Global dynamics and cost-effectiveness analysis of HIV pre-exposure prophylaxis and structured treatment interruptions based on a multi-scale model

Structured treatment interruptions (STI) were proposed to reduce costs and side effects for HIV infected individuals, but whether the possible viral rebound within hosts after treatment interruption would lead to more new infections and additional costs among the population remains unknown. Oral pre-exposure prophylaxis (PrEP) is shown as an effective but expensive strategy to prevent the acquisition of HIV infection. To investigate the effectiveness and cost-effectiveness of STI and PrEP, we develop a multi-scale model linking within-host and between-host dynamics in the presence of drug resistance. Lyapunov functionals are constructed to analyze the global dynamics of the coupled system. We fit this model to the annual AIDS incidence and death data from 1980 to 2014 among men who have sex with men (MSM) in San Francisco and compare the impact of six various intervention scenarios (low, medium, high PrEP coverage with or without STI) on new infections and cost-effectiveness over the next 20 years. We estimate the PrEP efficacy needed to eliminate the disease for different fraction of acquired drug resistance under the above six scenarios. Numerical simulations show that expanding PrEP coverage is very cost-effective, but whether implementing STI is cost-saving depends on the efficacy of second-line drugs. That is to say, STI could always save money, but it may lead to more (less) new infections than continuous therapy and thus less (more) health benefit for high (low) efficacy of second-line drugs. These results provide insights about the long-term effect of STI and PrEP on the disease control and cost-effectiveness.