Missed opportunities in the prevention of perinatal human immunodeficiency syndrome virus transmission

Mother to child transmission of human immunodeficiency virus (HIV) has decreased dramatically in the United States since the mid-1990s. Without antiretroviral therapy the risk of perinatal infection is as high as 25%; with treatment the risk drops to <1-2%. However, state surveillance data show a recent rise in the percentage of babies being born with HIV in Texas. No studies of perinatal HIV transmission in Texas have focused on the individual cases and identified what social/institutional barriers stood in the way of the index woman, her support system and her health providers in negotiating access to prenatal care and HIV treatment.^ The Texas Department of State Health Services identifies the babies born in Texas with HIV infection. This two year study will use mixed methods to identify barriers to the diagnosis and treatment of maternal HIV. In-depth interviews and chart reviews will be used to conduct the study. The abstracted medical record will give us demographic data and details of the timing of testing and treatment; interviews will provide information as to the individual and environmental factors that may have delayed testing and treatment. Little research has been done to assess the factors contributing to late prenatal HIV diagnosis and care in Texas and the interventions identified by mothers of affected babies that might overcome these obstacles.^ Conclusions from this study will guide the development of interventions to better educate the public, reduce structural barriers common to the underserved, and/or educate health care professionals. The study will also serve as a model for other states to undertake evaluation of their cases of perinatal infection. ^

{\it In vivo\/} induction of cytotoxic T lymphocytes against human immunodeficiency virus type 1 by synthetic viral peptides

Cytotoxic T lymphocytes (CTLs) play an important role in the suppression of initial viremia after acute infection with the human immunodeficiency virus (HIV), the causative agent of acquired immune deficiency syndrome (AIDS). Most HIV-infected individuals attain a high titer of anti-HIV antibodies within weeks of infection; however this antibody-mediated immune response appears not to be protective. In addition, anti-HIV antibodies can be detrimental to the immune response to HIV through enhancement of infection and participating in autoimmune reactions as a result of HIV protein mimicry of self antigens. Thus induction and maintenance of a strong HIV-specific CTL immune response in the absence of anti-HIV antibodies has been proposed to be the most effective means of controlling of HIV infection. Immunization with synthetic peptides representing HIV-specific CTL epitopes provides a way to induce specific CTL responses, while avoiding stimulation of anti-HIV antibody. This dissertation examines the capacity of synthetic peptides from the V3 loop region of the gp120 envelope protein from several different strain of HIV-1 to induce HIV-specific, MHC-restricted CD8$\sp+$ CTL response in vivo in a mouse model. Seven synthetic peptides representative of sequences found throughout North America, Europe, and Central Africa have been shown to prime CTLs in vivo. In the case of the MN strain of HIV-1, a 13 amino acid sequence defining the epitope is most efficient for optimal induction of specific CTL, whereas eight to nine amino acid sequences that could define the epitope were not immunogenic. In addition, synthesis of peptides with specific amino acid substitutions that are important for either MHC binding or T cell receptor recognition resulted in peptides that exhibited increased immunogenicity and induced CTLs that displayed altered specificity. V3 loop peptides from HIV-1 MN, SC, and Z321 induced a CTL population that was broadly cross-reactive against strains of HIV-1 found throughout the world. This research confirms the potential efficacy of using synthetic peptides for in vivo immunization to induce HIV-specific CTL-mediated responses and provides a basis for further research into development of synthetic peptide-based vaccines. ^

Isolation of Lautropia mirabilis from oral cavities of human immunodeficiency virus-infected children.

