Abstract
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.
Funder
Chantal Biya International Reference center for research on HIV/AIDS prevention and management
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Infectious Diseases,Microbiology (medical),Public Health, Environmental and Occupational Health
Reference18 articles.
1. Grinsztejn B, Hughes MD, Ritz J, et al. Third-line antiretroviral therapy in low-income and middle-income countries (ACTG A5288): a prospective strategy study. Lancet HIV. 2019;6(9):e588–600. https://doi.org/10.1016/S2352-3018(19)30146-8.
2. Phillips AN, Stover J, Cambiano V, et al. Impact of HIV drug resistance on HIV/AIDS-associated mortality, new infections, and antiretroviral therapy program costs in sub-Saharan Africa. J Infect Dis. 2017;215(9):1362–5. https://doi.org/10.1093/infdis/jix089.
3. Organization WH. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV - Interim guidance: Who; 2018. https://www.who.int/hiv/pub/guidelines/ARV2018update/en/.
4. Achieng L, Riedel DJ. Dolutegravir resistance and failure in a Kenyan patient. J Infect Dis. 2019;219:165–7.
5. Fourati S, Charpentier C, Amiel C, et al. Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir : a French national study of raltegravir-experienced HIV-1-infected patients. 2015:1–6. https://doi.org/10.1093/jac/dku535.