CHEMOSENSITIZATION OF HEPATOCELLULAR CARCINOMA TO GEMCITABINE BY NON-INVASIVE RADIOFREQUENCY FIELD-INDUCED HYPERTHERMIA

Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage through late S/ G2 phase of cell cycle in comparison to cells treated with gemcitabine alone. This coincides with inhibition of resolution of γH2AX foci. Our findings also demonstrate that thermal sensitization of human hepatocellular carcinoma cell lines to gemcitabine is mediated through an Mre11-dependent homologous recombination repair pathway. Combination of non-invasive radiofrequency field-induced hyperthermia and gemcitabine was superior to either therapy alone (p

A NEW TUMOR SUPPRESSOR GENE CANDIDATE REGULATED BY THE NON-CODING RNA PCA3 IN HUMAN PROSTATE CANCER

Prostate cancer is the second leading cause of cancer-related death and the most common non-skin cancer in men in the USA. Considerable advancements in the practice of medicine have allowed a significant improvement in the diagnosis and treatment of this disease and, in recent years, both incidence and mortality rates have been slightly declining. However, it is still estimated that 1 man in 6 will be diagnosed with prostate cancer during his lifetime, and 1 man in 35 will die of the disease. In order to identify novel strategies and effective therapeutic approaches in the fight against prostate cancer, it is imperative to improve our understanding of its complex biology since many aspects of prostate cancer initiation and progression still remain elusive. The study of tumor biomarkers, due to their specific altered expression in tumor versus normal tissue, is a valid tool for elucidating key aspects of cancer biology, and may provide important insights into the molecular mechanisms underlining the tumorigenesis process of prostate cancer. PCA3, is considered the most specific prostate cancer biomarker, however its biological role, until now, remained unknown. PCA3 is a long non-coding RNA (ncRNA) expressed from chromosome 9q21 and its study led us to the discovery of a novel human gene, PC-TSGC, transcribed from the opposite strand and in an antisense orientation to PCA3. With the work presented in this thesis, we demonstrate that PCA3 exerts a negative regulatory role over PC-TSGC, and we propose PC-TSGC to be a new tumor suppressor gene that contrasts the transformation of prostate cells by inhibiting Rho-GTPases signaling pathways. Our findings provide a biological role for PCA3 in prostate cancer and suggest a new mechanism of tumor suppressor gene inactivation mediated by non-coding RNA. Also, the characterization of PCA3 and PC-TSGC led us to propose a new molecular pathway involving both genes in the transformation process of the prostate, thus providing a new piece of the jigsaw puzzle representing the complex biology of prostate cancer.

Defining the role of IL-15 trans-presentation by distinct cell-types during the development and homeostasis of Natural Killer and invariant Natural Killer T cells

The immuno-regulatory functions displayed by NK and iNKT cells have highlighted their importance as key lymphocytes involved in innate and adaptive immunity. Therefore, understanding the dynamics influencing the generation of NK and iNKT cells is extremely important. IL-15 has been shown to provide a critical signal throughout the development and homeostasis of NK and iNKT cells; however, the cellular source of IL-15 has remained unclear. In this investigation, I provide evidence that the cell-type providing IL-15 to NK and iNKT cells via trans-presentation is determined by the tissue site and the maturation status of NK and iNKT cells. For NK cells, I revealed the non-hematopoietic compartment provides IL-15 to NK cells in the early stages of development while hematopoietic cells were crucial for the generation and maintenance of mature NK cells. Regarding iNKT cells in the thymus, IL-15 trans-presentation by non-hematopoietic cells was crucial for the survival of mature iNKT cells. In the liver, both hematopoietic and non-hematopoietic compartments provided IL-15 to both immature and mature iNKT cells. This IL-15 signal helped mediate the survival and proliferation of both NK and iNKT cells as well as induce the functional maturation of mature iNKT cells via enhanced T-bet expression. In conclusion, my work illustrates an important notion that the immunological niche of NK and iNKT cells is tightly regulated and that this regulation is meticulously influenced by the tissue microenvironment.

