Early antiretroviral therapy and potent second-line drugs could decrease HIV incidence of drug resistance

Area of Science:

• Epidemiology
• Mathematical Modeling
• Infectious Disease Dynamics

Background:

• Early antiretroviral therapy (ART) initiation for HIV reduces drug-sensitive transmission.
• However, early ART may inadvertently increase the transmission of drug-resistant HIV strains.

Purpose of the Study:

• To estimate the long-term population-level benefits of ART.
• To determine conditions under which earlier ART initiation decreases both total and drug-resistant HIV incidence.

Main Methods:

• An infection-age-structured mathematical model was developed.
• The model tracked transmission rates and life expectancy based on ART timing.
• Data from San Francisco MSM on AIDS incidence, deaths, resistance, and demographics were used for model fitting.

Main Results:

• Earlier ART initiation can decrease total and drug-resistant HIV incidence if second-line drug effectiveness exceeds 80%.
• The proportion of new infections that are drug-resistant may increase with earlier ART.
• Drug resistance may appear to increase paradoxically even as overall resistance decreases.

Conclusions:

• Earlier ART initiation is a viable strategy for reducing HIV incidence, including drug-resistant strains, under specific conditions.
• High effectiveness of second-line ART is crucial for mitigating the risk of increased drug-resistant HIV transmission.
• Population-level benefits of ART timing depend on a complex interplay of treatment initiation, resistance, and adherence.