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Selected Recent ARI Publications, 2005

Barboric M, Peterlin BM. A new paradigm in eukaryotic biology: HIV Tat and the control of transcriptional elongation. PLoS Biol. 2005 Feb;3(2):e76.

Bechtel JT, Winant RC, Ganem D. Host and viral proteins in the virion of Kaposi's sarcoma-associated herpesvirus. J Virol. 2005 Apr;79(8):4952-64.

Infection of cultured cells with Kaposi's sarcoma associated herpesvirus (KSHV) typically establishes a latent infection, in which only a few viral genes are expressed. Recently, it has been reported that a subset of lytic genes are transiently expressed very early after viral entry but that this burst of abortive lytic gene expression is terminated with the supervention of latency (H. H. Krishnan, P. P. Naranatt, M. S. Smith, L. Zeng, C. Bloomer, and B. Chandran, J. Virol. 78:3601-3620, 2004). To identify molecules imported into cells by KSHV that might influence this gene expression program, we have examined the protein composition of the KSHV particle. Immunoblotting of virus particles demonstrated that RTA, the lytic switch protein, and RAP, a viral protein that is a transcriptional and cell cycle modulator, were both incorporated into virus particles. In a second approach, polypeptides isolated from purified virions were identified by mass-spectrometric analysis of their constituent tryptic peptides. With this approach we were able to identify 18 major virion proteins, including structural, regulatory, and signaling proteins of both viral and cellular origin.

Behler C, Shade S, Gregory K, Abrams D, Volberding P. Anemia and HIV in the antiretroviral era: potential significance of testosterone. AIDS Res Hum Retroviruses. 2005 Mar;21(3):200-6.

Anemia, the most common hematological disorder in human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), is associated with decreased quality of life and survival. Hypogonadism is prevalent in advanced HIV disease, however, low testosterone levels have not been customarily implicated in HIV-associated anemia. This study was undertaken to determine whether there is a relationship between testosterone levels and androgen use with anemia in HIV, and to characterize other clinical correlates of HIV-associated anemia. This was a cross-sectional, observational study of 200 HIV-positive patients at a public hospital HIV clinic from July 2000 to August 2001. A written questionnaire detailed previous and current medication use, opportunistic infections, and malignancies. Hematological and virological parameters, testosterone, and erythropoietin levels were measured; CD4(+) T lymphocyte count and viral load nadir and peak levels were obtained from the computerized medical record . Anemia was defined as hemoglobin <13.5 g/dl in men and <11.6 g/dl in women. Twenty-four percent of women and 28% of men were anemic. Anemia was associated with lymphopenia (adjusted OR 4.0, 95% CI 1.36-11.80), high erythropoietin levels (adjusted OR 7.73, 95% CI 2.92-20.48), and low testosterone levels (adjusted OR 3.27, 95% CI 1.01-10.60). Anemia was negatively associated with female sex (adjusted OR 0.30, 95% CI 0.11-0.85), current antiretroviral therapy (adjusted OR 0.43, 95% CI 0.20-0.95), current androgen use (adjusted OR 0.20, 95% CI 0.05-0.84), and macrocytosis (adjusted OR 0.23, 95% CI 0.09-0.61). Low testosterone levels may have a positive association and supplemental androgens a negative association with anemia in HIV disease.

Brindis CD, Loo VS, Adler NE, Bolan GA, Wasserheit JN. Service integration and teen friendliness in practice: A program assessment of sexual and reproductive health services for adolescents. J Adolesc Health. 2005 Aug;37(2):155-62.

PURPOSE: To aid front-line program administrators and providers in adopting national reproductive health recommendations, this exploratory case study examines the implementation of service integration and teen friendliness as strategies to improve adolescent sexual and reproductive health. METHODS: The project team conducted semi-structured interviews with administrators, providers, and adolescent clients from 10 clinical adolescent sexual and reproductive health service agencies in Alameda County, California. Programs were placed into a topology of integrated service delivery models. The teen friendliness of each program was assessed. Spearman rank correlations were calculated to evaluate the relationship between integration and teen friendliness. RESULTS: Clinical programs exhibited a great range of service delivery models within the integration topology. Human immunodeficiency virus (HIV) counseling and testing services were poorly integrated into clinic services. Teen friendliness and integration show ed a negative, but not statistically significant, correlation (R = -.45, p = .19). CONCLUSION: Programs have made different levels of commitment to service integration or teen friendliness policies. Lessons learned through the integration of sexually transmitted disease (STD) and family planning services may assist efforts to better integrate HIV services for adolescents. Further work to elucidate the relationship between integration and teen friendliness is needed. Periodic reviews can ensure that recommended clinical guidelines, specifically annual risk assessment, are being met, as well as identifying achievable next steps to improve adolescent sexual and reproductive health service delivery.

Buchbinder SP, Vittinghoff E, Heagerty PJ, Celum CL, Seage GR 3rd, Judson FN, McKirnan D, Mayer KH, Koblin BA. Sexual risk, nitrite inhalant use, and lack of circumcision associated with HIV seroconversion in men who have sex with men in the United States. J Acquir Immune Defic Syndr. 2005 May 1;39(1):82-9.

Men who have sex with men (MSM) continue to account for the largest number of new HIV infections in the United States, but limited data exist on independent risk factors for infection beyond the early 1990s. The HIV Network for Prevention Trials Vaccine Preparedness Study enrolled 3257 MSM in 6 US cities from 1995 to 1997. HIV seroincidence was 1.55 per 100 person-years (95% confidence interval: 1.23-1.95) over 18 months of follow-up. On multi-variable analysis using time-dependent covariates, independent risk factors for HIV seroconversion were increased number of reported HIV-negative male sex partners (adjusted odds ratio (AOR) = 1.14 per partner, population attributable risk (PAR) = 28%), nitrite inhalant use (AOR = 2.2, PAR = 28%), unprotected receptive anal sex with an HIV unknown serostatus partner (AOR = 2.7, PAR = 15%) or HIV-positive partner (AOR = 3.4, PAR = 12%), protected receptive anal sex with an HIV-positive partner (AOR = 2.2, PAR = 11%), lack of circumcision (AOR = 2.0, PAR = 10%), and r eceptive oral sex to ejaculation with an HIV-positive partner (AOR = 3.8, PAR = 7%). Having a large number of male sex partners, nitrite inhalant use, and engaging in receptive anal sex explained the majority of infections in this cohort and should be targeted in prevention strategies for MSM.

Busch MP, Tobler LH, Saldanha J, Caglioti S, Shyamala V, Linnen JM, Gallarda J, Phelps B, Smith RI, Drebot M, Kleinman SH. Analytical and clinical sensitivity of West Nile virus RNA screening and supplemental assays available in 2003. Transfusion. 2005 Apr;45(4):492-9. Comment in: Transfusion. 2005 Apr;45(4):460-2.

BACKGROUND: Transfusion-transmitted West Nile virus (WNV) infections were first reported in 2002, which led to rapid development of investigational nucleic acid amplification tests (NAT). A study was conducted to evaluate sensitivities of WNV screening and supplemental NAT assays first employed in 2003. STUDY DESIGN AND METHODS: Twenty-five member-coded panels were distributed to NAT assay manufacturers. Panels included five pedigreed WNV standards (1, 3, 10, 30, and 100 copies/mL), 15 or 16 donor units with very-low-level viremia identified through 2003 screening, and four or five negative control samples. Samples were tested neat in 10 replicates by all assays; for NAT screening assays, 10 replicates were also performed on dilutions consistent with minipool (MP)-NAT. The viral load distribution for 142 MP-NAT yield donations was characterized, relative to the analytical sensitivity of MP-NAT systems. RESULTS: Analytical sensitivities (50% limits of detection [LoD] based on Poisson model of detection of WNV standards) for screening NAT assays ranged from 3.4 to 29 copies per mL; when diluted consistent with MP pool sizes, the 50 percent LoD of screening NAT assays was reduced to 43 to 309 copies per mL. Analytical sensitivity of supplemental assays ranged from 1.5 to 7.7 copies per mL (50% LoD). Detection of RNA in donor units varied consistent with analytical LoD of assays. Detection of low-level viremia after MP dilutions was particularly compromised for seropositive units, probably reflecting lower viral loads in the postseroconversion phase. Based on the viral load distribution of MP-NAT yield donations (median, 3519 copies/mL; range, < 50-690,000), 13 to 24 percent of units had viral loads below the 50 percent LoD of screening NAT assays run in MP-NAT format. CONCLUSION: WNV screening and supplemental assays had generally excellent analytical sensitivity, comparable to human immunodeficiency virus-1 and hepatitis C virus NAT assays. The presence of low-level viremic units during epidemic periods and the impact of MP dilutions on sensitivity, however, suggest the need for further improvements in sensitivity as well as a role for targeted individual-donation NAT in epidemic regions.

Busch MP, Glynn SA, Stramer SL, Strong DM, Caglioti S, Wright DJ, Pappalardo B, Kleinman SH; NHLBI-REDS NAT Study Group. A new strategy for estimating risks of transfusion-transmitted viral infections based on rates of detection of recently infected donors. Transfusion. 2005 Feb;45(2):254-64.

