Late entry into HIV care: lessons from Brazil, 2003 to 2006

Background: To ascertain the population rates and proportion of late entry into HIV care, as well as to determine whether such late entry correlates with individual and contextual factors. Methods: Data for the 2003-2006 period in Brazil were obtained from public health records. A case of late entry into HIV care was defined as one in which HIV infection was diagnosed at death, one in which HIV infection was diagnosed after the condition of the patient had already been aggravated by AIDS-related diseases, or one in which the CD4(+) T-cell count was <= 200 cells/mm(3) at the time of diagnosis. We also considered extended and stricter sets of criteria (in which the final criterion was <= 350 cells/mm(3) and <= 100 cells/mm(3), respectively). The estimated risk ratio was used in assessing the effects of correlates, and the population rates (per 100,000 population) were calculated on an annual basis. Results: Records of 115,369 HIV-infected adults were retrieved, and 43.6% (50,358) met the standard criteria for late entry into care. Diagnosis at death accounted for 29% (14,457) of these cases. Late entry into HIV care (standard criterion) was associated with certain individual factors (sex, age, and transmission category) and contextual factors (region with less economic development/increasing incidence of AIDS, lower local HIV testing rate, and smaller municipal population). Use of the extended criteria increased the proportion of late entry by 34% but did not substantially alter the correlations analyzed. The overall population rate of late entry was 9.9/100,000 population, specific rates being highest for individuals in the 30-59 year age bracket, for men, and for individuals living in regions with greater economic development/higher HIV testing rates, collectively accounting for more than half of the cases observed. Conclusions: Although the high proportion of late entry might contribute to spreading the AIDS epidemic in less developed regions, most cases occurred in large cities, with broader availability of HIV testing, and in economically developed regions.

The impact of late diagnosis on the survival of patients following their first AIDS-related hospitalization in Belo Horizonte, Brazil

The purpose of this study is to estimate the survival probability of patients following their first admission for the treatment of AIDS to an infectious disease reference hospital in Belo Horizonte, Brazil, during 2005. Study subjects were monitored during a 12-month period to identify factors associated with survival probability. Late diagnosis was recorded among many of the 250 study subjects: almost half (44.8%) were diagnosed less than 30 days prior to or during their hospitalization. A high mortality rate was also detected: 39.6% of the subjects died during the 12 months of monitoring. The cumulative survival probability of the cohort group was estimated at 68.0% after 3 months and at 61.2% after 12 months. However, certain patient subgroups analyzed had even lower cumulative survival probabilities after 12 months of monitoring: if diagnosed during hospitalization, it was estimated at only 48.0% and those with no record of antiretroviral treatment had a 48.5% cumulative survival probability. Patients with severe anemia had the lowest survival probability, similar among the two lymphocyte count groups (<1000 mm(3) and >= 1000 mm(3)), the former with a 45.5% survival probability and the latter with a 46.7% one. The proportional death risk was 2.5-fold higher for men residing in other area than the capital city of the State of Minas Gerais and greater metropolitan region when compared with women residing there. The findings of this study highlight the importance of early diagnosis for predicting patient survival and reinforce the necessity off acilitating HIV diagnosis.

Prior history of sexually transmitted diseases in women living with AIDS in Sao Paulo, Brazil

Objectives: To describe the epidemiological profile, risk behaviors, and the prior history of sexually transmitted diseases (STDs) in women living with acquired immunodeficiency syndrome (AIDS). Methods: Cross-sectional study, performed at the Centro de Referencia e Treinamento em DST/AIDS of Sao Paulo. The social, demographic, behavioral, and clinical data such as age, schooling, marital status, age at first sexual intercourse, number of sexual partners, parity, use of drugs, time of HIV diagnosis, CD4 count, and viral load determination were abstracted from the medical records of women living with AIDS who had gynecological consultation scheduled in the period from June 2008 to May 2009. Results: Out of 710 women who were scheduled to a gynecological consultation during the period of the study, 598 were included. Previous STD was documented for 364 (60.9%; 95% CI: 56.9%-64.8%) women. The associated factors with previous STDs and their respective risks were: human development index (HDI) <0.50 (ORaj = 5.5; 95% CI: 2.8-11.0); non-white race (ORaj = 5.2; 95% CI: 2.5-11.0); first sexual intercourse at or before 15 years of age (ORaj = 4.4; 95% CI: 2.3-8.3); HIV infection follow-up time of nine years or more (ORaj = 4.2; 95% CI: 2.3-7.8)]; number of sexual partners during the entire life between three and five partners (ORaj = 2.2; 95% CI: 1.1-4.6), and six or more sexual partners (ORaj = 3.9; 95% CI: 1.9-8.0%); being a sex worker (ORaj = 1.9; 95% CI: 1.1-3.1). Conclusions: A high prevalence of a prior history of STDs in the studied population was found. It is essential to find better ways to access HIV infection prevention, so that effective interventions can be more widely implemented. (C) 2012 Elsevier Editora Ltda. All rights reserved.

Prior history of sexually transmitted diseases in women living with AIDS in São Paulo, Brazil

OBJECTIVES: To describe the epidemiological profile, risk behaviors, and the prior history of sexually transmitted diseases (STDs) in women living with acquired immunodeficiency syndrome (AIDS). METHODS: Cross-sectional study, performed at the Centro de Referência e Treinamento em DST/AIDS of São Paulo. The social, demographic, behavioral, and clinical data such as age, schooling, marital status, age at first sexual intercourse, number of sexual partners, parity, use of drugs, time of HIV diagnosis, CD4 count, and viral load determination were abstracted from the medical records of women living with AIDS who had gynecological consultation scheduled in the period from June 2008 to May 2009. RESULTS: Out of 710 women who were scheduled to a gynecological consultation during the period of the study, 598 were included. Previous STD was documented for 364 (60.9%; 95% CI: 56.9%-64.8%) women. The associated factors with previous STDs and their respective risks were: human development index (HDI) < 0.50 (ORaj = 5.5; 95% CI: 2.8-11.0); non-white race (ORaj = 5.2; 95% CI: 2.5-11.0); first sexual intercourse at or before 15 years of age (ORaj = 4.4; 95% CI: 2.3-8.3); HIV infection follow-up time of nine years or more (ORaj = 4.2; 95% CI: 2.3-7.8)]; number of sexual partners during the entire life between three and five partners (ORaj = 2.2; 95% CI: 1.1-4.6), and six or more sexual partners (ORaj = 3.9; 95% CI: 1.9-8.0%); being a sex worker (ORaj = 1.9; 95% CI: 1.1-3.1). CONCLUSIONS: A high prevalence of a prior history of STDs in the studied population was found. It is essential to find better ways to access HIV infection prevention, so that effective interventions can be more widely implemented.

Clusters of leprosy transmission and of late diagnosis in a highly endemic area in Brazil: focus on different spatial analysis approaches

Objective The Brazilian National Hansens Disease Control Program recently identified clusters with high disease transmission. Herein, we present different spatial analytical approaches to define highly vulnerable areas in one of these clusters. Method The study area included 373 municipalities in the four Brazilian states Maranha o, Para ', Tocantins and Piaui '. Spatial analysis was based on municipalities as the observation unit, considering the following disease indicators: (i) rate of new cases / 100 000 population, (ii) rate of cases < 15 years / 100 000 population, (iii) new cases with grade-2 disability / 100 000 population and (iv) proportion of new cases with grade-2 disabilities. We performed descriptive spatial analysis, local empirical Bayesian analysis and spatial scan statistic. Results A total of 254 (68.0%) municipalities were classified as hyperendemic (mean annual detection rates > 40 cases / 100 000 inhabitants). There was a concentration of municipalities with higher detection rates in Para ' and in the center of Maranha o. Spatial scan statistic identified 23 likely clusters of new leprosy case detection rates, most of them localized in these two states. These clusters included only 32% of the total population, but 55.4% of new leprosy cases. We also identified 16 significant clusters for the detection rate < 15 years and 11 likely clusters of new cases with grade-2. Several clusters of new cases with grade-2 / population overlap with those of new cases detection and detection of children < 15 years of age. The proportion of new cases with grade-2 did not reveal any significant clusters. Conclusions Several municipality clusters for high leprosy transmission and late diagnosis were identified in an endemic area using different statistical approaches. Spatial scan statistic is adequate to validate and confirm high-risk leprosy areas for transmission and late diagnosis, identified using descriptive spatial analysis and using local empirical Bayesian method. National and State leprosy control programs urgently need to intensify control actions in these highly vulnerable municipalities.

Delay in the search for health services for the diagnosis of tuberculosis in Ribeirao Preto, Sao Paulo

The scope of this paper is to analyze delays in locating health services for the diagnosis of tuberculosis in Ribeirao Preto in 2009. An epidemiological and cross-sectional study was conducted with 94 TB patients undergoing treatment. A structured questionnaire, based on the Primary Care Assessment Tool adapted for TB care was used. A median (15 days or more) was established to characterize delay in health attendance. Using the Prevalence Ratio, the variables associated with longer delay were identified. The first healthcare services sought were the Emergency Services (ES) (57.5%). The longest period between seeking assistance occurred among males, aged between 50 and 59, who earned less than five minimum wages, had pulmonary TB, were new cases, were not co-infected with TB/HIV, did not consume alcohol, had satisfactory knowledge about TB before diagnosis (with a statistically significant association with delay) and who did not seek healthcare close to home before developing TB. There is a perceived need for training healthcare professionals about the signs and symptoms of the disease, reducing barriers of access to timely diagnosis of TB and widely disseminating it to the community in general.

Three Postpartum Antiretroviral Regimens to Prevent Intrapartum HIV Infection

BACKGROUND The safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants. METHODS Within 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth. RESULTS A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan-Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intrapartum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P=0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P=0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P=0.03 for the comparisons with the two-and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P < 0.001 for both comparisons with the other groups). CONCLUSIONS In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two-or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.)

Missed opportunities for prevention of mother-to-child transmission of HIV-1 in the NISDI Perinatal and LILAC cohorts

Objective: To evaluate cases of mother-to-child transmission of HIV-1 at multiple sites in Latin America and the Caribbean in terms of missed opportunities for prevention. Methods: Pregnant women infected with HIV-1 were eligible for inclusion if they were enrolled in either the NISDI Perinatal or LILAC protocols by October 20, 2009, and had delivered a live infant with known HIV-1 infection status after March 1, 2006. Results: Of 711 eligible mothers, 10 delivered infants infected with HIV-1. The transmission rate was 1.4% (95% CI, 0.7-2.6). Timing of transmission was in utero or intrapartum (n = 5), intrapartum (n = 2), intrapartum or early postnatal (n = 1), and unknown (n = 2). Possible missed opportunities for prevention included poor control of maternal viral load during pregnancy; late initiation of antiretrovirals during pregnancy; lack of cesarean delivery before labor and before rupture of membranes; late diagnosis of HIV-1 infection; lack of intrapartum antiretrovirals; and incomplete avoidance of breastfeeding. Conclusion: Early knowledge of HIV-1 infection status (ideally before or in early pregnancy) would aid timely initiation of antiretroviral treatment and strategies designed to prevent mother-to-child transmission. Use of antiretrovirals must be appropriately monitored in terms of adherence and drug resistance. If feasible, breastfeeding should be completely avoided. Presented in part at the XIX International AIDS Conference (Washington, DC; July 22-27, 2012); abstract WEPE163. (c) 2012 Published by Elsevier Ireland Ltd. on behalf of International Federation of Gynecology and Obstetrics.

Comparison of two laboratory-developed PCR methods for the diagnosis of Pulmonary Tuberculosis in Brazilian patients with and without HIV infection

Abstract Background Direct smear examination with Ziehl-Neelsen (ZN) staining for the diagnosis of pulmonary tuberculosis (PTB) is cheap and easy to use, but its low sensitivity is a major drawback, particularly in HIV seropositive patients. As such, new tools for laboratory diagnosis are urgently needed to improve the case detection rate, especially in regions with a high prevalence of TB and HIV. Objective To evaluate the performance of two in house PCR (Polymerase Chain Reaction): PCR dot-blot methodology (PCR dot-blot) and PCR agarose gel electrophoresis (PCR-AG) for the diagnosis of Pulmonary Tuberculosis (PTB) in HIV seropositive and HIV seronegative patients. Methods A prospective study was conducted (from May 2003 to May 2004) in a TB/HIV reference hospital. Sputum specimens from 277 PTB suspects were tested by Acid Fast Bacilli (AFB) smear, Culture and in house PCR assays (PCR dot-blot and PCR-AG) and their performances evaluated. Positive cultures combined with the definition of clinical pulmonary TB were employed as the gold standard. Results The overall prevalence of PTB was 46% (128/277); in HIV+, prevalence was 54.0% (40/74). The sensitivity and specificity of PCR dot-blot were 74% (CI 95%; 66.1%-81.2%) and 85% (CI 95%; 78.8%-90.3%); and of PCR-AG were 43% (CI 95%; 34.5%-51.6%) and 76% (CI 95%; 69.2%-82.8%), respectively. For HIV seropositive and HIV seronegative samples, sensitivities of PCR dot-blot (72% vs 75%; p = 0.46) and PCR-AG (42% vs 43%; p = 0.54) were similar. Among HIV seronegative patients and PTB suspects, ROC analysis presented the following values for the AFB smear (0.837), Culture (0.926), PCR dot-blot (0.801) and PCR-AG (0.599). In HIV seropositive patients, these area values were (0.713), (0.900), (0.789) and (0.595), respectively. Conclusion Results of this study demonstrate that the in house PCR dot blot may be an improvement for ruling out PTB diagnosis in PTB suspects assisted at hospitals with a high prevalence of TB/HIV.

Evaluation of Long-Term Outcomes, Cytogenetic and Molecular Responses with Imatinib Mesylate in Early and Late Chronic-Phase Chronic Myeloid Leukemia: A Report from a Single Institute

Here we compare the management and survival outcomes of chronic myeloid leukemia (CML) patients who had early or late imatinib mesylate (IM) therapy. The cytogenetic and molecular responses of 189 CML patients were analyzed. Of this group, 121 patients were classified as the early chronic phase (ECP) group and started IM within 12 months of diagnosis. The other 68 patients were classified as the late chronic phase (LCP) group who had been treated with interferon (IFN)-alpha-2 and crossed over to IM more than 12 months after diagnosis. The overall rates of complete cytogenetic response (CCyR) and major molecular response (MMR) at last follow-up were 83.6 and 78.1% in the ECP and LCP groups, respectively. The CCyR rates were 89.3 (for ECP patients) versus 73.5% (for LCP patients; p < 0.0001). At last follow-up, 82.4% ECP and 64.2% LCP patients had achieved an MMR (p < 0.0001). No significant differences were noted between the two groups with regard to survival outcomes. Our experience reveals that IM is an effective rescue therapy in most CML LCP patients who are intolerant or in whom IFN-alpha therapy fails. Such therapeutic options should be considered in LCP patients, particularly in countries where IM may not be available. Copyright (C) 2012 S. Karger AG, Basel

Quality of life among Brazilian women living with HIV/AIDS

The purpose of the present study was to assess quality of life (QoL) in Brazilian women living with HIV/AIDS, according to the World Health Organization Quality of Life HIV-BREF (WHOQoL-HIV-BREF) domains. A quantitative-based, cross-sectional, analytical study was carried out in healthcare centers specialized in assisting people living with HIV/AIDS, located in a municipality of the state of Sao Paulo, Brazil. One hundred and six women of age 18 years or more, users of the public healthcare system, participated in the study. Socio-demographic and clinical variables were collected using a specific questionnaire. Quality of life related variables were collected by means of the WHOQoL-HIV-BREF instrument. As per the QoL domains, study results show that the Spirituality domain reached a standardized mean score of 65.7, followed by the Physical (64.7), Psychological (60.6), Social Relationships (59.5), Independence (58.6), and Environment (54.5) domains. Results of the multiple regression analysis indicate that the women's employment or retirement, income greater than the minimum wage, and higher educational level were associated with a higher standardized mean score of QoL. However, recent HIV/AIDS diagnosis and exposure to antiretroviral agents for a period shorter than two years were negatively associated with QoL. It is critical that public policies favor an all-embracing social inclusion of these women, thus promoting better social conditions. Counseling, clinical follow-up immediately after the infection diagnosis, and initiation of antiretroviral treatment are crucial moments in the lives of these individuals.

JC virus-associated central nervous system diseases in HIV-infected patients in Brazil: clinical presentations, associated factors with mortality and outcome

Introduction: Several presentations of neurologic complications caused by JC virus (JCV) in human immunodeficiency virus (HIV)-infected patients have been described and need to be distinguished from the "classic" form of progressive multifocal leukoencephalopathy (PML). The objectives of this study were: 1) to describe the spectrum and frequency of presentations of JCV-associated central nervous system (CNS) diseases; 2) identify factors associated with in-hospital mortality of patients with JCV-associated CNS disease; and 3) to estimate the overall mortality of this population. Material and methods: This was a retrospective study of HIV-infected patients admitted consecutively for JCV-associated CNS diseases in a referral teaching center in Sao Paulo, Brazil, from 2002 to 2007. All patients with laboratory confirmed JCV-associated CNS diseases were included using the following criteria: compatible clinical and radiological features associated with the presence of JCV DNA in the cerebrospinal fluid. JCV-associated CNS diseases were classified as follows: 1) classic PML; 2) inflammatory PML; and 3) JC virus granule cell neuronopathy (GCN). Results: We included 47 cases. JCV-associated CNS diseases were classified as follows: 1) classic PML: 42 (89%); 2) inflammatory PML: three (6%); and 3) JC virus GCN: four (9%). Nosocomial pneumonia (p = 0.003), previous diagnosis of HIV infection (p = 0.03), and imaging showing cerebellar and/or brainstem involvement (p = 0.02) were associated with in-hospital mortality. Overall mortality during hospitalization was 34%. Conclusions: Novel presentations of JCV-associated CNS diseases were observed in our setting; nosocomial pneumonia, previous diagnosis of HIV infection, and cerebellar and/or brainstem involvement were associated with in-hospital mortality; and overall mortality was high. (C) 2012 Elsevier Editora Ltda. All rights reserved.

