Tese de Doutorado
Avaliação da efetividade do uso de darunavir e/ou raltegravir e/ouenfuvirtida na supressão viral, resposta imunológica e fatoresassociados falha terapêutica em pacientes com infecção pelo HIV-1com ampla resistência aos antirretrovirais; estudo brasileiromulticêntrico, retrospectivo de 2005 a 2011.
Autor
Mateus Rodrigues Westin
Institución
Resumen
Introduction: many studies have shown the efficacy and effectiveness of new antiretroviral drugs that made possible the use of new salvage therapies able to maintain HIV plasmatic levels below 50 copies/ml. However, the effectiveness of these therapies was not yet evaluated in Brazil. Objectives: to evaluate, among multi-drug-experienced patients, the virologic and immunologic effectiveness and the main factors related to therapeutic failure within 48 weeks of the use of a regimen with darunavir (DRV) and/or raltegravir (RAL) and/or enfuvirtide (ENF). Furthermore, we sought to analyze the clinical and laboratorial evolution among patients with viral load below 400 copies/ml who switched from ENF to RAL. Methods: a retrospective cohort was carried out with adultpatients from 14 reference centers in seven brazilian states. Enrolled patients started salvage regimens between 2005 and 2010 and were on virologic failure. Primary endpoints analyzed at week 48 ( four weeks) were the proportion of patients with viral load <50 copies/ml and the LTCD4 cells variation from baseline. Results were obtained on an intention-to-treat analyzes applied to observational studies. Missing data at week 48 were handled by a sensitivity analysis between two different strategies. Multiple logistic regression analyzes for the therapeutic failure factors was performed. Results: 595 patients were included (73.5% male, median age 44 years). The median of infection length was 11 years and 74.3% of the patients were CDC stage C. According to the first strategy for missing data handling, the percentual of virologic success were 72.6% / 79.3% / 65.2% and the median increase of LTCD4+ counts were 121 / 134 / 138 cells/mm3 for therapeutic regimens including DRV, RAL and ENF, respectively. Using the second strategy, the percentual of virologic success were 73.2% / 79.9% / 63.3% and the median increase of LTCD4+ counts were 108 / 122 / 114 cells/mm3 for therapeutic regimens including DRV, RAL and ENF, respectively. The multiple logistic regression models for virologic failure at week 48 on DRV group showed that patients with a raltegravir-containing regimen and baseline LTCD4+ >100 cel/ml had less chance of virologic failure: OR=0.42 (CI95% 0.26 0.67) and OR=0.42 (CI95%=0.29 0.59) respectively. Among patients onRAL group, high viral load (>50,000 or 100,000 copies/ml) was related with therapeutic failure (OR=2.84; CI95%=1.67 4.83 and OR=3.14; CI95%=1.82-5.42, both with p<0.001). However, at least according to the second strategy for handling missing data, concomitant use of DRV was protective against therapeutic failure in that population (OR=0.32; CI95%=0.14-0.73; p=0.007). Among the 87 patients on an enfuvirtide-containing therapy in whom the attending physician switched from enfuvirtide to raltegravir, the proportion of patients with HIV-RNA levels < 50 copies/ml were 86.2 / 88.5% and the median increase of CD4 cell counts from baseline was 41 / 64 cells/ml (p < 0.001), according tostrategies 1 / 2 respectively. Conclusion: Achieving and maintaining viral suppression are plausible objectives for most multi-drug-experienced patients who underwent salvage therapies with DRV and/or RAL and/or ENF, even in brazilian clinical practice. Our data reinforce the strategies used by brazilian Health Ministry for incorporation and release of new antiretroviral drugs, including the recommendation for switching ENF to RAL in patients with controlled viremia.