BACKGROUND: Estimates for human immunodeficiency virus (HIV)-1 and hepatitis C virus (HCV) transfusion-transmitted risks have relied on incidence derived from repeat donor histories and imprecise estimates for infectious, preseroconversion window periods (WPs). STUDY DESIGN AND METHODS: By use of novel approaches, WPs were estimated by back-extrapolation of acute viral replication dynamics. Incidence was derived from the yield of viremic, antibody-negative donations detected by routine minipool nucleic acid testing (MP-NAT) of 37 million US donations (1999-2002) or from sensitive/less-sensitive HIV-1 enzyme immunoassay (S/LS-EIA) results for seropositive samples from 6.5 million donations (1999). Incidences and WPs were combined to calculate risks and project yield of individual donation (ID)-NAT. RESULTS: The HIV-1 WP from presumed infectivity (1 copy/20 mL) to ID-NAT detection was estimated at 5.6 days, and the periods from ID to MP-NAT detection and from MP-NAT to p24 detection at 3.4 and 6.0 days, res pectively; corresponding estimates for HCV were 4.9, 2.5, and 50.9 days (the latter represents period from MP-NAT to HCV antibody detection). The HIV-1 incidence projected from MP-NAT yield or from S/LS-EIA data was 1.8 per 100,000 person-years, resulting in a corresponding HIV-1 transfusion-transmitted risk of 1 in 2.3 million. The HCV incidence from MP-NAT yield was 2.70 per 100,000 person-years with a corresponding risk of 1 in 1.8 million donations. Conversion from MP-NAT to ID-NAT was projected to detect two to three additional HIV-1 and HCV infectious units annually. CONCLUSIONS: MP-NAT yield and S/LS-EIA rates can accurately project transfusion risks. HCV and HIV-1 risks, currently estimated at 1 per 2 million units, could be reduced to 1 in 3 to 4 million units by ID-NAT screening.

Cardenas VA, Studholme C, Meyerhoff DJ, Song E, Weiner MW. Chronic active heavy drinking and family history of problem drinking modulate regional brain tissue volumes. Psychiatry Res. 2005 Feb 28;138(2):115-30.

The goals of this study were to measure if chronic active heavy drinking is associated with brain volume loss in non-treatment seeking men and women, and to assess the effect of positive family history of problem drinking on brain structure in heavy drinkers. Automated image processing was used to analyze high-resolution T1-weighted magnetic resonance images from 49 active heavy drinkers and 49 age- and sex-matched light drinkers, yielding gray matter, white matter and cerebrospinal fluid (CSF) volumes within the frontal, temporal, parietal and occipital lobes. Regional brain volume measures were compared as a function of group, sex and their interaction. Within heavy drinkers, volumes were correlated with measures of alcohol consumption and compared as a function of family history of problem drinking. Deformation morphometry explored localized patterns of atrophy associated with heavy drinking or severity of drinking. We found significant gray matter volume losses, but no white matter losses, in active h eavy drinkers compared with light drinkers. Women had greater gray matter and smaller white matter and CSF volumes as a percentage of intracranial vault than men. Within heavy drinkers, smaller gray matter volumes were associated with higher current levels of drinking and older age, while a positive family history of problem drinking was associated with smaller CSF volumes. Community-dwelling heavy drinkers who are not in alcoholism treatment have dose-related gray matter volume losses, and family history of problem drinking ameliorates some structural consequences of heavy drinking.

Catania JA, Osmond D, Neilands TB, Canchola J, Gregorich S, Shiboski S. Commentary on Schroder et al. (2003a, 2003b). Ann Behav Med. 2005 Apr;29(2):86-95; discussion 96-9. Comment on: Ann Behav Med. 2003 Oct;26(2):104-23. Ann Behav Med. 2003 Oct;26(2):76-103.

Charlebois ED, Maiorana A, McLaughlin M, Koester K, Gaffney S, Rutherford GW, Morin SF. Potential deterrent effect of name-based HIV infection surveillance. J Acquir Immune Defic Syndr. 2005 Jun 1;39(2):219-27.