Lautropia mirabilis, a pleomorphic, motile, gram-negative coccus, has been isolated from the oral cavities of 32 of 60 (53.3%) children infected with human immunodeficiency virus (HIV) and 3 of 25 (12.0%) HIV-uninfected controls; the association of L. mirabilis isolation with HIV infection is significant (P < 0.001). All children in the study, both HIV-infected children and controls, were born to HIV-infected mothers. The presence of this bacterium was not associated with clinical disease in these children. The HIV-infected children with L. mirabilis did not differ from the HIV-infected children without L. mirabilis in immunological status, clinical status, or systemic medications. The role of HIV infection itself or concomitant factors in the establishment of L. mirabilis in the oral cavity remains to be elucidated.

The role of substance abuse treatment in preventing human immunodeficiency virus transmission among injecting drug users

This exploratory study assesses the utility of substance abuse treatment as a strategy for preventing human immunodeficiency virus (HIV) transmission among injecting drug users (IDUs). Data analyzed in this study were collected in San Antonio, TX, 1989 through 1995 using both qualitative and quantitative methods. Qualitative data included ethnographic interviews with 234 active IDUs; quantitative data included baseline risk assessments and HIV screening plus interviews follow-up interviews administered approximately six months later to 823 IDUs participating in a Federally-funded AIDS community outreach demonstration project.^ Findings that have particularly important implications for substance abuse treatment as an HIV prevention strategy for IDUs are listed below. (1) IDUs who wanted treatment were significantly more likely to be daily heroin users. (2) IDUs who want treatment were significantly more likely to have been to treatment previously. (3) IDUs who wanted treatment at baseline reported significantly higher levels of HIV risk than IDUs who did not want treatment. (4) IDUs who went to treatment between their baseline and follow-up interviews reported significantly higher levels of HIV risk at baseline than IDUs who did not go to treatment. (5) IDUs who went to treatment between their baseline and follow-up interviews reported significantly greater decreases in injection-related HIV risk behaviors. (6) IDUs who went to treatment reported significantly greater decreases in sexual HIV risk behaviors than IDUs who did not go to treatment.^ This study also noted a number of factors that may limit the effectiveness of substance abuse treatment in reducing HIV risk among IDUs. Findings suggest that the impact of methadone maintenance on HIV risk behaviors among opioid dependent IDUs may be limited by the negative manner in which it is perceived by IDUs as well as other elements of society. One consequence of the negative perception of methadone maintenance held by many elements of society may be an unwillingness to provide public funding for an adequate number of methadone maintenance slots. Thus many IDUs who would be willing to enter methadone maintenance are unable to enter it and many IDUs who do enter it are forced to drop out prematurely. ^

Hepatitis C and human immunodeficiency virus infections in injecting drug users in drug treatment centers in Vietnam

