Dolutegravir Resistance in Mozambique: Insights from a Programmatic HIV Resistance Testing Intervention in a Highly Antiretroviral Therapy-Experienced Cohort
Abstract
1. Introduction
2. Materials and Methods
2.1. Setting
2.2. Study Design and Population
2.2.1. Eligible Participants
Algorithm for Selecting PLWH for Resistance Testing
Positive Predictive Value (PPV)
Genotypic HIV Drug-Resistance (HIVDR) Testing
2.2.2. Sampling and Sample Size of Program Participants
2.2.3. Program Data Collection
2.2.4. Program Data Analysis
3. Results
3.1. Cohort Main Characteristics
3.2. INSTI Mutations and Resistance
4. Discussion
4.1. Main Findings
4.2. Other Relevant Findings
4.3. Limitations of the Study
5. Conclusions and Recommendations
What Are the Bullet Points of This Study?
- High Detection of Dolutegravir Resistance: The study reveals a strikingly high detection of dolutegravir (DTG) resistance (89.5%) among individuals with virologic failure (VF) who had extensive prior exposure to antiretroviral therapy (ART). This underscores the risk of resistance in heavily ART-experienced populations and challenges the assumption that DTG resistance is still rare.
- Effective Algorithm for Resistance Identification: The study outlines a structured algorithm combining viral load monitoring, adherence reinforcement, and supervised ART support to identify individuals at high risk of resistance. The add-on approach demonstrated a high positive predictive value (89.5%), enabling targeted use of genotypic resistance testing where resources are limited.
- Mutational Patterns and Resistance Scores: The study documents the most common DTG-associated mutations (e.g., G118R, R263K, Q148RK) and provides detailed resistance scores, offering insights into the genetic basis of DTG resistance in this cohort.
- Programmatic Implications: The findings highlight the need for integrating resistance testing into ART programs in resource-limited settings, particularly for individuals with prolonged ART exposure and virologic failure. The study substantiates the need for adherence support and supervised interventions before considering regimen switches, which can help preserve effective treatment options like DTG. It also highlights the importance of elucidating the role of regular HIVDR surveillance vs. clinically driven individual resistance testing in settings where the affordability and feasibility of HIVDR testing are perceived as limited.
- Sex Disparities in Advanced HIV Disease: The study notes significant immunological differences between men and women in the cohort, with men exhibiting lower CD4 counts and higher rates of advanced HIV disease. This aligns with broader trends in sub-Saharan Africa and emphasizes the need for targeted interventions for male populations.
- Limitations and Future Directions: The study acknowledges the challenges of using dried blood spot (DBS) samples for resistance testing, particularly their lower sensitivity for detecting resistance in cases of low-level viremia. It calls for further research to validate the algorithm in different subpopulations and to explore plasma-based testing for improved sensitivity.
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
| ABC | Abacavir |
| AHD | Advanced HIV disease |
| ART | Antiretroviral therapy |
| ATV | Atazanavir |
| AZT | Zidovudine |
| CRAM | Centro de Referência de Alto-Mae |
| CDC | Centers for Disease Control and Prevention |
| D4T | Stavudine |
| DBS | Dried blood spot |
| DRV | Darunavir |
| DTG | Dolutegravir |
| DTG-R | Dolutegravir resistance testing |
| HRSA | Health Resources and Services Administration |
| HIV-GT | HIV genotypic resistance testing |
| IQR | Interquartile range |
| INSTI | Integrase strand transfer inhibitor |
| ITECH | International Training and Education Center for Health |
