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Updated: Jul 10, 2026
An Affordable HIV-1 Drug Resistance Monitoring Method for Resource Limited Settings
Published on: March 30, 2014
Emerging integrase resistance in an international perinatal virtual clinic
Ayolola Eni-Olotu1, Nicola E Mackie2, Jessica Glenn1
1Imperial College.
Insights
Emerging integrase inhibitor drug resistance mutations (INSTI-DRMs) were identified in children and adolescents with perinatally acquired HIV (CAWHIV) referred to a virtual clinic. These INSTI-DRMs were primarily observed in highly treatment-experienced individuals from low- and middle-income countries.
Area of Science:
- Virology and Infectious Diseases
- Pediatric HIV Management
- Drug Resistance Studies
Background:
- Integrase Strand Transfer Inhibitors (INSTIs) are a cornerstone of modern antiretroviral therapy (ART) for HIV.
- The emergence of drug resistance mutations (DRMs) can compromise treatment efficacy, particularly in resource-limited settings.
- Understanding INSTI-DRMs in children and adolescents with perinatally acquired HIV (CAWHIV) is crucial for optimizing global treatment strategies.
Purpose of the Study:
- To determine the prevalence of emergent integrase drug resistance mutations (INSTI-DRMs) in CAWHIV referred to a perinatal virtual clinic (PVC).
- To characterize the clinical and demographic features of CAWHIV with INSTI-DRMs.
- To inform treatment recommendations for complex HIV cases with virological failure.
Main Methods:
- Retrospective cohort study of 114 CAWHIV referred for virological failure between October 2018 and January 2024.
- Analysis of resistance mutations using the Stanford HIV Drug Resistance database.
- Data collected included ART history, viral load, CD4+ cell count, and comorbidities.
Main Results:
- Of 103 cases with available resistance sequences, 19 (31%) exhibited INSTI-DRMs following prior INSTI exposure (59%).
- Individuals with INSTI-DRMs were often highly treatment-experienced (median 3 prior regimens) and predominantly from low/middle-income countries (LMIC) (65%).
- Emergent INSTI-DRMs occurred on both first-line (2/19) and second+ line ART (17/19), necessitating complex salvage regimens.
Conclusions:
- Emerging INSTI resistance is a growing concern in highly treatment-experienced CAWHIV, particularly those from LMIC.
- The findings underscore the global need for improved access to effective salvage therapies, including boosted protease inhibitors and novel drug classes.
- Development of pediatric-friendly formulations for newer antiretrovirals is essential for children weighing less than 35 kg.
Objective:
The aim of this study was to identify the prevalence of emergent integrase drug resistance mutations (INSTI-DRMs) in international referrals to a perinatal virtual clinic (PVC).
Design:
A retrospective cohort study.
Setting:
Monthly multidisciplinary PVC reviewing complex case management for children and adolescents with perinatally acquired HIV (CAWHIV).
Participants:
One hundred fourteen cases referred for virological failure between October 2018 and January 2024.
Main Outcome Measures:
Data collected included age, sex, weight, country of residence, antiretroviral therapy (ART) history, HIV viral load, CD4 + cell count, and comorbidities. Resistance mutations were interpreted using the Stanford HIV Drug Resistance database with emergent major INSTI-DRMs described.
Results:
Of 114 referrals, 103 (90%) had resistance sequences available. Prior INSTI exposure was documented in 61/103 (59%) with 19/61 (31%) having INSTI-DRMs. For these 19, median (IQR) age was 11 years (6-14), weight 25 kg (17-50), CD4 + cell count 485 cells/μl (153-805), and viral load 84 000 copies/ml (2380-137 000). Twelve of 19 (65%) were from low/middle-income countries (LMIC), 6/19 (32%) had current AIDS diagnoses with 14/19 (74%) referred from 2022 onwards. There were a median three prior regimens with 13/19 (68%) having at least 3 class resistance. Two developed INSTI-DRMs on first-line dolutegravir (DTG)-based ART, 17 on second+ line therapy. PVC recommendations were for tenofovir+ lamivudine/emtricitabine (six split adult tablets) with boosted darunavir [19; six twice daily (b.i.d.)], with b.i.d. DTG (6), plus fostemsavir (1) and ibalizumab (1).
Conclusion:
Although uncommon, INSTI resistance is emerging, mainly in highly treatment experienced CAWHIV from LMIC, highlighting the global need for access to boosted protease inhibitors and novel classes, including formulations for children less than 35 kg.
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