Akash Shah

Date of Award

11-15-2006

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Michael J Kozal

Abstract

HIV-1 antiretroviral resistance has posed major challenges to treatment advances of the last decade. However, few studies have analyzed the prevalence and time trends of drug resistance among HIV+ patients on antiretroviral therapy followed longitudinally in clinical care. The purpose of this study is to determine the cumulative prevalence of HIV genotypic drug resistance and the dynamics of resistance development in HIV+ patients in care. We hypothesized that a >5% increase in resistance would occur per 6-month period and a >15% increase in drug resistance would occur over 18 months. This retrospective longitudinal study consisted of patients from the two largest HIV clinics in Connecticut who were enrolled in the Options Project Study from 2000-2003. HIV+ patients were consented and enrolled in the resistance substudy. HIV genotypic resistance testing was done on plasma samples available for each patient at study baseline and at ~6 month intervals for 18 months. HIV viral load and resistance data were matched to behavioral and demographic data for each patient. Genotypic drug resistance was defined according to the International AIDS Society 2004 guidelines. The chi-square test for linear trends was used to assess resistance trends. 396 HIV+ patients enrolled in the study and had archived plasma available for analysis. The cumulative prevalence of drug resistance increased from 32.1% to 46.3% for patients with 18 consecutive months of data, 31.9% to 50.7% for patients with 12 consecutive months of data, and 30.2% to 41.3% for patients with 6 consecutive months of data. During the period of study for this HIV+ patient care population, the cumulative prevalence of HIV genotypic drug resistance rose dramatically. The findings emphasize the need for addressing antiretroviral resistance in a clinical setting through physician education, reduction of transmission risks, regimen adjustments, newer agents, and utilization of genotype testing.

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This is an Open Access Thesis.

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