Prevalencia de resistencia a los anti-retrovirales en niños y adolescentes uruguayos infectados con el virus de la inmunodeficiencia humana en el Centro de Referencia VIH-SIDA. Centro Hospitalario Pereira Rossell. Montevideo-Uruguay / Prevalence of antiretroviral resistance in Uruguayan children and adolescents infected with the human immunodeficiency virus in the Reference Center HIV-AIDS. Centro Hospitalario Pereira Rossell, Montevideo, Uruguay

Resumen Introducción: A nivel mundial, la tasa global de resistencia primaria y secundaria a los anti-retrovirales (ARV) es de 15 y 40%, respectivamente. Se desconoce su prevalencia en Uruguay. Objetivo: Conocer la prevalencia de resistencia a los ARV en niños y adolescentes uruguayos bajo 15 años de edad infectados con VIH que se controlan en el Centro Hospitalario Pereira Rossell entre 2008 y 2016. Objetivos específicos: Cuantificar mutaciones de resistencia primarias y secundarias e identificar variables asociadas a resistencias; describir si el resultado del test de resistencia contribuyó a lograr una carga viral (CV) indetectable. Metodología: Descriptivo observacional, seguimiento longitudinal. Se incluyeron menores de 15 años con test de resistencia entre 1 de enero de 2008 y 15 de diciembre de 2016. Variables maternas y del niño. Resultados: Se incluyeron 56 niños. Tenían test de resistencia previo al inicio TARV 36 niños (64%) y por fallo terapéutico 20 (36%). La resistencia total fue 28,6% (16 niños): cuatro (11,1%) con mutaciones primarias y 12 (60%) secundarias. El test modificó el plan ARV en 15 (26,7%) de los 56 niños. El cambio logró CV indetectable a los seis meses en ocho casos. El cambio de TARV no se asoció con sida o muerte. Discusión: Los estudios de prevalencia son útiles para la toma de decisiones sobre la selección inicial de ARV. La prevalencia de mutaciones primarias fue similar a la publicada, mientras que la secundaria fue mayor.

Background: Primary and secondary antiretroviral (ARV) resistance rates of 15 and 40% respectively have been reported in worldwide. Its prevalence in Uruguay is unknown. Aim: To know the prevalence of ARV resistance in Uruguayan children under 15 years old infected with HIV that are controlled in the Centro Hospitalario Pereira Rossell between 2008 and 2016. Specific objectives: Quantify primary and secondary mutations, to identify variables associated with resistance; to describe if the result of the resistance test contributed to achieve undetectable viral load (VL). Methodos: Observational descriptive, longitudinal follow-up. Only children under 15 years with resistance test done between January first 2008 and December 31th 2016 were included in the study. Maternal and child variables. Results: Fifty six children were included. 36 children (64%) had resistance tests prior to the initiation of ART and the other 20 children (36%) due to therapeutic failure. Total resistance: 28.6% (16 children); 4 (11.1%) children with primary mutations and 12 (60%) secondary mutations. The test result changed the ARV plan in 15 (26.7%) of the 56 children. The change achieved undetectable CV in 8 children at month 6. The ART change was not associated with AIDS or death. Discussion: Prevalence studies are useful in making decisions about initial ARV treatment. The prevalence of primary mutations was similar to that published, while secondary prevalence was higher.

Primary resistance of HIV to antiretrovirals among individuals recently diagnosed at voluntary counselling and testing centres in the metropolitan region of Recife, Pernambuco

Determining the prevalence and type of antiretroviral (ARV) resistance among ARV-naïve individuals is important to assess the potential responses of these individuals to first-line regimens. The prevalence of primary resistance and the occurrence of recent infections among individuals with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) were identified among recently diagnosed patients at five sexually transmitted disease/AIDS testing and counselling centres in the metropolitan region of Recife (RMR), Pernambuco, Brazil, between 2007-2009. One-hundred and eight samples were analysed using the Calypte® BED assay. Males predominated (56%), as did patients aged 31-50 years. Twenty-three percent presented evidence of a recent HIV infection. The median CD4+ T lymphocyte count was 408 cells/mm³ and the median viral load was 3.683 copies/mL. The prevalence of primary resistance was 4.6% (confidence interval 95% = 1-8.2%) based on criteria that excluded common polymorphisms in accordance with the surveillance drug resistance mutation criteria. The prevalence of resistance to non-nucleoside reverse transcriptase, nucleoside/nucleotide reverse transcriptase and protease inhibitors were 3.8%, 1.5% and 0.8%, respectively. Fifty-seven percent of strains were from clade B, 37.7% were clade F and 3.1% were clade C; there were no statistically significant differences with respect to resistance between clades. Recent infection tended to be more common in men (p = 0.06) and in municipalities in the south of the RMR (Jaboatão dos Guararapes and Cabo de Santo Agostinho) (p = 0.046). The high prevalence of recent infection and the high prevalence of non-B strains in this poor Brazilian region merit further attention.