Background. Injecting drug users (IDUs) are at risk of infection with Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV). Independently, each of these viruses is a serious threat to health, with HIV ravaging the body’s immune system, and HCV causing cirrhosis, liver cancer and liver failure. Co-infection with HIV/HCV weakens the response to antiretroviral therapy in HIV patients. IDUs with HIV/HCV co-infection are at a 20 times higher risk of having liver-related morbidity and mortality than IDUs with HIV alone. In Vietnam, studies to ascertain the prevalence of HIV have found high rates, but little is known about their HCV status. ^ Purpose. To measure the prevalence of HCV and HIV infection and identify factors associated with these viruses among IDUs at drug treatment centers in northern Vietnam. ^ Methods. A cross-sectional study was conducted from November 2007 to February 2008 with 455 injecting drug users aged 18 to 39 years, admitted no more than two months earlier to one of four treatment centers in Northern Vietnam (Hatay Province) (response rate=95%). Participants, all of whom had completed detoxification and provided informed consent, completed a risk assessment questionnaire and had their blood drawn to test for the presence of antibody-HCV and antibody-HIV with enzyme immuno assays. Univariate and multivariable logistic regression models were utilized to explore the strength of association using HIV, HCV infections and HIV/HCV co-infection as outcomes and demographic characteristics, drug use and sexual behaviors as factors associated with these outcomes. Unadjusted and adjusted odds ratios and 95% confidence intervals were calculated. ^ Results. Among all IDU study participants, the prevalence of HCV alone was 76.9%, HIV alone was 19.8%. The prevalence of HIV/HCV co-infection was 92.2% of HIV-positive and 23.7% of HCV-positive respondents. No sexual risk behaviors for lifetime, six months or 30 days prior to admission were significantly associated with HCV or HIV infection among these IDUs. Only duration of injection drug use was independently associated with HCV and HIV infection, respectively. Longer duration was associated with higher prevalence. Nevertheless, while HCV infection among IDUs who reported being in their first year of injecting drugs were lower than longer time injectors, their rates were still substantial, 67.5%. ^ Compared with either HCV mono-infection or HIV/HCV non-infection, HIV/HCV co-infection was associated with the length of drug injection history but was not associated with sexual behaviors. Higher education was associated with a lower prevalence of HIV/HCV co-infection. When compared with HIV/HCV non-infection, current marriage was associated with a lower prevalence of HIV/HCV co-infection. ^ Conclusions. HCV was prevalent among IDUs from 18 to 39 years old at four drug treatment centers in northern Vietnam. Co-infection with HCV was predominant among HIV-positive IDUs. HCV and HIV co-infection were closely associated with the length of injection drug history. Further research regarding HCV/HIV co-infection should include non-injecting drug users to assess the magnitude of sexual risk behaviors on HIV and HCV infection. (At these treatment centers non-IDUs constituted 10-20% of the population.) High prevalence of HCV prevalence among IDUs, especially among HIV-infected IDUs, suggests that drug treatment centers serving IDUs should include not only HIV prevention education but they should also include the prevention of viral hepatitis. In addition, IDUs who are HIV-positive need to be tested for HCV to receive the best course of therapy and achieve the best response to HIV treatment. These data also suggest that because many IDUs get infected with HCV in the first year of their injection drug career, and because they also engaged in high risk sexual behaviors, outreach programs should focus on harm reduction, safer drug use and sexual practices to prevent infection among drug users who have not yet begun injecting drugs and to prevent further spread of HCV, HIV and co-infection. ^

Correlation of tuberculosis and human immunodeficiency virus in Harris County, Texas from 2009 through 2010 using Geographic Information Systems

A population based ecological study was conducted to identify areas with a high number of TB and HIV new diagnoses in Harris County, Texas from 2009 through 2010 by applying Geographic Information Systems to determine whether distinguished spatial patterns exist at the census tract level through the use of exploratory mapping. As of 2010, Texas has the fourth highest occurrence of new diagnoses of HIV/AIDS and TB.[31] The Texas Department of State Health Services (DSHS) has identified HIV infected persons as a high risk population for TB in Harris County.[29] In order to explore this relationship further, GIS was utilized to identify spatial trends. ^ The specific aims were to map TB and HIV new diagnoses rates and spatially identify hotspots and high value clusters at the census tract level. The potential association between HIV and TB was analyzed using spatial autocorrelation and linear regression analysis. The spatial statistics used were ArcGIS 9.3 Hotspot Analysis and Cluster and Outlier Analysis. Spatial autocorrelation was determined through Global Moran's I and linear regression analysis. ^ Hotspots and clusters of TB and HIV are located within the same spatial areas of Harris County. The areas with high value clusters and hotspots for each infection are located within the central downtown area of the city of Houston. There is an additional hotspot area of TB located directly north of I-10 and a hotspot area of HIV northeast of Interstate 610. ^ The Moran's I Index of 0.17 (Z score = 3.6 standard deviations, p-value = 0.01) suggests that TB is statistically clustered with a less than 1% chance that this pattern is due to random chance. However, there were a high number of features with no neighbors which may invalidate the statistical properties of the test. Linear regression analysis indicated that HIV new diagnoses rates (β=−0.006, SE=0.147, p=0.970) and census tracts (β=0.000, SE=0.000, p=0.866) were not significant predictors of TB new diagnoses rates. ^ Mapping products indicate that census tracts with overlapping hotspots and high value clusters of TB and HIV should be a targeted focus for prevention efforts, most particularly within central Harris County. While the statistical association was not confirmed, evidence suggests that there is a relationship between HIV and TB within this two year period.^

