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/mu L. conclusions as african countries transition to dolutegravir-based regimens, prior raltegravir-exposure may prompt selection (and potential transmission) of dolutegravir-resistance, supporting case surveillance.

Fokam, J., Takou, D., Semengue, E., Teto, G., Beloumou, G., Dambaya, B., et al. (2020). 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. ANTIMICROBIAL RESISTANCE AND INFECTION CONTROL, 9(1), 143 [10.1186/s13756-020-00799-2].

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

Santoro, Maria;Colizzi, Vittorio;Perno, Carlo-Federico;
2020-08-01

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/mu L. conclusions as african countries transition to dolutegravir-based regimens, prior raltegravir-exposure may prompt selection (and potential transmission) of dolutegravir-resistance, supporting case surveillance.
ago-2020
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
Settore MEDS-03/A - Microbiologia e microbiologia clinica
English
Cameroon; HIV drug resistance; Integrase inhibitors; Protease inhibitors; Viral tropism; Aged; Anti-HIV Agents;
CD4 Lymphocyte Count; Cameroon; Darunavir; HIV Infections; HIV-1; Heterocyclic Compounds, 3-Ring; Humans
Male; Oxazines; Piperazines; Pyridones; Raltegravir Potassium; Viral Load; Drug Resistance, Multiple, Viral
Fokam, J., Takou, D., Semengue, E., Teto, G., Beloumou, G., Dambaya, B., et al. (2020). 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. ANTIMICROBIAL RESISTANCE AND INFECTION CONTROL, 9(1), 143 [10.1186/s13756-020-00799-2].
Fokam, J; Takou, D; Semengue, Enj; Teto, G; Beloumou, G; Dambaya, B; Santoro, M; Mossiang, L; Billong, Sc; Cham, F; Sosso, Sm; Temgoua, Es; Nanfack, A...espandi
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
s13756-020-00799-2.pdf

accesso aperto

Tipologia: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 790.66 kB
Formato Adobe PDF
790.66 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/290083
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 11
social impact