HIV-1 drug resistance genotypic profiles in children with undetectable plasma viremia during antiretroviral therapy

Treatment of HIV-1 infection with highly active antiretroviral therapy has led to sustained viral suppression in the plasma in a large number of children. However, studies have suggested that the integrated provirus in resting CD4+ T lymphocytes could be a source of reactivatable virus and maintain drug-resistant virus. We evaluated the resistance-related mutations in children receiving antiretroviral therapy with prolonged viral suppression. Thirty-two peripheral blood mononuclear cell samples from 16 children with viral loads that had been below detection limits for at least 12 months were obtained at two different time points and the DNAs sequenced. The median CD4 cell count was 1,016 cells/mm³ (347-2,588) and 938 cells/mm³ (440-3,038) at the first and second time points, respectively. The median follow-up time was 15 months (9-27). Six (37.5 percent) and seven (43.75 percent) of the 16 patients showed at least one NRTI-associated mutation in the first and second samples, respectively. Two out of 16 (12.5 percent) had an NNRTI-associated mutation at the first time point and three out of 16 (18.75 percent) at the second. In addition, 14 out of 16 (87.5 percent) had at least one PI-associated mutation at both time points. Despite plasma HIV-1 RNA suppression for at least 12 months, resistance-related mutations from previous antiretroviral failures could still be detected in archival virus. Furthermore, viral evolution occurred at the reverse transcriptase region in spite of viral suppression to levels below 400 copies/mL. Persistence of archival resistant virus may be relevant when considering future treatment options.

HIV-1 resistance testing influences treatment decision-making

OBJECTIVE: To investigates how the use of HIV-1 resistance tests influences physician decision-making. METHODS: Ten experienced reference physicians from the Brazilian Network for Drug Resistance each received ten patients' case histories. The selected patients had experienced at least two virological failures. First, reference physicians were asked to empirically select a new regimen for each patient. Second, after genotype report (ViroSeq 2.6) was provided, and physicians were again asked to select a new regimen considering this additional information. Finally, they were asked to select a regimen after receiving a virtual phenotype result (vircoTYPE 3.9.00). RESULTS: In 79 percent of the cases, physicians changed their empirical choice of regimen after receiving the genotype report, resulting in an increase in the mean number of active drugs from 1.8 to 2.2 (p = 0.0003), while the average number of drugs/regimen remained at 4.0. After receipt of the virtual phenotype report, additional changes were made in 75 percent of the patient cases, resulting in an increase in the number of active drugs to 2.8 (p < 0.0001), while the average number of drugs/regimen remained at 4.0. After receipt of the genotype report, 48 percent of the changes were in NRTIs, 29 percent were in NNRTIs and 60 percent were in PIs; after consideration of the virtual phenotype, 61 percent, 10 percent and 49 percent of the changes, respectively, were in these categories of drugs. Fourteen percent of the physicians rated the genotype report as "extremely useful", whereas 34 percent rated the subsequent virtual phenotype report as "extremely useful" (p = 0.0003). CONCLUSIONS: Resistance testing has a significant impact on physicians' choices of antiretroviral salvage therapies, and it promotes the selection of more active drugs.

Molecular characterisation of newly identified HIV-1 infections in Curitiba, Brazil: preponderance of clade C among males with recent infections

As in many areas of Brazil, the AIDS epidemic in Curitiba is relatively stable, but surveillance is important to support public policy. The molecular characteristics of HIV may be instrumental for monitoring epidemic trends. We evaluated plasma HIV-1 RNA (n = 37) from 38 cases presenting with positive serology, who were among 820 consenting volunteers visiting the downtown counselling and serology testing centre. Seroprevalence was 4.6 percent (CI 95 percent 3.2-6.3) and the estimated HIV incidence, as defined by the BED assay, was 2.86 persons/years (CI 95 percent 1.04-4.68). An additional set of contemporaneous, anonymous samples from a local laboratory was also analysed (n = 20). Regions of the HIV-1 polymerase (n = 57) and envelope (n = 34) were evaluated for subtyping, determination of mosaic structure, primary drug resistance mutations (pDRM), envelope V3 loop motifs and amino acid signatures related to viral tropism. HIV-1 clade B was observed in 53 percent of cases; HIV-1C in 30 percent and BC mosaics in 14 percent, with one F genome and one CF mosaic. Clade C infection was associated with recent infections among males (p < 0.03). Stanford surveillance pDRM was observed in 8.8 percent of sequences, with 7 percent showing high level resistance to at least one antiretroviral drug. Tropism for CXCR4 co-receptor was predicted in 18 percent of envelope sequences, which were exclusively among clade B genomes and cases with serological reactivity to chronic infection.