Molecular evolution of primate immunodeficiency viruses and hepatitis delta virus

Primate immunodeficiency viruses, or lentiviruses (HIV-1, HIV-2, and SIV), and hepatitis delta virus (HDV) are RNA viruses characterized by rapid evolution. Infection by primate immunodeficiency viruses usually results in the development of acquired immunodeficiency syndrome (AIDS) in humans and AIDS-like illnesses in Asian macaques. Similarly, hepatitis delta virus infection causes hepatitis and liver cancer in humans. These viruses are heterogeneous within an infected patient and among individuals. Substitution rates in the virus genomes are high and vary in different lineages and among sites. Methods of phylogenetic analysis were applied to study the evolution of primate lentiviruses and the hepatitis delta virus. The following results have been obtained: (1) The substitution rate varies among sites of primate lentivirus genes according to the two parameter gamma distribution, with the shape parameter $\alpha$ being close to 1. (2) Primate immunodeficiency viruses fall into species-specific lineages. Therefore, viral transmissions across primate species are not as frequent as suggested by previous authors. (3) Primate lentiviruses have acquired or lost their pathogenicity several times in the course of evolution. (4) Evidence was provided for multiple infections of a North American patient by distinct HIV-1 strains of the B subtype. (5) Computer simulations indicate that the probability of committing an error in testing HIV transmission depends on the number of virus sequences and their length, the divergence times among sequences, and the model of nucleotide substitution. (6) For future investigations of HIV-1 transmissions, using longer virus sequences and avoiding the use of distant outgroups is recommended. (7) Hepatitis delta virus strains are usually related according to the geographic region of isolation. (8) Evolution of HDV is characterized by the rate of synonymous substitution being lower than the nonsynonymous substitution rate and the rate of evolution of the noncoding region. (9) There is a strong preference for G and C nucleotides at the third codon positions of the HDV coding region. ^

Molecular analysis of the human $\gamma$-chain T cell receptor genes

In our studies we have focused on the issue of variability and diversity of the $\gamma$ (or $\delta)$ chain T cell receptor (TCR) genes by studying cDNA transcripts in peripheral blood mononuclear cells or $\gamma\delta$ TCR+ T cell clones. The significance of these studies lies in the better understanding of the molecular biology of the $\gamma\delta$ T cell receptor as well as in answering the question whether certain molecular forms predominate in $\gamma\delta$ T cells exhibiting specific immunologic functions. We establish that certain $\gamma$-chain TCR genes exhibit particular patterns of rearrangements in cDNA transcripts in normal individuals. V$\gamma$I subgroup were shown to preferentially rearrange to J$\gamma$2C$\gamma$2 gene segments. These preferential VJC rearrangements, may have implications regarding the potential for diversity and polymorphism of the $\gamma$-chain TCR gene. In addition, the preferential association of V$\gamma$I genes with J$\gamma$2C$\gamma$2, which encode a non-disulfide-linked $\gamma\delta$ TCR, suggests that $\gamma$ chains utilizing V$\gamma$I are predominantly expressed as non-disulfide-linked $\gamma\delta$ TCR heterodimers. The implications of this type of expression remain to be determined. We identified two alternative splicing events of the $\gamma$-chain TCR genes occurring in high frequency in all the normal individuals examined. These events may suggest additional mechanisms of regulation and control as well as diversification of $\gamma\delta$ TCR gene expression. The question whether particular forms of $\gamma$ or $\delta$-chain TCR genes are involved in HLA Class I recognition by specific $\gamma\delta$ cytotoxic T cell clones was addressed. Our results indicated that the T cell clones expressed identical $\gamma$ but distinct $\delta$-chains suggesting that the specificity for recognition of HLA-A2 or HLA-A3 may be conferred by the $\delta$-chain TCR. The issue of the degree of diversity and polymorphism of the $\delta$-chain TCR genes in a patient with a primary immunodeficiency (Omenn's syndrome) was addressed. A limited pattern of rearrangements in peripheral blood transcripts was found, suggesting that a limited $\gamma\delta$ TCR repertoire may be expressed in this particular primary immunodeficiency syndrome. Overall, our findings suggest that $\delta$-chain TCR genes exhibit the potential for significant diversity and that there are certain preferential patterns of expression that may be associated with particular immunologic functions. ^

