An M184V/I mutation may not influence virologic failure risk among patients with HIV infection who switch to dolutegravir plus lamivudine.
An M184V/I mutation may have little to no impact on virologic suppression among patients with HIV infection who switch to dolutegravir (DTG) plus lamivudine (3TC), According to study findings published in Open Forum Infectious Diseases.
The resistance-associated mutation M184V/I is frequently observed among patients with HIV infection who have experienced at least occurrence of virologic failure during receipt of 3TC- or emtricitabine (FTC)-containing antiretroviral regimens.
To evaluate real-world evidence on the impact the M184V/I mutation has on DTG+3TC outcomes in suppressed-switch settings, investigators at ViiV Healthcare searched publication databases through November 2022 for relevant studies. A total of 5 studies met the inclusion criteria for this systematic review and meta-analysis.
Results of all 5 studies indicated low incidence of virologic failure events at weeks 24, 48, and 96 among patients with vs without an M184V/I mutation. Virologic failure among patients in whom the mutation was present prior to switching to DTG+3TC occurred at a proportion of 0.01 (95% CI, 0.00-0.03; I2, 42%; P =.18) at week 24, 0.03 (95% CI, 0.01-0.06; I2, 0%; P =.49) at week 48, and 0.04 (95% CI, 0.01-0.06; I2, 17%; P =.30) at week 96.
The incidence of virologic failure among patients without prior mutation was 0.00 (95% CI, 0.00-0.01; I2, 90%; P <.01) at week 24, 0.01 (95% CI, 0.01-0.02; I2, 86%; P <.01) at week 48, and 0.02 (95% CI, 0.01-0.03; I2, 91%; P <.01) at week 96.
There was no evidence that an M184V/I mutation was associated with virologic failure after a switch to DTG+3TC. However, data from 1 study showed that the presence of the mutation predicted a shorter time to virologic failure relative to its absence.
Data captured in 1 real-world study (n=712) indicated the occurrence of treatment-emergent M184V/I at the time of virologic failure in 1 (0.15%) patient with no history of the mutation.
In a sensitivity analysis among patients with an M184V/I mutation prior to switching to DTG+3TC, virologic failure occurred at a proportion of 0.00 (95% CI, 0.00-0.02; I2, 0%; P =1.00) at week 24, 0.00 (95% CI, 0.00-0.01; I2, 0%; P =1.00) at week 48, and 0.00 (95% CI, 0.00-0.03; I2, 0%; P =1.00) at week 96.
Limitations of this analysis include the lack of genotypic data at the time of virologic failure, the low incidence of virologic failure, and potentially insufficient power to detect differences in virologic failure between patients with vs without preswitch M184V/I mutations.
According to the researchers, “More outcomes data are needed for future analyses to resolve whether duration of virologic suppression pre-switch, M184V/I timing, or other factors impact DTG + 3TC effectiveness…”
Disclosures: This research was supported by ViiV Healthcare, and multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
By Jessica Nye, PhD
References:
Kabra M, Barber TJ, Allavena C, et al. Virologic response to dolutegravir + lamivudine in people with suppressed HIV-1 and historical M184V/I: a systematic literature review and meta-analysis. Open Forum Infect Dis. Published online October 27, 2023. doi:10.1093/ofid/ofad526
Source : Infectious Disease Advisor
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