AN ESTIMATION OF IN UTERO DRUG EXPOSURE BY DETERMINANTS OF FREQUENCY AND DISTRIBUTION OF MATERNAL DRUG CONSUMPTION

Data derived from 1,194 gravidas presenting at the observation unit of a city/county hospital between October 11, 1979 through December 7, 1979 were evaluated with respect to the proportion ingesting drugs during pregnancy. The mean age of the mother at the time of the interview was 22.0 years; 43.0 percent were Black; 34.0 percent Latin-American, 21.0 percent White and 2.0 percent other; mean gravida was 2.5 pregnancies; mean parity was 1.0; and mean number of previous abortions was 0.34. Completed interview data was available for 1,119 gravida, corresponding urinalyses for 997 subjects. Ninety and one-tenth percent (90.1 percent) of the subjects reported ingestion of one or more drug preparation(s) (prescription, OTC, or substances used for recreational purposes) during pregnancy with a range of 0 to 11 substances and a mean of 2.7. Dietary supplements (vitamins and minerals) were most frequently reported followed by non-narcotic analgesics. Seventy-six and one tenth percent (76.1 percent) of the population reported consumption of prescription medication, 42.5 percent reported consumption of over-the-counter medications, 45.7 percent reported consumption of a substance for recreational purposes and 4.3 percent reported illicit consumption of a substance. For selected substances, no measurable difference was found between obtaining the information from the interview method or from a urinalysis assay. ^

B cell memory and idiotype network regulation

This investigation examined the clonal dynamics of B-cell expression and evaluated the role of idiotype network interactions in shaping the expressed secondary B-cell repertoire. Three interrelated experimental approaches were applied. The first approach was designed to distinguish between regulatory influences controlled by the major histocompatibility complex (MHC) and regulatory influences controlled by non-MHC factors including the idiotype network. This approach consisted of studies on the clonal dynamics and heterogeneity of the expressed IgG antibody repertoire of BALB/c mice. The second approach involved the analysis of the clonal dynamics of antibody responses of outbred rabbits. This analysis was coupled with studies to detect the occurrence and activity of constituents of the idiotype network. In the third approach the transfer of rabbit lymphocytes from immunized donors to MHC matched naive recipients was used to examine the effects of recipient non-MHC immunoregulatory influences on the expression of donor memory B-cells. Although many memory B cells were unaffected by non-MHC influences, these data show that non-MHC immunoregulatory influences can affect the expression of B-cells in the secondary response of inbred mice and outbred rabbits. The results also indicate that most IgG antibody responses are heterogeneous and are characterized by a stable group of dominant clonotypes. Clonal dominance and B-cell memory were found to be established early in an immune response. The expression of B memory clones appeared to be favored over the expression of virgin B cells. The injection of anti-tetanus antibody induced the antigen independent production of anti-tetanus antibody, probably through idiotypic mechanisms. These results demonstrate that both antibody and antigen can affect the expressed B-ceIl repertoire. Thus, idiotypic interactions are capable of influencing the expression of B-cells and these findings support the existence and function of an idiotype network with strong immunoregulatory potential. ^

A cellular cleavage pathway for the Moloney murine leukemia virus precursor protein, Pr65$\rm\sp{gag}$: Identification of a new viral protein containing CAp30 and NCp10 sequences

