First case of Dolutegravir and Darunavir/r multi drug-resistant HIV-1 in Cameroon following exposure to Raltegravir: lessons and implications in the era of transition to Dolutegravir-based regimens.

Autor: Fokam J; Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé, Cameroon. fokamjoseph@circb.cm.; Faculty of Health Sciences, University of Buea, Buea, Cameroon. fokamjoseph@circb.cm.; National HIV Drug Resistance Working Group, Ministry of Public Health, Yaoundé, Cameroon. fokamjoseph@circb.cm.; Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon. fokamjoseph@circb.cm., Takou D; Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé, Cameroon., Semengue ENJ; Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé, Cameroon.; University of Rome Tor Vergata, Rome, Italy.; Evangelic University of Cameroon, Bandjoun, Cameroon., Teto G; Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé, Cameroon., Beloumou G; Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé, Cameroon., Dambaya B; Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé, Cameroon., Santoro MM; University of Rome Tor Vergata, Rome, Italy., Mossiang L; HIV Treatment Centre, Yaoundé Central Hospital, Yaoundé, Cameroon., Billong SC; Faculty of Health Sciences, University of Buea, Buea, Cameroon.; Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon.; Central Technical Group, National AIDS Control Committee, Yaoundé, Cameroon., Cham F; World Health Organisation, Regional Office for Africa (AFRO), Brazzaville, Congo., Sosso SM; Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé, Cameroon., Temgoua ES; Central Technical Group, National AIDS Control Committee, Yaoundé, Cameroon., Nanfack AJ; Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé, Cameroon., Moudourou S; Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé, Cameroon., Kamgaing N; Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé, Cameroon., Kamgaing R; Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé, Cameroon., Ngako Pamen JN; Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon.; Department of Disease, Epidemics and Pandemics Control, Ministry of Public Health, Yaoundé, Cameroon., Etame MMN; HIV Treatment Centre, Military Hospital, Yaoundé, Cameroon., Bissek AZ; Faculty of Health Sciences, University of Buea, Buea, Cameroon.; Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon.; Division of Health Operational Research, Yaoundé, Cameroon., Elat JN; Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon.; Central Technical Group, National AIDS Control Committee, Yaoundé, Cameroon., Moussi EE; Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé, Cameroon., Colizzi V; Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé, Cameroon.; University of Rome Tor Vergata, Rome, Italy.; Evangelic University of Cameroon, Bandjoun, Cameroon., Perno CF; Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé, Cameroon.; University of Rome Tor Vergata, Rome, Italy.; University of Milan, Milan, Italy., Ndjolo A; Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé, Cameroon.; National HIV Drug Resistance Working Group, Ministry of Public Health, Yaoundé, Cameroon.; Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon.
Jazyk: angličtina
Zdroj: Antimicrobial resistance and infection control [Antimicrob Resist Infect Control] 2020 Aug 26; Vol. 9 (1), pp. 143. Date of Electronic Publication: 2020 Aug 26.
DOI: 10.1186/s13756-020-00799-2
Abstrakt: Background: Sub-Saharan African countries are transitioning to dolutegravir-based regimens, even for patients with extensive previous drug exposure, including first-generation integrase strand-transfer inhibitors (INSTI) such as raltegravir. Such exposure might have implications on cross-resistance to dolutegravir-based antiretroviral therapies (ART).
Case Presentation: We report a 65 years old Cameroonian, previously exposed to raltegravir, and failing on third-line treatment with multi-drug resistance to darunavir/r and dolutegravir. Genotypic resistance testing (GRT) and viral tropism were performed during monitoring time points. The patient initiated ART in August 2007. At the time point of the first (29.04.2010), second (01.12.2017) and third (08.08.2019) GRT, prior ART exposure included 3TC, d4T, NVP and EFV; additionally TDF, DRV/r and RAL; and additionally ABC and DTG respectively. First GRT revealed mutations associated with resistance only to first-generation Non-nucleoside reverse transcriptase inhibitors (NNRTI). Second GRT revealed mutations associated with high-level resistance to all NRTIs, first generation NNRTIs, all ritonavir boosted protease inhibitors (PI/r), and all INSTI, while viral tropism (using geno2pheno) revealed a CCR5-tropic virus with a false positive rate (FPR) of 60.9% suggesting effectiveness of maraviroc (MRV). The third GRT showed high-level resistance to NRTI, NNRTI, all PI and all INSTI, with additional mutations (H221HY for NNRTI and S147G for INSTI), and a CCR5-tropic virus with a slightly reduced FPR (57.0%). Without any locally available active therapeutic option, the patient has been on a maintenance therapy with "DRV/r (600mg x 2/day)+TDF+3TC" and patient/family-centered adherence has been reinforced. Since the first viral load (VL) measurement in 2010, the patient has had 12 VL tests with the VL ranging from 4.97 Log to 6.44 Log copies/mL and the CD4 count never exceeded 200 cells/μL.
Conclusions: As African countries transition to dolutegravir-based regimens, prior raltegravir-exposure may prompt selection (and potential transmission) of dolutegravir-resistance, supporting case surveillance.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje