HIV testing histories and risk factors among migrants and recent immigrants who received rapid HIV testing from three community-based organizations.

Migrants and recent immigrants in the US constitute a large population that is vulnerable to HIV. From March 2005 to February 2007, three community-based organizations conducted rapid HIV testing among migrants in five states. Participants were asked to complete a survey on sociodemographics, HIV-risk behaviors, and HIV-testing histories with the aim of understanding factors associated with HIV testing. Among 5,247 persons tested, 6 (0.1 %) were HIV-positive. Among 3,135 persons who completed surveys, more than half had never been tested for HIV previously (59 %). Participants reported high levels of HIV-risk behaviors in the past year, including 2 or more sex partners (45 %), sex while high/drunk (30 %), and transactional sex (29 %). Multivariate analysis identified several factors independently associated with decreased likelihood of prior HIV testing, including poor spoken English. Continued efforts are needed to ensure that migrant populations have improved access to HIV testing and prevention services. Understanding factors associated with migrants' lack of previous HIV testing may help focus these efforts.

Partner Referral by HIV-Infected Persons to Partner Counseling and Referral Services (PCRS) - Results from a Demonstration Project.

OBJECTIVE: The objectives of this article are to determine factors associated with refusal and agreement to provide partner information, and evaluate the effectiveness of referral approaches in offering PCRS. METHODS: Index clients from 5 sites that used 3 different PCRS approaches were interviewed to obtain demographic and risk characteristics and choice of partner referral method for PCRS. Logistic regression was used to assess factors associated with providing partner information. RESULTS: The percentage of index clients who refused to provide partner information varied by site (7% to 88%). Controlling for PCRS approach, index clients who were older than 25 years, male, or reported having male-male sex in the past 12 months were more likely (p <0.01) to refuse to provide partner information. Overall, 72% of named partners referred by index clients were located and offered PCRS. The proportion of partners who were located and offered PCRS differed by referral approach used, ranging from 38% using contract referral (index clients agree to notify their partners within a certain timeframe, else a disease intervention specialist or health care provider will notify them) to 98% using dual referral (index clients notify their partners with a disease intervention specialist or provider present). CONCLUSION: Success in obtaining partner information varied by the PCRS approach used and effectiveness in locating and notifying partners varied by the referral approach selected. These results provide valuable insights for enhancing partner services.

Costs and effectiveness of finding new HIV diagnoses by using rapid testing in transgender communities.

We assessed the costs and effectiveness of rapid HIV testing services provided to transgender communities in New York City and San Francisco from April 2005 to December 2006. Program costs were estimated based on service provider's perspective and included the costs attributable to staff time, incentives, transportation, test kits, office space, equipment, supplies, and utilities. The average annual numbers of persons tested were 195 and 106 persons and numbers notified of new HIV diagnoses were 35 (18.2%) in New York City and 8 (7.3%) in San Francisco, respectively. The estimated annual program costs were $125,879 and $64,323 and average costs per person notified of new diagnosis were $3,563 and $8,284 in New York City and San Francisco, respectively. The primary reason for differences in program costs by site was differences in the proportion of undiagnosed HIV infection among persons tested. Our findings can inform decisions about program planning and allocation of limited HIV testing resources.

Sex with bisexual men among black female students at historically black colleges and universities.

BACKGROUND: Human immunodeficiency virus (HIV) disproportionately affects black women. Nearly two-thirds of all female HIV cases reported to the CDC are black, and HIV is the leading cause of death among black women aged 25 to 34 years. The greatest HIV transmission risk among black women is sexual intercourse with a man, although the role of bisexual men is not clear. METHODS: The CDC and collaborating partners conducted behavioral surveys at 7 historically black colleges and universities from January 2005 to April 2007. RESULTS: Of the 2705 black female students aged 18 to 29 years who were surveyed, 2040 (75%) reported being sexually active in the previous 12 months and, among sexually active women, 291 (14%) reported having sex with a bisexual man in the previous 12 months. Women who reported sex with a bisexual man were more likely than women who did not to report having at least 2 sex partners in the previous 12 months, having male and female sex partners, not using a condom at last intercourse, being in a committed relationship, never or infrequently attending church, and believing they were at increased risk for HIV infection. CONCLUSION: Heterosexually active black women who have engaged in sexual intercourse with bisexual men have a different HIV risk profile than other heterosexually active black women.

Costs and effectiveness of partner counseling and referral services with rapid testing for HIV in Colorado and Louisiana, United States.

OBJECTIVE: Health departments offer partner counseling and referral services (PCRS) to HIV-infected index patients and their partners. Point-of-care rapid HIV testing makes it possible for partners of index patients to learn their HIV serostatus in nonclinical settings. STUDY DESIGN: We assessed costs and effectiveness of PCRS with rapid HIV testing in Colorado and Louisiana (April 2004-January 2006). Colorado provided PCRS to the index patients and partners statewide; Louisiana provided PCRS to those in Baton Rouge and New Orleans. The key effectiveness measures were number of partners tested and number of partners informed of a new HIV diagnosis after rapid testing. We obtained program costs for personnel, travel, utilities, supplies, equipment, and facility space. RESULTS: Colorado identified a yearly average of 328 index patients and 253 partners and tested 43 partners. Louisiana identified a yearly average of 81 index patients and 138 partners and tested 83 partners. The rates of previously undiagnosed HIV infection among partners tested were 6.6% in Colorado and 9.9% in Louisiana. The average costs per partner tested and per partner informed of a new HIV diagnosis were $1459 and $22,243 in Colorado and $714 and $7231 in Louisiana. CONCLUSIONS: Program costs varied substantially by location. Our analysis helps program managers and health care providers to understand the resources needed for implementing the PCRS in diverse settings.

Molecular anatomy of the recombination mediator function of Saccharomyces cerevisiae Rad52.

A helical filament of Rad51 on single-strand DNA (ssDNA), called the presynaptic filament, catalyzes DNA joint formation during homologous recombination. Rad52 facilitates presynaptic filament assembly, and this recombination mediator activity is thought to rely on the interactions of Rad52 with Rad51, the ssDNA-binding protein RPA, and ssDNA. The N-terminal region of Rad52, which has DNA binding activity and an oligomeric structure, is thought to be crucial for mediator activity and recombination. Unexpectedly, we find that the C-terminal region of Rad52 also harbors a DNA binding function. Importantly, the Rad52 C-terminal portion alone can promote Rad51 presynaptic filament assembly. The middle portion of Rad52 associates with DNA-bound RPA and contributes to the recombination mediator activity. Accordingly, expression of a protein species that harbors the middle and C-terminal regions of Rad52 in the rad52 Delta327 background enhances the association of Rad51 protein with a HO-made DNA double-strand break and partially complements the methylmethane sulfonate sensitivity of the mutant cells. Our results provide a mechanistic framework for rationalizing the multi-faceted role of Rad52 in recombination and DNA repair.

Implementation of rapid HIV testing programs in community and outreach settings: perspectives from staff at eight community-based organizations in seven U.S. cities.

OBJECTIVES: The goals of this research were to evaluate perceptions of staff about the effectiveness of methods used by eight community-based organizations (CBOs) to implement human immunodeficiency virus (HIV) counseling and rapid testing in community and outreach settings in seven U.S. cities, and to identify operational challenges. METHODS: A survey was administered to CBO staff to determine their perceptions about the effectiveness of methods used to select testing venues, promote their testing programs, recruit people for testing, provide test results, and link HIV-positive people to health care. Using a Likert scale, respondents rated the effectiveness of methods, their agreement with statements about using mobile testing units (MTUs) and rapid HIV test kits, and operational challenges. RESULTS: Most respondents perceived the methods they used for selecting testing venues, and particularly using recommendations from people receiving testing, to be effective. Most respondents also thought their promotional activities were effective. Respondents believed that using MTUs improved their capacity to reach high-risk individuals, but that MTUs were associated with substantial challenges (e.g., costs to purchase and maintain them). Programmatic challenges included training staff to provide counseling and testing, locating and providing confirmatory test results to people with reactive rapid tests, and sustaining testing programs. CONCLUSIONS: CBO staff thought the methods used to select venues for HIV testing were effective and that using MTUs increased their ability to provide testing to high-risk individuals. However, using MTUs was expensive and posed logistical difficulties. CBOs planning to implement similar programs should take these findings into consideration and pay particular attention to training needs and program sustainability.

Rapid HIV testing in transgender communities by community-based organizations in three cities.

