OUTCOMES OF HIV-INFECTED THERAPY INCLUDING

Transcription

1 UNIVERSIDADE FEDERAL DA BAHIA FACULDADE DE MEDICINA DA BAHIA PROGRAMA DE PÓS-GRADUAÇÃO EM MEDICINA E SAÚDE OUTCOMES OF HIV-INFECTED PATIENTS RECEIVING RESCUE THERAPY INCLUDING RALTEGRAVIR Patino-Escarcina JE 1, Netto EM 1,2, Brites C 1,2 1. School of Medicine, Federal University of Bahia, Posgraduate Program in Medicine & Health, Salvador/BA, Brazil. 2. Research Laboratory of Infectious Diseases, Edgard Santos Federal University Hospital, Salvador, Bahia, Brazil. 8º Congresso Brasileiro sobre HIV-AIDS e Vírus relacionados, Salvador BA/Brazil

2 BACKGROUND New antiretroviral drug classes and combined antiretroviral therapy (cart) have an optimal therapeutic response and a positive effect on survival and risk of AIDS-related illnesses. (Mills et al., 2017) (Croxford et al., 2017) Approximately 20% of patients receiving cart did not achieve virologic suppression (Ministério da Saúde Brasil, 2018) (Unaids, 2018) 2

3 BACKGROUND Virologic failure and antiretroviral therapy resistance emerge because of different and multiple factors that are also related to mortality. (Ji et al., 2017) (Hogg et al., 2006) (Bekolo et al., 2013) The management of treatment experienced patients remains a complex issue around the world. (Hill, Cho and Mrus, 2011) (Wainberg, Zaharatos and Brenner, 2011) 3

4 BACKGROUND In Brazil, Raltegravir-based regimens are suggested as one of the rescue therapy options for highly drug-resistant HIV infections. (World Health Organization, 2013) (Ministério da Saúde Brasil, 2018) Raltegravir was the first integrase inhibitor commercialized agent, that blocks HIV replication hindering proviral DNAstrand transfer. (Hazuda et al., 2000) (Espeseth et al., 2000) 4

5 BACKGROUND Raltegravir has shown potent and durable efficacy, good tolerability and a favorable safety profile in treatment-naive patients and in treatment-experienced patients. (Steigbigel et al., 2008) (Okeke and Hicks, 2011) (Ramkumar and Neamati, 2010) Knowledge about the optimal combination of ARVs in salvage regimens is scarce. (World Health Organization, 2013) (Ministério da Saúde, 2018). 5

6 BACKGROUND Recommendations regarding which agents to use are lacking and management of heavily treatment-experienced patients remains as a complex and challenging issue. (Temesgen et al., 2006) (Pou et al., 2014). To date there is not much evidence comparing benefits of RALbased regimens with other salvage regimens. (Mata-Marín et al., 2017) 6

7 OBJECTIVES Evaluate the impact of RAL compared with other third line drugs as part of salvage regimens for treatment-experienced patients failing ART. 7

8 OBJECTIVES Secondary objectives include: Predictors for mortality. Virologic success, treatment failure, toxicity and discontinuation. 8

9 STUDY POPULATION A retrospective cohort study was conducted on 168 adults. Complexo Hospitalar Prof. Edgard Santos, Federal University of Bahia. January 01, December 31,

10 STUDY POPULATION 367 HIV-1 infected patients receiving third-line drug based regimens 83 for other causes but virologic failure. (32 adverse events, 21 intolerance, 30 other clinical criteria) 32 not adults 48 followed-up in other institutions 11 lack of follow-up 25 with <60 days of follow-up 168 initiating third-line regimens after virologic failure 123 RAL-based regime 5 lost 6 died 45 other drugs 2 lost 3 died 10

11 STUDY POPULATION Treatment failure was 2 consecutive HIV RNA tests >1000 copies/ml. Genotypic antiretroviral resistance testing (GRT) suggesting the use of third line regimens. Initiating rescue therapy including Raltegravir or other thirdline drug (Darunavir/Ritonavir, Maraviroc, Etravirine or Enfuvirtide) 11

12 METHODS Information about epidemiologic, virologic, immunologic and clinical characteristics were extracted from medical records. Mortality data were ascertained using information provided by System of Information about Mortality (Sistema de Informações de Mortalidade, SIM). 12

13 METHODS We analyzed time to the event (virologic success, death or loss of follow-up data) from rescue antiretroviral therapy initiation to December 31, 2016 Time to death and virologic success were compared in both groups with Kaplan-Meier survival function and Wilcoxon test. Cox s proportional hazard model were used to identify independent predictors of mortality. 13

14 METHODS Test were two-sided, and p values <.05 were considered to be statistically significant. This clinical research has been performed in concordance with the Good Clinical Practice Guidelines, the National Regulation of Research and approved by the HUPES Ethic Committee. 14

