Cristina B. Hofer

Pregnancy outcome in women infected with HIV-1 receiving combination antiretroviral therapy before versus after conception

Objective: The potential adverse effects of antiretroviral drugs during pregnancy are discrepant and few studies, mostly from Europe, have provided information about pregnancy outcomes of those already on treatment at conception. The aim of this study was to investigate the impact of antiretrovirals (ARVs) on pregnancy outcome according to the timing of treatment initiation in a cohort of pregnant women from Brazil infected with HIV. Methods: A prospective cohort of 696 pregnant women followed up in one single centre between 1996 and 2006 was studied. Patients who had ARV treatment before pregnancy were compared with those treated after the first trimester. The outcomes evaluated were preterm delivery (PTD) (<37 weeks), severe PTD (<34 weeks), low birth weight (LBW) (<2500 g) and very LBW (<1500 g). Results: Patients who were using ARVs pre-conception had higher rates of LBW (33.3% vs 16.5%; p<0.001) and a similar trend for PTD (26.3% vs 17.7%; p = 0.09). Stratification by type of therapy (dual vs highly active antiretroviral therapy (HAART)) according to timing of initiation of ARVs showed that patients who use HAART pre-conception have a higher rate of PTD (20.2% vs 10.2%; p = 0.03) and LBW (24.2% vs 10.2%; p = 0.002). After adjusting for several factors, HAART used pre-conception was associated with an increased risk for PTD (AOR 5.0; 95% CI 1.5 to 17.0; p = 0.009) and LBW (OR 3.6; 95% CI 1.7 to 7.7; p = 0.001). Conclusions: We identified an increased risk for LBW and PTD in patients who had HAART prior to pregnancy.

Effectiveness of antiretroviral therapy among patients who attend public HIV clinics in Rio de Janeiro, Brazil.

Objective:Brazil provides antiretroviral therapy (ART) to HIV-infected persons free of charge. The objective of this study was to investigate factors associated with ART failure in patients receiving free ART in public clinics in Brazil. Methods:This is a cross-sectional study of adults taking ART for 6 to 24 months in 5 public clinics in Rio de Janeiro. Patients were interviewed and their charts were reviewed. The following definitions of response to therapy at 6 months were used: virologic responders (VR), ≥1 log reduction in plasma viral load (VL); immunologic responders (IR), increase of ≥50 CD4+ cells/mL; complete responders (CR), both VR and IR; and nonresponders (NR), neither VR nor IR. Results:Of 211 patients enrolled, 173 (82%) were VR, IR, or CR and 38 (18%) were NR. Of the responders, 28 (13%) were IR, 32 (15%) were VR, and 113 (53%) were CR. In multivariate analysis, factors associated with NR were less than 80% adherence (OR = 8.6; 95% CI, 2.9–25.7), baseline CD4+ count (OR = 0.5 per 50 cells/mL; 95% CI, 0.2–1.1), interval between starting ART and first VL/CD4+ testing (OR = 1.4 for each month; 95% CI, 1.1–1.8), opportunistic disease after starting ART (OR = 6.8; 95% CI, 1.4–34.0), inability to read prescription (OR = 3.9; 95% CI, 1.4–10.9), not believing physician is knowledgeable about HIV (OR = 4.0; 95% CI, 1.1–15.0), not having a friend with HIV (OR = 6.1; 95% CI, 1.7–21.8), believing ART will make him/her ill (OR = 5.6; 95% CI, 1.7–18.8), and believing ART will delay HIV progression (OR = 0.001; 95% CI, 0.0–0.2). Conclusion:The proportion of patients responding to ART in Brazil was similar to reports from developed countries, suggesting that ART can be used successfully in developing countries. Variables related to adherence, knowledge, and perceptions about ART were associated with a lack of response to ART. These findings have important implications for developing nations that are considering increased access to ART.

Sorovares de Listeria monocytogenes e espécies relacionadas, isoladas de material clínico humano

Using phenotype techniques, characterization was realized of species and serovars of 255 strains of Listeria isolated from human material: 220-86.3% were from patients with possible invasive disease, while 35-13.7% were from colonized healthy individuals. The strains were collected in several regions of Brazil from 1969-2000. In individuals aged 0-10 or 41-60 years old Listeria monocytogenes was isolated more often in cerebral spinal fluid than in blood cultures, including samples from renal transplant recipients. All Listeria monocytogenes serovars were detected in blood culture strains. The predominant serovars characterized were 4b (154-60.3%) and 1/2a (74-29%). In this study, Listeria monocytogenes causing invasive diseases, such as meningitis or septicemia, or colonizing individuals, were identified. Consequently further studies focusing on clinical and pathological as well as epidemiological issues, including risk factors associated with foodborne transmission should be pursued.

RFLP patterns and risk factors for recent tuberculosis transmission among hospitalized tuberculosis patients in Rio de Janeiro, Brazil

Isolates of Mycobacterium tuberculosis from 120 tuberculosis patients seen in the 12 months ending September 1994 at 2 tertiary-care centres in Rio de Janeiro were characterized by IS6110 restriction fragment length polymorphism (RFLP) analysis. Ninety-seven patients (81%) had isolates with unique RFLP patterns, while 23 patients (19%) had isolates that belonged to 11 different RFLP cluster patterns. The strains from the latter patients were distributed among 1 group of 3 patients and 10 groups of 2 patients each. The cluster-pattern strains were not associated with gender, age, HIV infection, type of residence, living in shelter, homelessness or previous history of tuberculosis. However, clustering was strongly associated with multidrug resistance (P = 0.006). These data suggest that recent exogenous transmission may be important for the development of new cases of multidrug-resistant disease in patients attending tertiary-care centres in Rio de Janeiro, Brazil.

Gender and survival after AIDS in Rio de Janeiro Brazil.

The relation between gender and survival after a diagnosis of AIDS was studied in a cohort of patients with HIV infection in Rio de Janeiro, Brazil. During the study period, 124 of 617 patients (20%) developed AIDS. Of this group, 91 patients were men and 33 were women. There were no gender related differences regarding the access to antiretroviral therapy or to prophylaxis for Pneumocystis carinii pneumonia. Survival was shorter among women (hazard ratio [HR] = 4.43; p < .001) after adjustment for age and AIDS-defining condition. Adjusting for CD4+ and CD8+ counts reduced the difference between genders (HR = 3.33; p = .017). These results suggest that survival after an AIDS diagnosis may be shorter among women than men in Brazil. Further studies are needed to determine the factors that may be negatively influencing the prognosis of women with AIDS in Brazil.

Antiretroviral adherence during pregnancy and postpartum in Latin America

Adherence to antiretrovirals by pregnant women (and postpartum women if breastfeeding) is crucial to effectively decrease maternal viral load and decrease the risk of mother-to-child transmission of HIV. Our objectives were to describe self-reported adherence to antiretrovirals during the antepartum (after 22 weeks of pregnancy) and postpartum periods (6-12 weeks and 6 months), and identify predictors of adherence among HIV-infected women enrolled and followed in a prospective cohort study from June 2008 to June 2010 at multiple sites in Latin America. Adherence was evaluated using the number of missed and expected doses during the 3 days before the study visit. At the pre-delivery visit, 340 of 376 women (90%) reported perfect adherence. This rate significantly decreased by 6-12 weeks (171/214 [80%]) and 6 months postpartum (163/199 [82%], p<0.01). The odds for less than perfect adherence at the pre-delivery visit was significantly higher for pregnant women with current tobacco use (odds ratio [OR]=2.9, 95% confidence interval [CI]: 1.46-6.14; p=0.0029). At 6-12 weeks postpartum, the probability of non-perfect adherence increased by 6% for each 1 year increase in age (OR=1.06, 95% CI: 1.00-1.12, p=0.0497). At 6 months postpartum, the odds of nonperfect adherence was higher for those who were currently using alcohol (OR=3.04, 95% CI: 1.34-6.90; p=0.0079). Although a self-report measure of adherence based on only 3 days may lead to overestimation of actual adherence over time, women with perfect adherence had lower viral loads and higher CD4 counts. Adherence to antiretrovirals decreased significantly postpartum. Interventions should target women at high risk for lower adherence during pregnancy and postpartum, including tobacco and alcohol users.

Characteristics of children hospitalized with dengue fever in an outbreak in Rio de Janeiro, Brazil

During a dengue epidemic in Rio de Janeiro in 2007-2008 the Instituto de Puericultura e Pediatria Martagão Gesteira Hospital was a reference for admitted children. The World Health Organization (WHO) considered several manifestations as warning signs of severe dengue This is a retrospective cohort study of all children admitted with dengue fever. Clinical variables considered warning signs by WHO were evaluated in the multivariate analysis, to investigate if they were independently associated with severe dengue. One hundred and eighty one children were admitted, aged from 4 months to 15 years; 30 were classified as severe dengue. Abdominal pain (OR=2.63, 95% CI 1.06-6.53) and lethargy (OR=3.40, 95% CI 1.45-7.99) were independently associated with severe dengue.

