Magda Maruza

Risk factors for default from tuberculosis treatment in HIV-infected individuals in the state of Pernambuco, Brazil: a prospective cohort study

BackgroundConcomitant treatment of Human Immunodeficiency Virus (HIV) infection and tuberculosis (TB) presents a series of challenges for treatment compliance for both providers and patients. We carried out this study to identify risk factors for default from TB treatment in people living with HIV.MethodsWe conducted a cohort study to monitor HIV/TB co-infected subjects in Pernambuco, Brazil, on a monthly basis, until completion or default of treatment for TB. Logistic regression was used to calculate crude and adjusted odds ratios, 95% confidence intervals and P-values.ResultsFrom a cohort of 2310 HIV subjects, 390 individuals (16.9%) who had started treatment after a diagnosis of TB were selected, and data on 273 individuals who completed or defaulted on treatment for TB were analyzed. The default rate was 21.7% and the following risk factors were identified: male gender, smoking and CD4 T-cell count less than 200 cells/mm3. Age over 29 years, complete or incomplete secondary or university education and the use of highly active antiretroviral therapy (HAART) were identified as protective factors for the outcome.ConclusionThe results point to the need for more specific actions, aiming to reduce the default from TB treatment in males, younger adults with low education, smokers and people with CD4 T-cell counts < 200 cells/mm3. Default was less likely to occur in patients under HAART, reinforcing the strategy of early initiation of HAART in individuals with TB.

[Treatment outcome and laboratory confirmation of tuberculosis diagnosis in patients with HIV/AIDS in Recife, Brazil].

OBJECTIVE To compare the frequency of unfavorable outcome (death or default and treatment failure) between tuberculosis (TB)/HIV co-infected patients treated for TB after laboratory confirmation of the diagnosis and TB/HIV co-infected patients who were so treated without diagnostic confirmation. METHODS A retrospective cohort of TB/HIV co-infected patients who started TB treatment between July of 2002 and June of 2004 at an HIV/AIDS referral center in Recife, Brazil. The main exposure variable, laboratory confirmation of TB, was adjusted for three different sets of variables: sociodemographic variables; HIV/AIDS-related variables; and TB-related variables. In order to evaluate the statistical significance of the results, we calculated odds ratios, with 95% confidence intervals, and p values (from chi-square tests and likelihood ratio tests). RESULTS A total of 262 patients were studied. No association was found between laboratory confirmation of the diagnosis of TB at treatment outset and unfavorable outcome, even after adjustment for confounders. In the final multiple logistic regression model, the following variables remained: the presence of other opportunistic diseases; CD4 lymphocyte count below 50 cells/mm(3); viral load between 10,000 and 100,000 copies/mL; dyspnea; the disseminated form of TB; and change in the TB treatment regimen due to adverse reactions or intolerance. CONCLUSIONS Our results suggest that TB treatment in TB/HIV co-infected patients without etiologic confirmation of TB, at the discretion of experienced physicians in referral centers, did not increase the risk of unfavorable outcomes. In addition, it allowed the identification of groups that should be closely monitored due to a greater risk of unfavorable outcomes.

Incidence and risk factors for tuberculosis in people living with HIV: cohort from HIV referral health centers in Recife, Brazil.

Objective To identify the incidence of and risk factors for tuberculosis in people living with HIV (PLHIV). Design Observational, prospective cohort study. Methods A total of 2069 HIV-infected patients was observed between July 2007 and December 2010. The Kaplan-Meier method was used to estimate the probability of survival free of tuberculosis, and Cox regression analysis to identify risk factors associated with the development of tuberculosis. Results Survival free of tuberculosis (TB) was 91%. The incidence rate of tuberculosis was 2.8 per 100 persons/years. Incidence of tuberculosis was higher when subjects had CD4 cell count <200 cells/mm3; were not on antiretroviral therapy; in those who had, a body mass index <18.5 kg/m2, anemia (or were not tested for it), were illiterate or referred previous tuberculosis treatment at entry into the cohort. Those not treated for latent TB infection had a much higher risk (HR = 7.9) of tuberculosis than those with a negative tuberculin skin test (TST). Having a TST≥5 mm but not being treated for latent TB infection increased the risk of incident tuberculosis even in those with a history of previous tuberculosis. Conclusions Preventive actions to reduce the risk of TB in people living with HIV should include an appropriate HAART and treatment for latent TB infection in those with TST≥5 mm. The actions towards enabling rigorous implementation of treatment of latent TB infection and targeting of PLHIV drug users both at the individual and in public health level can reduce substantially the incidence of TB in PLHIV.

Survival of HIV-infected patients after starting tuberculosis treatment: a prospective cohort study.

OBJECTIVES To estimate the probability of survival and to evaluate risk factors for death in a cohort of persons living with human immunodeficiency virus (PLHIV) who had started tuberculosis (TB) treatment. METHODS A prospective cohort study was conducted between June 2007 and December 2009 with HIV-infected patients who had started anti-tuberculosis treatment in the State of Pernambuco, Brazil. Survival data were analysed using the Kaplan-Meier estimator, the log-rank test and the Cox model. Hazard ratios and their respective 95%CIs were estimated. RESULTS Of a cohort of 2310 HIV-positive individuals, 333 patients who had commenced treatment for TB were analysed. The mortality rate was 5.25 per 10,000 person-years (95%CI 4.15-6.63). The probability of survival at 30 months was 74%. Risk factors for death in the study population were being female, age ≥30 years, having anaemia, not using highly active antiretroviral therapy (HAART) during treatment for TB and disseminated TB. Protective factors for death were a CD4 lymphocyte count >200 cells/mm(3) and treatment for TB having started in an out-patient clinic. CONCLUSIONS The use of HAART can prevent deaths among HIV-TB patients, corroborating the efficacy of starting HAART early in individuals with TB.

Prevalence of human papillomavirus infection, distribution of viral types and risk factors in cervical samples from human immunodeficiency virus-positive women attending three human immunodeficiency virus-acquired immune deficiency syndrome reference centres in northeastern Brazil.

Human immunodeficiency virus (HIV)-positive patients have a greater prevalence of coinfection with human papillomavirus (HPV) is of high oncogenic risk. Indeed, the presence of the virus favours intraepithelial squamous cell lesion progression and may induce cancer. The aim of this study was to evaluate the prevalence of HPV infection, distribution of HPV types and risk factors among HIV-positive patients. Cervical samples from 450 HIV-positive patients were analysed with regard to oncotic cytology, colposcopy and HPV presence and type by means of polymerase chain reaction and sequencing. The results were analysed by comparing demographic data and data relating to HPV and HIV infection. The prevalence of HPV was 47.5%. Among the HPV-positive samples, 59% included viral types of high oncogenic risk. Multivariate analysis showed an association between HPV infection and the presence of cytological alterations (p = 0.003), age greater than or equal to 35 years (p = 0.002), number of partners greater than three (p = 0.002), CD4+ lymphocyte count < 200/mm3 (p = 0.041) and alcohol abuse (p = 0.004). Although high-risk HPV was present in the majority of the lesions studied, the low frequency of HPV 16 (3.3%), low occurrence of cervical lesions and preserved immunological state in most of the HIV-positive patients were factors that may explain the low occurrence of precancerous cervical lesions in this population.

Prevalence and socioeconomic factors associated with smoking in people living with HIV by sex, in Recife, Brazil

INTRODUCTION Smoking is the leading cause of preventable death in the world. The prevalence of smoking is higher in people infected with HIV than in the general population. Although it is biologically plausible that smoking increases the morbidity and mortality of people living with HIV/AIDS, few studies in developing countries have analyzed the determinants and consequences of smoking in HIV infected people. OBJECTIVE To estimate the prevalence of smoking and identify the socioeconomic factors associated with smoking and smoking cessation in patients with HIV by sex. METHODS A cross-sectional study was conducted with baseline data, obtained from an ongoing prospective cohort study of patients with HIV attending two referral centers in Recife, Northeast Region of Brazil, between July 2007 and October 2009. RESULTS The prevalence of current smoking was 28.9%. For both sexes, smoking was independently associated with heavy alcohol drinking and marijuana use. Among women, smoking was associated with living alone, not being married and illiteracy; and among men, being 40 years or older, low income and using crack. Compared with ex-smokers, current smokers were younger and more likely to be unmarried, heavy drinkers and marijuana users. CONCLUSIONS It is important to incorporate smoking cessation interventions for the treatment of heavy alcohol drinkers and marijuana users with HIV/AIDS, which may increase life expectancy and quality of life, as smoking is related to risk of death, relapse of tuberculosis, and non communicable diseases.

Associated factors for treatment delay in pulmonary tuberculosis in HIV-infected individuals: a nested case-control study.

BackgroundThe delay in initiating treatment for tuberculosis (TB) in HIV-infected individuals may lead to the development of a more severe form of the disease, with higher rates of morbidity, mortality and transmissibility. The aim of the present study was to estimate the time interval between the onset of symptoms and initiating treatment for TB in HIV-infected individuals, and to identify the factors associated to this delay.MethodsA nested case-control study was undertaken within a cohort of HIV-infected individuals, attended at two HIV referral centers, in the state of Pernambuco, Brazil. Delay in initiating treatment for TB was defined as the period of time, in days, which was greater than the median value between the onset of cough and initiating treatment for TB. The study analyzed biological, clinical, socioeconomic, and lifestyle factors as well as those related to HIV and TB infection, potentially associated to delay. The odds ratios were estimated with the respective confidence intervals and p-values.ResultsFrom a cohort of 2365 HIV-infected adults, 274 presented pulmonary TB and of these, 242 participated in the study. Patients were already attending 2 health services at the time they developed a cough (period range: 1 – 552 days), with a median value of 41 days. Factors associated to delay were: systemic symptoms asthenia, chest pain, use of illicit drugs and sputum smear-negative.ConclusionThe present study indirectly showed the difficulty of diagnosing TB in HIV-infected individuals and indicated the need for a better assessment of asthenia and chest pain as factors that may be present in co-infected patients. It is also necessary to discuss the role played by negative sputum smear results in diagnosing TB/HIV co-infection as well as the need to assess the best approach for drug users with TB/HIV.

