Impacts of HIV Treatment Regimens on Archived Drug Resistance

Impact of Antiretroviral Therapy (ART) Switch on Archived HIV-1 Drug Resistance in Virally Suppressed Patients: A Prospective Cohort Study

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.

Study Overview

• Status: Recruiting
• Conditions: Antiretroviral Therapy; HIV -1 Infection; Drug Resistance, Microbial

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.

• Study Type: Observational
• Enrollment (Estimated): 420

Contacts and Locations

• Study Contact: Name: Shui Shan Lee, MD; Phone Number: +852 22528812; Email: sslee@cuhk.edu.hk
• Study Contact Backup: Name: Ngai Sze Wong, PhD; Phone Number: +852 22528862; Email: candy_wong@cuhk.edu.hk

Study Locations

• China
  • Hong Kong
    • Hong Kong, Hong Kong, China, 0000
      • Recruiting
      • S.H. Ho Research Centre for Infectious Diseases, The Chinese University of Hong Kong
      • Contact: Shui Shan Lee, MD; Phone Number: +852 22528812; Email: sslee@cuhk.edu.hk
      • Contact: Ngai Sze Wong, PhD; Phone Number: +852 22528862; Email: candy_wong@cuhk.edu.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients living with HIV and who are attendees of HIV specialist clinics in the public service in Hong Kong

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patients on ART planning for regimen switch; virally suppressed with viral undetectable at 2 consecutive timepoints prior to enrolment
Patients on ART not for regimen switch; with and without low level viraemia prior to enrolment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportional difference of drug resistance mutation at short term after regimen switch	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	from enrolment to 3-6 months
Proportional difference of drug resistance mutation at long term 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	From enrolment to 2-3 years after regimen switch

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of drug resistance mutation	Percentage of patients on antiretroviral therapy with drug resistance mutation (DRM) detected by proviral DNA testing at baseline	at enrolment
Proportional Difference of drug resistance mutation prevalence between patients with and without by low level viremia	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	at enrolment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of virologic failure	Prevalence of virologic failure in patients on antiretroviral therapy at 2-3 years after enrolment	From enrolment to 2-3 years

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Shui Shan Lee, MD, S.H. Ho Research Centre for Infectious Diseases, The Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2025
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: June 8, 2026
• First Submitted That Met QC Criteria: June 10, 2026
• First Posted (Actual): June 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 10, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: HIV infection; antiretroviral therapy; low level viremia; regimen switch; archived resistance; proviral DNA
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections
• Other Study ID Numbers: HK HIV archived DRM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual data are protected as per provision of the approval of the Ethics Committee

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No