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

Springer Science and Business Media LLC - Tập 9 Số 1 - 2020
Joseph Fokam1, Désiré Takou1, Ezéchiel Ngoufack Jagni Semengue2, Georges Této1, Grâce Beloumou1, Béatrice Dambaya1, Maria Mercedes Santoro2, Leonella Mossiang3, Serge Clotaire Billong4,5, Fatim Cham6, Samuel Martin Sosso1, Edith Temgoua7, Aubin Nanfack1, Sylvie Moudourou1, Nelly Kamgaing1, Rachel Kamgaing1, Joelle Nounouce Ngako Pamen5, Mireille Mpoudi Ngole Etame8, Anne-Cécile Zoung-Kanyi Bissek4,5, Jean-Bosco Nfetam Elat5, Emmanuel Eben Moussi1, Vittorio Colizzi2, Carlo Federico Perno9,2, Alexis Ndjolo5
1Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé, Cameroon
2University of Rome Tor Vergata, Rome, Italy
3HIV Treatment Centre, Yaoundé Central Hospital, Yaoundé, Cameroon
4Faculty of Health Sciences, University of Buea, Buea, Cameroon
5Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
6World Health Organisation, Regional Office for Africa (AFRO), Brazzaville, Congo
7Central Technical Group, National AIDS Control Committee, Yaoundé, Cameroon
8HIV Treatment Centre, Military Hospital, Yaoundé, Cameroon
9University of Milan, Milan, Italy

Tóm tắt

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.

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