MRKAd5 HIV-1 Gag/Pol/Nef Vaccine-Induced T-Cell Responses Inadequately Predict Distance of Breakthrough HIV-1 Sequences to the Vaccine or Viral Load

Background: The sieve analysis for the Step trial found evidence that breakthrough HIV-1 sequences for MRKAd5/HIV-1 Gag/Pol/Nef vaccine recipients were more divergent from the vaccine insert than placebo sequences in regions with predicted epitopes. We linked the viral sequence data with immune response and acute viral load data to explore mechanisms for and consequences of the observed sieve effect. Methods: Ninety-one male participants (37 placebo and 54 vaccine recipients) were included; viral sequences were obtained at the time of HIV-1 diagnosis. T-cell responses were measured 4 weeks post-second vaccination and at the first or second week post-diagnosis. Acute viral load was obtained at RNA-positive and antibody-negative visits. Findings: Vaccine recipients had a greater magnitude of post-infection CD8+ T cell response than placebo recipients (median 1.68% vs 1.18%; p = 0.04) and greater breadth of post-infection response (median 4.5 vs 2; p = 0.06). Viral sequences for vaccine recipients were marginally more divergent from the insert than placebo sequences in regions of Nef targeted by pre-infection immune responses (p = 0.04; Pol p = 0.13; Gag p = 0.89). Magnitude and breadth of pre-infection responses did not correlate with distance of the viral sequence to the insert (p. 0.50). Acute log viral load trended lower in vaccine versus placebo recipients (estimated mean 4.7 vs 5.1) but the difference was not significant (p = 0.27). Neither was acute viral load associated with distance of the viral sequence to the insert (p>0.30). Interpretation: Despite evidence of anamnestic responses, the sieve effect was not well explained by available measures of T-cell immunogenicity. Sequence divergence from the vaccine was not significantly associated with acute viral load. While point estimates suggested weak vaccine suppression of viral load, the result was not significant and more viral load data would be needed to detect suppression.

HOPE IN HIV-POSITIVE WOMEN

The objective of this study was to assess the hope in the lives of HIV-positive women, using the Herth Hope Scale (HHS). Participants were 111 HIV-positive women who attended a referral outpatient clinic in Fortaleza-CE. From January to May 2009, interviews were held to collect biopsychosocial variables, and the HHS was applied. Data were analyzed using SPSS-8.0 and revealed an average hope index of 34.86, indicating that these women have little hope in life in view of their diagnosis of HIV. The scale item with the highest score was faith. This probably derives from the fact that Aids is incurable, transmissible and generates negative stigma, in addition to its relation with the idea of imminent death. In conclusion, measuring hope among HIV patients through the use of an instrument permits intervention assessment and planning, promoting assistance and motivation to live better and maintain a hopeful attitude.

Circulating Glial-derived neurotrophic factor is reduced in late-life depression

Background: The Glial Cell-line derived neurotrophic factor (GDNF) is part of the TGF-beta superfamily and is abundantly expressed in the central nervous system. Changes in GDNF homeostasis have been reported in affective disorders. Aim: To assess serum GDNF concentration in elderly subjects with late-life depression, before antidepressant treatment, as compared to healthy elderly controls. Methods: Thirty-four elderly subjects with major depression and 37 age and gender-matched healthy elderly controls were included in this study. Diagnosis of major depression was ascertained by the SCID interview for DSM-IV and the severity of depressive symptoms was assessed by the Hamilton Depression Rating Scale (HDRS-21). Serum GDNF concentration were determined by sandwich ELISA. Results: Patients with major depression showed a significant reduction in GDNF levels as compared to healthy elderly controls (p < 0.001). Also, GDNF level was negatively correlated with HDRS-21 scores (r = -0.343, p = 0.003). Discussion: Our data provide evidence that GDNF may be a state marker of depressive episode in older adults. Changes in the homeostatic control of GDNF production may be a target to development of new antidepressant strategies. (C) 2011 Elsevier Ltd. All rights reserved.