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HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon

Article scientifique 2019 Anglais

Résumé

With the phase-out of stavudine (d4T), change to first-line regimens with zidovudine (AZT) or tenofovir (TDF) in resource-limited settings (RLS) might increase risks of cross-resistance to nucleos(t) ide reverse transcriptase inhibitors (NRTI). This would restrict the scope of switching to the World Health Organisation (WHO)-recommended standard second-line combinations (SLC) without HIV drug resistance (HIVDR)-testing in routine clinical practice. An observational study was conducted among 101 Cameroonian patients (55.4% male, median [IQR] age 34 [10–41] years) failing first-line antiretroviral therapy (ART) in 2016, and stratified into three groups according to NRTIs exposure: exposure to both thymidine analogues AZT “and” D4T (group-A, n = 55); exposure to both TDF and AZT “or” D4T (group-B, n = 22); exposure solely to D4T (group-C, n = 24). Protease-reverse transcriptase HIVDR was interpreted using the HIVdb penalty scores (≥60: high-resistance; 20–59: intermediate-resistance; < 20: susceptible). The acceptable threshold for potential-efficacy was set at 80%. The median [IQR] CD4, viral RNA, and time on ART, were respectively 129 [29–466] cells/μl, 71,630 [19,041-368,000] copies/ml, and 4 [2–5] years. Overall HIVDR-level was 89.11% (90/101), with 83.2% harbouring M184 V (high-level 3TC/FTC-resistance) and only 1.98% (2/101) major HIVDR-mutations to ritonavir-boosted protease-inhibitors (PI/r). Thymidine-analogue mutations (TAMs)-1 [T215FY (46.53%), M41 L (22.77%), L210 W (8.91%)], with cross-resistance to AZT and TDF, were higher compared to TAMs-2 [D67N (21.78%), K70R (19.80%), K219QE (18.81%)]. As expected, K65R was related with TDF-exposure: 0% (0/55) in group-A, 22.72% (5/22) group-B, 4.17% (1/24) group-C ( p = 0.0013). The potential-efficacy of AZT vs. TDF was respectively 43.64% (24/55) vs. 70.91% (39/55) in group-A ( p = 0.0038); 63.64% (14/22) vs. 68.28% (15/22) in group-B ( p = 1.0000); and 37.50% (9/24) vs. 83.33% (20/24) in group-C ( p = 0.0032). CRF02_AG was the prevailing subtype (63.40%), followed by CRF11.cpx (8.91%), A 1 (7.92%), G (5.94%); without any significant effect of the subtype-distribution on HIVDR (92.2% in CRF02_AG vs. 83.8% in non-AG; p = 0.204). First-line ART-failure exhibits high-level NRTI-resistance, with potential lower-efficacy of AZT compared to TDF. Significantly, using our 80% efficacy-threshold, only patients without NRTI-substitution on first-line could effectively switch to SLC following the WHO-approach. Patients with multiple NRTI-substitutions (exposed to both thymidine-analogues and TDF) on first-line ART would require HIVDR-testing to select active NRTIs for SLC.

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Takou, D., Fokam, J., Této, G., Santoro, M., Ceccherini‐Silberstein, F., Nanfack, A., Sosso, S., Dambaya, B., Salpini, R., Billong, S., Gori, C., Fokunang, C., Cappelli, G., Colizzi, V., Perno, C., Ndjolo, A. (2019). HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon. https://doi.org/10.1186/s12879-019-3871-0

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Auteur(s)

Désiré Takou Joseph Fokam Georges Této Maria Mercedes Santoro Francesca Ceccherini‐Silberstein Aubin Nanfack Samuel Martin Sosso Béatrice Dambaya Romina Salpini Serge Clotaire Billong Caterina Gori Charles Fokunang Giulia Cappelli Vittorio Colizzi Carlo Federico Perno Alexis Ndjolo

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