To meet federal recommendations to collect case reports of HIV infection, California has adopted a non-name code system to conduct HIV surveillance. The objective of this study was to evaluate among HIV test takers the acceptability and preferences for the 3 major types of HIV infection reporting-name, name-to-code, and non-name code. Interviewer-administered exit surveys with spoken scripts and matching printed materials clearly outlining the 3 HIV reporting options were conducted among HIV test takers immediately following appointments for pretest HIV counseling and blood collection. The study enrolled 208 HIV test takers at 14 publicly funded HIV testing sites in 4 California counties (Los Angeles, Riverside, Fresno, and Santa Clara). Overall with respect to which would be the most acceptable system, 67% reported non-name code, 19% reported name-to-code, and 12% reported name-based HIV reporting (P < 0.0001). A second sample of 226 exit surveys taken 1 year following implementation of California's non- name code HIV infection reporting system continued to show a significant preference for non-name code HIV infection reporting. Significant independent predictors of a preference for coded HIV reporting in both the pre- and postimplementation period were men who have sex with men (odds ratio [OR] = 5.7, 95% CI: 1.2-26 in the preperiod) and having just taken an anonymous HIV test (OR = 3.6, 95% CI: 1.4-9.3, P = 0.009 preperiod). Were the state to adopt name-based HIV reporting, significantly fewer individuals report being likely in the next 12 months to have a confidential HIV test than report being likely to have an anonymous HIV test (51% likely confidential vs. 76% likely anonymous, P < 0.0001). This analysis documents strong support, among HIV test takers in California, for a non-name coded HIV reporting system and indicates a high probability of a shift away from confidential testing toward anonymous testing under a scenario of name-based reporting. This shift is of concern as confidential HIV testing is the basis of US HIV surveillance systems.

Chin-Hong PV, Vittinghoff E, Cranston RD, Browne L, Buchbinder S, Colfax G, Da Costa M, Darragh T, Benet DJ, Judson F, Koblin B, Mayer KH, Palefsky JM. Age-related prevalence of anal cancer precursors in homosexual men: The EXPLORE study. J Natl Cancer Inst. 2005 Jun 15;97(12):896-905.

BACKGROUND: Infection with human papillomavirus (HPV) is causally linked to the development of anal and cervical cancer. In the United States, the incidence of anal cancer among men who have sex with men (MSM) is higher than the incidence of cervical cancer among women. Anal squamous intraepithelial lesions (ASILs) are anal cancer precursors comprising low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs). The prevalence of cervical cancer precursor lesions peaks at around 30 years of age. The age-related prevalence of ASILs in HIV-negative MSM is unknown. METHODS: We conducted a cross-sectional analysis of the prevalence and determinants of ASILs in 1262 HIV-negative MSM aged 18-89 years recruited from four U.S. cities. Anal cytology and behavioral data were obtained. Anal HPV infection status was assessed by polymerase chain reaction. Independent predictors of ASILs were identified using logistic regression. All statistical tests were two-sided. RESUL TS: The prevalences of LSILs and HSILs were 15% and 5%, respectively, and did not change with age. In a multivariable analysis, the risk of LSILs was associated with having more than five male receptive anal sex partners (P = .03), any use of poppers (alkyl nitrites) in the previous 6 months [odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.1 to 2.5; P = .03] or use of injection drugs two or more times per month during the previous 6 months [OR = 19, 95% CI = 1.3 to 277; P = .03], older age at first receptive anal intercourse (P = .004), and infection with a greater number of HPV types (P < .001 for linear trend). The risk of HSILs was associated with any anal HPV infection (OR = 3.2, 95% CI = 1.1 to 9.4; P = .039) and infection with an increasing number of HPV types (P < .001 for linear trend). CONCLUSIONS: Sexually active HIV-negative MSM in all age groups have a high prevalence of ASILs, possibly reflecting their ongoing sexual exposure to HPV.

Chirenje ZM. HIV and cancer of the cervix. Best Pract Res Clin Obstet Gynaecol. 2005 Apr;19(2):269-76.

Cancer of the cervix is the second most common cause of cancer-related death in women worldwide, and in some low resource countries accounts for the highest cancer mortality in women. The highest burden of the HIV/AIDS epidemic is currently in sub-Saharan Africa, where more than half of the people infected are women who have no access to cervical cancer screening. The association between HIV and invasive cervical cancer is complex, with several studies now clearly demonstrating an increased risk of pre-invasive cervical lesions among HIV-infected women. However, there have not been significantly higher incidence rates of invasive cervical cancer associated with the HIV epidemic. The highest numbers of HIV-infected women are in poorly-resourced countries, where the natural progression of HIV disease in the absence of highly active antiretroviral treatment sometimes results in deaths from opportunistic infections before the onset of invasive cervical cancer. This chapter will discuss the association of HIV and cervical intraepithelial neoplasia, the treatment of pre-invasive lesions, and invasive cervical cancer in HIV-infected women. The role of screening and the impact of antiretroviral treatment on the progression of pre-invasive and invasive cancer will also be discussed.

Comfort M, Grinstead O, McCartney K, Bourgois P, Knight K. "You cannot do nothing in this damn place": Sex and intimacy among couples with an incarcerated male partner. J Sex Res. 2005 Feb;42(1):3-12.

In an effort to deepen our understanding of how circumstances of forced separation and the interdiction of physical contact affect women's sexual behavior, we investigated the development and maintenance of heterosexual couples' intimacy when the male partner is incarcerated. As HIV-prevention scientists who work with women visiting men at a California state prison, we recognize that correctional control extends to these women's bodies, both when they are within the facility's walls visiting their mates and when they are at home striving to remain connected to absent men. This paper analyzes the impact of a peculiar public "place", a penitentiary, on couples' romantic and sexual interactions, drawing out the implications of imprisonment for relationship decision making, sexual health, and HIV risk. Using qualitative interviews with 20 women who visit their incarcerated partners and 13 correctional officers who interact with prison visitors, we examined how institutional constraints such as the regulation of women's apparel, the prohibition of physical contact, and the lack of forums for privacy result in couples forging alternative "spaces" in which their relationships occur. We describe how romantic scripts, the build-up of sexual tension during the incarceration period, and conditions of parole promote unprotected sexual intercourse and other HIV/STD risk behavior following release from prison.

Cowan FM, Hargrove JW, Langhaug LF, Jaffar S, Mhuriyengwe L, Swarthout TD, Peeling R, Latif A, Bassett MT, Brown DW, Mabey D, Hayes RJ, Wilson D. The appropriateness of core group interventions using presumptive periodic treatment among rural Zimbabwean women who exchange sex for gifts or money. J Acquir Immune Defic Syndr. 2005 Feb 1;38(2):202-7.

To map the characteristics of rural based sex workers in Zimbabwe with regard to demographics, mobility, behavior, HIV and sexually transmitted infection (STI) prevalence, to explore the appropriateness and feasibility of presumptive periodic treatment (PPT) for bacterial STIs as an HIV prevention intervention among these women, and to compare tolerability of 2 PPT regimens (1 g of azithromycin and 2 g of metronidazole+/-500 mg of ciprofloxacin). Five commercial farms and 2 mines in Mashonaland West, Zimbabwe. Three hundred sixty-three sex workers were recruited and completed a structured interviewer-administered questionnaire. Each participant had blood tested for antibody to HIV, herpes simplex virus 2 (HSV-2), and syphilis; urine tested for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); and a vaginal swab tested for Trichomonas vaginalis (TV). Women were randomly assigned to receive a single dose of 1 of 2 PPT regimens and then followed to assess rates of side effects and reinfection. The o verall prevalence of antibody to HIV was 55.7% (95% confidence interval [CI]: 50.6-60.9) and that of HSV-2 was 80.8% (95% CI: 76.7-84.9). The prevalence of CT and NG was low (CT=1.7%, 95% CI: 0.3-3.0); (NG=1.9%, 95% CI: 0.5-3.4), with a much higher prevalence of TV (TV=19.3%, 95% CI: 15.2-23.4). Prevalence of CT, NG, and TV was appreciably reduced 1 month after PPT but rose to pretreatment levels at the 2- and 3-month visits. The rate of moderate or severe side effects after PPT was low, but it was higher in the women who received ciprofloxacin in addition to azithromycin and metronidazole (P=0.007). It was feasible to access women who reported exchanging money or gifts for sex in rural communities, although many of these women engaged in sex work only infrequently. The prevalence of bacterial STIs was low, suggesting that PPT may not be an appropriate intervention in this setting. Rapid reinfection after PPT suggests that this needs to be given at monthly intervals to reduce prevalence of STIs.

Downing M, Riess TH, Vernon K, Mulia N, Hollinquest M, McKnight C, Jarlais DC, Edlin BR. What's community got to do with it? Implementation models of syringe exchange programs. AIDS Educ Prev. 2005 Feb;17(1):68-78.

Syringe exchange programs (SEPs) have been shown to be highly effective in reducing HIV transmission among injection drug users (IDUs). Despite this evidence, SEPs have not been implemented in many communities experiencing HIV epidemics among IDUs. We interviewed 17 key informants in nine U.S. cities to identify factors and conditions that facilitated or deterred the adoption of SEPs. Cities were selected to represent diversity in size, geographic location, AIDS incidence rates, and SEP implementation. Key informants included HIV prevention providers, political leaders, community activists, substance use and AIDS researchers, and health department directors. SEPs were established by one or more of three types of implementation models: (a) broad community coalition support, (b) community activist initiative, and (c) top-down decision making by government authorities. In each model, coalition building and community consultation were critical steps for the acceptance and sustainability of SEPs. When others w ere not prepared to act, community activists spearheaded SEP development, taking risks in the face of opposition, but often lacked the resources to sustain their efforts. Leadership from politicians and public health officials provided needed authority, clout, and access to resources. Researchers and scientific findings lent force and legitimacy to the effort. Rather than adopting adversarial positions, successful SEP implementers worked with or avoided the opposition. Fear of repercussions and lack of leadership were the greatest barriers to implementing SEPs. Communities that successfully implemented SEPs were those with activists willing to push the agenda, public officials willing to exercise leadership, researchers able to present authoritative findings, and proponents who effectively mobilized resources and worked to build community coalitions, using persistent but nonadversarial advocacy.

Earle KE, Tang Q, Zhou X, Liu W, Zhu S, Bonyhadi ML, Bluestone JA. In vitro expanded human CD4+CD25+ regulatory T cells suppress effector T cell proliferation. Clin Immunol. 2005 Apr;115(1):3-9.

Regulatory T cells (Tregs) have been shown to be critical in the balance between autoimmunity and tolerance and have been implicated in several human autoimmune diseases. However, the small number of Tregs in peripheral blood limits their therapeutic potential. Therefore, we developed a protocol that would allow for the expansion of Tregs while retaining their suppressive activity. We isolated CD4+CD25 hi cells from human peripheral blood and expanded them in vitro in the presence of anti-CD3 and anti-CD28 magnetic Xcyte Dynabeads and high concentrations of exogenous Interleukin (IL)-2. Tregs were effectively expanded up to 200-fold while maintaining surface expression of CD25 and other markers of Tregs: CD62L, HLA-DR, CCR6, and FOXP3. The expanded Tregs suppressed proliferation and cytokine secretion of responder PBMCs in co-cultures stimulated with anti-CD3 or alloantigen. Treg expansion is a critical first step before consideration of Tregs as a therapeutic intervention in patients with autoimmune or g raft-versus-host disease.

Eggena MP, Barugahare B, Okello M, Mutyala S, Jones N, Ma Y, Kityo C, Mugyenyi P, Cao H. T cell activation in HIV-seropositive Ugandans: Differential associations with viral load, CD4+ T cell depletion, and coinfection. J Infect Dis. 2005 Mar 1;191(5):694-701. Epub 2005 Jan 31.

Immune activation is thought to play a major role in the pathogenesis of human immunodeficiency virus (HIV). This effect may be particularly relevant in Africa, where endemic coinfections may contribute to disease progression, perhaps as a consequence of enhanced immune activation. We investigated the expression of CD38 and human leukocyte antigen (HLA)-DR on T cells in 168 HIV-seropositive volunteers in Uganda. We observed higher levels of CD4(+) and CD8(+) T cell activation in Uganda, compared with those reported in previous studies from Western countries. Coexpression of CD38 and HLA-DR on both CD4(+) and CD8(+) T cell subsets was directly correlated with viral load and inversely correlated with CD4(+) T cell counts. In antiretroviral therapy (ART)-naive volunteers, viral load and CD4(+) T cell count had stronger associations with CD8(+) and CD4(+) T cell activation, respectively. Virus suppression by ART was associated with a reduction in T cell activation, with a stronger observed effect on reducing CD8(+) compared with CD4(+) T cell activation. The presence of coinfection was associated with increased CD4(+) T cell activation but, interestingly, not with increased CD8(+) T cell activation. Our results suggest that distinct mechanisms differentially drive activation in CD4(+) and CD8(+) T cell subsets, which may impact the clinical prognostic values of T cell activation in HIV infection.

Elbeik T, Nassos P, Kipnis P, Haller B, Ng VL. Evaluation of the VACUTAINER PPT plasma preparation tube for use with the Bayer VERSANT assay for quantification of human immunodeficiency virus type 1 RNA. J Clin Microbiol. 2005 Aug;43(8):3769-71.

Separation and storage of plasma within 2 h of phlebotomy is required for the VACUTAINER PPT Plasma Preparation Tube (PPT) versus 4 h for the predecessor VACUTAINER EDTA tube for human immunodeficiency virus type 1 (HIV-1) viral load (HIVL) testing by the VERSANT HIV-1 RNA 3.0 assay (branched DNA). The 2-h limit for PPT imposes time constraints for handling and transporting to the testing laboratory. This study compares HIVL reproducibility from matched blood in EDTA tubes and PPTs and between PPT pairs following processing within 4 h of phlebotomy, stability of plasma HIV-1 RNA at 24- and 72-h room temperature storage in the tube, and comparative labor and supply requirements. Blood from 159 patients was collected in paired tubes (EDTA/PPT or PPT/PPT): 86 paired EDTA tubes and PPTs were processed 4 h following phlebotomy and their HIVLs were compared, 42 paired PPT/PPT pairs were analyzed for intertube HIVL reproducibility, and 31 PPT/PPT pairs were analyzed for HIV-1 RNA stability by HIVL. Labor and sup ply requirements were compared between PPT and EDTA tubes. PPTs produce results equivalent to standard EDTA tube results when processed 4 h after phlebotomy. PPT intertube analyte results are reproducible. An average decrease of 13% and 37% in HIVL was observed in PPT plasma after 24 and 72 h of room temperature storage, respectively; thus, plasma can be stored at room temperature up to 24 h in the original tube. PPTs offer labor and supply savings over EDTA tubes.

Havlir DV, Koelsch KK, Strain MC, Margot N, Lu B, Ignacio CC, Miller MD, Wong JK; Gilead 903 Study Team. Predictors of residual viremia in HIV-infected patients successfully treated with efavirenz and lamivudine plus either tenofovir or stavudine. J Infect Dis. 2005 Apr 1;191(7):1164-8. Epub 2005 Feb 28.

In human immunodeficiency virus (HIV)-infected patients successfully treated with highly active antiretroviral therapy (HAART), a low level of HIV RNA persists in plasma at steady state for years and varies among patients. To understand predictors of residual viremia, we measured HIV RNA levels <50 copies/mL in patients after 1 year of treatment with efavirenz and lamivudine plus either tenofovir disoproxil fumarate (n=55) or stavudine (n=45), by use of an HIV RNA assay with a limit of detection of 2.5 copies/mL. The mean posttreatment HIV RNA levels were 0.58 log(10) copies/mL (3.8 copies/mL) in the tenofovir arm and 0.61 log(10)copies/mL (4.1 copies/mL) in the stavudine arm (P=.24). Forty-seven percent of patients receiving tenofovir, compared with 29% of patients receiving stavudine, had undetectable residual viremia (P=.07). In multivariate analyses, we found that lower baseline HIV RNA levels in plasma, lower HIV DNA levels in peripheral blood mononuclear cells, and inclusion in the tenofovir arm eac h independently predicted undetectable residual viremia (P<.05). However, a level of residual viremia <50 copies/mL was not associated with CD4 cell count changes or risk of virologic rebound through 72 weeks of follow-up.

Hurst EA, Mauro T. Sarcoidosis associated with pegylated interferon alfa and ribavirin treatment for chronic hepatitis C: A case report and review of the literature. Arch Dermatol. 2005 Jul;141(7):865-8.

BACKGROUND: At least 2.7 million Americans are infected with chronic hepatitis C. An increasing number are treated with interferon alfa plus ribavirin regimens. Not surprisingly, this immune stimulation is associated with the development of autoimmune and cutaneous diseases. Several cases of sarcoidosis have been reported with hepatitis C treatment, most recently in association with pegylated interferon alfa plus ribavirin. Systemic manifestations of sarcoidosis are usually treated with oral steroids, which unfortunately often increase the hepatitis C viral load. Thus, it is important to ascertain whether systemic corticosteroids are required to treat interferon alfa-associated sarcoidosis. OBSERVATIONS: We report the third case of cutaneous sarcoidosis in association with pegylated interferon alfa plus ribavirin treatment. Our patient had both cutaneous and pulmonary involvement, which has been spontaneously resolving since his treatment regimen was completed. In addition, we review the 12 previously rep orted cases of cutaneous sarcoidosis that occurred in patients undergoing hepatitis C treatment with interferon alfa. CONCLUSIONS: As the number of patients being treated with interferon alfa and ribavirin for hepatitis C increases, it is essential that dermatologists recognize the association of this treatment with sarcoidosis, because skin lesions may provide the first clue to diagnosis. Development of sarcoidosis may relate to hepatitis C as a possible antigenic trigger in the presence of an enhanced helper T cells type 1 response from treatment. Sarcoidosis with skin lesions in patients undergoing hepatitis C treatment often follows a benign course, and interferon alfa therapy may sometimes be continued with resolution of sarcoidosis occurring spontaneously or within a few months of completing treatment. Cautious use of systemic corticosteroids is warranted given their adverse effects on hepatitis C viral loads.

Jarvis GA, Janoff EN, Cheng H, Devita D, Fasching C, McCulloch CE, Murphy EL. Human T lymphotropic virus type II infection and humoral responses to pneumococcal polysaccharide and tetanus toxoid vaccines. J Infect Dis. 2005 Apr 15;191(8):1239-44. Epub 2005 Mar 14.

Infection with human T lymphotropic virus type II (HTLV-II) has been linked to an increased incidence of bacterial pneumonia. To determine whether HTLV-II infection is associated with impaired humoral immune responses, we immunized a cohort of HTLV-II-infected subjects and matched uninfected control subjects with 23-valent pneumococcal polysaccharide and tetanus toxoid vaccines. The pneumococcal polysaccharide vaccine elicited comparable and significant increases in concentrations of IgG against all 5 serotypes tested at 1 and 6 months after immunization in both groups. The avidity and opsonophagocytic functions of the anticapsular IgG were similar. The concentrations of tetanus toxoid-specific IgG also increased comparably and significantly over time in both groups. Thus, HTLV-II-infected persons develop robust humoral responses to potentially protective polysaccharide and protein vaccines.

