Dolutegravir (DTG) in combination with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC) is a fixed-dose combination that has been shown to increase adherence and has a good resistance profile. For kids and teens who haven’t responded to abacavir (ABC), zidovudine (AZT), or TDF-containing regimens, researchers looked at how well TLD (TDF-3TC-DTG) was expected to work. A retrospective dataset of patients 19 years old who had failed therapy with ABC (n = 293), AZT (n = 288), or TDF (n = 69) was evaluated for drug-resistant mutations. Sequences of Pol were uploaded to the Stanford HIVdb v8.9. There were several DTG-based treatment plans evaluated for their genotypic susceptibility ratings. About 650 people, with a median age of 14, had their genotypes evaluated (IQR 10-17 years). Protease inhibitor (PI) based regimens had a higher failure rate (78.3%) than non-nucleoside reverse transcriptase inhibitors (NNRTI) based regimens (21.7%). Many more people in the AZT group (n = 288; 94.4% of them) failed a PI-based regimen than did those in the TDF (n = 69) or ABC (n = 293) groups (71.0% and 64.2%, respectively). Only 8.5% and 9.4% of those exposed to ABC and AZT, respectively, had genotypic sensitivity scores 2 to TLD, but 23.2% of those exposed to TDF did. The M184V mutation was shown to be much more prevalent in the ABC group (70.6%) compared to the TDF group (60.0%) and the AZT group (52.4%). Reduced TLD susceptibility was typically caused by an accumulation of nucleoside reverse transcriptase inhibitor (NRTI) mutations, while the occurrence of K65R was uncommon (n = 13, 2.0%). Because of the low rates of cross-resistance to TDF, using TLD in young people is less of a cause for alarm. Subsequently, the NADIA trial demonstrated that patients who did not respond to a TDF/3TC/EFV regimen might safely transfer to a TLD regimen, but similar data for patients who did not respond to an ABC/3TC/NNRTI or PI regimen was not available. Particularly for children who are still on ABC as their backbone treatment, regular virological surveillance is advised after the switch to DTG. Clinical trials are needed to correlate predicted resistance with clinical outcomes, especially in contexts where genotyping is unavailable.
Source: journals.lww.com/pidj/Fulltext/2022/10000/Minimal_Cross_resistance_to_Tenofovir_in_Children.9.aspx