Hepatotoxicity during Treatment for Tuberculosis in People Living with HIV/AIDS.

Hepatotoxicity is frequently reported as an adverse reaction during the treatment of tuberculosis. The aim of this study was to determine the incidence of hepatotoxicity and to identify predictive factors for developing hepatotoxicity after people living with HIV/AIDS (PLWHA) start treatment for tuberculosis. This was a prospective cohort study with PLWHA who were monitored during the first 60 days of tuberculosis treatment in Pernambuco, Brazil. Hepatotoxicity was considered increased levels of aminotransferase, namely those that rose to three times higher than the level before initiating tuberculosis treatment, these levels being associated with symptoms of hepatitis. We conducted a multivariate logistic regression analysis and the magnitude of the associations was expressed by the odds ratio with a confidence interval of 95%. Hepatotoxicity was observed in 53 (30.6%) of the 173 patients who started tuberculosis treatment. The final multivariate logistic regression model demonstrated that the use of fluconazole, malnutrition and the subject being classified as a phenotypically slow acetylator increased the risk of hepatotoxicity significantly. The incidence of hepatotoxicity during treatment for tuberculosis in PLWHA was high. Those classified as phenotypically slow acetylators and as malnourished should be targeted for specific care to reduce the risk of hepatotoxicity during treatment for tuberculosis. The use of fluconazole should be avoided during tuberculosis treatment in PLWHA.

ASSOCIATION BETWEEN SMOKING, CRACK COCAINE ABUSE AND THE DISCONTINUATION OF COMBINATION ANTIRETROVIRAL THERAPY IN RECIFE, PERNAMBUCO, BRAZIL

Despite the effectiveness of combination antiretroviral therapy in the treatment of people living with HIV/AIDS (PLWHA), nonadherence to medication has become a major threat to its effectiveness. This study aimed to estimate the prevalence of self-reported irregular use of antiretroviral therapy and the factors associated with such an irregularity in PLWHA. A cross-sectional study of PLWHA who attended two referral centers in the city of Recife, in Northeastern Brazil, between June 2007 and October 2009 was carried out. The study analyzed socioeconomic factors, social service support and personal habits associated with nonadherence to antiretroviral therapy, adjusted by multivariable logistic regression analysis. The prevalence of PLWHA who reported irregular use of combination antiretroviral therapy (cART) was 25.7%. In the final multivariate model, the irregular use of cART was associated with the following variables: being aged less than 40 years (OR = 1.66, 95%-CI: 1.29-2.13), current smokers (OR = 1.76, 95%-CI: 1.31-2.37) or former smokers (OR = 1.43, 95%-CI: 1.05-1.95), and crack cocaine users (OR = 2.79, 95%-CI: 1.24-6.32). Special measures should be directed towards each of the following groups: individuals aged less than 40 years, smokers, former smokers and crack cocaine users. Measures for giving up smoking and crack cocaine should be incorporated into HIV-control programs in order to promote greater adherence to antiretroviral drugs and thus improve the quality of life and prolong life expectancy.

Evaluation of four molecular methods for the diagnosis of tuberculosis in pulmonary and blood samples from immunocompromised patients

The present study analysed the concordance among four different molecular diagnostic methods for tuberculosis (TB) in pulmonary and blood samples from immunocompromised patients. A total of 165 blood and 194 sputum samples were collected from 181 human immunodeficiency virus (HIV)-infected patients with upper respiratory complaints, regardless of suspicious for TB. The samples were submitted for smear microscopy, culture and molecular tests: a laboratory-developed conventional polymerase chain reaction (PCR) and real-time quantitative PCR (qPCR) and the Gen-Probe and Detect-TB Ampligenix kits. The samples were handled blindly by all the technicians involved, from sample processing to results analysis. For sputum, the sensitivity and specificity were 100% and 96.7% for qPCR, 81.8% and 94.5% for Gen-Probe and 100% and 66.3% for Detect-TB, respectively. qPCR presented the best concordance with sputum culture [kappa (k) = 0.864)], followed by Gen-Probe (k = 0.682). For blood samples, qPCR showed 100% sensitivity and 92.3% specificity, with a substantial correlation with sputum culture (k = 0.754) and with the qPCR results obtained from sputum of the corresponding patient (k = 0.630). Conventional PCR demonstrated the worst results for sputa and blood, with a sensitivity of 100% vs. 88.9% and a specificity of 46.3% vs. 32%, respectively. Commercial or laboratory-developed molecular assays can overcome the difficulties in the diagnosis of TB in paucibacillary patients using conventional methods available in most laboratories.