Mathematical modeling of HIV-1 transmission risk from condomless anal intercourse in HIV-infected MSM by the type of initial ART

Abstract

Background: Initiation of antiretroviral therapy (ART) for HIV infection using regimens that include integrase strand transfer inhibitors (INSTIs) is associated with a faster decline in HIV-1 RNA than what is observed with regimens that are anchored by other ART drug classes. We compared the impact of ART regimens that include dolutegravir (DTG), raltegravir (RAL), efavirenz (EFV), or darunavir/ritonavir (DRV/r), in treatment naïve men who have sex with men (MSM) on the probability of HIV-1 sexual transmission events (HIV-TE).

Setting: Mathematical model.

Methods: We used discrete event simulation modeling to estimate HIV-TE during the first 8 weeks after initiation of ART. HIV-1 RNA decay in men was modeled from the databases of three clinical trials: Single (DTG vs. EFV), Spring-2 (DTG vs. RAL) and Flamingo (DTG vs. DRV/r).

Results: All regimens substantially reduced the number of HIV-TE compared to no treatment. DTG led to fewer HIV-TE than its comparator in each of the three trials: 22.72% fewer transmissions than EFV; 0.52% fewer transmissions than RAL; and 38.67% fewer transmissions than DRV/r. The number of patients needed to treat with DTG to prevent one transmission event instead of comparator was 48 vs EFV, 2,194 vs RAL, and 31 vs DRV/r.

Conclusion: Unsurprisingly, this mathematical model showed that all regimens reduced HIV-TE compared to no treatment. The results also suggest that that initial use of INSTIs, by virtue of their superior viral decay kinetics, have the potential to reduce HIV-1 horizontal transmission following initiation of ART in naïve MSM.

Trial registration: ClinicalTrials.gov NCT03183154.

Conflict of interest statement

J. Berenguer has received research grants from AbbVie, Gilead Sciences, Merck, and ViiV; as well as honoraria for speaking or advisory board participation from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV. J. Parrondo has received consultancy fees from Biogen, BMS, Lilly, Pfizer, PierrreFabre, Roche, Servier, Takeda and ViiV. R.J. Landovitz has received honoraria for speaking or advisory board participation from Gilead Sciences, Merck Sharpe & Dohme, and Roche. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Key input and output variables in the model.

Abbreviations: DES, discrete simulation events.

Fig 2. Comparison between DTG and comparators (EFV in Single, RAL in Spring-2, and DRV/r in Flamingo) in the relative reduction of new simulated sexually transmitted infections in comparison to no treatment for the full 0 to week 8 period.

Base case scenario: probability of transmission according to the mean value of the β0 parameter in the Wilson equation. Sensitivity analysis 1: probability of transmission according to the lower 95% confidence interval value of the β0 parameter in the Wilson equation. Sensitivity analysis 2: probability of transmission according to the upper 95% confidence interval value of the β0 parameter in the Wilson equation. Abbreviations: DTG, dolutegravir; RAL, raltegravir; DRVr, darunavir/ritonavir.