Update on the Prevalence of Antiretroviral Drug Resistance in Treatment-Naive Individuals

We previously published our data on the prevalence of drug resistance in antiretroviral-naive individuals accessing care in our US-based urban HIV clinic. ¹ Genotypic resistance assays were collected in 100 patients from July 2006 to July 2008, with clinically significant resistance detected in 8% of the population. Given the concerns over increasing rates of transmitted antiretroviral resistance, we sought to monitor these data in our clinic population on an ongoing basis.

A retrospective chart review from October 2009 to October 2011 included all antiretroviral-naive individuals in our clinic who had a genotypic resistance assay performed prior to initiation of antiretroviral therapy. Information collected included patient demographics, baseline CD4 count, and HIV RNA measurements and documented IAS-USA-defined drug resistance–associated mutations. A total of 66 patients with a 20-month median duration of diagnosed HIV infection prior to genotypic resistance testing met the inclusion criteria. Baseline CD4 count and HIV RNA were 310 cells/mm³ and 29 120 copies/mL, respectively. Mutations were identified in reverse transcriptase (V90I, K103N/S, and E138A) and protease (L10I, G16E, K20I/R, D30N, M36I/L/V, M46I/L, D60E, I62V, L63P, H69K, A71V/T, V77I, V82T, L89M, and I93L) genes in 13.6% and 62.1% of the assays, respectively.

Since our previous report, clinically significant resistance in our population has increased greatly from 8% to 13.6%. Our current cohort reflects increased diversity and the impact of novel mutations (K103S, E138A) in the reverse transcriptase gene. Notably, with all current mutations affecting susceptibility to nonnucleoside reverse transcriptase inhibitors (NNRTIs), the prevalence of NNRTI resistance has more than doubled from 6% to 13.6% over the past 3 years (Table 1). However, no clinically significant mutations in the protease gene were detected in either cohort. The most prevalent mutation in our previous cohort was L63P, identified in more than 50% of the individuals. With the updated cohort, the L63P occurred in 10.6% of the individuals while more atazanavir (ATV)-associated mutations were detected (eg, M36I/L/V, D60E, I62V, I93L), likely reflecting the shift in protease inhibitor usage from lopinavir/ritonavir to ATV-based regimens. Monitoring resistance trends across geographic areas will continue to be important to optimize antiretroviral usage. Changes in treatment paradigms will continue to drive the development of novel mutations as well as shifts in the prevalence of existing mutations.

Table 1.

Clinically Significant Antiretroviral Resistance Mutations.

Mutations	2006-2008 No. of Patients (%)	2009-2011 No. of Patients (%)
	N = 100	N = 66
M41L	1 (1)	0 (0)
V90I	0 (0)	1 (1.5)
A98G	1 (1)	0 (0)
K103N/S	2 (2)	5 (7.6)
V108I	1 (1)	0 (0)
E138A	0 (0)	3 (4.5)
V179D	1 (1)	0 (0)
M184V	1 (1)	0 (0)
Y188H	1 (1)	0 (0)
Total	8 (8)	9 (13.6)
NRTI	2 (2)	0 (0)
NNRTI	6 (6)	9 (13.6)

Abbreviations: NNRTI, nonnucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor.