D Armenia1,2, D Di Carlo3, P Flandre4, Y Bouba2,5, V Borghi6, F Forbici7, A Bertoli2, C Gori7, L Fabeni2, W Gennari8, C Pinnetti9, A Mondi9, S Cicalini9, R Gagliardini9, A Vergori9, R Bellagamba9, V Malagnino10, F Montella11, M Colafigli12, A Latini12, R Marocco13, M Licthner13, M Andreoni10, C Mussini6, F Ceccherini-Silberstein2, A Antinori9, C F Perno7, M M Santoro2. 1. UniCamillus International University of Health and Medical Sciences, Rome, Italy. 2. University of Rome 'Tor Vergata', Department of Experimental Medicine, Rome, Italy. 3. University of Milan, Pediatric Clinical Research Center 'Romeo and Enrica Invernizzi', Milan, Italy. 4. INSERM, Sorbonne Université, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP) équipe Epidémiologie clinique des maladies virales chroniques, Paris, France. 5. Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management (CIRCB), Yaoundé, Cameroon. 6. Clinic of Infectious Diseases, University Hospital, University of Modena and Reggio Emilia, Modena, Italy. 7. Laboratory of Virology, National Institute for Infectious Diseases 'Lazzaro Spallanzani', IRCCS, Rome, Italy. 8. Microbiology Unit, University Hospital of Modena, Modena, Italy. 9. HIV/AIDS Department, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy. 10. Clinical Infectious Diseases, University Hospital 'Tor Vergata', Rome, Italy. 11. Infectious disease Unit, San Giovanni Addolorata Hospital, Rome, Italy. 12. Unit of Dermatology and Sexually Transmitted Diseases, San Gallicano Dermatological Institute IRCCS, Rome, Italy. 13. Infectious Diseases Unit, 'Sapienza' University, Polo Pontino, Latina, Italy.
Abstract
OBJECTIVES: To evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy. METHODS: Dynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999-2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm). RESULTS: Among 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P < 0.001), then remained relatively constant at ∼40% during 2010-18, with the proportion of resistance to three or more classes also stable (∼5%). After 2008, integrase inhibitor resistance slightly increased from 5.6% to 9.7% in 2018 and contributed to resistance, particularly in isolates with resistance to three or more classes (one class, 8.4%; two classes, 15.3%; three or more classes, 34.7%, P < 0.001). Among 1827 failing patients with an available follow-up, by 1 year after genotype-guided therapy start the probability of VS was 87.6%. Patients with cumulative resistance to three or more classes and receiving a poorly active regimen showed the lowest probability (62.6%) of VS (P < 0.001) compared with all other patients (≥81.8%). By Cox regression analysis, cumulative MDR and receiving poorly active antiretroviral regimens were associated with a lower hazard of VS compared with those without resistance. CONCLUSIONS: A dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.
OBJECTIVES: To evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infectedpatients over the past two decades in Italy. METHODS: Dynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999-2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm). RESULTS: Among 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P < 0.001), then remained relatively constant at ∼40% during 2010-18, with the proportion of resistance to three or more classes also stable (∼5%). After 2008, integrase inhibitor resistance slightly increased from 5.6% to 9.7% in 2018 and contributed to resistance, particularly in isolates with resistance to three or more classes (one class, 8.4%; two classes, 15.3%; three or more classes, 34.7%, P < 0.001). Among 1827 failing patients with an available follow-up, by 1 year after genotype-guided therapy start the probability of VS was 87.6%. Patients with cumulative resistance to three or more classes and receiving a poorly active regimen showed the lowest probability (62.6%) of VS (P < 0.001) compared with all other patients (≥81.8%). By Cox regression analysis, cumulative MDR and receiving poorly active antiretroviral regimens were associated with a lower hazard of VS compared with those without resistance. CONCLUSIONS: A dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.
Authors: Margaret Gartland; Pedro Cahn; Edwin DeJesus; Ricardo Sobhie Diaz; Robert Grossberg; Michael Kozal; Princy Kumar; Jean-Michel Molina; Fernando Mendo Urbina; Marcia Wang; Fangfang Du; Shiven Chabria; Andrew Clark; Louise Garside; Mark Krystal; Frank Mannino; Amy Pierce; Peter Ackerman; Max Lataillade Journal: Antimicrob Agents Chemother Date: 2022-05-03 Impact factor: 5.938