Dynamic Monitoring Strategies for HIV-Positive Individuals

Abstract

The benefits of immunologic and virologic monitoring for the management of HIV-positive individuals are well established. However, the optimal frequency with which CD4 cell count and HIV RNA should be monitored remains unknown. In this dissertation, we use observational data from two collaborations of prospective cohort studies from high-income countries to estimate the effect of CD4 cell count and HIV RNA monitoring strategies on clinical, virologic, and immunologic outcomes in virologically suppressed HIV-positive patients. In Chapter 1, we compare three CD4 cell count and HIV-RNA monitoring strategies applied to virologically suppressed individuals on combined antiretroviral therapy (cART) without AIDS: once every (i) 3±1 months, (ii) 6±1 months, and (iii) 9-12 ±1 months. We find that monitoring frequency can be decreased from every 3 months to every 6, 9, or 12 months in the short term with respect to clinical outcomes. In Chapter 2, we compare strategies corresponding to three CD4 cell count thresholds at which monitoring frequency is decreased from every 3-6 months to every 9-12 months: 200 cells/µl, 350 cells/µl, and 500 cells/µl. We find that decreasing monitoring from every 3-6 months to every 9-12 months while CD4 cell count>200 cells/µl does not worsen the short-term clinical and immunologic outcomes of HIV-positive, virologically suppressed individuals on cART without AIDS. Our estimates also suggest that decreasing monitoring frequency when CD4 cell count>200 cells/µl compared with when CD4 cell count>500 cells/µl may result in an increased risk of virologic failure at 24 months of follow-up. In Chapter 3, we compare joint monitoring and treatment switching strategies. The strategies expand on those described in Chapter 2 by including two HIV-RNA threshold at which individuals should switch to a new antiretroviral regimen: 200 copies/ml and 1,000 copies/ml. We find that the studied monitoring-switching strategies have little impact on the short-term clinical outcomes of HIV-positive individuals on cART. In summary, we illustrate an approach to compare monitoring strategies in HIV-positive individuals, and provide estimates of the comparative effectiveness of strategies used in clinical practice. Since effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.