THPE063 - Poster Exhibition
Horizontal transmission of HIV-1 exhibiting resistance to four antiretroviral drug classes, including integrase inhibitors
C. Walworth1, D. Ward2, L. Napolitano1, C. Petropoulos1, J. Volpe1
1Monogram Biosciences, South San Francisco, United States, 2Dupont Circle Physicians Group, Washington, United States
Background: Transmission of HIV-1 strains exhibiting resistance to protease (PR) and reverse transcriptase (RT) inhibitors is well documented. To date, only a few cases of transmission of HIV-1 strains exhibiting resistance to integrase (IN) inhibitors have been documented. Here we report transmission of multi-drug resistant HIV-1 with resistance to PR, nucleoside- and non-nucleoside RT and IN inhibitors in a previously documented HIV-1 negative patient.
History: the patient was hospitalized with a severe viral illness of unknown etiology. HIV-1 antibody testing was negative at that time. Viral load (VL) testing was not performed. Follow-up HIV-1 testing six months later was positive by ELISA and confirmed by Western Blot.
Methods: Genotypic drug resistance analysis, CD4 cell count and HIV-1 VL were obtained by a physician at a baseline evaluation. Additional specimens were collected nine days later to confirm initial findings. Testing included phenotypic PR-RT resistance testing and genotypic IN testing. Additional confirmatory/exploratory resistance testing was performed: phenotypic IN testing, combined PR-RT phenotypic and genotypic testing and phenotypic tropism determination.
[Genotypic Resistance Analysis]
|Genotypic Testing||M41L, D67N, L74V, V118I||K101E, Y181C, V189I, G190S||L10Y, I13V, K20I E35D, M36I, K43T,
I62I/V, V82A||G140S, Q148H|
The baseline CD4 cell count was 376 cells/mm3 and HIV-1 VL was 211,540 copies/mL. Genotypic analysis of the baseline virus identified mutations associated with drug resistance (table). Susceptibility to PR, RT, and IN inhibitors was characterized by phenotypic testing. Large reductions (>150-fold) in susceptibility to the IN inhibitor raltegravir and NNRTIs were observed. Co-receptor tropism testing identified R5-tropic virus. Based on the established drug resistance profile, an initial regimen of ritonavir-boosted darunavir, tenofovir/emtricitabine, and maraviroc was started. Complete suppression of viral replication was achieved by week 12 of antiretroviral therapy.
Conclusions: This case demonstrates HIV-1 transmission exhibiting four drug class resistance, including an integrase inhibitor. To our knowledge, this is the third documented case of transmitted integrase inhibitor resistant HIV-1. It also demonstrates the value of baseline integrase inhibitor drug resistance testing.
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