Forecasting Prevalence of HIV-1 Integrase Strand Transfer Inhibitor (INSTI) Drug Resistance: A Modeling Study

Antiretroviral therapy (ART) is a cornerstone of HIV-1 treatment and provides significant health benefits for patients with responsive HIV-1 strains. Integrase strand transfer inhibitors (INSTIs) are the newest class of ART. Although most HIV-1 cases are responsive, a small number are already resistant. Here, we forecast the prevalence of INSTI resistance amid wide-spread use. We developed a stochastic model to simulate HIV-1 dynamics and INSTI resistance for raltegravir, elvitegravir, and dolutegravir. We forecast prevalence of INSTI resistance in adults living with HIV-1 over a 30-year period using parameter values and initial conditions that mimic HIV-1 dynamics Washington DC. We used the model to predict the amount of transmitted drug resistance (TDR) versus regimen-acquired drug resistance. We forecast the prevalence of HIV-1 cases resistant to raltegravir as 0.41 (minimum: 0.21; maximum: 0.57), resistant to elvitegravir as 0.44 (minimum: 0.26; maximum: 0.60), and resistant to dolutegravir as 0.44 (minimum: 0.25; maximum: 0.65). Model output was greatly affected by the proportion of those living with HIV-1 on ART and the rate of converting from an INSTI-sensitive strain to an INSTI-resistant strain for chronically infected ART-experienced cases. We forecast that TDR will contribute minimally-if at all-to the overall proportion of resistant HIV-1 cases. INSTI drug resistance has the potential to be a public health concern in the next 30 years. Although several parameters influence the predicted prevalence of INSTI drug resistance, TDR is unlikely to contribute substantially to future trends.