HIV-related malignancies: A community-based study using a linkage of cancer registry and HIV registry data

Background. Increased incidence of cancer is documented in immunosuppressed transplant patients. Likewise, as survival increases for persons infected with the Human Immunodeficiency Virus (HIV), we expect their incidence of cancer to increase. The objective of this study was to examine the current gender specific spectrum of cancer in an HIV infected cohort (especially malignancies not currently associated with Acquired Immunodeficiency Syndrome (AIDS)) in relation to the general population.^ Methods. Cancer incidence data was collected for residents of Harris County, Texas who were diagnosed with a malignancy between 1975 and 1994. This data was linked to HIV/AIDS registry data to identify malignancies in an HIV infected cohort of 14,986 persons. A standardized incidence ratio (SIR) analysis was used to compare incidence of cancer in this cohort to that in the general population. Risk factors such as mode of HIV infection, age, race and gender, were evaluated for contribution to the development of cancer within the HIV cohort, using Cox regression techniques.^ Findings. Of those in the HIV infected cohort, 2289 persons (15%) were identified as having one or more malignancies. The linkage identified 29.5% of these malignancies (males 28.7% females 60.9%). HIV infected men and women had incidences of cancer that were 16.7 (16.1, 17.3) and 2.9 (2.3, 3.7) times that expected for the general population of Harris County, Texas, adjusting for age. Significant SIR's were observed for the AIDS-defining malignancies of Kaposi's sarcoma, non-Hodgkin's lymphoma, primary lymphoma of the brain and cancer of the cervix. Additionally, significant SIR's for non-melanotic skin cancer in males, 6.9 (4.8, 9.5) and colon cancer in females, 4.0 (1.1, 10.2) were detected. Among the HIV infected cohort, race/ethnicity of White (relative risk 2.4 with 95% confidence intervals 2.0, 2.8) or Spanish Surname, 2.2 (1.9, 2.7) and an infection route of male to male sex, with, 3.0 (1.9, 4.9) or without, 3.4 (2.1, 5.5) intravenous drug use, increased the risk of having a diagnosis of an incident cancer.^ Interpretation. There appears to be an increased risk of developing cancer if infected with the HIV. In addition to the malignancies routinely associated with HIV infection, there appears to be an increased risk of being diagnosed with non-melanotic skin cancer in males and colon cancer in females. ^

Are free condoms associated with the frequent use of condoms among men who have sex with men?

Introduction. The National Behavioral HIV Surveillance (NHBS) is a self-reported cross-sectional survey that monitors the spread of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). The 2004 survey asked if the participant received a free condom, used it, and if receiving a free condom made him more likely to use a condom. The aim of this cross-sectional study is to examine the Houston MSA sub-dataset to determine if there was a self-expressed association between receiving a free condom and likelihood of using a condom at next intercourse, and to determine if the strength of that association varied by demographic subgroup.^ Methods. The Houston MSA 2004 NHBS had 502 participants who were men who have sex with men (MSM). The present analysis examined the answers to the questions: "In the past 12 months, have you received free condoms?" "Have you used any of the free condoms you received?" and "Did getting these free condoms make you more likely to use condoms during sex?".^ Results. Out of 502 participants, 500 answered the question about receiving free condoms, 406 (81.2%) answered all three questions, and 204 (50.2%) answered "yes" to all three questions. In the subgroup analyses, Hispanics were significantly less likely and men under 29 years of age were significantly more likely to report that their condom use behavior was influenced by receiving a free condom. ^ Conclusion. The effect of receipt of free condoms on likelihood of condom use varies by demographic subgroup, but these potentially important preliminary findings will require further investigation to validate them and further explicate the possible underlying dynamics.^

