HIV Genotypic Mutation Characterization in a Rural US State

Background: Recent reports show an increasing incidence of human immunodeficiency virus (HIV) in the Southern United States, including Kentucky (a rural southern state). The study objective was to determine whether an association exists between Kentucky's incidence of HIV, and the incidences of antiretroviral class (ARV) resistance for the protease (PI), non-nucleoside reverse transcriptase (NNRTI), and nucleos(t)ide reverse transcriptase (NRTI) inhibitors by characterizing therapeutic drug resistance (TDR) of newly diagnosed individuals.

Methods: Data was retrieved for newly HIV diagnosed patients from January 2004 to December 2014 from the University of Kentucky HealthCare database. Data collected included age, sexual identity, ethnicity, mode of exposure, HIV-1 subtype, TDR, and date of HIV diagnosis and genotyping. Patients over 18 years old, diagnosed at our institution with an initial genotype completed within six months of diagnosis were included. Individuals were excluded for: prior HIV diagnosis or newly diagnosed with either no genotype records or ones after six months of diagnosis. Incidence of mutations was calculated per year for each ARV class and analyzed using linear regression.

Results: Overall, 35% (346/988) of individuals met inclusion criteria, resulting in 144 cases of TDR. Patient demographics included a median age of 40 years, 35% non-white, 93% sexually transmitted HIV, 94% HIV-1 subtype B, and 30% diagnosed with AIDS within six months of HIV diagnosis. Predominant non-polymorphic mutations were V179D/E, K103N, and M41L. Percent of patients with baseline TDR is illustrated in the table below. An insignificant trend for incidences of baseline TDR was identified for NNRTI (p=0.66), NRTI (p=0.3) and PI (p=0.55) classes according to the linear regression.

Location	Years	NRTI (%)	NNRTI (%)	PI (%)
Kentucky	2004-14	11.6	21.7	8.4
Washington DC (Swierzbinski et al. JAHR. 2015)	2007-10	3.8	14.3	1.5
North Carolina (Hurt et al. Antivir Ther. 2009)	1998-2007	7.5	9.5	3.2

Conclusion: The incidence of baseline TDR from 2004-2014 among ARV classes did not increase significantly over time. While baseline TDR is unlikely to explain increasing incidences of HIV in Kentucky, the overall rates of baseline TDR are high compared to other areas and warrant further investigation.