当前位置： SCI文献检索 > Antimicrobial Resistance and Infection Control期刊下所有文献 > 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.

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.

Abstract：

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.

journal_name

Antimicrob Resist Infect Control

journal_title

Antimicrobial resistance and infection control

authors

Fokam J,Takou D,Semengue ENJ,Teto G,Beloumou G,Dambaya B,Santoro MM,Mossiang L,Billong SC,Cham F,Sosso SM,Temgoua ES,Nanfack AJ,Moudourou S,Kamgaing N,Kamgaing R,Ngako Pamen JN,Etame MMN,Bissek AZ,Elat JN,Moussi E

doi

10.1186/s13756-020-00799-2

subject

Has Abstract

pub_date

2020-08-26 00:00:00

pages

143

issue

issn

2047-2994

pii

10.1186/s13756-020-00799-2

journal_volume

pub_type

杂志文章

在线工具

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.