Transmitted antiretroviral drug resistance among acute and recent HIV infections in North Carolina from 1998 to 2007

Abstract

Background: Transmitted drug resistance (TDR) limits antiretroviral options and thus complicates the management of HIV-positive patients. HIV disproportionately affects the southern US, but available national estimates of TDR prevalence principally reflect large metropolitan centres outside this region.

Methods: The Duke/UNC Acute HIV Program has collected data on acute or recent HIV infections (ARHI) in North Carolina since 1998. Acute infections represent antibody-negative, RNA-positive patients. Recent infection was determined by history of HIV testing or concordance between detuned ELISA and antibody avidity assays. Genotypic sequence data from the earliest collected pretreatment plasma samples were analysed with the Stanford HIV Database and screened for surveillance drug resistance mutations (SDRMs).

Results: A total of 253 individuals with ARHI between May 1998 and May 2007 had complete genotypic sequence data for analysis; 39.5% were acute infections, 78.7% were male, 64.8% were non-White and 53.8% were men who have sex with men. The overall prevalence of TDR was 17.8%, with SDRMs for non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs) in 9.5% of the cohort. Mutations for nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) were detected in 7.5% and for protease inhibitors (PIs) in 3.2%. K103N was the most common mutation (7.5%). Thymidine analogue mutations were found in 4.7% of samples; the most common PI SDRM was L90M (2.4%). Dual- or triple-class antiretroviral resistance was rare, encountered in only six (2.4%) samples.

Conclusions: The prevalence of TDR in North Carolina is similar to estimates from the US metropolitan areas. These findings have implications for initial regimen selection and secondary prevention efforts outside of large, metropolitan HIV epicentres.

Figure 1. Acute or recent HIV infections in North Carolina, 1998 to 2007

Over the period, 253 cases were identified across the entire state. Case identification improved markedly after the 2002 implementation of RNA-based screening for acute HIV at all publicly-funded testing and counseling sites statewide.

Figure 2. Time trends in prevalence of SDRM mutations, 1998 to 2007

Panel A shows the prevalence of any SDRM by year, with bars representing 95% confidence intervals. Class-specific trends by year are shown in panel B. (NRTI, nucleos(t)ide reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor).