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      Virological suppression in children and adolescents is not influenced by genotyping, but depends on optimal adherence to antiretroviral therapy

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          Abstract

          Objective

          To evaluate the virological outcomes in children and adolescents infected with HIV-1 in Salvador, Bahia according to genotyping results.

          Methods

          We retrospectively evaluated the rates of virological suppression of children and adolescents submitted to HIV-1 genotyping test from January/2008 to December/2012. The participants were followed in the two referral centers for pediatric AIDS care, in Salvador, Brazil. Resistance mutations, drug sensitivity profiles, and viral subtypes were analyzed using the Stanford HIV-1 Drug Resistance Database. Adherence was estimated by drugs withdrawal at pharmacies of the two sites.

          Results

          101 subjects were included: 35 (34.6%) were drug-naïve, and the remaining 66 were failing ART. In drug-naïve group, 3 (8.6%), presented with NNRTIs resistance mutations, along with polymorphic mutations to PIs in most (82.8%) of them. Among the failing therapy group, we detected a high frequency (89.4%) of resistance mutations to PIs, NRTI (84.8%), and NNRTI (59.1%). Virological suppression after introduction/modification of genotyping-guided ART was achieved only for patients (53.1%) with drug withdrawal over 95%. Main detected HIV-1 subtypes were B (67.3%), F (7.9), C (1.9%), and recombinant forms (22.9%).

          Conclusions

          Despite the use of genotyping tests in guidance of a more effective antiretroviral regimen, poor adherence to ART seems to be the main determinant of low virological suppression rate for children and adolescents, in Salvador, Brazil.

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          Most cited references37

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          HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy.

          J M Coffin (1995)
          Several recent reports indicate that the long, clinically latent phase that characterizes human immunodeficiency virus (HIV) infection of humans is not a period of viral inactivity, but an active process in which cells are being infected and dying at a high rate and in large numbers. These results lead to a simple steady-state model in which infection, cell death, and cell replacement are in balance, and imply that the unique feature of HIV is the extraordinarily large number of replication cycles that occur during infection of a single individual. This turnover drives both the pathogenic process and (even more than mutation rate) the development of genetic variation. This variation includes the inevitable and, in principle, predictable accumulation of mutations such as those conferring resistance to antiviral drugs whose presence before therapy must be considered in the design of therapeutic strategies.
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            Antiretroviral therapy adherence in Brazil.

            This study evaluated the adherence to antiretroviral therapy (ART) in 322 Brazilian outpatient services located in seven states providing care to 87,000 patients (72%) under ART. A previous study classified the 322 health services into four levels of quality of care. Sixty of them were randomly chosen on the basis of these levels. A cross-section of 1972 patients under ART visiting these services was interviewed using a structured questionnaire. Patients who reported taking more than 95% of the prescribed antiretroviral pills in the past 3 days were considered adherent. The chi-square test was first used to compare the prevalence of non-adherence among two or more categories of variables. A chi-square test for linear trend was used for ordinal variables. Three multivariate models were applied using health services predictors, treatment predictors, and personal characteristics predictors. The predictors were fitted into logistic regression models using backward elimination procedures. The adherence prevalence was 75% (95% confidence interval 73.08-76.95). The level of quality of care was not associated with non-adherence. The models showed the following predictors of non-adherence: related to health services: services with 100 patients or less and missed appointments; related to treatment: more complex regimens and a high number of pills; related to personal characteristics: under 2 years of formal education. The adherence prevalence was similar to the rates currently obtained in developed countries. However, services with few patients need to be carefully monitored to maintain high rates. Care planning that prioritizes patients at risk also needs to be improved.
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              Drug-resistance genotyping in HIV-1 therapy: the VIRADAPT randomised controlled trial.

              Growing evidence has linked HIV-1 resistance mutations and drug failure. The use of genotypic-resistance analysis to assist therapeutic decision-making in patients failing therapy has not been investigated. We assessed the virological and immunological impact of genotypic-resistance testing. We did a prospective, open, randomised, controlled study of HIV-1-infected patients in whom combination therapy was not successful. We randomly assigned patients standard care (control, n=43) or treatment according to the resistance mutations in protease and reverse-transcriptase genes (genotypic group, n=65). The major endpoint was the change in HIV-1 RNA viral load. Analysis was by intention to treat. 108 patients were enrolled. All patients were similar for risk factors, age, sex, previous treatment, CD4-cell count (214/microL [SD14]) and log HIV-1 RNA viral load at baseline (4.7 copies/mL [0.1]). At month 3, the mean change in HIV-1 RNA was -1.04 log (0.14) in the study group compared with -0.46 log (0.17) in the control group (mean difference 0.58 log [95% CI 0.14-1.02], p=0.01). At month 6, changes were -1.15 (0.15) log copies/mL, and -0.67 (0.19) log copies/mL in the genotypic group and the control group, respectively (mean difference 0.48 log [0.01-0.97], p=0.05). Difference in the drop in viral load combined at 3 months and 6 months was significant (p=0.015). At month 3, HIV-1 RNA was lower than detection level (200 copies/mL) in 29% (19/65) of patients in the genotypic group versus 14% (6/43) in the control group (p=0.017). At month 6, the values were 32% (21/65) and 14% (6/43) (p=0.067) for the genotypic group and the control group, respectively. Therapy was generally well tolerated, with ten patients (six in the genotypic group, four in the control group) requiring toxic-effect-related drug modification. We found genotypic-resistance testing to have a significant benefit on the virological response when choosing a therapeutic alternative. Further study of the use of genotypic-resistance testing in assisting clinical decision-making is warranted.
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                Author and article information

                Contributors
                Journal
                Braz J Infect Dis
                Braz J Infect Dis
                The Brazilian Journal of Infectious Diseases
                Elsevier
                1413-8670
                1678-4391
                27 February 2017
                May-Jun 2017
                27 February 2017
                : 21
                : 3
                : 219-225
                Affiliations
                [0005]Universidade Federal da Bahia, Laboratótio de Retrovirologia, Salvador, BA, Brazil
                Author notes
                [* ] Corresponding author. crbrites@ 123456gmail.com
                Article
                S1413-8670(17)30146-0
                10.1016/j.bjid.2017.02.001
                9427598
                28253476
                5711301d-dda2-4c16-9a5d-9eab58408faf
                © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 27 April 2016
                : 8 February 2017
                Categories
                Original Article

                children,virological suppression,genotyping,adherence
                children, virological suppression, genotyping, adherence

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