months | Percentage difference between the prevalence of drug resistance mutation (DRM) detected by proviral DNA testing at baseline and short term (3-6 months) after regimen switch |
| Proportional difference of drug resistance mutation at long term after regimen switch | From enrolment to 2-3 years after regimen switch | Percentage difference between the prevalence of drug resistance mutation (DRM) detected by proviral DNA testing at baseline and long term (2-3 years) after regimen switch |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of drug resistance mutation | at enrolment | Percentage of patients on antiretroviral therapy with drug resistance mutation (DRM) detected by proviral DNA testing at baseline |
| Proportional Difference of drug resistance mutation prevalence between patients with and without by low level viremia | at enrolment | Percentage difference in the prevalence of drug resistance mutation (DRM) detected by proviral DNA testing between the presence and absence of low level viremia at baseline |
Countries
China
Contacts
CONTACTShui Shan Lee, MD
CONTACTNgai Sze Wong, PhD
PRINCIPAL_INVESTIGATORShui Shan Lee, MD
S.H. Ho Research Centre for Infectious Diseases, The Chinese University of Hong kong
Outcome results
None listed