The origin and structure of P55$\sp{\rm gag},$ a gag encoded polyprotein lacking the nucleocapsid protein, NCp10, have been explored. Evidence shows that P55$\sp{\rm gag}$ is formed by non-viral proteolytic cleavage of the Moloney murine leukemia virus (MoMuLV)gag precursor protein, Pr65$\sp{\rm gag}.$ P55$\sp{\rm gag}$ is produced in cells infected by a viral protease deletion mutant and by a recombinant murine sarcoma virus known to lack the protease gene, implying that a cellular protease is responsible for the cleavage. Structural and immunological studies show that the protein cleavage site is upstream of the CAp30-NCp10 viral proteolytic junction, implying that P55$\sp{\rm gag}$ lacks the carboxy-terminal residues of CAp30. During the course of studying P55$\sp{\rm gag},$ another protein was discovered, which I named nucleocapsid-related protein(NCRP). NCRP possesses the portion of CAp30 that is lacking in P55$\sp{\rm gag}.$ NCRP possesses antigenic epitopes present in CAp30 and NCp10. NCRP was observed in virus lysates and in nuclear lysates of MoMuLV infected cells; it was not detected in the cytoplasmic fractions of MoMuLV infected cells. Our results indicated that NCRP originates from Pr65$\sp{\rm gag},$ resulting from the same cellular proteolytic cleavage event that produces the viral cellular protein P55$\sp{\rm gag}.$ P55$\sp{\rm gag}$- and NCRP-like proteins also were observed in AKV murine leukemia virus (AKV MuLV) and feline leukemia virus (FeLV) infected cells and in their respective virus particles. The site of cleavage that yields P55$\sp{\rm gag}$ and NCRP is within the carboxy terminus of CAp30, likely within a motif highly conserved among mammalian type C retroviruses. This new motif, called the capsid conserved motif (CCM), overlaps a region containing both a possible bipartite nuclear targeting sequence and a region homologous with the U1 small nuclear ribonucleoprotein 70-kD protein. This domain, when intact, may act as a nuclear targeting sequence for the gag precursor proteins Pr65$\sp{\rm gag}$ and CAp30. Nuclei of cells infected with MoMuLV were examined for the presence of gag proteins. Both Pr65$\sp{\rm gag}$ and CAp30 were detected in the nuclear fraction of MoMuLV, AKV MuLV and FeLV infected cells. P55$\sp{\rm gag}$ was never detected in the nucleus of MoMuLV, AKV MuLV and FeLV infected cells or in their respective virus particles. I propose that NCRP may be involved in sequestering viral genomic RNA for the purposes of encapsidation and intracellular viral genomic RNA dimerization. ^

Integrins in human T cell function: Transdominant regulation, conformational constraints, and intracellular effectors

Integrin adhesion molecules have both positive and negative potential in the regulation of peripheral blood T cell (PB T cell) activation, yet their mechanism of action in the mediation of human T lymphocyte function remains largely undefined. The goals of this study then were to elucidate integrin signaling mechanisms in PB T cells.^ By ligating $\beta$1 integrins with mAb 18D3, it was demonstrated that costimulation of PB T cell proliferation induced by coimmobilizing antibodies specific for $\beta$1, $\beta$2, and $\beta$7 integrin subfamilies in conjunction with the anti-CD3 mAb OKT3 was inhibited. Costimulation of T cell proliferation induced by non-integrins CD4, CD26, CD28, CD44, CD45RA, or CD45RO was unaffected. Inhibition of costimulation correlated with diminished IL-2 production. In his manner, $\beta$1 integrins could regulate heterologous integrins of the $\beta$2 and $\beta$7 subfamilies in a transdominant fashion. It was also demonstrated that integrin costimulation of T cell activation was acutely sensitive to the structural conformation of $\beta$1 integrins. Using the cyclic hexapeptide CWLDVC (TBC772, which is based on the $\alpha4\beta1$ integrin binding site in fibronectin) in soluble form, it was shown that integrins locked into a conformation displaying a neo-epitope called the ligand induced binding site (LIBS) recognized by mAb 15/7 were inhibited from sending mitogenic signals to T cells. When BSA-conjugated TBC772 was coimmobilized with anti-CD3 mAb OKT3, costimulation of proliferation occurred. This suggested that temporally uncoupling integrin receptor occupancy from receptor crosslinking inhibited $\beta$1 integrin signaling mechanisms. When subsets of PB T cells were examined to determine those initially activated by integrins within 6 hours of activation, costimulation induced intracellular accumulation of IL-2 predominantly in the CD4$\sp+$ and CD45RO$\sp+$ T cell subsets. This was similar to a number of PB T cell costimulatory molecules including CD26, CD43, CD44. Only CD28 costimulated IL-2 production from both CD45RA$\sp+$ and CD45RO$\sp+$ subpopulations.^ The GTPase Rho has been implicated in regulating integrin mediated stress fiber formation and anchorage dependent growth in fibroblasts, so studies were initiated to determine if Rho played a role in integrin dependent T cell function. In order to perform this, a technique based on scrape-loading was developed to incorporate macromolecules into PB T cells that maintained their functional activity. With this technique, C3 exoenzyme from Clostridium botulinum was incorporated into PB T cells. C3 ADP-ribosylates Rho proteins on Asn$\sp{41},$ which is in close proximity to the Rho effector domain, rendering it inactive. It was demonstrated that functional Rho is not required for basal or upregulated PB T cell adhesion to $\beta$1 integrin substrates, however PB T cell homotypic aggregation induced by PMA, which is an event mediated predominantly by the integrin $\rm\alpha L\beta2,$ was delayed. PB T cells lacking Rho function displayed altered cell morphology on $\beta$1 integrin ligands, producing stellate, dendritic-like pseudopodia. Rho activity was also found to be required for integrin dependent costimulation of proliferation. When intracellular accumulation of IL-2 was measured, inactivation of Rho prevented both integrin and CD28 costimulatory activity. Rho was identified to lie upstream of signals mediating PKC activation and Ca$\sp{++}$ fluxes, as PMA and ionomycin activation of PB T cells was unaffected by the inactivation of Rho. ^

PLASMA MEMBRANE GLYCOPROTEINS OF RAT HEPATOCELLULAR CARCINOMA CELLS

Previous investigations have demonstrated qualitative differences in the plasma membrane glycoproteins of normal and malignant rat liver cells. The present investigations were designed to identify and characterize the spectrum of glycoproteins present on the surface of Novikoff and AS-30D hepatocellular carcinoma cells. Three cell-surface radiolabeling techniques were employed to tag specifically the plasma membrane glycoproteins: lactoperoxidase catalyzed iodination, specific for tyrosine residues; galactose oxidase/NaB{('3)H}(,4), specific for galactosyl residues; and NaIO(,4)/NaB{('3)H}(,4), specific for sialic acids. The glycoproteins were resolved by one- and two-dimensional gel electrophoresis and visualized by fluorography or autoradiography. It was found that these glycoproteins are a complex population of molecules. The complexity of this system is reflected not only in the number of individual components that can be detected (> 25), but in the charge heterogeneity of individual glycoproteins due to variable sialic acid content. Certain glycoproteins behaved anamolously on SDS-polyacrylamide gel electrophoresis; the apparent molecular weight decreasing with increasing acrylamide concentrations suggesting a high % carbohydrate. Cell-surface radiolabeling techniques were employed in combination with lectin affinity chromatography, using lectins of different saccharide specificity, to analyze the saccharide determinants present on the spectrum of cell-surface molecules. It was also found that particular glycoproteins differed in their lability to protease or neuraminidase digestion and in their extractability by non-ionic detergents. From these studies, detailed models of the plasma membrane of Novikoff and AS-30D cells were constructed which incorporates information concerning the structure and accessibility of heterosaccharide and peptide moieties, the relationship of the glycolipids, and the interaction of particular glycoproteins with the lipid bilayer. These investigations provide basic information concerning the molecular composition and properties of the plasma membrane of glycoproteins of malignant rat liver cells and lay the groundwork for future comparison to normal hepatocytes. ^

