Pharmacogenetic predictors of variability in efavirenz pharmacokinetics in an admixed Brazilian HIV cohort.

AIMS: To investigate the influence of pharmacogenetic polymorphisms on efavirenz (EFV) exposure and metabolism in HIV-infected Brazilians under treatment with EFV-containing antiretroviral (ART) regimens. METHODS: HIV-positive adults (n = 82) on stable ART regimens containing 600 mg EFV once daily for at least 6 months were recruited at 2 university hospitals. Blood samples collected at mid-dose interval were used to quantify the plasma concentrations of EFV (denoted [EFV]), its major metabolite 8-OH-EFV ([8-OH-EFV]) and [8-OH-EFV]/[EFV] metabolic ratio, and to genotype single nucleotide polymorphisms in CYP2B6 (rs3745274, c.516G > T; rs28399499, c.983 T > C) and ABCB1 (rs3842, c.4036G > A). CYP2B6 metabolic phenotypes were inferred from the CYP2B6 diplotypes. Linear regression modelling was applied to identify sociodemographic, clinical and pharmacogenetic predictors of [EFV] and [8-OH-EFV]/[EFV] metabolic ratio. RESULTS: Wide (50-fold) interindividual variation in [EFV], [8-OH-EFV] and [8-OH-EFV]/[EFV] was observed; 69.5% of participants had [EFV] within the nominal therapeutic range (1000-4000 ng/mL), while 19.5 and 11.0% had [EFV] below and above this range, respectively. Multiple regression modelling retained only CYP2B6 metabolic phenotypes or the combined rs3745274 and rs28399499 genotypes, as significant predictors of [EFV] and [8-OH-EFV]/[EFV]. CONCLUSION: EFV exposure and disposition varied widely among HIV-infected Brazilians under stable treatment with EFV-containing ART regimens. About 1/10 of the participants had [EFV] exceeding nominal supratherapeutic concentration (4000 ng/mL), but reported tolerance to the ARV regimens, while 1/5 of participants had nominal subtherapeutic [EFV] (<1000 ng/mL) but adequate virological response. Genotype for the 2 CYP2B6 single nucleotide polymorphisms studied explained 48% of variation in [EFV] and 35% of variation in [8-OH-EFV]/[EFV].

Yellow fever in two unvaccinated French tourists to Brazil, January and March, 2018.

We report two yellow fever cases in unvaccinated French travellers in Brazil in January and March 2018, respectively; one exposed during an excursion in Minas Gerais and the other in Ilha Grande. Both presented with fever, hepatitis, thrombocytopenia and leucopenia. Yellow fever diagnosis was based on RT-PCR and serological tests. Both patients recovered within a few days. The increasing occurrence of cases in unvaccinated travellers highlights the need to reinforce vaccination recommendation for travellers at-risk.

Danger in the streets: exposures to bloodborne pathogens after community sharp injuries in Rio de Janeiro, Brazil

ABSTRACT Objective: Exposures to sharps injuries occurring in the community are relatively frequent. We describe characteristics of community sharp exposures reported in the city of Rio de Janeiro from 1997 to 2010. Methods: A cross-sectional analysis of exposure reports to sharps in the community reported to a surveillance system, designed for health care workers, of the Municipal Health Department of Rio de Janeiro. The characteristics of exposed individuals analyzed included types of exposure, the circumstances of the accident, and the prophylaxis offered. Results: 582 exposures were studied. Median age was 30 years and 83 (14%) involved children with less than 10 years of age. Two hundred and seventeen (37%) occurred with sharps found in the streets. The exposure was percutaneous in 515 (89%) and needles where involved in 406 (70%) of them. The sharps were present in the trash in 227 (39%) or in the environment in 167 (29%) of the reports. Professionals who work with frequent contact with domestic or urban waste were 196 (38%). The source was known in 112 (19%) of the exposures and blood was involved in 269 (46%). Only 101 (19%) of the injured subjects reported a complete course of vaccination for hepatitis B. Antiretroviral prophylaxis was prescribed for 392 (68%) of the exposed subjects. Conclusions: Sharps injuries occurring in the community are an important health problem. A great proportion would be avoided if practices on how to dispose needles and sharps used outside health units were implemented.

Danger in the streets: exposures to bloodborne pathogens after community sharp injuries in Rio de Janeiro, Brazil.

OBJECTIVE: Exposures to sharps injuries occurring in the community are relatively frequent. We describe characteristics of community sharp exposures reported in the city of Rio de Janeiro from 1997 to 2010. METHODS: A cross-sectional analysis of exposure reports to sharps in the community reported to a surveillance system, designed for health care workers, of the Municipal Health Department of Rio de Janeiro. The characteristics of exposed individuals analyzed included types of exposure, the circumstances of the accident, and the prophylaxis offered. RESULTS: 582 exposures were studied. Median age was 30 years and 83 (14%) involved children with less than 10 years of age. Two hundred and seventeen (37%) occurred with sharps found in the streets. The exposure was percutaneous in 515 (89%) and needles where involved in 406 (70%) of them. The sharps were present in the trash in 227 (39%) or in the environment in 167 (29%) of the reports. Professionals who work with frequent contact with domestic or urban waste were 196 (38%). The source was known in 112 (19%) of the exposures and blood was involved in 269 (46%). Only 101 (19%) of the injured subjects reported a complete course of vaccination for hepatitis B. Antiretroviral prophylaxis was prescribed for 392 (68%) of the exposed subjects. CONCLUSIONS: Sharps injuries occurring in the community are an important health problem. A great proportion would be avoided if practices on how to dispose needles and sharps used outside health units were implemented.

Osteomyelitis caused by Sporothrix schenckii in an immunocompetent patient.

Sporotrichosis is the most common subcutaneous mycosis in South America and its association with zoonotic transmission remains a relevant public health problem in Rio de Janeiro, Brazil. The disease most commonly presents as subacute or chronic cutaneous lesions, although dissemination to various organs and systems occurs in rare cases, mainly in immunosuppressed individuals. This report describes a case of sporotrichosis with severe bone and subcutaneous damage in an immunocompetent patient who did not exhibit the characteristic skin lesions of sporotrichosis, including ulcers, nodules, and lymphangitis.

Osteomyelitis caused by Sporothrix schenckii in an immunocompetent patient

Abstract Sporotrichosis is the most common subcutaneous mycosis in South America and its association with zoonotic transmission remains a relevant public health problem in Rio de Janeiro, Brazil. The disease most commonly presents as subacute or chronic cutaneous lesions, although dissemination to various organs and systems occurs in rare cases, mainly in immunosuppressed individuals. This report describes a case of sporotrichosis with severe bone and subcutaneous damage in an immunocompetent patient who did not exhibit the characteristic skin lesions of sporotrichosis, including ulcers, nodules, and lymphangitis.

Evaluation of thyroid function and autoimmunity in HIV-infected women.

Autoimmune thyroid diseases (AITD) are the main causes of thyroid dysfunction and the most common autoimmune diseases in the world. An association between AITD and infections with the human immunodeficiency virus (HIV), in combination with the effects of highly active anti-retroviral therapy (HAART), has been suggested by several research groups. The aim of the present study was to evaluate the frequency of thyroid dysfunction and AITD in women > 35 years of age infected with HIV, and to identify factors associated with the emergence of these thyroid abnormalities. HIV-infected women (n = 153) selected from the infectious disease outpatient clinic at a University Hospital in Rio de Janeiro were characterized based on their circulating CD4+ lymphocytes levels, viral loads, serum TSH levels, and the presence of FT4 and anti-thyroperoxidase antibodies (TPO-Ab). A total of 129 participants were on HAART and 24 were not. The frequency of thyroid disorders was 7.8% (12/153 patients) and all were on HAART at the time of diagnosis, yielding a prevalence of 9.3% in patients receiving HAART compared with 0% in patients not on HAART. AITD, hyper, and hypothyroidism were detected in 4.6%, 3.1%, and 4.1% of HAART patients. It was not detected any thyroid dysfunction or autoimmunity in HIV-infected women not on HAART. This study demonstrated an association between HAART and the development of AITD. In addition AITD only developed in HAART patients also presenting with undetectable viral loads and slightly elevated CD4+ T cell counts.

Evaluation of thyroid function and autoimmunity in HIV-infected women / Avaliação da função tiroidiana e autoimunidade em mulheres infectadas pelo HIV

Autoimmune thyroid diseases (AITD) are the main causes of thyroid dysfunction and the most common autoimmune diseases in the world. An association between AITD and infections with the human immunodeficiency virus (HIV), in combination with the effects of highly active anti-retroviral therapy (HAART), has been suggested by several research groups. The aim of the present study was to evaluate the frequency of thyroid dysfunction and AITD in women > 35 years of age infected with HIV, and to identify factors associated with the emergence of these thyroid abnormalities. HIV-infected women (n = 153) selected from the infectious disease outpatient clinic at a University Hospital in Rio de Janeiro were characterized based on their circulating CD4+ lymphocytes levels, viral loads, serum TSH levels, and the presence of FT4 and anti-thyroperoxidase antibodies (TPO-Ab). A total of 129 participants were on HAART and 24 were not. The frequency of thyroid disorders was 7.8% (12/153 patients) and all were on HAART at the time of diagnosis, yielding a prevalence of 9.3% in patients receiving HAART compared with 0% in patients not on HAART. AITD, hyper, and hypothyroidism were detected in 4.6%, 3.1%, and 4.1% of HAART patients. It was not detected any thyroid dysfunction or autoimmunity in HIV-infected women not on HAART. This study demonstrated an association between HAART and the development of AITD. In addition AITD only developed in HAART patients also presenting with undetectable viral loads and slightly elevated CD4+ T cell counts.

Doenças tiroidianas autoimunes (DTAI) são a maior causa de disfunção tiroidiana e são as doenças autoimunes mais comuns no mundo. A associação entre DTAI e infecções com o vírus da imunodeficiência humana (HIV), em combinação com a terapia antirretroviral altamente ativa (HAART), foi sugerida por vários grupos de pesquisadores. O objetivo do presente estudo foi avaliar a fre-quência de disfunção tiroidiana e DTAI em mulheres com mais 35 anos de idade infectadas com o HIV e identificar fatores associados com a emergência dessas anormalidades tiroidianas. As mulheres infectadas com HIV (n = 153), selecionadas do ambulatório de doenças infecciosas de um hospital universitário do Rio de Janeiro, foram caracterizadas com base no nível de linfócitos CD4+ circulantes, carga viral, níveis de TSH sérico e presença de anticorpos FT4 e antitiroperoxidase (TPO-Ab). Um total de 129 participantes se tratava com HAART e 24 não. A frequência de desordens da tiroide foi 7,8% (12/153 pacientes) e todas estavam em tratamento com HAART no momento do diagnóstico, levando a uma prevalência 9,3% em pacientes recebendo HAART, em comparação com 0% em pacientes não tratadas com HAART. DTAI, hipertireoidismo e hipotireoidismo foram detectados em 4,6%, 3,1% e 4,1% das pacientes tratadas com HAART. Não foram detectadas disfunção tiroidiana ou autoimunidade em mulheres infectadas com HIV e não tratadas com HAART. Este estudo demonstrou uma associação entre a HAART e o desenvolvimento de DTAI. Além disso, a DTAI apenas se desenvolveu em pacientes tratadas com HAART e que apresentavam cargas virais indetectáveis e contagens de células CD4+ T levemente elevadas.

Low rates of sustained virologic response with peginterferon plus ribavirin for chronic hepatitis C virus infection in HIV infected patients in Rio de Janeiro, Brazil.

BACKGROUND: The standard treatment for chronic hepatitis C virus (HCV) infection in HIV-infected subjects is the combination of alfapeginterferon (PEG-IFN) plus ribavirin. We designed this study to evaluate the rate of SVR and predictors of SVR in a public health setting in Rio de Janeiro, Brazil. METHODS: Retrospective cohort study of HCV/HIV co-infected patients treated with PEG-IFN plus ribavirin from 2004 to 2011 in 3 outpatient units in Rio de Janeiro. Exposure variables included age, sex, CD4+ cell count, HCV genotype, HCV and HIV viral loads, liver histology (METAVIR fibrosis scoring system) and previous treatment. The main outcome measurement was SVR. RESULTS: 100 patients were included in this analysis. Median age was 47 years and 68% were male. 80%, 4%, 14% and 2% were infected with HCV genotypes 1, 2, 3 and 4, respectively. At baseline, 77% had HCV viral load greater than 800,000 IU/ml, 99% had CD4+ greater than 200 cells/mm(3) and 10% had a diagnosis of cirrhosis. The treatment was withdrawn in 9% of the subjects (5% with adverse effects and 4% dropped out). SVR was observed in 27 (27%) of the 100 patients included. 13 (13%) subjects were classified as null-responders, 33(33%) as non-responders, 9 (9%) as breakthrough and 9(9%) as relapsers. In the multivariate model only being infected with genotype 2 or 3 (p<0.01) and having low levels of gamma glutamyl transferase (GGT) at baseline (p = 0.04), were predictive of SVR. CONCLUSION: SVR in HCV/HIV co-infected subjects in a public health setting is similar to that observed in clinical trials, albeit very low. A delay in therapy initiation should be considered until new therapies as direct acting antiviral drugs (DAA) become widely available and tested in coinfected subjects.

Changing patterns of AIDS: impact on the indications and diagnostic yield of bone marrow biopsies.

After the advent of HAART, the clinical course of HIV infection has dramatically improved. Therefore, it seems appropriate to reevaluate the performance of bone marrow biopsy (BMB) as a diagnostic tool. The aim of the present study was to compare the reasons for performing a BMB and its diagnostic yield in HIV-patients before and after HAART. A total of 165 BMB specimens obtained from HIV-infected patients receiving care at the Hospital of Universidade Federal do Rio de Janeiro in two different periods (1986-1994 and 1999-2004) were analysed. The main reason for BMB examination in the first period was fever (88%), which decreased in the second period (57%, p < 0.0001), when cytopenia (51%) was the leading reason for BMB, whereas in the first period it accounted for only 30% (p = 0.008). A definitive diagnosis (infection, granulomas or lymphomas) was obtained in 28% of patients in the first period and in 19% during the second period (p = 0.20). The diagnosis turned out as infections decreased from 16% in period 1 to 2% in period 2 (p = 0.003). Despite the the limitations in the evaluation of fever, the use of BMB must be considered on an individual basis, whenever less invasive alternatives have been exhausted, and should be complemented by a bone marrow aspiration for microbiological studies.

Changing patterns of AIDS: impact on the indications and diagnostic yield of bone marrow biopsies

After the advent of HAART, the clinical course of HIV infection has dramatically improved. Therefore, it seems appropriate to reevaluate the performance of bone marrow biopsy (BMB) as a diagnostic tool. The aim of the present study was to compare the reasons for performing a BMB and its diagnostic yield in HIV-patients before and after HAART. A total of 165 BMB specimens obtained from HIV-infected patients receiving care at the Hospital of Universidade Federal do Rio de Janeiro in two different periods (1986-1994 and 1999-2004) were analysed. The main reason for BMB examination in the first period was fever (88 percent), which decreased in the second period (57 percent, p < 0.0001), when cytopenia (51 percent) was the leading reason for BMB, whereas in the first period it accounted for only 30 percent (p = 0.008). A definitive diagnosis (infection, granulomas or lymphomas) was obtained in 28 percent of patients in the first period and in 19 percent during the second period (p = 0.20). The diagnosis turned out as infections decreased from 16 percent in period 1 to 2 percent in period 2 (p = 0.003). Despite the the limitations in the evaluation of fever, the use of BMB must be considered on an individual basis, whenever less invasive alternatives have been exhausted, and should be complemented by a bone marrow aspiration for microbiological studies.

Risk-based assessment does not distinguish between recent and chronic HIV-1 infection in Rio de Janeiro, Brazil

