RESUMO
SETTING: Timely diagnosis of tuberculous meningitis (TBM) in patients with human immunodeficiency virus (HIV) infection remains a challenge. Despite the current scale-up of the Xpert® MTB/RIF assay, other molecular diagnostic tools are necessary, particularly in referral centres in low- and middle-income countries without Xpert testing. OBJECTIVE: To determine the diagnostic performance of nested real-time polymerase chain reaction (nRT-PCR) in HIV-infected TBM patients categorised according to standardised clinical case definitions. DESIGN: Based on clinical, laboratory and imaging data, HIV-infected patients with suspected TBM were prospectively categorised as 'definite TBM', 'probable TBM', 'possible TBM' or 'not TBM'. We evaluated nRT-PCR sensitivity and specificity in diagnosing TBM among definite TBM cases, and among definite + probable TBM cases. RESULTS: Ninety-two participants were enrolled in the study. nRT-PCR sensitivity for definite TBM (n = 8) was 100% (95%CI 67-100) and 86% (95%CI 60-96) for both definite and probable TBM (n = 6). Assuming that 'not TBM' patients (n = 74) were true-negatives, nRT-PCR specificity was 100% (95%CI 95-100). The possible TBM group (n = 4) had no nRT-PCR positives. CONCLUSIONS: The nRT-PCR is a useful rule-in test for HIV-infected patients with TBM according to international consensus case definitions. As nRT-PCR cannot exclude TBM, studies comparing and combining nRT-PCR with other assays are necessary for a rule-out test
Assuntos
Humanos , Tuberculose Meníngea/diagnóstico , Infecções por HIV , Reação em Cadeia da PolimeraseRESUMO
SETTING: Timely diagnosis of tuberculous meningitis (TBM) in patients with human immunodeficiency virus (HIV) infection remains a challenge. Despite the current scale-up of the Xpert® MTB/RIF assay, other molecular diagnostic tools are necessary, particularly in referral centres in low- and middle-income countries without Xpert testing. OBJECTIVE: To determine the diagnostic performance of nested real-time polymerase chain reaction (nRT-PCR) in HIV-infected TBM patients categorised according to standardised clinical case definitions. DESIGN: Based on clinical, laboratory and imaging data, HIV-infected patients with suspected TBM were prospectively categorised as 'definite TBM', 'probable TBM', 'possible TBM' or 'not TBM'. We evaluated nRT-PCR sensitivity and specificity in diagnosing TBM among definite TBM cases, and among definite + probable TBM cases. RESULTS: Ninety-two participants were enrolled in the study. nRT-PCR sensitivity for definite TBM (n = 8) was 100% (95%CI 67-100) and 86% (95%CI 60-96) for both definite and probable TBM (n = 6). Assuming that 'not TBM' patients (n = 74) were true-negatives, nRT-PCR specificity was 100% (95%CI 95-100). The possible TBM group (n = 4) had no nRT-PCR positives. CONCLUSIONS: The nRT-PCR is a useful rule-in test for HIV-infected patients with TBM according to international consensus case definitions. As nRT-PCR cannot exclude TBM, studies comparing and combining nRT-PCR with other assays are necessary for a rule-out test.
Assuntos
Infecções por HIV/epidemiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Tuberculose Meníngea/diagnóstico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Depending on the presence of mutations that determine isoniazid (INH) susceptibility (katG and inhA), Mycobacterium tuberculosis may be susceptible to high doses of INH or ethionamide (ETH). OBJECTIVE: To describe the INH resistance profile and association of katG mutation with previous INH treatment and level of drug resistance based on rapid molecular drug susceptibility testing (DST) in southern Brazil and central Mozambique. DESIGN: Descriptive study of 311 isolates from Ribeirão Preto, São Paulo, Brazil (2011-2014) and 155 isolates from Beira, Mozambique (2014-2015). Drug resistance patterns and specific gene mutations were determined using GenoType(®) MTBDRplus. RESULTS: katG gene mutations were detected in 12/22 (54.5%) Brazilian and 32/38 (84.2%) Mozambican isolates. inhA mutations were observed in 9/22 (40.9%) isolates in Brazil and in 4/38 (10.5%) in Mozambique. Both katG and inhA mutations were detected in respectively 1/22 (5%) and 2/38 (5.2%). The difference in the frequency of katG mutations in Brazil and Mozambique was statistically significant (P = 0.04). katG mutations were present in 68.8% (33/48) of patients previously treated with INH and 31.2% (15/48) of patients without previous INH. This difference was not statistically significant (P = 0.223). CONCLUSION: INH mutations varied geographically; molecular DST can be used to guide and accelerate decision making in the use of ETH or high doses of INH.
Assuntos
Antituberculosos/uso terapêutico , Proteínas de Bactérias/genética , Catalase/genética , Análise Mutacional de DNA , Farmacorresistência Bacteriana Múltipla/genética , Etionamida/uso terapêutico , Isoniazida/uso terapêutico , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Oxirredutases/genética , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Brasil/epidemiologia , Tomada de Decisão Clínica , Humanos , Testes de Sensibilidade Microbiana , Moçambique/epidemiologia , Mycobacterium tuberculosis/genética , Seleção de Pacientes , Valor Preditivo dos Testes , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologiaRESUMO
OBJECTIVE: To study the impact of chemoprophylaxis for tuberculosis on the survival of HIV-infected patients with a positive tuberculin skin test. DESIGN: Prospective observational cohort study. SETTING: Outpatient clinic of a university hospital, in Rio de Janeiro, Brazil. PATIENTS: Two-hundred and ninety-seven patients with a positive tuberculin skin test (reaction > or = 5mm) who were admitted to the cohort between January 1991 and December 1994. Follow-up ended on September 30, 1998. INTERVENTION: The use of chemoprophylaxis for tuberculosis. MAIN OUTCOME MEASURES: Death was the primary outcome variable. The occurrence of tuberculosis was studied as a secondary outcome. Cox regression models were used in these analyses. RESULTS: The median follow-up time was 43.6 months. Chemoprophylaxis was used by 128 (43%) of the patients. The use of chemoprophylaxis was associated with a reduction in risk for tuberculosis (hazard ratio, 0.38; 95% confidence interval, 0.14-1.04; P = 0.05). In a regression model adjusted for baseline CD4 cell count, chemoprophylaxis was associated with longer survival (hazard ratio, 0.24; 95% confidence interval, 0.09-0.65; P = 0.002). CONCLUSIONS: Anti-tuberculosis chemoprophylaxis was associated with a substantially prolonged survival among purified protein derivative-positive HIV-infected patients in Brazil. These data have important implications for the clinical care of patients with HIV infection in areas of the world with a high prevalence of Mycobacterium tuberculosis infection.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antituberculosos/uso terapêutico , Infecções por HIV/complicações , Tuberculose Pulmonar/mortalidade , Tuberculose Pulmonar/prevenção & controle , Adulto , Brasil/epidemiologia , Quimioprevenção , Estudos de Coortes , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Análise de Sobrevida , Teste TuberculínicoRESUMO
BACKGROUND: Symptoms associated with HIV infection are common among HIV seroconverters, but the acute retroviral syndrome (ARS) is a diagnostic challenge because of the absence of a sensitive and specific case definition. We conducted an analysis of HIV seroconverters in Projeto Praça Onze, a HIVNET HIV seroincidence study among homosexual men in Rio de Janeiro. METHODS: Information from study subjects enrolled in Projeto Praça Onze who were documented HIV seroconverters were compared with nonseroconverters. At each semiannual study visit, participants were asked about HIV seroconversion symptoms and sexually transmitted diseases (STDs) during the preceding 6 months. All information was collected before the laboratory evaluation. A classification tree analysis was used to identify an ARS case definition, first using clinical information and then after including risk factor data for seroconversion in our cohort. RESULTS: As of July 1998, 674 volunteers were enrolled and 34 of these seroconverted; information was available for 33 of these. Among the seroconverters, 11 (34%) denied any symptoms, and 22 (66%) reported one or more symptoms, the most common of which were fever (25% of seroconverters versus 7% of nonseroconverters; p <.01), night sweats (9% versus 2%, respectively; p =.05), incapacitating disease (ID) for >/=3 days (27% versus 7%, respectively; p <.001), and weight loss of >/=2 kg (21% versus 9%, respectively; p =.05). STDs were more common in seroconverters (gonorrhea: 9% versus 1%, respectively; p <.01 and condyloma: 9% versus 3%, respectively; p =. 08). The first case definition was ID for >3 days, fever, pharyngitis, and myalgia (seroconverters, 3 of 32, versus nonseroconverters, 2 of 640). The second case definition was was ID for >3 days, anti-core hepatitis b-positive, and age <21 years (seroconverters: 6 of 32 versus nonseroconverters 4 of 640). The sensitivity and specificity for the first and second case definitions were: 9.4%, 99.4%, and 18.8%, 99.8%, respectively. CONCLUSIONS: Among HIV seroconverters, symptoms consistent with ARS were common. We were unable to identify a sensitive case definition that could be used as a screening tool. Although the clinical case definition was not validated, the specificity of our case definitions was high, suggesting that subjects within this HIV risk group who fulfill the case definition should be tested for HIV.