OBJECTIVES: This article describes the demographic and behavioral characteristics, human immunodeficiency virus (HIV) testing history, and results of HIV testing of transgender (TG) people recruited for rapid HIV testing by community-based organizations (CBOs) in three cities. METHODS: CBOs in Miami Beach, Florida, New York City, and San Francisco offered TG people rapid HIV testing and prevention services, and conducted a brief survey. Participants were recruited in outreach settings using various strategies. The survey collected information on demographic characteristics, HIV risk behaviors, and HIV testing history. RESULTS: Among 559 male-to-female (MTF) TG participants, 12% were newly diagnosed with HIV infection. None of the 42 female-to-male participants were newly diagnosed with HIV. A large proportion of MTF TG participants reported high-risk behaviors in the past year, including 37% who reported unprotected receptive anal intercourse and 44% who reported commercial sex work. Several factors were independently associated with increased likelihood of being newly diagnosed with HIV infection among MTF TG participants, including having a partner of unknown HIV status in the past year; being 20-29 or > or = 40 years of age; having last been tested for HIV more than 12 months ago; and having been recruited at the New York City site. CONCLUSIONS: Based on the high proportion of undiagnosed HIV infection among those tested, TG people represent an important community for enhanced HIV testing and prevention efforts. MTF TG people should be encouraged to have an HIV test at least annually or more often if indicated, based upon clinical findings or risk behaviors. Efforts should continue for developing novel strategies to overcome barriers and provide HIV testing and prevention services to TG people.

Cost-effectiveness of finding new HIV diagnoses using rapid HIV testing in community-based organizations.

OBJECTIVE: We assessed the cost-effectiveness of determining new human immunodeficiency virus (HIV) diagnoses using rapid HIV testing performed by community-based organizations (CBOs) in Kansas City, Missouri, and Detroit, Michigan. METHODS: The CBOs performed rapid HIV testing during April 2004 through March 2006. In Kansas City, testing was performed in a clinic and in outreach settings. In Detroit, testing was performed in outreach settings only. Both CBOs used mobile testing vans. Measures of effectiveness were the number of HIV tests performed and the number of people notified of new HIV diagnoses, based on rapid tests. We retrospectively collected program costs, including those for personnel, test kits, mobile vans, and facility space. RESULTS: The CBO in Kansas City tested a mean of 855 people a year in its clinic and 703 people a year in outreach settings. The number of people notified of new HIV diagnoses was 19 (2.2%) in the clinic and five (0.7%) in outreach settings. The CBO in Detroit tested 976 people a year in outreach settings, and the number notified of new HIV diagnoses was 15 (1.5%). In Kansas City, the cost per person notified of a new HIV diagnosis was $3,637 in the clinic and $16,985 in outreach settings. In the Detroit outreach settings, the cost per notification was $13,448. CONCLUSIONS: The cost of providing a new HIV diagnosis was considerably higher in the outreach settings than in the clinic. The variation can be largely explained by differences in the number of undiagnosed infections among the people tested and by the costs of purchasing and operating a mobile van.

HIV risk behaviors and testing history in historically black college and university settings.

OBJECTIVES: From 2001 through 2005, African Americans accounted for the largest percentage of new cases of human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome (AIDS) in all age categories, especially among people aged 13 to 24 years. Although students attending historically black colleges and universities (HBCUs) report many of the behaviors that promote HIV transmission, their risk behaviors and HIV testing practices have not been well-characterized. We compared the demographic and behavioral characteristics of people who have been previously tested for HIV with those of people tested for the first time in this demonstration project to increase HIV testing at HBCUs. METHODS: The Centers for Disease Control and Prevention and collaborating partners conducted rapid HIV testing and behavioral surveys at HBCUs in Arkansas, Georgia, Mississippi, and Washington, D.C., from January 2005 to April 2007. We recruited a convenience sample of students and community members at different campus venues including student health centers, dormitories, and student activity centers. RESULTS: Our analysis included 5,291 people, 42% of whom reported they had never been tested for HIV. People who had been tested in the past were more likely to be older, believe they were at high risk for infection, have visited a health-care facility, and report behaviors that increased their risk of HIV infection. CONCLUSION: Respondents who believed they were at increased risk for HIV infection or reported behaviors that increased their risk for infection were more likely to have been tested for HIV. Future research should compare actual vs. perceived risk for HIV infection and contrast how each impacts HIV testing.

Incorporating rapid HIV testing into partner counseling and referral services.

OBJECTIVES: Partner counseling and referral services (PCRS) provide a unique opportunity to decrease transmission of human immunodeficiency virus (HIV) by notifying sex and drug-injection partners of HIV-infected individuals of their exposure to HIV. We incorporated rapid HIV testing into PCRS to reduce barriers associated with conventional HIV testing and identify undiagnosed HIV infection within this high-risk population. METHODS: From April 2004 through June 2006, HIV-infected people (index clients) were interviewed, and their partners were notified of their potential exposure to HIV and offered rapid HIV testing at six sites in the United States. The numbers of index clients participating and the numbers of partners interviewed and tested were compared by site. Descriptive and bivariate analyses were performed. RESULTS: A total of 2,678 index clients were identified, of whom 779 (29%) provided partner locating information. A total of 1,048 partners were elicited, of whom 463 (44%) were both interviewed and tested for HIV. Thirty-seven partners (8%) were newly diagnosed with HIV. The number of index clients interviewed to identify one partner with newly diagnosed HIV infection ranged from 10 to 137 at the participating sites. CONCLUSIONS: PCRS provides testing and prevention services to people at high risk for HIV infection. Incorporating rapid HIV testing into PCRS and identifying previously undiagnosed infections likely confer individual and public health benefits. Further evaluation is needed to determine the best methods of identifying partners with previously unrecognized HIV infection.

Implementing rapid HIV testing in outreach and community settings: results from an advancing HIV prevention demonstration project conducted in seven U.S. cities.

OBJECTIVES: The goals of this project were to assess the feasibility of conducting rapid human immunodeficiency virus (HIV) testing in outreach and community settings to increase knowledge of HIV serostatus among groups disproportionately affected by HIV and to identify effective nonclinical venues for recruiting people in the targeted populations. METHODS: Community-based organizations (CBOs) in seven U.S. cities conducted rapid HIV testing in outreach and community settings, including public parks, homeless shelters, and bars. People with reactive preliminary positive test results received confirmatory testing, and people confirmed to be HIV-positive were referred to health-care and prevention services. RESULTS: A total of 23,900 people received rapid HIV testing. Of the 267 people (1.1%) with newly diagnosed HIV infection, 75% received their confirmatory test results and 64% were referred to care. Seventy-six percent were from racial/ethnic minority groups, and 58% identified themselves as men who have sex with men, 72% of whom reported having multiple sex partners in the past year. Venues with the highest proportion of new HIV diagnoses were bathhouses, social service organizations, and needle-exchange programs. The acceptance rate for testing was 60% among sites collecting this information. CONCLUSIONS: Findings from this demonstration project indicate that offering rapid HIV testing in outreach and community settings is a feasible approach for reaching members of minority groups and people at high risk for HIV infection. The project identified venues that would be important to target and offered lessons that could be used by other CBOs to design and implement similar programs in the future.

Oxidative DNA damage causes mitochondrial genomic instability in Saccharomyces cerevisiae.

Mitochondria contain their own genome, the integrity of which is required for normal cellular energy metabolism. Reactive oxygen species (ROS) produced by normal mitochondrial respiration can damage cellular macromolecules, including mitochondrial DNA (mtDNA), and have been implicated in degenerative diseases, cancer, and aging. We developed strategies to elevate mitochondrial oxidative stress by exposure to antimycin and H(2)O(2) or utilizing mutants lacking mitochondrial superoxide dismutase (sod2Delta). Experiments were conducted with strains compromised in mitochondrial base excision repair (ntg1Delta) and oxidative damage resistance (pif1Delta) in order to delineate the relationship between these pathways. We observed enhanced ROS production, resulting in a direct increase in oxidative mtDNA damage and mutagenesis. Repair-deficient mutants exposed to oxidative stress conditions exhibited profound genomic instability. Elimination of Ntg1p and Pif1p resulted in a synergistic corruption of respiratory competency upon exposure to antimycin and H(2)O(2). Mitochondrial genomic integrity was substantially compromised in ntg1Delta pif1Delta sod2Delta strains, since these cells exhibit a total loss of mtDNA. A stable respiration-defective strain, possessing a normal complement of mtDNA damage resistance pathways, exhibited a complete loss of mtDNA upon exposure to antimycin and H(2)O(2). This loss was preventable by Sod2p overexpression. These results provide direct evidence that oxidative mtDNA damage can be a major contributor to mitochondrial genomic instability and demonstrate cooperation of Ntg1p and Pif1p to resist the introduction of lesions into the mitochondrial genome.

Biological consequences of oxidative stress-induced DNA damage in Saccharomyces cerevisiae.

