BACKGROUND Distinct N-acetyltransferase 2 (NAT2) slow acetylators genotypes have been associated with a higher risk to develop anti-tuberculosis drug-induced hepatotoxicity (DIH). However, studies have not pointed the relevance of different acetylation phenotypes presented by homozygotes and compound heterozygotes slow acetylators on a clinical basis. OBJECTIVES This study aimed to investigate the association between NAT2 genotypes and the risk of developing DIH in Brazilian patients undergoing tuberculosis treatment, focusing on the discrimination of homozygotes and compound heterozygotes slow acetylators. METHODS/FINDINGS The frequency of NAT2 genotypes was analysed by DNA sequencing in 162 patients undergoing tuberculosis therapy. The mutation analyses revealed 15 variants, plus two new NAT2 mutations, that computational simulations predicted to cause structural perturbations in the protein. The multivariate statistical analysis revealed that carriers of NAT2*5/*5 slow acetylator genotype presented a higher risk of developing anti-tuberculosis DIH, on a clinical basis, when compared to the compound heterozygotes presenting NAT2*5 and any other slow acetylator haplotype [aOR 4.97, 95% confidence interval (CI) 1.47-16.82, p = 0.01]. CONCLUSION These findings suggest that patients with TB diagnosis who present the NAT2*5B/*5B genotype should be properly identified and more carefully monitored until treatment outcome in order to prevent the occurrence of anti-tuberculosis DIH.

BACKGROUND Rifamycins are a group of antibiotics mainly used in the treatment of tuberculosis (TB), however they interact with antiretroviral therapy (ART). Rifabutin allows more regimens options for concomitant imunodeficiency virus (HIV) treatment compared to rifampicin. OBJECTIVE Compare the outcomes of TB-HIV co-infected patients who used rifampicin or rifabutin. METHODS We analysed data from a prospective cohort study at National Institute of Infectious Diseases Evandro Chagas, Rio de Janeiro (RJ), Brazil. Patients who were treated for TB and HIV with rifampicin or rifabutin, from February 2011 to September 2016 were included. FINDINGS There were 130 TB-HIV patients, of whom 102 were treated with rifampicin and 28 with rifabutin. All patients in the rifabutin-treated group and 55% of the rifampicin-treated group patients were ART-experienced. Patients treated with rifampicin had similar abandon and cure rates, interruptions in treatment due to adverse reactions, immune reconstitution inflammatory syndrome and a similar mortality rate as those treated with rifabutin. However, rifampicin-treated patients had higher CD4 counts and more frequently undetectable HIV viral load by the end of treatment (67% versus 18%, p < 0.001) compared to rifabutin-treated patients, even when only ART-experienced patients were evaluated (66,6% versus 36,3%, p = 0.039). CONCLUSIONS Patients who used rifabutin had worst immune and virological control. This group had more ART-experienced patients. New and simpler regimens are needed for patients who do not respond to previous antiretroviral therapies.

BACKGROUND Cutaneous tuberculosis (CTB) is a rare extrapulmonary form of tuberculosis (TB). Despite the increase in the number of cases of TB and HIV, few cases of CTB have been reported. OBJECTIVE To describe CTB cases among patients with HIV infection from a cohort with tuberculosis. METHODS We describe a series of 15 CTB and HIV cases, based on secondary data from 2000 to 2016. Diagnosis was based on isolation of Mycobacterium tuberculosis in culture or clinical response to anti-tuberculous treatment associated with positive smear or histopathologic findings from affected skin or an adjacent lymph node. FINDINGS Scrofuloderma was present in 12 (80%) patients and solitary gumma in three (20%) patients. One case of scrofuloderma was associated with papulonecrotic tuberculid. Seven (46.6%) patients had pulmonary TB. Diagnosis was based on culture in nine patients (60%). The median CD4 cell count was 262 cells/µL. All patients were cured at the end of treatment (median time 6 months). Three patients presented with immune reconstitution inflammatory syndrome. CONCLUSIONS In this study, CTB associated with HIV infection presented as localised forms or in association with pulmonary TB. In patients with HIV who have subacute and chronic skin lesions, CTB should be considered in differential diagnosis, which may represent a good opportunity for early diagnosis of active TB.

OBJETIVO: Comparar a acurácia do teste amplified Mycobacterium tuberculosis direct (AMTD) com métodos de referência para o diagnóstico laboratorial de tuberculose em pacientes HIV positivos. MÉTODOS: Estudo de acurácia diagnóstica comparando os resultados do teste AMTD com os de cultura em Löwenstein-Jensen (LJ) e de BACTEC Mycobacteria Growth Indicator Tube 960 (sistema BACTEC MGIT 960) em amostras respiratórias analisadas no Laboratório de Bacteriologia e Bioensaios do Instituto de Pesquisa Clínica Evandro Chagas da Fundação Oswaldo Cruz, no Rio de Janeiro (RJ). RESULTADOS: Foram analisadas amostras respiratórias de 118 pacientes, dos quais 88 (74,4%) eram do sexo masculino. A média de idade foi de 36,6 ± 10,6 anos. O complexo M. tuberculosis foi identificado em 31,0%, 29,7% e 27,1% das amostras através do teste AMTD, sistema BACTEC MGIT 960 e LJ, respectivamente. Na comparação com a cultura em LJ, o teste AMTD apresentou sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo de 87,5%, 89,4%, 75,7% e 95,0%, respectivamente, enquanto na comparação com o sistema BACTEC MGIT 960, os valores foram de 88,6%, 92,4%, 83,8% e 94,8%, respectivamente. CONCLUSÕES: O teste AMTD mostrou boa sensibilidade e especificidade na população estudada, possibilitando a detecção laboratorial do complexo M. tuberculosis em espécimes respiratórios paucibacilares.

OBJECTIVE: To compare the accuracy of the amplified Mycobacterium tuberculosis direct (AMTD) test with reference methods for the laboratory diagnosis of tuberculosis in HIV-infected patients. METHODS: This was a study of diagnostic accuracy comparing AMTD test results with those obtained by culture on Löwenstein-Jensen (LJ) medium and by the BACTEC Mycobacteria Growth Indicator Tube 960 (BACTEC MGIT 960) system in respiratory samples analyzed at the Bioassay and Bacteriology Laboratory of the Oswaldo Cruz Foundation Evandro Chagas Clinical Research Institute in the city of Rio de Janeiro, Brazil. RESULTS: We analyzed respiratory samples collected from 118 patients, of whom 88 (74.4%) were male. The mean age was 36.6 ± 10.6 years. Using the AMTD test, the BACTEC MGIT 960 system, and LJ culture, we identified M. tuberculosis complex in 31.0%, 29.7%, and 27.1% of the samples, respectively. In comparison with LJ culture, the AMTD test had a sensitivity, specificity, positive predictive value, and negative predictive value of 87.5%, 89.4%, 75.7%, and 95.0%, respectively, for LJ culture, whereas, in comparison with the BACTEC MGIT 960 system, it showed values of 88.6%, 92.4%, 83.8%, and 94.8%, respectively. CONCLUSIONS: The AMTD test showed good sensitivity and specificity in the population studied, enabling the laboratory detection of M. tuberculosis complex in paucibacillary respiratory specimens.

OBJETIVO: Analisar os desfechos do tratamento da tuberculose e seus preditores. MÉTODOS: Estudo longitudinal de coorte de pacientes com tuberculose tratados entre 2004 e 2006 no Instituto de Pesquisa Evandro Chagas, na cidade do Rio de Janeiro. As razões de risco ajustadas (RRa) dos preditores foram estimadas. RESULTADOS: Foram incluídos 311 pacientes. As taxas de cura, de abandono, de mortalidade e de falha terapêutica foram, respectivamente, 72%, 19%, 6% e 2%. A troca de regime terapêutico por eventos adversos foi necessária em 8%. O alcoolismo (RRa, 0,30), uso do regime estreptomicina+etambutol+ofloxacina (SEO; RRa, 0,32), infecção por HIV sem tratamento antirretroviral (TARV; RRa, 0,36) e o uso do regime rifampicina+isoniazida+pirazinamida+etambutol (RRa, 0,58) reduziram a probabilidade de cura. A faixa etária mais jovem (RRa, 3,84) e o alcoolismo (RRa, 1,76) aumentaram a probabilidade do abandono. Não foi possível determinar as RRa para os demais desfechos devido a suas baixas prevalências. Entretanto, medidas do risco relativo (RR) identificaram os seguintes potenciais preditores do óbito: uso de esquema SEO (RR, 11,43), infecção pelo HIV sem TARV (RR, 9,64), forma clínica disseminada (RR, 9,09), ausência de confirmação bacteriológica (RR, 4,00), diabetes mellitus (RR, 3,94) e comportamento homo/bissexual (RR, 2,97). A baixa renda (RR, 11,70) foi potencial preditor para falha terapêutica, ao passo que infecção pelo HIV com uso de TARV (RR, 2,46) e forma clínica disseminada (RR, 3,57) foram potenciais preditores para troca do esquema por evento adverso. CONCLUSÕES: O esquema SEO deve ser utilizado transitoriamente quando possível. Os dados confirmam a importância de TARV e sugerem a necessidade de seu início precoce.

OBJECTIVE: To analyze tuberculosis treatment outcomes and their predictors. METHODS: This was a retrospective longitudinal cohort study involving tuberculosis patients treated between 2004 and 2006 at the Instituto de Pesquisa Evandro Chagas, in the city of Rio de Janeiro. We estimated adjusted risk ratios (ARRs) for the predictors of treatment outcomes. RESULTS: Among 311 patients evaluated, the rates of cure, treatment abandonment, treatment failure, and mortality were 72%, 19%, 2%, and 6%, respectively. Changes in the treatment regimen due to adverse events occurred in 8%. The factors found to reduce the probability of cure were alcoholism (ARR, 0.30), use of the streptomycin+ethambutol+ofloxacin (SEO) regimen (ARR, 0.32), HIV infection without the use of antiretroviral therapy (ART; ARR, 0.36), and use of the rifampin+isoniazid+pyrazinamide+ethambutol regimen (ARR, 0.58). Being younger and being alcoholic both increased the probability of abandonment (ARR, 3.84 and 1.76, respectively). It was impossible to determine the ARR for the remaining outcomes due to their low prevalence. However, using the relative risk (RR), we identified the following potential predictors of mortality: use of the SEO regimen (RR, 11.43); HIV infection without ART (RR, 9.64); disseminated tuberculosis (RR, 9.09); lack of bacteriological confirmation (RR, 4.00); diabetes mellitus (RR, 3.94); and homosexual/bisexual behavior (RR, 2.97). Low income was a potential predictor of treatment failure (RR, 11.70), whereas disseminated tuberculosis and HIV infection with ART were potential predictors of changes in the regimen due to adverse events (RR, 3.57 and 2.46, respectively). CONCLUSIONS: The SEO regimen should not be used for extended periods. The data confirm the importance of ART and suggest the need to use it early.

Tuberculosis and intestinal parasites affect primarily low social and economic level populations, living clustered in precarious habitational settings. One of the interesting aspects of this interaction is the parasitism influence in cellular response to tuberculosis. In the present study, we evaluated the prevalence of enteroparasitosis in tuberculosis patients, HIV-infected and non HIV infected, and we observed the influence of helminth presence in the response to tuberculin skin test (TST) and tuberculosis clinical outcomes. From 607 clinical records reviewed, 327 individuals met the study inclusion criteria and did not present any exclusion criteria. The prevalence of enteroparasites observed was 19.6%. There was no significant association among TST result and the variables related to the presence of: helminthes, protozoa, and stool test for parasites result (p>0.5). Considering the survival of this cohort, we may observe that there is no significant difference (p>0.05) between the survival curves of parasited and non parasited individuals. Solely the variable "eosinophils" presents a statistically significant association (p<0.001) with helminthes, all other associations are considered not significant. Our findings neither show an association between helminthic infection and a favorable tuberculosis outcome, nor between parasitism and TST response, unlike other in vitro studies. Apparently, experimental data do not correspond to the clinical findings.

This study evaluated the effectiveness of two HAART regimens concomitant to rifampicin based tuberculosis (TB) treatment. Patients with TB/HIV diagnosis followed at the TB program between June 2000 and March 2005 were prospectively evaluated. The different HAART regimens in antiretrovirals (ARV) treatment naïve and ARV experienced patients were compared. The effectiveness of HAART was defined as a VL <80 copies/mL from month 4 to month 10 after TB treatment. One hundred and forty-two patients were included. Among these, 68 (47%) were treatment naïve and 76 (53%) previously exposed. Odds ratio (OR) in naïve patients treated with efavirenz (EFV) based regimen (n=42) compared to ritonavir/saquinavir (RTV/SQV) based regimen (n=26) was 8.0 (CI=1.67-38.35, p=0.008). OR from ARV experienced patients treated with RTV/SQV based regimen compared to EFV was 3.08 (CI=0.65-14.6, p=0.15), although with no statistical significance. Better effectiveness and tolerability were observed in antiretrovirals treatment naïve patients using EFV based regimens. Although not statistically significant, a favorable virologic response and a better tolerability were observed in the ARV experienced patients group who received a RTV/SQV based regimen.

The clinical and epidemiological characteristics, adverse events, treatment adherence and effectiveness of isoniazid chemoprophylaxis were analyzed in a cohort of 138 tuberculosis/HIV-coinfected patients. An open, non-randomized, pragmatic prophylactic trial was conducted on adult patients with a normal chest X-ray and positive tuberculin skin test (> 5 mm) who received isoniazid chemoprophylaxis (300 mg/day) for six months. The mean of follow up was 2.8 years (SD 1.3). Adherence to chemoprophylaxis was 87.7% (121/138). Only one patient presented tuberculosis after the end of chemoprophylaxis, corresponding to 0.3 cases per 100 persons per year. The relative risk of some adverse effects was 4.6 times higher (95% CI: 1.9-11.5) in patients with positive anti-HCV serology (4/9, 44.4%) compared to those with negative serology (12/129, 9.6%) (p = 0.002). This study provides evidence regarding the effectiveness and safety of a short and self-administered isoniazid regimen. We recommend the implementation of this routine by health service practitioners.

We made a retrospective longitudinal study from January 2000 to January 2003 to examine cases of immune reconstitution syndrome (IRS) and its incidence rate in tuberculosis (TB)-human immunodeficiency virus (HIV) co-infected patients. The incidence rate (IR) was calculated using a Poisson regression. The confidence interval (CI) that was stipulated was 95%. IRS occurred in 10/84 HIV and TB-positive patients; nine of them were on highly active anti-retroviral therapy (HAART) during a mean of 61.7 (±59) days following the introduction of antiretrovirals. Lymph-node enlargement was the sole clinical manifestation. CD4 counts were <100 cells/mm³in 50% of the patients, at the time of TB diagnosis. All but two patients were treated with prednisone, and recovered from TB within a mean of 91 days (±30 days). One relapse of TB was observed, but there were no IRS-related deaths. The incidence rate was higher (IR=11.18; CI, 1.41-88.76) in patients that had superficial lymph node enlargement at the moment of TB diagnosis (not associated with TB), extrapulmonary TB (IR=1.97; CI, 0.44-8.79), were antiretroviral naive (IR=1.85; CI, 0.48-7.16), and CD4 counts <100 cells/mm³ (IR=1.50; CI, 0.40-5.59), although with a wide CI. IRS was frequent in our sample, occurred more frequently in HIV-naive patients with lymph-node enlargement and extrapulmonary TB. No cases of new pulmonary lesions or worsening of pulmonary infiltrates were observed.

Hepatitis B virus (HBV) molecular profiles were determined for 44 patients who were infected with human immunodeficiency virus (HIV) type 1 and had antibodies to the hepatitis B core antigen (anti-HBc), with and without other HBV serological markers. In this population, 70% of the patients were under lamivudine treatment as a component of antiretroviral therapy. HBV DNA was detected in 14 (32%) patients. Eight out of 12 (67%) HBsAg positive samples, 3/10 (30%) anti-HBc only samples, and 3/22 (14%) anti-HBs positive samples were HBV DNA positive. HBV DNA loads, measured by real time polymerase chain reaction, were much higher in the HBsAg positive patients (mean, 2.5 × 10(9) copies/ml) than in the negative ones (HBV occult infection; mean, 2.7 × 10(5) copies/ml). Nine out of the 14 HBV DNA positive patients were under lamivudine treatment. Lamivudine resistant mutations in the polymerase gene were detected in only three patients, all of them belonging to the subgroup of five HBsAg positive, HBV DNA positive patients. A low mean HBV load (2.7 × 10(5) copies/ml) and an absence of lamivudine resistant mutations were observed among the cases of HBV occult infection.

OBJECTIVE: Evaluate the incidence of mycobacterial disease and the colonization of the respiratory and gastrointestinal tracts by Mycobacterium avium complex (MAC) bacteria in AIDS patients. METHODS: Inclusion criteria: HIV-positive individuals with at least one CD4+ count < 100 cells/mm³. Exclusion criteria: Mycobacterial disease and MAC prophylaxis. Stool, sputum, and blood cultures were prospectively obtained every month from September, 1997, to December, 1999. The incidence was calculated using Poisson regression. Survival was estimated by the Kaplan Meier method and the Cox proportional hazard model. RESULTS: We followed-up 79 patients during a median period of 428 days. Blood cultures (n = 742) were negative for all mycobacteria. Positive cultures (25 samples) were obtained from non-sterile sites: Stools (19/703 specimens = 2.7%) and sputum (14/742 specimens = 1.9%). MAC was isolated in 7/703 stool samples (1%) and 1/32 sputum specimens (0.1%). The incidence of patient colonization with MAC was 0.09 /year (CI=0.05 - 0.18). CD4 counts in patients colonized with MAC were below 100 cells/mm³ in only 2 out of 8 cases. Restoration of CD4+ counts >100 cells/mm³ (HR = 0.18; CI = 0.05 - 0.70) predicted a lower risk of death (P<0.05) but was not protective for MAC colonization (HR=0.52;CI =0.62 - 4.35, P=0.55). CONCLUSION: The absence of DMAC infection in colonized individuals argues in favor of a HAART protective effect against; DMAC; however, restoration of CD4 counts did not protect patients against MAC colonization.

As doenças oportunistas (DO) são a causa mais comum de morte em pacientes com AIDS. Para acessar a incidência de DO e a sobrevida na imunodeficiência avançada, foram incluídos 79 pacientes com AIDS tratados no Hospital Evandro Chagas (FIOCRUZ) no período de Setembro de 1997 a Dezembro de 1999, com ao menos uma contagem de células CD4 <= 100/mm³. A incidência de DO foi analisada pela regressão de Poisson e a sobrevida pela analise de Kaplan Meier e Cox, considerando um período retrospectivo (anterior à contagem de CD4 <= 100 cels/mm³) e um prospectivo (após a contagem de CD4 <= 100 cels/mm³) e controlando-se características demográficas clínicas e laboratoriais. O intervalo de confiança estipulado foi o de 95%. O período médio de acompanhamento foi de 733 dias (IC = 683 - 782). Durante o estudo, nove (11,4%) pacientes morreram. A sobrevida a partir do diagnóstico de AIDS foi em média de 2589 dias (IC = 2363 - 2816) e da data da contagem de CD4 <= 100 cels/mm³ foi em média de 1376 dias (IC = 1181 - 1572). A incidência de DO foi de 0,51 pp/ano no período pré-CD4 <= 100 cels/mm³ e 0,29 pp/ano no período pós-CD4 <= 100 cels/mm³. Um menor número de DO acumuladas no período pré-CD4 <= 100 cels/mm³ foi associado com taxas de incidência menores no período pós-CD4 <= 100 cels/mm³.O diagnóstico de AIDS baseado em contagem de CD4+ <= 200 cels/mm³ foi associado com menores taxas de incidência durante o período pós-CD4 <= 100 cels/mm³. As contagens basais de células CD4 acima de 50 cel/mm³ (HR = 0,16) foram associadas a um menor risco de morte assim como a restauração da contagem basal acima de 100 cels/mm³ (HR = 0,16). Controlando-se ambas, somente a restauração da contagem basal manteve sua significância estatística (HR = 0,22, p = 0,04) Encontramos uma baixa incidência de DO durante o período pós-CD4 <= 100 cels/mm³ e uma sobrevida longa após CD4 <= 100 cels/mm³. A sobrevida foi significativamente associada com a restauração das contagens de CD4 basais.

