Prevention of Mother-to-Child Transmission of HIV: Compliance with the Recommendations of the Brazilian National STD/AIDS Control Program for Prenatal and Perinatal HIV Testing in Porto Alegre, Brazil

In order to benefit from antiretroviral therapy, pregnant women infected with HIV must be tested and diagnosed. Not infrequently, however, women present in labor without prior prenatal care and are thus unable to benefit fully from HIV testing and, if infected, antiretroviral therapy. In this study we evaluated the need for rapid perinatal HIV testing for untested mothers presenting in labor in a public maternal–child hospital that provides care for metropolitan Porto Alegre, Brazil, and potentially modifiable risk factors for noncompliance with national recommendations. We surveyed a consecutive sample of women who gave birth at Hospital Materno–Infantil Presidente Vargas (Presidente Vargas Mother-and-child Hospital) in August–October 2001and administered a structured questionnaire to consenting participants. The questionnaire consisted of demographic data, information on health-seeking behavior, knowledge of HIV infection, and testing during pregnancy. We confirmed information on HIV testing, syphilis, and hepatitis B by examination of the patient's prenatal records. We also obtained data regarding laboratory testing and treatment during labor and delivery (e.g., HIV testing, antiretroviral treatment, and suppression of lactation) from hospital inpatient charts. Of 214 eligible participants, 209 (98%) agreed to participate in the study. Overall 173 (83%) of the 209 participants had had a previous HIV test and 36 (17%) had not. Women with fewer pregnancies were more likely to have been tested (p = .017), as were women with lower family incomes (p = .007). No women had received rapid tests in the delivery room. Of the 209 participants, 201 (96%) had had at least one prenatal visit and 169 (81%) had had three or more visits; 12 (6%) of these reported that they had not been offered an HIV test, 5 (2%) did not know if testing had been offered or not, and 191 (95%) reported that they had been offered a test. We were able to obtain prenatal records for 190 (95%) of the 201participants who had received prenatal care. HIV testing was not mentioned in 9% of charts. Results of syphilis tests were recorded on prenatal records or hospital charts for 167 (80%)participants, and results of hepatitis B surface antigen were found for 93 (45%). Women who to 30pchad had three or more prenatal visits were significantly more likely to have been tested for to 30pcHIV (OR 46.96, 95% CI, 15.92–144.85, .0001), syphilis (OR 31.64, 95% CI, 11.81–87.42, p < .0001) or HBsAg (OR, 4.88, 95% CI, 1.91–12.99, p < .0001) than women who had had two prenatal visits or fewer. Our study showed shown that in 12% of the pregnancies included in our sample national recommendations for prenatal or perinatal testing were not followed, and in an additional 5%, HIV testing, though offered, was not obtained. These women could potentially have benefited from rapid HIV testing. As knowledge of HIV and risk factors for transmission were almost universal in our sample, we believe that the passive health-seeking behavior we observed may offer an opportunity for targeting new efforts to promote the importance of prenatal care and prenatal diagnosis of HIV.     

Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy

BACKGROUND: Although untreated human immunodeficiency virus (HIV)-infected patients maintaining undetectable plasma HIV RNA levels (elite controllers) have high HIV-specific immune responses, it is unclear whether they experience abnormal levels of T cell activation, potentially contributing to immunodeficiency. METHODS: We compared percentages of activated (CD38(+)HLA-DR(+)) T cells between 30 elite controllers, 47 HIV-uninfected individuals, 187 HIV-infected individuals with undetectable viremia receiving antiretroviral therapy (antiretroviral therapy suppressed), and 66 untreated HIV-infected individuals with detectable viremia. Because mucosal translocation of bacterial products may contribute to T cell activation in HIV infection, we also measured plasma lipopolysaccharide (LPS) levels. RESULTS: Although the median CD4(+) cell count in controllers was 727 cells/mm(3), 3 (10%) had CD4(+) cell counts <350 cells/mm(3) and 2 (7%) had acquired immunodeficiency syndrome. Controllers had higher CD4(+) and CD8(+) cell activation levels (P < .001 for both) than HIV-negative subjects and higher CD8(+) cell activation levels than the antiretroviral therapy suppressed (P = .048). In controllers, higher CD4(+) and CD8(+) T cell activation was associated with lower CD4(+) cell counts (P = .009 and P = .047). Controllers had higher LPS levels than HIV-negative subjects (P < .001), and in controllers higher LPS level was associated with higher CD8(+) T cell activation (P = .039). CONCLUSION: HIV controllers have abnormally high T cell activation levels, which may contribute to progressive CD4(+) T cell loss even without measurable viremia.     

Mental Health of HIV-Seropositive Women During Pregnancy and Postpartum Period: A Comprehensive Literature Review

With growing numbers of HIV-seropositive (HIV+) women of child-bearing age and increased access to effective clinical protocols for preventing mother-to-child transmission (MTCT) of HIV, mental health-related factors have become increasingly relevant due to their potential to affect the women’s quality of life, obstetric outcomes and risk of MTCT. This review synthesizes evidence from 53 peer-reviewed publications examining mental health-related variables in pregnant and postpartum HIV+ women. The presentation of results is organized by the level of socioeconomic resources in the countries where studies were conducted (i.e., high-, middle-, and low-income countries). It is concluded that psychiatric symptoms, particularly depression, and mental health vulnerabilities (e.g., inadequate coping skills) are widespread among pregnant HIV+ women globally and have a potential to affect psychological well-being, quality of life and salient clinical outcomes. The current body of evidence provides rationale for developing and evaluating clinical and structural interventions aimed at improving mental health outcomes and their clinical correlates in pregnant HIV+ women.     

Haemogregarina spp. in a wild population from Podocnemis unifilis Troschel, 1848 in the Brazilian Amazonia

The study objectives were to characterize the morphology of the parasitic forms and describe the prevalence and intensity of Haemogregarina spp. in a population of the turtle Podocnemis unifilis as well as to examine the relationships between parasitism and turtle variables such as gender, size, and weight. Samples were taken in the Tapajós and Jamanxim rivers, Itaituba, Pará state, Brazil. Blood was collected from the tail vein of 72 P. unifilis specimens, including 35 males, 36 females, and one unsexed juvenile. The prevalence of Haemogregarina spp. was 98 % (n?=?71). The mean parasite intensity of Haemogregarina spp. was 118 (1–582) parasites/2000 blood cells (6 %). There was no significant difference in the mean parasite intensity between male (137.68?±?121.8, n?=?35) and female turtles (101.42?±?123.59, n?=?35). There was no relationship between parasite intensity and carapace length. Although the relationship between parasite intensity and host body weight was significant, the relationship was weak. This is the first study on Haemogregarina parasitism with a relatively high number of turtles in Brazil.     

Cyclodextrin Reduces Intravenous Toxicity of a Model Compound

Solubilization of new chemical entities for toxicity assessment must use excipients that do not negatively impact drug pharmacokinetics and toxicology. In this study, we investigated the tolerability of a model freebase compound, GDC-0152, solubilized by pH adjustment with succinic acid and complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD) to enable intravenous use. Solubility, critical micelle concentration, and association constant with HP-β-CD were determined. Blood compatibility and potential for hemolysis were assessed in vitro. Local tolerability was assessed after intravenous and subcutaneous injections in rats. A pharmacokinetic study was conducted in rats after intravenous bolus administration.GDC-0152 exhibited pH-dependent solubility that was influenced by self-association. The presence of succinic acid increased solubility in a concentration-dependent manner. HP-β-CD alone also increased solubility, but the extent of solubility enhancement was significantly lower than succinic acid alone. Inclusion of HP-β-CD in the solution of GDC-0152 improved blood compatibility, reduced hemolytic potential by ～20-fold in vitro, and increased the maximum tolerated dose to 80 mg/kg.     

Predictive molecular markers in metastases to the central nervous system: recent advances and future avenues

Metastases to the central nervous system (CNS) are common in several cancer types. For most primary tumors that commonly metastasize to the CNS, molecular biomarker analyses are recommended in the clinical setting for selection of appropriate targeted therapies. Therapeutic efficacy of some of these agents has been documented in patients with brain metastases, and molecular testing of CNS metastases should be considered in the clinical setting. Here, we summarize the clinically relevant biomarker tests that should be considered in neurosurgical specimens based on the current recommendations of the European Society of Medical Oncology (ESMO) or the National Comprehensive Cancer Network (NCCN) for the most relevant primary tumor types: lung cancer (EGFR mutations, ALK rearrangement, BRAF mutations), breast cancer (HER2 amplification, steroid receptor overexpression), melanoma (BRAF mutations), and colorectal cancer (RAS mutations). Furthermore, we discuss emerging therapeutic targets including novel oncogenic alterations (ROS1 rearrangements, FGFR1 amplifications, CMET amplifications, and others) and molecular features of the tumor microenvironment (including immune-checkpoint molecules such as CTLA4 and PD-1/PD-L1). We also discuss the potential role of advanced biomarker tests such as next-generation sequencing and “liquid biopsies” for patients with CNS metastases.     

Psychosocial Correlates of Suicidal Ideation in Rural South African Adolescents

Suicide is a prevalent problem among young people in Southern Africa, but prevention programs are largely absent. This survey aimed to identify the behavioral and psychosocial correlates of suicidal ideation among adolescents in Limpopo. A two-stage cluster sample design was used to establish a representative sample of 591 adolescents. Bivariate correlations and multiple linear regression analyses were conducted. Findings show that suicidal ideation is prevalent among adolescents. The psychosocial factors perceived social support and negative feelings about the family and the behavioral factors forced sexual intercourse and physical violence by the partner were found to increase the risk of suicidal ideation. Depression mediated the relationship between these psychosocial and behavioral risk factors and suicidal ideation. This study increased our understanding of the psychosocial and behavioral predictors of adolescent suicidal ideation. The findings provide target points for future intervention programs and call for supportive structures to assist adolescents with suicidal ideation.