Requirements for Staphylococcus aureus in vitro cellular internalization

Staphylcoccus aureus is a prokaryotic organism capable of causing numerous superficial and severe human infections. Adhesion of S. aureus to host tissues or cells is believed to be a crucial event in S. aureus infections. Subsequently, S. aureus can seed into the bloodstream resulting in metastasis of the infection. Several reports show that S. aureus can be internalized by non-professional phagocytes, a process which has been proposed to be important in S. aureus dissemination. An intracellular residence has also been proposed to provide safe harbor to reservoirs of dormant bacteria contributing to the persistence of infection. This dissertation describes an investigation into the molecular mechanisms of S. aureus internalization into both fibroblast and epithelial cells. Bacterial requirements for internalization were found to be limited to expression of proteins that bind the extracellular matrix protein fibronectin. A previously unknown fibronectin-binding region in the S. aureus fibronectin-binding protein A was discovered after showing competitive inhibition of S. aureus internalization. This novel fibronectin-binding activity is characterized. Internalization also required cell-based factors. The presence of fibronectin and cell surface receptors of the β1 integrin class, which are known to bind and internalize fibronectin, were found to be necessary for optimal internalization of S. aureus. These results led to the conclusion that fibronectin acts as a bridge between the bacterium and integrins on the host cells. The internalization process exhibits features characteristic of integrin-mediated cell migration on fibronectin-coated surfaces. Both processes involved an active form of the β1 integrin subunit and the protein tyrosine kinase Src. Finally, a Src inhibitor previously shown to be effective in reducing osteoporosis in an in vivo rat model is capable of greatly reducing S. aureus internalization. ^

Evaluation of Mycobacterium avium complex lung disease in women

Mycobacterium avium complex (MAC) is a ubiquitous organism responsible for most pulmonary and disseminated disease caused by non-tuberculosis (NTM) mycobacteria. Though MAC lung disease without predisposing factors is uncommon, in recent years it has been increasingly described in middle-aged and elderly women. Recognition and correct diagnosis, is often delayed due to the indolent nature of the disease. It is unclear if these women have significant clinical disease as or if their airways are simply colonized by the bacterium. This study describes the clinical presentation, identifies risk factors, and describes the clinical significance of MAC lung disease in HIV-negative women aged 50 or greater. ^ A hybrid study design utilizing both cross-sectional and case-control methodologies was used. A comparison population was selected from previously identified tuberculosis suspects found throughout Harris County. The study population had at least one acid fast bacillus pulmonary culture performed between 1/1/1998 and 12/31/2000 from a pulmonary source. Clinical presentation and symptoms were analyzed using a cross-sectional design. Past medical history and other risk factors were evaluated using a traditional case-control study design. Differences in categorical variables were estimated with the Chi Square or Fisher's Exact test as appropriate. Odds ratios and 95% confidence intervals were utilized to evaluate associations. Multivariate logistic regression was used to identify predictive factors for MAC. All statistical tests were two-sided and P-values <0.05 were considered statistically significant. ^ Culture confirmed MAC pulmonary cases were more likely to be white, have bronchiectasis, scoliosis, evidence of cavitation and pleural changes on chest radiography and granulomas on histopathologic examination than women whose pulmonary cultures were AFB negative. After controlling for selected risk factors, white race continued to be significantly associated with MAC lung disease (OR = 4.6, 95% CI = 2.3, 9.2). In addition, asthma history, smoking history and alcohol use were less likely to be evident among MAC cases in a multivariate analysis. Right upper and right middle lobe disease was further noted among clinically significant cases. Based on population data, MAC lung disease appears to represent a significant clinical syndrome in HIV-negative women thus supporting the theory of the Lady Windermere Syndrome. ^

The effect of immigration status on racial differences in health insurance coverage, access to care, and utilization in the United States