Ethnic comparisons of adolescent sexual risk -taking and preventive behavior

For adolescents, unprotected sexual intercourse is the primary cause of sexually transmitted disease (STD), including Human Immunodeficiency Virus (HIV) infection (virus which causes Acquired Immunodeficiency Syndrome (AIDS)), and pregnancy. Although many studies on adolescent sexual behavior have addressed racial/ethnic differences, few studies have examined the relation between race/ethnicity while controlling for other sociocultural and psychosocial variables. The purpose of this study is to examine the relationship between racial/ethnic categories and selected sociocultural and psychosocial variables, with reported adolescent sexual risk-taking and preventive behavior.^ A self-administered questionnaire was used to collect information from 3132 students in a Texas school district (Section 3.5.2). The instrument contained approximately 100 questions on demographic characteristics, sexual behavior, and psychosocial determinants of sexual behavior. Based on the findings of this study, the following major conclusions are made: (1) There are differences in reported sexual risk-taking and preventive behavior among Black, Hispanic and White adolescents in this study. The stratified analysis by gender further suggests significant gender differences in reported sexual behavior among the three racial/ethnic groups. (2) Gender, living arrangement, academic grades, and language spoken at home modified the association between reported sexual risk-taking and preventive behavior and race/ethnicity in this study. This suggests that these sociocultural variables should be considered in future research and practice involving multicultural populations. (3) There are differences in selected psychosocial determinants among the three racial/ethnic groups and between males and females. These differences were consistent with the reported sexual risk-taking and preventive behaviors among race/ethnicity and gender for adolescents in this study. The findings support the consideration of psychosocial determinants in research and interventions addressing adolescent sexual behavior among different racial/ethnic groups.^ Based on the results of this study, two recommendations for practice are made. First, health professionals developing interventions for adolescents from different cultural backgrounds and gender need to be familiar with the specific sociocultural and psychosocial factors which will reduce risky sexual behavior, and promote protective behavior. Second, the need for immediate, realistic, and continuous HIV/STD and pregnancy prevention programs for children and adolescents should be considered. ^

A decade of AIDS literature.

From 1983 through mid-1991, more than 200,000 MEDLINE entries were AIDS-related. Close to 60% of the journals indexed in MEDLINE published at least one article on AIDS during the past ten years. As reflected by a subset of 29,077 MEDLINE records, the literature of AIDS has grown to encompass 29 languages and 65 countries. A bibliometric study of the medical literature helps to demonstrate the progression of AIDS as a world health problem and the concomitant expansion of the research effort underway to control it.

Multicentric hepatic EBV-associated smooth muscle tumors in an AIDS patient: a case report, investigation of mTOR activation and review of the literature.

Epstein-Barr virus (EBV) - associated smooth muscle tumors (EBV-SMT) are a rare, recently recognized distinct group of mesenchymal tumors that develop exclusively in patients with immunosuppression. It is believed that tumorigenesis is, at least in part, through the activation of the Akt/mammalian target of rapamycin (mTOR) signal pathway. We describe the clinicopathologic and immunohistochemical features of a multifocal hepatic EBV-SMT in a 34-year-old acquired immunodeficiency syndrome (AIDS) patient and investigate the activation status of the mTOR signal pathway in this tumor. In addition, we provide a review of the literature on the clinicopathologic findings of hepatic EBV-SMT in adult AIDS patients, and discuss their biologies and possible therapeutic strategies.