Background: In a previous mathematical model, we found that initial treatment with DTG and RAL-based regimens provide advantages over both EFV- and DRVr-based ART for the reduction of HIV-1 transmission risk from anal intercourse in HIV-infected MSM. This analysis aims to analyze the effect of time to initiation of first ART after diagnosis on the probability of HIV-1 transmission events (HIV-TE) in HIV-1-infected MSM by mathematical modeling.
Methods: We used discrete event simulation modeling to estimate the probability of HIV-TE in the first 8W after ART initiation; we varied ART initiation from D0 to D28 after simulated “diagnosis”. The model inputs used sexual behavior parameters from the MSM population of the START trial, and transmission rates per-sex act and HIV-1 RNA level from recent meta-analyses. HIV-1 RNA decay curves(W0 to W8)were modeled by fractional polynomial regressionof repeated measurements of HIV-1 RNA from the databases of the Single, Spring-2, and Flamingo trials. ART starts at D0 through D28, compared with D28 initiation by ART type were modeled with 106theoretical patients for each comparison.
Results: The number of simulated HIV-TE per patient in the first 8 weeks after ART initiation in the INSTI, EFV, and DRVr arms increased linearly from 0.03, 0.08, and 0.14 for ART initiation on D0 to 0.26, 0.31, and 0.33 for ART initiation on D28. The percent reduction in the number of simulated HIV-TE in the first 8 weeks, compared to initiation of ART on D28 in the INSTI, EFV, and DRVr arms, decreased linearly from 87%, 74%, and 59% for ART initiation on D0 to 2%, 1%, and 1% for ART initiation on D28.
Conclusions: These results support the notion that ART initiation rapidly after diagnosis of HIV for MSM has the potential to maximally impact HIV-1 horizontal transmission when compared to waiting one month, as is current practice. Statistically significant advantages of INSTI over EFV and DRVr were also noted supporting evolving guidelines recommendations for INSTI-based initial therapy.