Drug Resistance Patterns among Hospitalized Tuberculous Patients in Rio de Janeiro, Brazil, 1993-1994

The purpose of this study was to analyze the prevalence and risk factors for drug resistance among hospitalized patients in two tertiary care centers, an acquired immunodeficiency syndrome (AIDS) reference center and a sanatorium, in Rio de Janeiro, Brazil. From 1993-1994, 389 patients were diagnosed as having tuberculosis (TB). Isolates from 265 patients were tested for in vitro susceptibility to rifampin and isoniazid. Resistance to one or more drugs was detected in 44 patients (16.6%) and was significantly more common among recurrent cases in both hospitals (p=0.03 in the AIDS center and p=0.001 in the sanatorium). Twenty seven patients (10.2%) had isolates resistant to both isoniazid and rifampin. Multi-drug resistance was associated with human immunodeficiency virus (HIV) infection among patients who had never been treated for TB. In conclusion, drug-resistant TB is high in hospitalized patients in Rio de Janeiro, especially among HIV infected patients. Therefore, measures to control TB and prevent nosocomial transmission need urgently to be set up in the Brazilian hospitals.

Growth parameters in HIV-vertically-infected adolescents on antiretroviral therapy in Rio de Janeiro, Brazil.

Abstract Background: Growth failure in HIV-infected children is an important factor in either initiating or changing antiretroviral therapy (ART). This study assesses the impact of HIV infection on growth parameters of adolescents who acquired HIV vertically. Methods: This retrospective, longitudinal study involved adolescents aged 10–20 years with vertically-acquired HIV infection who were followed up in one of the three main referral centres for paediatric HIV/AIDS in Rio de Janeiro, Brazil. Length, weight and variables related to demographic, clinical and laboratory issues were analysed. Results: 108 subjects were enrolled. Median age was 12.7 years, median duration of follow-up was 97.2 months and 61 (56.5%) were female. The difference between the baseline and final weight Z-scores was −0.31 (p=0.02). Patients with final weight Z-scores ≤ −2 used more ART regimens (average 4.13) than those with Z-scores > −2 (average 2.90, p<0.01) and also had a lower final CD4+ cell percentage — average 19% vs 24% (p<0.01), respectively. The difference between baseline and final-height Z-scores was −0.27 (p<0.01). Several factors were associated with a final-height Z-score ≤ −2: clinical stage C during follow-up (RR 1.60, 95% CI 1.11–2.31), chronic diarrhoea during follow-up (RR 2.02, 95% CI 1.04–3.90), HAART use (RR 1.41, 95% CI 1.16–1.71), number of ART regimens (p<0.01) and final CD4+ cell percentage (p<0.01). In multivariate analysis, presentation in clinical stage C during follow-up was the only significant variable (OR 4.04, 95% CI 1.23–13.28). Conclusion: Even on HAART, HIV-infected adolescents have lower growth parameters than the normal population and this is associated with a worse prognosis.

Factors associated with lack of antiretroviral adherence among adolescents in a reference centre in Rio de Janeiro, Brazil

The objective of this study was to describe the adherence to antiretroviral therapy (ART) among adolescents followed-up in Rio de Janeiro. This cross-sectional study included all adolescents (aged 10–19 years) followed at Instituto de Puericultura e Pediatria Martagão Gesteira and Hospital Universitário Clementino Fraga Filho. Adherence was determined by self-report (number of missed ART doses in three days prior to the interview). Adherence was categorized as taking ≥95% of the ARTs (adherent), or <95% (non-adherent). Variables related to demographics and treatment were evaluated and if P value ≤0.15, they were selected for a logistic regression analysis. One hundred and one adolescents were interviewed. The mean time on ART was 91 months and the mean adherence was 94% of this, 21 were non-adherent, and 80 adherent. The risk factors associated with non-adherence were: if the patient was not concerned about ART, odds ratio (OR) = 3.47 (95% confidence interval [CI] = 1.13–10.68); if they do not carry an extra dose of ART, OR = 6.63 (95% CI = 1.73–25.47); if a healthcare worker taught them how to take ART, OR = 0.27 (95% CI = 0.08–0.93). Adherence among adolescents was higher than expected. Factors associated with lack of adherence were: interviewees being unaware of ARTs and lack of commitment to the treatment. Interventions involving these factors must be evaluated.