Reactive oxygen species (ROS), generated by endogenous and exogenous sources, cause significant damage to macromolecules, including DNA. To determine the cellular effects of induced, oxidative DNA damage, we established a relationship between specific oxidative DNA damage levels and biological consequences produced by acute H2O2 exposures in yeast strains defective in one or two DNA damage-handling pathways. We observed that unrepaired, spontaneous DNA damage interferes with the normal cellular response to exogenous oxidative stress. In addition, when base excision repair (BER) is compromised, there is a preference for using recombination (REC) over translesion synthesis (TLS) for handling H2O2-induced DNA damage. The global genome transcriptional response of these strains to exogenous H2O2 exposure allowed for the identification of genes responding specifically to induced, oxidative DNA damage. We also found that the presence of DNA damage alone was sufficient to cause an increase in intracellular ROS levels. These results, linking DNA damage and intracellular ROS production, may provide insight into the role of DNA damage in tumor progression and aging. To our knowledge, this is the first report establishing a relationship between H2O2-induced biological endpoints and specific oxidative DNA damage levels present in the genome.

Spontaneous DNA damage in Saccharomyces cerevisiae elicits phenotypic properties similar to cancer cells.

To determine the spectrum of effects elicited by specific levels of spontaneous DNA damage, a series of isogenic Saccharomyces cerevisiae strains defective in base excision repair (BER) and nucleotide excision repair (NER) were analyzed. In log phase of growth, when compared with wild type (WT) or NER-defective cells, BER-defective cells and BER/NER-defective cells possess elevated levels of unrepaired, spontaneous oxidative DNA damage. This system allowed establishment of a range of approximately 400 to 1400 Ntg1p-recognized DNA lesions per genome necessary to provoke profound biological changes similar in many respects to the phenotypic properties of cancer cells. The BER/NER-defective cells are genetically unstable, exhibiting mutator and hyper-recombinogenic phenotypes. They also exhibit aberrations in morphology, DNA content, and growth characteristics compared with WT, BER-defective, and NER-defective cells. The BER/NER-defective cells also possess increased levels of intracellular reactive oxygen species, activate the yeast checkpoint response pathway via Rad53p phosphorylation in stationary phase, and show profound changes in transcription patterns, a subset of which can be ascribed to responses resulting from unrepaired DNA damage. By establishing a relationship between specific levels of spontaneous DNA damage and the ensuing deleterious biological consequences, these yeast DNA excision repair-defective strains are an informative model for gauging the progressive biological consequences of spontaneous DNA damage accumulation and may have relevancy for delineating underlying mechanisms in tumorigenesis.

Characterization of AP lyase activities of Saccharomyces cerevisiae Ntg1p and Ntg2p: implications for biological function.

Saccharomyces cerevisiae possesses two Escherichia coli endonuclease III homologs, NTG1 and NTG2, whose gene products function in the base excision repair pathway and initiate removal of a variety of oxidized pyrimidines from DNA. Although the glycosylase activity of these proteins has been well studied, the in vivo importance of the AP lyase activity has not been determined. Previous genetic studies have suggested that the AP lyase activities of Ntg1p and Ntg2p may be major contributors in the initial processing of abasic sites. We conducted a biochemical characterization of the AP lyase activities of Ntg1p and Ntg2p via a series of kinetic experiments. Such studies were designed to determine if Ntg1p and Ntg2p prefer specific bases located opposite abasic sites and whether these lesions are processed with a catalytic efficiency similar to Apn1p, the major hydrolytic AP endonuclease of yeast. Our results indicate that Ntg1p and Ntg2p are equally effective in processing four types of abasic site-containing substrates. Certain abasic site substrates were processed with greater catalytic efficiency than others, a situation similar to Apn1p processing of such substrates. These biochemical studies strongly support an important biological role for Ntg1p and Ntg2p in the initial processing of abasic sites and maintenance of genomic stability.

Interaction with Rad51 is indispensable for recombination mediator function of Rad52.

In the yeast Saccharomyces cerevisiae, the RAD52 gene is indispensable for homologous recombination and DNA repair. Rad52 protein binds DNA, anneals complementary ssDNA strands, and self-associates to form multimeric complexes. Moreover, Rad52 physically interacts with the Rad51 recombinase and serves as a mediator in the Rad51-catalyzed DNA strand exchange reaction. Here, we examine the functional significance of the Rad51/Rad52 interaction. Through a series of deletions, we have identified residues 409-420 of Rad52 as being indispensable and likely sufficient for its interaction with Rad51. We have constructed a four-amino acid deletion mutation within this region of Rad52 to ablate its interaction with Rad51. We show that the rad52delta409-412 mutant protein is defective in the mediator function in vitro even though none of the other Rad52 activities, namely, DNA binding, ssDNA annealing, and protein oligomerization, are affected. We also show that the sensitivity of the rad52delta409-412 mutant to ionizing radiation can be complemented by overexpression of Rad51. These results thus demonstrate the significance of the Rad51-Rad52 interaction in homologous recombination.