15 *: Mann Whitney U test, : Pearson χ 2 test, : Fisher s exact test; were used to compare groups. B ASELINE CHARACTERISTICS (1/3) Characteristics HIV infected patients receiving third-line therapy Raltegravir Other ARV (n = 123) (n = 45) pvalue Age (yr.) - med(iqr) 43.8 ( ) 46.2 ( ).20 * Male sex - no. (%) 78 (63.4) 34 (75.6).13 Black race - no. (%) 108 (87.8) 37 (82.2).36 Time of follow up (yr.) - med(iqr) 3.7 ( ) 6.4 ( ).00 * Years receiving ART (yr.) - med(iqr) 11 (9-14) 10 (7-12).03 * Prev. treatment failures - med(iqr) 2 (2-3) 2 (1-2).30 * 2 ARV failures - no. (%) 94 (76.4) 32 (71.1).48 15

16 B ASELINE CHARACTERISTICS (2/3) Characteristics HIV infected patients receiving third-line therapy Raltegravir Other ARV (n = 123) (n = 45) pvalue Alcohol use - no. (%) 58 (47.2) 16 (35.6).20 Cigarette smoking - no. (%) 41 (33.3) 13 (28.9).63 Illicit drug use - no. (%) 15 (12.2) 4 (8.9).78 HIV-1 RNA (log10 copies/ml) med(iqr) 4.5 ( ) 4.1 ( ).02 * > copies/ml - no. (%) 32 (26) 5 (11.1) CD4 count (cells/µl) - med(iqr) 181 (58-368) 292 ( ).00 * < 200 cells/µl - no. (%) 65 (52.8) 12 (26.7).00 Hemoglobin (g/dl) - med(iqr) 12.7 ( ) 13.4 ( ).03 * < 9 g/dl - no. (%) 7 (5.7) 0 (0).19 *: Mann Whitney U test, : Pearson χ 2 test, : Fisher s exact test; were used to compare groups. 16

17 B ASELINE CHARACTERISTICS (1/3) Characteristics HIV infected patients receiving third-line therapy Raltegravir Other ARV (n = 123) (n = 45) pvalue Body mass index (kg/m 2 ) - med(iqr) 22.4 ( ) 23.8 ( ).02 * Existing comorbidities - no. (%) 58 (47.5) 23 (51.1) Diabetes mellitus - no. (%) 10 (8.2) 3 (6.7).99 Blood hypertension - no. (%) 20 (16.4) 13 (28.9).07 Hyperlipidemia - no. (%) 21 (17.2) 11 (24.4).29 Others - no. (%) 31 (25.4) 19 (42.2) Past coinfections - no. (%) 68 (55.7) 27 (60.0) Pulmonary TB - no. (%) 27 (22.1) 10 (22.2).99 CNS toxoplasmosis - no. (%) 26 (21.3) 5 (11.1).13 Syphilis - no. (%) 12 (9.8) 5 (11.1).78 Others - no. (%) 41 (33.6) 17 (37.8) *: Mann Whitney U test, : Pearson χ 2 test, : Fisher s exact test; were used to compare groups. 17

18 RESULTS The total time contributed were 750 person-years with median follow up of 4.5 years. The mortality rate of this cohort was 1.2 person per 100 person-years. 18

19 EVENTS DURING FOLLOW-UP Event HIV infected patients initiating third-line therapy Raltegravir (n = 123) Other ARV (n = 45) pvalue * HIV-1 RNA <50 copies/ml - no. (%) 90 (73.8) 36 (80.0).67 Discontinuation - no. (%) 16 (13.1) 1 (2.2) Toxicity - no. (%) 3 (2.5) 1 (2.2) Virologic failure - no. (%) 3 (2.5) 2 (4.4) Death - no. (%) 6 (4.9) 3 (6.7).36 Loss of follow-up - no. (%) 4 (3.3) 2 (4.4) 19 *: Wilcoxon test

20 TIME TO DEATH FROM ANY C AUSE (1/2) 20

21 TIME TO DEATH FROM ANY C AUSE (2/2) 21

22 TIME TO VIROLOGIC SUCCESS (1/2) 22

23 TIME TO VIROLOGIC SUCCESS (2/2) 23

24 TIME TO ANY EVENT 24

25 PREDICTORS OF MORTALITY Characteristics Univariate analysis Crude Hazard Ratio p-value Ral-based regimens Multivariate analysis Adjusted Hazard Ratio [95% CI] Male sex [ ] No. previous ART failure [ ] Alcohol use [ ] Previous Hemoglobin (g/dl) [ ] Previous Body mass index (kg/m 2 ) [ ] Diabetes mellitus [ ] 25

26 CONCLUSIONS It was not observed difference in time to virologic success, and survival when RAL was included in rescue therapies. Some basal patients characteristics influence independently in survival. Number of previous ART failures, lower BMI and the presence of DM, affect mortality. 26

27 CONCLUSIONS The election of RAL or other third-line drug as part of the rescue therapy may not overcome the existing risks for the patients failing previous ART and with indication of rescue therapy. The better understanding of the characteristics of patients initiating third-line regimens could help to improve survival and future virologic failures. 27

28 THANK YOU 8º Congresso Brasileiro sobre HIV-AIDS e Vírus relacionados, Salvador BA/Brazil