Opimització del tractament antiretroviral en pacients amb infecció crònica pel vih

Resumo

Since the emergence of highly-active antiretroviral treatment, HIV infection has become a chronic infection and, nowadays, people living with HIV have a similar life expectancy to the general population. However, like all chronic pathologies, new challenges must be addressed: adherence to chronic treatment, early detection of virological failure to prevent the appearance of resistances and the need for complex drug combinations or simplification of complex regimens to promote therapeutic compliance in the long term. The objective of the three works of this thesis is to search strategies to optimize the management of patients with a large therapeutic experience and with a greater risk of virological failure. In the first work, we analyzed the virological efficacy of a multidisciplinary adherence program aimed at patients with poor compliance of the treatment. Factors associated with having an undetectable viral load were also evaluated. At baseline, 76% of the patients showed a treatment adherence less than 30% according to self-administered questionnaires and all had detectable viral load. At 48 weeks after the implementation of the program, 48% of the patients had an undetectable viral load and adherence less than 30% decreased to 17%. The collection of medication in pharmacy was a more reliable adherence indicator than that referred by the patient through self-administered questionnaires and it was the only factor associated with viral suppression (OR 22.1; 95%CI 5.3-92.4, p<0.001), along with receiving a regimen twice a day vs. once daily (OR 12.5; 95%CI 1.81-86.4, p=0.010). Thereafter, we analyzed the incidence of low level viraemias in patients with stable treatment and undetectable viral load and their association with virological failure, as well as factors associated with it. A total of 17.3% patients showed detectable viraemias. From them, 7.7% had virological failure, a higher percentage than those without detectable viraemias (1.5%). In the multivariate analysis, viraemia >200 copies/mL (HR 266; 95%CI 61-1150, p<0.01), PI-based dual therapies (HR 6.7, 95%CI 1.6-28.9, p=0.01) and IP/b monotherapies (HR 5; 95%CI 1.2-5.2, p=0.05) were associated with a higher risk of virological failure. Finally, the effectiveness and safety of the combination of dolutegravir and boosted darunavir was evaluated as a simplification strategy in a cohort of heavily-treated patients. Historical genotypes available in 44 patients (88%) showed that 41 patients (93.2%) had resistance to NRTIs, 32 (72.7%) had mutations to NNRTIs, and 12 (27.3%) had primary resistance mutations to PIs; 7 patients (15.9%) had any mutation to DRV. No patients had resistance to INSTI. After more than 2 years of follow-up, 98% of patients had an undetectable viral load. Estimated glomerular filtration decreased 1.4 mL/minute (IQR 0-18.5 mL/min, p=0.013) in the first month of follow-up, remaining stable thereafter. On the other hand, there was an increase in total cholesterol (+9 mg/dL [IQR 8-40], p=0.019) and LDL cholesterol (+16 mg/dL [IQR 9-40], p=0.019) at the end of study. In conclusion, a multidisciplinary adherence program focused on those patients with a higher risk for a poor compliance of the treatment achieved a remarkable efficacy in achieving viral suppression. Patients with detectable viraemia >200 copies/mL have a higher risk of virological failure, as well as those who are receiving PI-based monotherapies or dual therapies. Finally, in heavily-treated patients with undetectable viral load, the switch to dolutegravir plus boosted darunavir has shown a high virological effectiveness.