| pd | Probability of direction (pd) |
| PIs | Protease inhibitors |
| PLWH | People living with HIV |
| LPV | Lopinavir |
| MSF | Médecins Sans Frontières |
| NRTI | Nucleotide reverse transcriptase inhibitors |
| RTV | Ritonavir |
| RAL | Raltegravir |
| TDF | Tenofovir |
| VF | Virologic failure |
| WHO | World Health Organization |
| 95% Crl | 95% Bayesian credible interval |
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| All | DTG-Based | PI-Based | |
|---|---|---|---|
| N | 106 | 62 | 44 |
| Sex Women, N (%) | 57 (53.8) | 30 (48.4) | 27 (61.4) |
| Men, N (%) | 49 (46.2) | 35 (53.8) | 17 (38.6) |
| Age, median (IQR) | 42 (38, 48) | 42 (38, 48) | 42 (37, 50) |
| Time on ART (years), median (IQR) | 11.6 (9.1, 14.5) | 11.2 (6.5, 14.4) | 12.1 (10.4, 14.6) |
| Time on current ART regimen (years), median (IQR) | 3.2 (2.2, 4.5) | 2.5 (1.9, 3.3) | 4.8 (3.7, 6.0) |
| TDF backbone, N (%) | 80 (75.5) | 49 (79.0) | 31 (70.5) |
| Non-first-line ART, N (%) | 102 (96.2) | 60 (96.8) | 42 (95.5) |
| Viral load (log10), median (IQR) | 4.6 (4.2, 5.2) | 4.7 (4.3, 5.2) | 4.6 (4.2, 4.9) |
| CD4, median (IQR) | 134 (58, 234) | 128 (56, 233) | 146 (59, 258) |
| Advanced HIV, N (%) 1 | 72 (67.9) | 43 (69.4) | 29 (65.9) |
| Subtype C, N (%) | 99 (93.4) | 58 (93.5) | 41 (93.2) |
| All | DTG-Based | PI-Based | |
|---|---|---|---|
| Number of NRTI mutations, median (IQR) 1 | 3 (2, 5) | 4 (2, 5) | 3 (2, 5) |
| TDF-R score, median (IQR) | 20 (5, 35) | 20 (13.8, 36.2) | 15 (0, 28.8) |
| TDF-R score ≥ 5, N (%) | 78 (76.5) | 48 (80.0) | 30 (71.4) |
| AZT-R score, median (IQR) | 57.5 (0, 90) | 60 (0, 90) | 55 (5, 88.8) |
| AZT-R score ≥ 5, N (%) | 73 (71.5) | 41 (68.3) | 32 (76.2) |
| Number of PI mutations, median (IQR) 2 | 2 (0, 5) | 1 (0, 2) | 5 (4, 7) |
| ATV-R score, median (IQR) | 0 (0, 70) | 0 (0, 0) | 65 (17.5, 110) |
| ATV-R score ≥ 5, N (%) | 51 (49.5) | 12 (20.0) | 39 (90.7) |
| DRV-R score, median (IQR) | 0 (0, 0) | 0 (0, 0) | 0 (0, 0) |
| DRV-R score ≥ 5, N (%) | 14 (13.6) | 6 (10.0) | 8 (18.6) |
| Number of INSTI mutations, median (IQR) 3 | 0.5 (0, 3) | 3 (1, 4) | 0 (0, 0) |
| DTG-R score, median (IQR) | 30 (0, 80) | 75 (40, 81.2) | 0 (0, 0) |
| DTG-R score ≥ 5, N (%) | 51 (53.6%) | 51 (91.1%) | 0 (0%) |
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Share and Cite
Ruano, M.; Flores, A.; Couto, A.; Gaspar, I.; Yerly, S.; Zamudio, A.G.G.; Bene, R.; Maiela, A.; Macuacua, H.; Lane, J.; et al. Dolutegravir Resistance in Mozambique: Insights from a Programmatic HIV Resistance Testing Intervention in a Highly Antiretroviral Therapy-Experienced Cohort. Infect. Dis. Rep. 2025, 17, 123. https://doi.org/10.3390/idr17050123
Ruano M, Flores A, Couto A, Gaspar I, Yerly S, Zamudio AGG, Bene R, Maiela A, Macuacua H, Lane J, et al. Dolutegravir Resistance in Mozambique: Insights from a Programmatic HIV Resistance Testing Intervention in a Highly Antiretroviral Therapy-Experienced Cohort. Infectious Disease Reports. 2025; 17(5):123. https://doi.org/10.3390/idr17050123
Chicago/Turabian StyleRuano, Maria, Antonio Flores, Aleny Couto, Irénio Gaspar, Sabine Yerly, Ana Gabriela Gutierrez Zamudio, Rosa Bene, Adelina Maiela, Helder Macuacua, Jeff Lane, and et al. 2025. "Dolutegravir Resistance in Mozambique: Insights from a Programmatic HIV Resistance Testing Intervention in a Highly Antiretroviral Therapy-Experienced Cohort" Infectious Disease Reports 17, no. 5: 123. https://doi.org/10.3390/idr17050123
APA StyleRuano, M., Flores, A., Couto, A., Gaspar, I., Yerly, S., Zamudio, A. G. G., Bene, R., Maiela, A., Macuacua, H., Lane, J., Mudender, F., & Nacarapa, E. (2025). Dolutegravir Resistance in Mozambique: Insights from a Programmatic HIV Resistance Testing Intervention in a Highly Antiretroviral Therapy-Experienced Cohort. Infectious Disease Reports, 17(5), 123. https://doi.org/10.3390/idr17050123