Opportunistic diseases (OD) are the most common cause of death in AIDS patients. To access the incidence of OD and survival in advanced immunodeficiency, we included 79 patients with AIDS treated at Hospital Evandro Chagas (FIOCRUZ) from September 1997 to December 1999 with at least one CD4 count <=100 cells/mm³. The incidence of OD was analyzed by Poisson's regression, and survival by Kaplan Meier and Cox analysis, considering a retrospective (before CD4 <=100 cells/mm³) and a prospective (after CD4 <=100 cells/mm³) period, and controlling for demographic, clinical and laboratory characteristics. The confidence interval estipulated was 95%. Mean follow-up period was 733 days (CI = 683-782). During the study 9 (11.4%) patients died. Survival from AIDS diagnosis was a mean of 2589 days (CI = 2363-2816) and from the date of the CD4 count CD4 <=100 cells/mm³ was a mean of 1376 (CI = 1181-1572) days. Incidence of OD was 0.51 pp/y before CD4 <= 100 cells/mm³ and 0.29 pp/y after CD4 <= 100 cells/mm³. A lower number of ODs before CD4 < 100 cells/mm³ was associated with lower incidence rates after CD4 <= 100 cells/mm³. AIDS diagnosis based on CD4+ counts <= 200 cells/mm³ was associated with lower incidence rates after CD4 <= 100 cells/mm³. Baseline CD4 counts above 50 cells/mm³ (HR = 0.13) and restoration of baseline CD4+ counts above 100 cells/mm³ (HR = 0.16) were associated with a lower risk of death. Controling both variables, only restoration of baseline counts was statistically significant (HR = 0.22, p = 0.04). We found a very low incidence of OD and long survival after CD4 < 100 cells/mm³. Survival was significantly associated with restoration of baseline CD4 counts above 100 cells/mm³.

Um estudo caso/controle pareado foi realizado no período compreendido entre janeiro de 1991 e junho de 1992, a fim de determinar a associação de manifestações clínicas e laboratoriais com a DMAC em pacientes com AIDS. Como a DMAC é habitualmente associada com imunodeficiência avançada e portanto também com outras doenças oportunistas, além do número de linfócitos CD4+, casos e controles foram pareados utilizando-se os seguintes critérios: data do diagnóstico de AIDS e terapêutica anti-retroviral, número e gravidade das infecções oportunistas associadas e quando possível, tipo de profilaxia para Pneumocystis carinii, idade e sexo, nesta ordem de importância. Os casos (definidos como pacientes que apresentaram ao menos uma cultura positiva para MAC em sítio normalmente estéril) e controles apresentaram contagem de linfócitos CD4+ abaixo de 50/mm3. Uma prevalência significativamente alta de sinais gerais digestivos e respiratórios, elevação nos níveis de DHL, níveis baixos de hemoglobina e células CD4+ foi observada nos casos comparados aos controles. A elevação da <FONT FACE="Symbol">g</font>GT e fosfatase alcalina observada nos casos foram também observadas nos controles. Em conclusão, a estratégia utilizada por nós para selecionar os controles nos permitiu detectar exames laboratoriais associados à DMAC não observadas em outros pacientes com AIDS e imunossupressão avançada sem DMAC.

A pair matched case/control study was conducted from January 1991 to 30 June 1992 in order to define clinical and laboratory findings associated with DMAC infection in AIDS patients. Since DMAC infection is usually associated with advanced immunodeficiency, and therefore also with other opportunistic illnesses, in addition to the number of CD4+ lymphocytes, cases and controls were matched using the following criteria: date of AIDS diagnosis and antiretroviral therapy, number and severity of associated opportunistic infections and, whenever possible, type of Pneumocystis carinii prophylaxis, age and gender, in this order of relevance. Cases (defined as patients presenting at least one positive culture for MAC at a normally sterile site) and controls presented CD4+ lymphocyte counts below 50 cel/mm3. A significantly higher prevalence of general, digestive and respiratory signs, increased LDH levels, low hemoglobin levels and CD4+ cell counts were recorded for cases when compared to controls. Increases in <FONT FACE="Symbol">g</font>GT and alkaline phosphatase levels seen in cases were also recorded for controls. In conclusion, the strategy we used for selecting controls allowed us to detect laboratory findings associated to DMAC infection not found in other advanced immunossupressed AIDS patients without DMAC.