|
Basic Characteristics of Mutations
|
|
Mutation Site
|
T66A |
|
Mutation Site Sentence
|
Drug resistance mutations were found in 5 PWH (Malawi 4, Zambia 1); 2 had major mutations (G118R, E138K, T66A and G118R, E138K) leading to high-level dolutegravir resistance. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
IN |
|
Standardized Encoding Gene
|
gag-pol:155348
|
|
Genotype/Subtype
|
HIV-1 |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
Acquired Immunodeficiency Syndrome
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
Y |
|
Treatment
|
dolutegravir |
|
Location
|
Malawi;Zambia |
|
Literature Information
|
|
PMID
|
38847281
|
|
Title
|
Virologic Failure and Drug Resistance After Programmatic Switching to Dolutegravir-based First-line Antiretroviral Therapy in Malawi and Zambia
|
|
Author
|
Skrivankova VW,Huwa J,Muula G,Chiwaya GD,Banda E,Buleya S,Chihota B,Chintedza J,Bolton C,Tweya H,Kalua T,Hossmann S,Kouyos R,Wandeler G,Egger M,Lessells RJ
|
|
Journal
|
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
|
|
Journal Info
|
2025 Feb 5;80(1):120-128
|
|
Abstract
|
BACKGROUND: People with human immunodeficiency virus (PWH) on first-line, nonnucleoside reverse-transcriptase inhibitor-based antiretroviral therapy (ART) were routinely switched to tenofovir-lamivudine-dolutegravir. We examined virologic outcomes and drug resistance in ART programs in Malawi, where switching was irrespective of viral load, and Zambia, where switching depended on a viral load <1000 copies/mL in the past year. METHODS: We compared the risk of viremia (>/=400 copies/mL) at 1 and 2 years by viral load at switch and between countries using exact methods and logistic regression adjusted for age and sex. We performed HIV-1 pol Sanger sequencing on plasma samples with viral load >/=1000 copies/mL. RESULTS: A total of 2832 PWH were eligible (Malawi 1422, Zambia 1410); the median age was 37 years, and 2578 (91.0%) were women. At switch, 77 (5.4%) were viremic in Malawi and 42 (3.0%) in Zambia (P = .001). Viremia at switch was associated with viremia at 1 year (adjusted odds ratio (OR), 6.15; 95% confidence interval [CI], 3.13-11.4) and 2 years (7.0; 95% CI, 3.73-12.6). Viremia was less likely in Zambia than in Malawi at 1 year (OR, 0.55; 0.32-0.94) and 2 years (OR, 0.33; 0.18-0.57). Integrase sequencing was successful for 79 of 113 eligible samples. Drug resistance mutations were found in 5 PWH (Malawi 4, Zambia 1); 2 had major mutations (G118R, E138K, T66A and G118R, E138K) leading to high-level dolutegravir resistance. CONCLUSIONS: Restricting switching to dolutegravir-based ART to PWH with a viral load <1000 copies/mL may reduce subsequent viremia and, consequently, the emergence of dolutegravir drug resistance mutations. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov (NCT04612452).
|
|
Sequence Data
|
-
|
|
|