HIV infection in Wisconsin: an overview of epidemiologic trends, 1983-1999.

A review of HIV case surveillance data shows that the number of persons reported with HIV infection in Wisconsin steadily increased during the 1980s, leveled in the early 1990s and since 1993 has tended to decline. Cases reported in 1999 represented a 44% decrease compared to the 1990-1993 average. The number of deaths among persons with HIV infection declined 64% from 1993 to 1999; as a result, the number of persons living with HIV infection nearly doubled during the 1990s. Comparing cases reported 1995-1999 with cases reported in the 1980s, a higher percentage was attributed to injection drug use and high-risk heterosexual contact. A higher percentage of HIV cases also occurred among females and racial and ethnic minorities.

HIV infection in Wisconsin: state and national resources for clinicians and patients.

The authors review state and national resources for clinicians and patients regarding HIV infection, high-lighting pertinent resources in the Wisconsin AIDS/HIV Program as well as select local and national resources.

HIV seropositivity rates in outreach-based counseling and testing services: program evaluation.

A common assumption is that outreach-based HIV counseling and testing services reach a clientele with a higher HIV seroprevalence than clinic-based counseling and testing. To examine this assumption, we analyzed Wisconsin's anonymous counseling and testing client records for 62,299 contacts (testing episodes) from 1992 to 1995. Bivariate analysis of counseling and testing service setting (outreach-based or clinic-based) and HIV test results suggested that outreach contacts were 23% (odds ratio [OR], 1.23; 95% confidence interval [95% CI], 1.0-1.5) more likely to test HIV-seropositive than clinic-based contacts. Relations between HIV test outcome and variables for client age, race, gender, previous testing history, mode of risk exposure, and region, as well as service setting, were examined by logistic regression. An inverted relation between service setting and seropositivity (OR, 0.65; 95% CI, 0.5-0.8) indicated that, within some subpopulations, outreach contacts were significantly less likely to test HIV-positive than clinic-based contacts. Analysis of interactions among the covariates identified race as a critical codeterminant in the relation between service setting and test outcome. These results support retargeting outreach services to enhance their overall effectiveness. Specific recommendations include the need for aggressive strategies to better "market" HIV counseling and testing to nonwhite populations, and to focus resources more selectively on gay/bisexual men of all races.

PIP: The assumption that outreach-based HIV counseling and testing services reach a clientele with a higher HIV seroprevalence than similar clinic-based services was investigated as part of a comprehensive evaluation of the state of Wisconsin's (US) HIV counseling and testing program in 1992-95. Client records were available for 62,299 anonymous outreach- and clinic-based testing episodes. 0.9% of outreach and 0.8% of clinic clients tested HIV-positive. Although contacts in the high-exposure risk group were 13.7 times more likely to be HIV-infected than those in lower risk categories, they were only 1.9 times more likely to have been served in an outreach setting. Among non-White counseling and testing clients, the odds of selection through outreach (odds ratio (OR), 3.34; 95% confidence interval (CI), 3.2-3.5) was similar to the overall seropositivity risk (OR, 3.01; 95% CI, 2.5-3.6). An inverted relation between service setting and seropositivity (OR, 0.65; 95% CI, 0.5-0.8) indicated that, within some subpopulations, outreach contacts were significantly less likely to test HIV-positive than clinic clients. In fact, multivariate analysis revealed a negative association between HIV positivity and outreach when demographic and contextual factors were controlled. 22% of HIV-positive White male clients who reported sex with men were identified through outreach, but this was the only risk exposure category for Whites in which the proportion of outreach among seropositive cases exceeded the overall success rate for outreach (20.5%). Men reporting sex with men represented 41.5% of all seropositive cases among non-Whites. These findings indicate a need to re-target outreach services, especially toward non-Whites and gay/bisexual men, to enhance their overall effectiveness.

Wisconsin statutes regarding HIV testing in primary care: frequent questions and answers.

The authors review Wisconsin statutes related to human immunodeficiency virus (HIV) testing in primary care, including the areas of written informed consent, documentation of consent, testing without consent, testing of minors, disclosure of test results without the consent of the test subject, reporting requirements, discrimination, access by insurance companies and third-party payors to HIV test results, and civil liabilities and criminal penalties associated with violation of HIV-related state statutes. During the course of the HIV epidemic in Wisconsin, many individuals (service providers, legislators, consumers and advocates) supported the enactment of HIV-related legislation. Today, Wisconsin has some of the nation's most comprehensive HIV legislation. These laws have set a legal framework that balances the rights of individuals with protection of public's health. The relatively low seroprevalence of HIV infection in Wisconsin can be attributed, in part, to the state's HIV-related legislation. While Wisconsin HIV legislation is broadly focused, much of it is concerned with HIV testing. This article examines common questions as they pertain to HIV testing in primary care and to the following areas addressed by state statutes: counseling and referral for health and support services [Wisconsin statute s. 252 14(3)] informed consent for testing or disclosure [Wisconsin statute s. 252.15(2)] written consent to disclose [Wisconsin statute s. 252.15(3) & (4)] testing without consent of the test subject [Wisconsin statute s. 252.15(2)] confidentiality of an HIV test [Wisconsin statute s. 252.15(5)] reporting of positive test results [Wisconsin statute s. 252.15(7)] discrimination [Wisconsin statute s. 252.14(2)] civil and criminal liabilities [Wisconsin statute s. 252.14(4); 252.15(8) & (9)].

Meeting the challenge of early identification of HIV infection in primary care.

The authors review the role of human immunodeficiency virus (HIV) testing in primary care, including an overview of epidemiologic trends of the HIV epidemic; avenues for HIV counseling and testing; HIV testing assays; guidelines for HIV test counseling in primary care; special situations involving testing of pregnant women, infants, and young children; post-exposure prophylaxis; and related resources available to Wisconsin primary care clinicians. HIV disease is a major cause of premature death and disability in the United States. Advances in the understanding of the pathogenesis of HIV and developments of newer antiretroviral therapies have resulted in dramatic changes in the management of HIV disease. Combination antiretroviral drug therapy has resulted in prolonged and near complete suppression of detectable HIV replication in many HIV-infected persons. These clinical developments underscore the importance of early identification and intervention in HIV disease. Intervention during primary HIV infection, the time when the viral burden "set point" is achieved, may present a special window of opportunity to effectively intervene in limiting viral replication in an infected individual. This earliest intervention may have major benefits for infected persons and society at large. Decreasing viral load during primary HIV infection may decrease an individual's infectiousness and thereby decrease the overall rate of transmission of infection to others. Primary care clinicians play a critical role in diagnosing, managing, and preventing HIV infection. Because of the ongoing relationship between patient and health care provider, the primary health care clinician is in the best position to provide HIV risk assessment, testing, related prevention education, and coordination of needed health care. This article presents guidelines for conducting HIV counseling and testing in primary care for purposes of furthering the public health objective of early identification of HIV infection. Clinicians can achieve this objective by including HIV risk assessment during the initial history and physical exam of every patient.

Setting standards for the Wisconsin HIV Counseling and Testing Program: an application of threshold analysis.

Human immunodeficiency virus (HIV) counseling and testing (CT) services are an important component of any comprehensive HIV prevention program. Because resources are limited and must be used wisely, it is important to determine if the expenditures on CT services are sufficiently effective that they might be considered cost-saving or cost-effective to society. The policy analysis technique of "threshold analysis" was employed to determine how many HIV infections the publicly funded Wisconsin CT program would have to prevent in order to be considered cost-saving or cost-effective. Depending on the calculation method used, the threshold for the minimum number of HIV infections that must be averted ranges between approximately 1 and 18 (for the year 1994). Although the exact number of HIV infections prevented by these services in Wisconsin in unknown, the best estimate of this number is well over the required threshold. Hence, HIV CT services in the state of Wisconsin appear to be cost-saving to society.

The evaluation of HIV counseling-and-testing services: making the most of limited resources.

The evaluation of HIV counseling, testing, referral, and partner notification (CTRPN) services are especially important given the rapid, relevant changes in counseling strategies, public policies, and testing technologies. Here we briefly review the important components of a comprehensive HIV CTRPN evaluation. However, resources for evaluation are usually quite limited, thus making comprehensive evaluations impossible. Yet even with limited resources, meaningful evaluative activities can be performed and some pressing evaluation questions answered. As an illustration, we present a practical evaluation project (conducted with limited resources) that assessed at a systems level the HIV counseling and testing (HIV CT) program in the state of Wisconsin. We describe how some of this evaluative information was utilized by the state's division of health.

Clinical and epidemiologic features of a massive waterborne outbreak of cryptosporidiosis in persons with HIV infection.

During March and April 1993, a massive outbreak of Cryptosporidium infection resulted from contamination of the public water supply in Milwaukee, Wisconsin. The health impact of this outbreak in HIV-infected persons was unknown but was perceived as severe. We surveyed HIV-infected persons who resided in the greater Milwaukee area to examine the acute health impact of cryptosporidiosis on this population. Data from a random-digit dialing survey in the general population residing in the same area were used for comparison. The attack rate of watery diarrhea suggestive of cryptosporidiosis was lower in HIV-infected persons (32%) than in the general population (51%). There was no significant difference in attack rate in HIV-infected persons based on CD4+ T-lymphocyte count. In persons with watery diarrhea, HIV-infected persons were more likely to experience cough (42%), fever (52%), and dehydration (55%). In HIV-infected persons with watery diarrhea, persons with CD4+ T-lymphocyte counts <200/microl had longer duration of diarrhea and were more likely to seek medical attention and be hospitalized. During this massive waterborne outbreak, HIV-infected persons were not more likely to experience symptomatic Cryptosporidium infection than the general population. However, once infected, the duration and severity of illness was greater in HIV-infected persons, especially if the CD4+ T-lymphocyte count was <200/microl.

Cloning and physical mapping of RNA polymerase genes from Methanobacterium thermoautotrophicum and comparison of homologies and gene orders with those of RNA polymerase genes from other methanogenic archaebacteria.

The structural genes encoding the four largest subunits of RNA polymerase, A, B', B", and C, were physically mapped in Methanobacterium thermoautotrophicum Winter. The genes formed a cluster in the order B", B', A, C and had a common orientation. DNA hybridization experiments yielded different degrees of homology between RNA polymerase gene sequences of different species of Methanobacterium and Methanococcus voltae. No homology was detectable between Methanobacterium thermoautotrophicum and Methanosarcina barkeri. From Southern hybridization experiments in which probes of the four genes from Methanobacterium thermoautotrophicum Winter and restriction digests of the genomic DNAs of the different methanogens were used, a common gene order of the RNA polymerase genes could be deduced.

Structure of the carbohydrate moiety of human interferon-beta secreted by a recombinant Chinese hamster ovary cell line.

The carbohydrate structure of the major oligosaccharide of human interferon-beta (IFN-beta) synthesized by a genetically engineered Chinese hamster ovary cell line has been determined. Analysis of the glycopeptidase F-released carbohydrates by sequential exoglycosidase treatment, methylation analysis, and fast atom bombardment-mass spectrometry revealed that 95% of the IFN-beta oligosaccharides had the following structure: (Formula: see text). The remaining 5% of the carbohydrates are probably tri- or higher antennary oligosaccharide chains. The major oligosaccharide of the recombinant IFN-beta is remarkably homogeneous with respect to terminal galactose sialylation. NeuAc, which is alpha 2-3-linked to galactose in the human IFN-beta secreted by Chinese hamster ovary cells, can be re-incorporated with an alpha 2-6 linkage in vitro, into enzymatically desialylated IFN-beta using rat liver Gal beta 1-4GlcNAc alpha 2-6 sialyltransferase. The sugar chain is important for maintaining protein solubility as shown by the fact that IFN-beta protein precipitates after deglycosylation with glycopeptidase F.