This study investigated the risk factors associated with recent and chronic HIV infections among individual attending a voluntary counseling and testing (VCT) site in Rio de Janeiro, Brazil. In a cross-sectional study, recent HIV infections were detected by the sensitive/less-sensitive test, using Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS) strategy, and compared to chronic HIV infection and HIV negative individuals. Seroincidence was estimated and risk factors associated with recent and chronic infections were assessed using multinomial logistic regression. Among the 7,379 individuals tested between June 2006 and April 2007, the overall prevalence and incidence of HIV infection were 7.5 percent; and 1.39/100 PY, respectively. In multivariate analysis, having a HIV positive steady partner was a risk factor for recent and for chronic HIV infection for MSM, heterosexual male and women. No differences in risk factors for recent and chronic infections were found between MSM and heterosexual males. Among women, chronic infected individuals were more likely than HIV negatives to be older. Recently HIV infected women were more likely than HIV negatives to be less educated; and more likely than HIV negatives and chronically infected to report having more partners. Routinely used risk-based assessment in testing centers in Brazil lack sensitivity to distinguish between recent and chronic infections, particularly among MSM and heterosexual males. Steady relationships and serosorting may be playing a key role in maintaining the HIV epidemics in Brazil.

Risk-based assessment does not distinguish between recent and chronic HIV-1 infection in Rio de Janeiro, Brazil.

This study investigated the risk factors associated with recent and chronic HIV infections among individual attending a voluntary counseling and testing (VCT) site in Rio de Janeiro, Brazil. In a cross-sectional study, recent HIV infections were detected by the sensitive/less-sensitive test, using Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS) strategy, and compared to chronic HIV infection and HIV negative individuals. Seroincidence was estimated and risk factors associated with recent and chronic infections were assessed using multinomial logistic regression. Among the 7,379 individuals tested between June 2006 and April 2007, the overall prevalence and incidence of HIV infection were 7.5%; and 1.39/100 PY, respectively. In multivariate analysis, having a HIV positive steady partner was a risk factor for recent and for chronic HIV infection for MSM, heterosexual male and women. No differences in risk factors for recent and chronic infections were found between MSM and heterosexual males. Among women, chronic infected individuals were more likely than HIV negatives to be older. Recently HIV infected women were more likely than HIV negatives to be less educated; and more likely than HIV negatives and chronically infected to report having more partners. Routinely used risk-based assessment in testing centers in Brazil lack sensitivity to distinguish between recent and chronic infections, particularly among MSM and heterosexual males. Steady relationships and serosorting may be playing a key role in maintaining the HIV epidemics in Brazil.

Leprosy reaction and immune reconstitution syndrome in Aids / Reação hansênica e síndrome de reconstituição imunológica na Aids

The authors report seven cases of borderline leprosyin AIDS patients whose presentation form was of a typeI reaction diagnosed soon HAART introduction, whichled to the discussion of the immunological aspects involved in the reaction to leprosy and the immune reconstitution syndrome. The patients were in frank AIDS-induced immune deterioration, which was the reason they met the criteria to initiate HAART treatment. It is likely that due to this fact, the amount of CD4 cells increased at the same time that a reduction of the viral load occurred, allowing the installation of a basically Th1 immunological profile. Therefore, the leprosy infection, which was dormant and unable to express itself was exteriorized in the form of a reverse reaction.

Genital HIV-1 viral load is correlated with blood plasma HIV-1 viral load in Brazilian women and is reduced by antiretroviral therapy.

CONTEXT: Cervicovaginal secretions represent the primary vehicle in mother to infant and sexual HIV-1 transmission. Understanding the viral dynamics in this compartment is important to improve interventions to decrease HIV transmission. OBJECTIVES: To evaluate the correlation of HIV-1 blood plasma viral load and cervicovaginal HIV-1 viral load and the effect of antiretroviral therapy (ART) on cervicovaginal HIV-1 viral load. METHODS: A cross-sectional study among HIV-1 infected women recruited between February 2002 and January 2003 and a longitudinal study that included 11 women who initiated ART were performed. HIV-1 viral load was measured in the female genital tract and in blood plasma using the Nuclisens assay before and 1 month after ART introduction. RESULTS: HIV-1 viral load in cervicovaginal lavage was significantly correlated with HIV-1 blood plasma viral load (n = 27, Spearman rho = 0.73, p<0.001). In the longitudinal study, antiretroviral therapy was associated with a reduction of 1.44 log10 on genital HIV-1 viral load (95% CI = 0.57-2.30, p = 0.004, Student's t-test). CONCLUSIONS: HIV-1 viral load in female genital secretions is correlated with blood plasma HIV-1 viral load. Antiretroviral therapy substantially reduces HIV-1 viral load in the female genital tract.