HIV subtypes may influence treatment failure
Variations in drug-resistant mutations appeared to correspond with specific subtype designations in patients with HIV who failed first-line treatment, according to recent findings.
“Subtype designations are … widely used to represent genetic background variation in HIV sequences,” the researchers wrote. “While high viral genetic diversity and variable ART adherence is known to contribute to drug resistance and ART failure, subtype contributions to treatment outcomes remains actively researched through in vitro and surveillance methods.”
The researchers evaluated a multicohort, multisubtype dataset of reverse transcriptase (RT) isolates from patients failing WHO-recommended first-line ART. The analysis included 1,425 sequences, including 202 subtype B sequences, 696 subtype C sequences, 44 subtype G sequences, 351 CRF01_AE sequences, 58 CRF02_AG sequences and 74 other subtypes. They used a hierarchical model to characterize resistance mutation variations as pertained to treatment histories and subtype genetic backgrounds.
Subtype B, predominately found in the United States and Western Europe, generally demonstrated lower resistance mutation frequencies. In contrast, subtype C, the most common subtype worldwide (largely found in South African and India), as well as subtype CRF01_AE, commonly found in Southeast Asia, demonstrated higher resistance mutation frequencies to both nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI).
Compared with subtype B, thymidine analogue mutation (TAM) frequency in subtype C and CRF01_AE increased by 9% to 20% at RT positions 41L (RR = 1.9-5.2), 67N (RR = 2.2-5.3), 70R/E (RR = 2.4-5.8), 184 V/I (RR = 1.2-1.6), 215 F/Y (RR = 1.9-4.3), and 219Q/E (RR = 1.8-5.6).
Furthermore, subtype C and CRF01_AE were projected to have greater cross-resistance to future treatment approaches vs. subtype B (42% and 48% vs. 60%, respectively).
“Given the higher levels of resistance observed in subtype C and CRF01_AE population, interventions that minimize ecological contributions to resistance such as increased monitoring, viral load testing or use of boosted [protease inhibitor-based] regimens may warrant consideration,” the researchers wrote.
“Future studies should further disentangle the role of ecological and biological contributors for higher levels of resistance in subtype C and CRF01_AE. Identifying the correct causal explanations for the patterns of resistance characterized here is crucial to optimizing ART among populations infected with non-B HIV-1 subtypes.” – by Jen Byrne
Disclosure: Huang reports currently being a principal scientist at Pfizer. Please see the full study for a list of all other authors’ relevant financial disclosures.