Assuntos
Infecções por HIV/diagnóstico , Soropositividade para HIV/diagnóstico , Homossexualidade , Adolescente , Adulto , Análise de Variância , Brasil/epidemiologia , Infecções por HIV/complicações , Soropositividade para HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Sexualmente Transmissíveis/diagnóstico , SíndromeRESUMO
BACKGROUND: The effect of antiretroviral therapy on seminal HIV shedding in the community remains unknown. OBJECTIVE: To evaluate the effect of antiretroviral therapy on HIV shedding in semen. DESIGN: Prospective cohort study. SETTING: University hospital in Rio de Janeiro, Brazil. PATIENTS: 93 HIV-infected men. INTERVENTION: Antiretroviral therapy as prescribed by each patient's physician. MEASUREMENT: HIV RNA in semen and blood plasma before and after introduction of therapy. RESULTS: At baseline, HIV RNA was detected in 69 semen samples (74%) and 89 blood samples (96%). Six months after introduction of therapy, HIV RNA was detected in 29 semen samples (33%) and 33 blood samples (38%). The mean reduction in levels of HIV RNA in semen at 6 months was 1.65 log10 units. CONCLUSIONS: Antiretroviral therapy reduces shedding of HIV in semen, which probably in tum reduces HIV transmissibility. However, a substantial proportion of patients may still be infectious and may have drug-resistant strains of the virus.
Assuntos
Fármacos Anti-HIV/farmacologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Sêmen/virologia , Eliminação de Partículas Virais/efeitos dos fármacos , Adulto , Quimioterapia Combinada , HIV/genética , HIV/isolamento & purificação , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , RNA Viral/análise , RNA Viral/sangue , Estatísticas não Paramétricas , Carga ViralRESUMO
The study of interventions to prevent HIV transmission requires access to populations with a high rate of HIV transmission. We estimated HIV incidence among heterosexual males and females who were seen at an HIV testing site in Rio de Janeiro, Brazil. Stored sera from individuals who visited the site between March and December 1998 were analyzed using the sensitive/less sensitive (S/LS) assay and a chart abstraction was performed. During the study period, 6353 serum samples were tested. Of those tested, 1203 were found to be HIV-seropositive or indeterminate, of which 1050 (87%) remained available for further testing. In addition, 84 serum samples, representing 63 adults, were found to produce results suggesting early HIV infection. Of these, 14 were heterosexual and female (median age, 38 years), and 19 were heterosexual and male (median age, 25 years). The estimated HIV seroincidence was 1.9 (95% confidence limits (CL), 0.9%-3.9%) and 2.8 (95% CL, 1.4%-5.3%) per 100 person-years among heterosexual women and men, respectively. A survey on willingness to participate in future placebo-controlled HIV vaccine trials in this population indicated that 54.5% and 53.9% of heterosexual women and men, respectively, indicated that they would definitely be willing to participate. We have identified a heterosexual population in Rio de Janeiro with a high rate of HIV transmission willing to participate in placebo-controlled vaccine trials. This study demonstrates the usefulness of the newly described S/LS assay, which allows one to estimate HIV incidence from single serum specimens.
Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Heterossexualidade , Assunção de Riscos , Saúde da População Urbana , Adulto , Brasil/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Anticorpos Anti-HIV/sangue , Infecções por HIV/transmissão , Soronegatividade para HIV , Soropositividade para HIV/epidemiologia , Humanos , Masculino , Sensibilidade e EspecificidadeRESUMO
HIV-1 serotype B-Br (GWGR) is rare in the United States but predominates in Brazil. Differences in prognosis for patients infected with serotype B-Br or serotype B (GPGR) have not been addressed previously. In this prospective cohort study, we compared the rate of disease progression between patients infected with the HIV-1 V3 serotype B or B-Br in Brazil. Progression to AIDS or death was studied by the Kaplan-Meier and Cox proportional hazard methods. Among 445 HIV-infected patients who were tested with a specific enzyme immune assay, 204 (46%) had serotype B-Br infection and 127 (28%) had serotype B infection. Both groups were similar with regard to baseline CD4+ cell count, serum HIV RNA viral load, initial clinical stage, and the proportions who were treated with antiretroviral drugs. Patients with serotype B infection were significantly younger (p = 0.005) and tended to report homosexual behavior more frequently (p = 0.08). Mean follow-up was 30 +/- 13.5 months. During the study period, 41 (32%) patients infected with serotype B and 44 (22%) infected with serotype B-Br developed AIDS (p = 0.03). In a regression model adjusted for age and risk factor for HIV infection, progression to AIDS was faster in patients infected with serotype B (hazard ratio [HR] 1.59; 95% CI, 1.03-2.43; p = 0.03). A similar trend was observed in a model that considered AIDS or death as the outcome (HR, 1.43; 95% CI, 0.95-2.0; p = 0.09). These results suggest that patients infected with closely related HIV-1 serotypes may differ in the rate of progression to AIDS and indicate that serotype should be taken into account in HIV vaccine studies in Brazil.
Assuntos
Síndrome da Imunodeficiência Adquirida/virologia , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/fisiologia , Fragmentos de Peptídeos/imunologia , Síndrome da Imunodeficiência Adquirida/fisiopatologia , Brasil , Estudos de Coortes , Progressão da Doença , Feminino , Infecções por HIV/mortalidade , HIV-1/genética , HIV-1/imunologia , Humanos , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , SorotipagemRESUMO
Evaluation of HIV vaccines requires high-risk individuals willing to participate in a vaccine trial. We investigated the willingness to participate in HIV vaccine trials of initially HIV-seronegative homosexual men enrolled in an HIV seroincidence cohort study. Of 815 initially HIV-seronegative participants, 569 (69.8%) reported willingness to participate in an HIV vaccine trial. Altruism was the primary reason given for wanting to participate. Fear of HIV infection from the study's immunizations and a vaccine-induced positive HIV test result were the main reasons for not wanting to participate. Of the 34 study subjects who eventually had HIV seroconversion, 29 (85%) had indicated a willingness to participate. In a univariate analysis, factors associated with willingness to participate included HIV seroconversion during follow-up (odds ratio [OR]. 2.6; p =.04), low educational level (OR, 1.6; p =.005), low family income (p =.02), and exchanging sex for housing, food, or clothing (OR 6.1; p =.005). Students were less likely to be willing to participate in a trial (OR, 0.7; p = .03), as well as those who reported sex at the first encounter (OR, 0.7; p = .05). In a multivariate analysis, low education level, infection with Condyloma, and exchanging sex for housing, food, or clothing were positively associated with willingness to participate, whereas being a student and reporting sex at first encounter were negatively associated. In general, factors indicative of high-risk of HIV infection were associated with a higher willingness. These data demonstrate that this high-risk homosexual male cohort has a high willingness to participate in HIV vaccine trials.
Assuntos
Vacinas contra a AIDS , Ensaios Clínicos como Assunto , Conhecimentos, Atitudes e Prática em Saúde , Homossexualidade Masculina , Motivação , Adulto , Brasil , Infecções por HIV/prevenção & controle , Soronegatividade para HIV , Homossexualidade Masculina/psicologia , Humanos , Masculino , Comportamento Sexual , Inquéritos e QuestionáriosRESUMO
Argentine hemorrhagic fever (AHF) is a potentially lethal infection in Argentina. The case-fatality ratio is >15%, but treatment reduces the mortality rate to <1%. Diagnosis is based on clinical and laboratory criteria, but no case definition has been validated. A chart review was conducted for patients hospitalized with suspected AHF. Individuals with a fourfold rise in antibody titer were classified as cases. The combination of a platelet count of <100,000/mm3 and a white blood cell (WBC) count of <2,500/mm3 had a sensitivity and specificity of 87% and 88%, respectively, thus suggesting that the use of these criteria in a case definition would be helpful for epidemiological studies of AHF. The combination of a platelet count of <100,000/mm3 and a WBC count of <4,000/mm3 had a sensitivity of 100% and a specificity of 71%; the use of these criteria in a case definition should be helpful for screening patients for therapy with immune plasma in the region where AHF is endemic.