Four-class drug-resistant HIV-1 subtype C in a treatment experienced individual on dolutegravir-based antiretroviral therapy in Botswana

Abstract

: There are limited data on the effectiveness of dolutegravir (DTG)-based combination antiretroviral therapy (ART) in real-life settings in southern Africa where HIV-1 subtype C predominates. We report a patient infected with HIV-1 subtype C on DTG-based ART previously exposed to raltegravir who developed multidrug resistance mutations to four antiretroviral classes. There is need for drug resistance monitoring and clinical vigilance to ensure effectiveness of HIV treatment programs even in the era of DTG-based ART.

Fig. 1.. Plasma viral loads, CD4⁺ T-cell count and HAART regimens at different time points over a 14-year period for the patient.

Horizontal line within chart depicts viral load of 400 copies/ml. Numbered rectangular callouts depict when drug resistance testing was done. (1) Mar 2009; ^†nucleotide reverse-transcriptase inhibitors, D67N, K70R, M184V; nonnucleotide reverse-transcriptase inhibitors, Y181C; protease inhibitors major resistance mutations, V32I, I47V, I54L, I84V, ^†protease inhibitors accessory resistancemutations, L33F, G73V, L89T; integrase strand transfer inhibitors, not tested. (2) Apr 2009; ^†nucleotide reverse-transcriptase inhibitors, D67N, K70R, M184V, K219N; ^†nonnucleotide reverse-transcriptase inhibitors, Y181C; ^†protease inhibitors major resistance mutations, V32I, I47V, I54L, I84V, protease inhibitors accessory resistance mutations, L33F, G73V, L89T; integrase strand transfer inhibitors, not tested. (3) May 2015; ^†nucleotide reverse-transcriptase inhibitors, K65KR, D67DN, K70KR, M184MV, K219KHNQ; ^†nonnucleotide reverse-transcriptase inhibitors, none; ^†protease inhibitors major resistance mutations, V32VI, I54IL, I84IV, ^†protease inhibitors accessory resistance mutations, L33LF, G73GV, L89IMT; ^†integrase strand transfer inhibitors major resistance mutations, E138K, G140A, Q148R, integrase strand transfer inhibitors accessory resistance mutations, none; (4) Aug 2016; ^†nucleotide reverse-transcriptase inhibitors, D67N, K70R, M184V; ^†nonnucleotide reverse-transcriptase inhibitors, none; ^†protease inhibitors major resistance mutations, V32I, I47V, I54L, I84V, ^†protease inhibitors accessory resistance mutations, L33F, G73V, L89T; integrase strand transfer inhibitors, not tested. (5) Nov 2017; ^†integrase strand transfer inhibitors major resistance mutations, E138K, G140A, S147G, Q148R, integrase strand transfer inhibitors accessory resistance mutations, T97A; ^‡fusion inhibitors, none; entry inhibitors, ^§R5 tropic; nucleotide reverse-transcriptase inhibitors, not tested; nonnucleotide reverse-transcriptase inhibitors, not tested. 3TC, lamivudine; ABC, abacavir; AZT, zidovudine; d4T, didanosine; ddI, didanosine; DRV/r, ritonivir boosted darunavir; DTG, dolutegravir; EI, entry inhibitor; FI, fusion inhibitor; FTC, emtricitabine; INSTI, integrase strand transfer inhibitor; LPV/r, ritonovir boosted lopinavir; NFV, nelfinavir; NNRTI, nonnucleotide reverse-transcriptase inhibitor; NRTI, nucleoside/nucleotide reverse transcriptase inhibitor; NVP, nevirapine; PI, protease inhibitor; RAL, raltegravir; RM, resistance mutation; SQV/r, ritonivir-boosted saquinavir; TDF, tenofovir; VF, virological failure. Drug resistance mutations interpreted using ^†Stanford University HIV Drug resistance database; ^‡International Antiviral Society USA 2017 mutational list; ^§coreceptor usage assessed with geno2pheno_[coreceptor]. Source: modified version from http://bioafrica.mrc.ac.za/workshops/PDFs/deOliveiraRegaDB.pdf.