Background. Lack of coverage, lack of access, and failure to utilize health care services have all been linked to dismal health outcomes in the US. Such consequences have been a longstanding challenge that US minorities are faced with, in the context of a health care system believed to be lacking efficiency and equity. National population surveys in the US suggest that the number of uninsured approaches 50 millions, while some concerns and suspicions are raised by opponents to the growing number of foreign born US residents, many of whom are Hispanic. Research shows that race is a significant predictor of lack of coverage, access, and utilization, while age, gender, education, and income are also linked to these outcomes. We investigated the potential effect of immigration status or duration in the US on the association between coverage, access, use, and race. Methods. Using National Health Interview Survey (NHIS) data of 2006, we selected 22, 667 individuals of Non-Hispanic Black, Hispanic, and Non-Hispanic White descent, at least 18 years of age, US-born and foreign-born who reported their duration of residence in the US. Through complex sample survey logistic regression analysis, we computed odds ratios, beta coefficients, and 95% confidence intervals using models which excluded then included immigration status. Results. Although a significant predictor of the outcomes, immigration status did not change the relationship between each of the dependent variables (coverage, access, utilization), and the factor race, while adjusting for age, gender, education, and income. Our results show that Hispanics were least likely to have coverage (OR=.58; 95% CI[.49, .68]), access (OR=.62; 95% CI[.50, .76]), and to utilize services (OR=.60; 95% CI[.46, .79]) followed by Non-Hispanic Blacks, and Non-Hispanic Whites. These results were not changed by stratification, or the inclusion of interaction terms to eliminate the potential effect of relationships between independent variables. Recent immigrants (<5 years in US) were 0.12 times less likely to be insured, but also 0.26 times less likely to utilize services (p<0.001), and in addition they represented only 7.3% of the uninsured and 1.9% of the US population in 2006. Furthermore, 12% of the Non-Hispanic White population in the US was not covered, and 65% of the uninsured individuals were US-Born Citizens. Other predictors of lack of coverage, access and use were age below 45, male gender, education at high school or below, and income of less than $20,000. Conclusion. This investigation shows that the high percentage of uninsured was not directly caused by Hispanics, and immigration status alone could not explain racial differences in coverage, access, and utilization. An immigration reform may not be the solution to the healthcare crisis, and more specifically, will not stop the increase in the number of uninsured in the US, nor reduce the cost of health care. As a better alternative, universal health insu rance coverage should be considered, when aiming to eliminate racial disparities, and to solve the health care crisis. ^ Keywords. health insurance, coverage, access, utilization, race, immigration, disparities.^

Safety, pharmacokinetics, and antiretroviral activity of multiple doses of ibalizumab (formerly TNX-355), an anti-CD4 monoclonal antibody in HIV-1 infected adults