Replication strategy of human hepatitis B virus.

To study the replication strategy of the human hepatitis B virus, the 5' end of the RNA pregenome and the initiation sites of DNA plus and minus strands have been mapped. The RNA pregenome was found to be terminally redundant by 120 nucleotides; it is initiated within the pre-C region and may also function as mRNA for synthesis of the major core protein and the hepatitis B virus reverse transcriptase. The hepatitis B virus DNA minus strand is initiated within the direct repeat sequence DR1, it contains a terminal redundancy of up to eight nucleotides, and its synthesis does not require any template switch. The DNA plus strand is primed by a short oligoribonucleotide probably derived from the 5' end of the RNA pregenome, and its synthesis is initiated close to the direct repeat sequence DR2. For its elongation to pass the discontinuity in the DNA minus strand an intramolecular template switch occurs using the terminal redundancy of this template. Thus, the route of reverse transcription and DNA replication of hepatitis B viruses is fundamentally different from that of retroviruses.

Transcripts and the putative RNA pregenome of duck hepatitis B virus: implications for reverse transcription.

Duck hepatitis B virus (DHBV) is a DNA virus that replicates by reverse transcription. We have examined transcripts of DHBV to elucidate mechanisms of gene expression and replication. Three major transcripts were characterized and related to the expression of the genes for the core antigen (DHBcAg), the surface antigen (DHBsAg), and the pre-S/DHBs protein, respectively. They are unspliced and overlap partially since they start at different promoter sites, but they terminate near a common polyadenylation signal. The messenger RNA related to DHBcAg expression is the only major transcript of more than genome length and therefore also represents the putative template for reverse transcription (pregenome). Its structure predicts a strategy of replication of hepatitis B viruses different from that of retroviruses.

Structure and function of mutants in the P gene of bacteriophage lambda leading to the pi phenotype.

The location of 14 independently isolated spontaneous pi A and pi B point mutants in the lambda P gene and their base exchanges were determined. It was found that the pi B mutation is one unique type mapping close to other pi A mutants. The number of possible pi A mutation sites could be estimated. The mutation sites are distributed asymmetrically in the gene. The N-terminal half of the protein is unchanged. It is assumed to be required for the interaction with the lambda O protein. The P protein can be changed by substitution of a limited number of amino acids at the C-terminus. All functional proteins of this type have pi character. pi proteins do not appear to have altered intracellular levels or stabilities as compared to wild-type P protein. The plating characteristics of our mutants on two groP- mutants located in the dnaJ and dnaK genes, respectively, are strikingly different.

[Pericarditis in chronic compensated renal insufficiency]. / Perikarditis bei chronisch kompensierter Niereninsuffizienz.

In 80 patients with renal insufficiency we found 15 cases of pericarditis, demonstrated by the diagnostic means of echocardiography. The incidence of pericarditis increased with the rise in serum-creatinin and the severity of hypalbuminemia. These findings confirm the assumption that toxic capillary damage combined with lowered oncotic pressure might be a cause of pericardial effusion. Echocardiography as a reliable and non-invasive diagnostic method should be applied routinely in patients with chronic renal insufficiency--regarding potential therapeutic consequences--especially in patients with a concomitant incidence of hypalbuminemia and pleural effusion.

Cloning of the replication gene O of E. coli bacteriophage lambda and its expression under the control of the lac promoter.

The expression of the replication gene O of bacteriophage lambda was put under the control of the lac promoter-operator region integrated into the pBR322 cloning vehicle. The new plasmid pKK104 was introduced into minicells and the O gene induced by isopropyl-beta-thiogalactoside (IPTG). The O protein could be identified as a major component in extracts from these cells, in association with the cell membrane fractions. The molecular weight of the O protein in SDS gels is about 33 000, and it is metabolically unstable but apparently stable upon isolation as a membrane-associated fraction.