Prevalence of Transmitted Drug Resistance Mutations among Naive HIV-infected patients ( ) in Northwest Spain

Transcription

1 Prevalence of Transmitted Drug Resistance Mutations among Naive HIV-infected patients ( ) in Northwest Spain Berta Pernas 1, Andrés Tabernilla 1, Marta Grandal 1, Angelina Cañizares 2, Sofía Ortún 1, Ángeles Castro- Iglesias 1, Álvaro Mena 1, Iria Rodríguez-Osorio 1, Héctor Meijide 1, Eva Poveda 1. 1 Grupo de Virología Clínica. Instituto de Investigación Biomédica de A Coruña (INIBIC)-Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade de A Coruña (UDC). A Coruña, España. 2 Servicio de Microbiología. Instituto de Investigación Biomédica de A Coruña (INIBIC)-Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS. A Coruña, España.

2 BACKGROUND Antiretroviral Treatment (ART) has dramatically changed the natural history of HIV infection, reducing viral burden and HIV-related morbidity and mortality. 1 The transmission of drug resistance among adults recently infected is a consequence of the widespread use of antiviral agents. 2,3 Transmitted Drug Resistance (TDR) in naïve HIV-infected patients has been associated with suboptimal response to antiretroviral drugs. 4 Active surveillance of TDR provides important information about the factors involved in the transmission of resistant HIV strains and in the selection of ART components. 5,6 1 Palella et al. N Engl J Med Johnson et al. Top HIV Med Yebra et al. Med Clin (Barc.) Monge et al. PLoS One Hecht et al. J Infect Dis Ambrosioni et al. PLoS One 2015.

3 Integrase inhibitors (INI)-based regimens are recommended as first line therapies ABC/3TC/DTG TFV/FTC+DTG TFV/FTC+RAL TAF/FTC/EVG/COBI ABC/3TC/TDG TAF/FTC or TDF/FTC+DTG TAF/FTC/EVG/c or TDF/FTC/EVG/c TAF/FTC or TDF/TFC + RAL TAF/FTC or TDF/FTC + DRV/c or DRV/r TAF/FTC/RPV or TDF/FTC/RPV ABC/3TC/DTG TAF/FTC or TDF/FTC+DTG TAF/FTC/EVG/c or TDF/FTC/EVG/c TAF/FTC or TDF/TFC + RAL TAF/FTC or TDF/FTC + DRV/r

4 Drug-Resistance Testing Se recomienda realizar un estudio genotípico de resistencias del VIH-1 a la transcriptasa inversa y proteasa en todos los pacientes antes de iniciar el TAR (A-II). Se debe conocer el resultado del estudio genotípico si se va a iniciar TAR con ITINN (A-II). Solo se recomienda estudiar resistencias basales en la integrasa si existe alta sospecha de transmisión de resistencias a esta familia (C-III). Genotypic resistance testing is recommended prior to initiation of ART, ideally at the time of HIV diagnosis; otherwise before initiation of ART. HIV drug-resistance testing is recommended for persons with HIV infection at entry into care to guide selection of the initiation of ART regimen (AII). If therapy is deferred, repeat testing may be considered at the time of ART initiation (CIII). In special circumstances (e.g. in patients with acute or recent HIV infection and in pregnant HIV-infected women), ART initiation should not be delayed while awaiting resistance testing results; the regimen can be modified once results are reported (AIII). Standard genotypic drug-resistance testing in ARV-naive persons involves testing for mutations in the reverse transcriptase (RT) and protease (PR) genes. If transmistted integrase strand transfer inhibitor (INSTI) resistance is a concern, providers should ensure that genotypic resistance testing also includes INSTI genotype testing.

5 OBJECTIVE The goal of the study was to evaluate the prevalence of TDR to reverse transcriptase, protease and integrase inhibitors among naïve HIVinfected patients in the medical area of A Coruña.

6 MATERIAL and METHODS All naïve HIV-infected patients in clinical follow-up during were identified. Epidemiological and immune-virological characteristics were recorded. HIV reverse transcriptase, protease and integrase regions were amplified and sequenced from plasma samples and FASTA format sequences were obtained. The presence of TDR was evaluated following the last HIV drug resistance update of WHO and International AIDS Society (2017). HIV-1 subtypes were assigned using the Stanford University Drug Resistance Database algorithm.

7 n = 92 Gender (male) 84 (91.3) Age (years) 37 ± 11 Spanish nationality 76 (86.4) Route of Transmission MSM Heterosexual IDU 57 (66.3) 24 (27.9) 5 (5.8) AIDS-defining Disease 3 (3.3) Late Diagnosis (CD4 350 cells/µl and/or AIDS-defining disease) 24 (27.9) Mean CD4+ cell count at diagnosis time (cells/µl) 503 ± 287 Mean Viral Load (HIV-RNA) at diagnosis time (log copies/ml) 4.75 ± 0.74 Viral Hepatitis Co-Infection HBsAg positive HCV antibodies Data are presented as n (%) Baseline Characteristics of the Study Population 2 (2.2) 8 (8.7)

8 Prevalence of TDR (%) Major TDR mutations for INI were not identified % % % 3 2.2% 2 1.1% 1 0% 0 Total NRTI NNRTI PI INI T97A* * The accessory INI T97A mutation was recognized in naive HIV-infected patients diagnosed before 2014.

9 No significant differences in TDR prevalence were observed between subtypes B and F 2.2% 2.2% 1.1% 1.1% 2.2% 3.3% B p = % Subtype B Subtype F p = % 23.9% 64.1% F A G CRF01_AE CRF02_AG C K Prevalence of TDR (%) % p = % 3.4% p = % 1.7% 0 0% TDR NRTI NNRTI PI

10 All TDR mutations for RT and Protease were identified in HIV-infected patients diagnosed during TDR NRTI Reverse Transcriptase NNRTI M41L 2 (2.2) K103N 2 (2.2) Subtype F Major T69D 1 (1.1) E138A 1 (1.1) T219R 1 (1.1) Y181V 1 (1.1) G190A 1 (1.1) Minor V106I 19 (20.7) V179D 1 (1.1) Data are presented as n (%)

11 TDR at HIV Protease Major Minor and/or Polymorphisms D30N 1 (1.1) L10I 9 (9.8) Protease polymorphisms were common (57.6%) N88D 1 (1.1) L10V 20 (21.7) K20R 3 (3.3) K20M 1 (1.1) K20I 4 (4.3) Subtype B 100% p < % Subtype F 90.9% M36I 41 (44.6) M36L 2 (2.2) M36V 1 (1.1) L63P 29 (31.5) A71T 9 (9.8) A71V 4 (4.3) V77I 23 (25) V82I 3 (3.3) HIV-infected patients with TDR (%) % 1.7% 18.6% L89M 33 (35.9) I93L 24 (26.1) Polymorphism L10V M36I Protease Polymorphisms Data are presented as n (%)

12 CONCLUSIONS TDR prevalence in naïve HIV-infected patients was 3.3%, 5.4% and 1.1% for NRTI, NNRTI and PI, respectively, similar to those previously reported. Although no major TDR for INI were identified, mutation T97A was identified in 2.2% of patients. These results suggest that testing resistance to INI is not necessary yet before initiating treatment among HIV-infected naïve patients.

13 ACKNOWLEDGEMENTS Grupo de Virología Clínica