Context: Despite tremendous strides in HIV treatment over the past decade, resistance remains a major problem. A growing number of patients develop resistance and require new therapies to suppress viral replication. ^ Objective: To assess the safety of multiple administrations of the anti-CD4 receptor (anti-CD4) monoclonal antibody ibalizumab given as intravenous (IV) infusions, in three dosage regimens, in subjects infected with human immunodeficiency virus (HIV-1). ^ Design: Phase 1, multi-center, open-label, randomized clinical trial comparing the safety, pharmacokinetics and antiviral activity of three dosages of ibalizumab. ^ Setting: Six clinical trial sites in the United States. ^ Participants: A total of twenty-two HIV-positive patients on no anti-retroviral therapy or a stable failing regimen. ^ Intervention: Randomized to one of two treatment groups in Arms A and B followed by non-randomized enrollment in Arm C. Patients randomized to Arm A received 10 mg/kg of ibalizumab every 7 days, for a total of 10 doses; patients randomized to Arm B received a total of six doses of ibalizumab; a single loading dose of 10 mg/kg on Day 1 followed by five maintenance doses of 6 mg/kg every 14 days, starting at Week 1. Patients assigned to Arm C received 25 mg/kg of ibalizumab every 14 days for a total of 5 doses. All patients were followed for safety for an additional 7 to 8 weeks. ^ Main Outcome Measures: Clinical and laboratory assessments of safety and tolerability of multiple administrations of ibalizumab in HIV-infected patients. Secondary measures of efficacy include HIV-1 RNA (viral load) measurements. ^ Results: 21 patients were treatment-experienced and 1 was naïve to HIV therapy. Six patients were failing despite therapy and 15 were on no current HIV treatment. Mean baseline viral load (4.78 log 10; range 3.7-5.9) and CD4+ cell counts (332/μL; range 89-494) were similar across cohorts. Mean peak decreases in viral load from baseline of 0.99 log10(1.11 log10, and 0.96 log 10 occurred by Wk 2 in Cohorts A, B and C, respectively. Viral loads decreased by >1.0 log10 in 64%; 4 patients viral loads were suppressed to < 400 copies/mL. Viral loads returned towards baseline by Week 9 with reduced susceptibility to ibalizumab. CD4+ cell counts rose transiently and returned toward baseline. Maximum median elevations above BL in CD4+ cell counts for Cohorts A, B and C were +257, +198 and +103 cells/μL, respectively and occurred within 3 Wks in 16 of 22 subjects. The half-life of ibalizumab was 3-3.5 days and elimination was characteristic of capacity-limited kinetics. Administration of ibalizumab was well tolerated. Four serious adverse events were reported during the study. None of these events were related to study drug. Headache, nausea and cough were the most frequently reported treatment emergent adverse events and there were no laboratory abnormalities related to study drug. ^ Conclusions: Ibalizumab administered either weekly or bi-weekly was safe, well tolerated, and demonstrated antiviral activity. Further studies with ibalizumab in combination with standard antiretroviral treatments are warranted.^

Understanding causes of hospitalization and access to care among newly diagnosed HIV patients in Houston, TX

More than a quarter of patients with HIV in the United States are diagnosed in hospital settings most often with advanced HIV related conditions.(1) There has been little research done on the causes of hospitalization when the patients are first diagnosed with HIV. The aim of this study was to determine if the patients are hospitalized due to an HIV related cause or due to some other co-morbidity. Reduced access to care could be one possible reason why patients are diagnosed late in the course of the disease. This study compared the access to care of patients diagnosed with HIV in hospital and outpatient setting. The data used for the study was a part of the ongoing study “Attitudes and Beliefs and Steps of HIV Care”. The participants in the study were newly diagnosed with HIV and recruited from both inpatient and outpatient settings. The primary and the secondary diagnoses from hospital discharge reports were extracted and a primary reason for hospitalization was ascertained. These were classified as HIV-related, other infectious causes, non–infectious causes, other systemic causes, and miscellaneous causes. Access to care was determined by a score based on responses to a set of questions derived from the HIV Cost and Services Utilization Study (HCSUS) on a 6 point scale. The mean score of the hospitalized patients and mean score of the patients diagnosed in an outpatient setting was compared. We used multiple linear regressions to compare mean differences in the two groups after adjusting for age, sex, race, household income educational level and health insurance at the time of diagnosis. There were 185 participants in the study, including 78 who were diagnosed in hospital settings and 107 who were diagnosed in outpatient settings. We found that HIV-related conditions were the leading cause of hospitalization, accounting for 60% of admissions, followed by non-infectious causes (20%) and then other infectious causes (17%). The inpatient diagnosed group did not have greater perceived access-to-care as compared to the outpatient group. Regression analysis demonstrated a statistically significant improvement in access-to-care with advancing education level (p=0.04) and with better health insurance (p=0.004). HIV-related causes account for many hospitalizations when patients are first diagnosed with HIV. Many of these HIV-related hospitalizations could have been prevented if patients were diagnosed early and linked to medical care. Programs to increase HIV awareness need to be an integral part of activities aimed at control of spread of HIV in the community. Routine testing for HIV infection to promote early HIV diagnosis can prevent significant morbidity and mortality.^