HIV-1 DNA Testing in Viremic Patients Identifies More Drug Resistance Than HIV-1 RNA Testing

Dusica Curanovic; Sharon K Martens; Milka A Rodriguez; Hunter A Hammill; Christos J Petropoulos; Charles M Walworth

doi:10.1093/ofid/ofad146

HIV-1 DNA Testing in Viremic Patients Identifies More Drug Resistance Than HIV-1 RNA Testing

Open Forum Infect Dis. 2023 Mar 22;10(4):ofad146. doi: 10.1093/ofid/ofad146. eCollection 2023 Apr.

Authors

Dusica Curanovic¹, Sharon K Martens¹, Milka A Rodriguez¹, Hunter A Hammill², Christos J Petropoulos¹, Charles M Walworth¹

Affiliations

¹ Monogram Biosciences, Laboratory Corporation of America Holdings, South San Francisco, California, USA.
² AIDS Healthcare Foundation Healthcare Center, Houston Fannin, Texas, USA.

Abstract

Background: The Department of Health and Human Services HIV-1 Treatment Guidelines recommend drug resistance testing in HIV-1 RNA to guide the selection of antiretroviral therapy in patients with viremia. However, resistance-associated mutations (RAMs) in HIV-1 RNA may reflect only the patient's current regimen and can be lost during prolonged absence of therapy. We determined if HIV-1 DNA testing can provide drug resistance information beyond that identified in contemporaneous plasma virus.

Methods: This was a retrospective database review of results obtained for patients with viremia for whom commercial HIV-1 RNA and HIV-1 DNA drug resistance testing was ordered on the same day. Resistance-associated mutations and drug susceptibility calls were compared between paired tests, and the effect of HIV-1 viral load (VL) on test concordance was assessed using Spearmen's rho correlation.

Results: Among 124 paired tests, more RAMs were identified in HIV-1 DNA in 63 (50.8%) cases, and in HIV-1 RNA in 11 (8.87%) cases. HIV-1 DNA testing captured all contemporaneous plasma virus RAMs in 101/117 (86.3%) cases and identified additional RAMs in 63/117 (53.8%) cases. There was a significant positive correlation between the viral load at the time of resistance testing and the percentage of plasma virus RAMs detected in HIV-1 DNA (r_s = 0.317; P < .001). In 67 test pairs demonstrating pan-sensitive plasma virus, resistance in HIV-1 DNA was seen in 13 (19.4%) cases.

Conclusions: HIV-1 DNA testing identified more resistance than HIV-1 RNA testing in most patients with viremia and may be informative in patients whose plasma virus reverts to wild-type following therapy discontinuation.

Keywords: HIV-1 DNA; HIV-1 drug resistance; PBMC compartment; proviral HIV-1.