Jeremy RJ, Kim S, Nozyce M, Nachman S, McIntosh K, Pelton SI, Yogev R, Wiznia A, Johnson GM, Krogstad P, Stanley K; Pediatric AIDS Clinical Trials Group (PACTG) 338 & 377 Study Teams. Neuropsychological functioning and viral load in stable antiretroviral therapy-experienced HIV-infected children. Pediatrics. 2005 Feb;115(2):380-7.

OBJECTIVE: Neuropsychological functioning and its correlation with viral load were investigated for previously treated HIV-infected children who underwent a change in treatment regimen. METHODS: Thirteen age-appropriate measures of cognitive, neurologic, and behavioral functioning were administered to 489 HIV-infected children who were aged 4 months to 17 years and had been treated previously for at least 16 weeks with antiretroviral therapy. These clinically and immunologically stable children were randomized onto 1 of 7 drug treatment combinations, 6 of which included a protease inhibitor (PI), and evaluated prospectively for 48 weeks with respect to changes in neuropsychological performance and viral load. RESULTS: Neuropsychological functioning was significantly poorer at baseline for the HIV-infected children as compared with established norms for their age. Children with higher viral load had poorer cognitive, both-hands fine-motor, and neurologic signs at baseline, but single-hand fine-motor and be havioral functioning were not correlated with viral load. After 48 weeks of treatment with PI-containing combination therapy, there was significant improvement in only the vocabulary score. Neuropsychological changes did not differ among the 6 PI-containing combination regimens. At week 48, even children with a viral load response below the level of detection (RNA < or =400 copies/mL) still showed poorer neuropsychological functioning compared with established norms. CONCLUSION: Poor neuropsychological functioning was seen for HIV-infected children and was worse for children with higher viral loads. Only 1 measure of neuropsychological functioning showed improvement after treatment with PI-containing combination therapy, and the extent of that improvement was relatively minor. Treatment strategies for children with HIV disease need to be reevaluated so that they consider restoration of neuropsychological functioning in addition to lowering the viral load.

Khalili M, Bernstein D, Lentz E, Barylski C, Hoffman-Terry M. Pegylated interferon alpha-2a with or without ribavirin in HCV/HIV coinfection: Partially blinded, randomized multicenter trial. Dig Dis Sci. 2005 Jun;50(6):1148-55.

We evaluated the safety and efficacy of peginterferon alpha-2a (pegIFNalpha-2a), with or without ribavirin, in 154 HCV/HIV coinfected patients. All received pegIFNalpha-2a (180 microg/week) for 12 weeks, with those achieving an early virologic response (EVR) continued on monotherapy through week 48. Patients without an EVR were randomized at week 14 to also receive ribavirin (800 mg/day) or placebo through week 48. Patients with detectable HCV RNA at week 24 were discontinued. An EVR occurred in 59 of 154 patients on monotherapy, and a sustained virologic response (SVR) occurred in 19 of 55 of those achieving an EVR and continuing monotherapy through week 48. One week 12 nonresponder receiving pegIFNalpha-2a plus ribavirin, and none receiving pegIFNalpha-2a plus placebo, achieved a SVR. Discontinuations for adverse events occurred in 10 of 154 patients before, and 16 of 131 after, week 14. HIV RNA and CD4 counts did not change significantly during treatment. PegIFNalpha-2a was therefore at least as effect ive as standard interferon and ribavirin combination therapy and was well tolerated, without a negative impact on HIV parameters.

Knight KR, Purcell D, Dawson-Rose C, Halkitis PN, Gomez CA; Seropositive Urban Injectors Study Team. Sexual risk taking among HIV-positive injection drug users: Contexts, characteristics, and implications for prevention. AIDS Educ Prev. 2005 Feb;17(1 Suppl A):76-88

HIV-positive injection drug users (IDUs) ( N = 161) were recruited to complete a qualitative interview and a quantitative survey about sexual behavior and transmission risk. We identified two contexts in which exposure encounters occurred most commonly for HIV-positive IDUs: in intimate serodiscordant relationships and in the drug/sex economy. Salient characteristics in both contexts included the role of intimacy, drug use and sexual decision making, disclosure of HIV status, and perceived responsibility. Although these characteristics emerged in both risk contexts, they operated differently within each context. The preservation of intimacy was paramount among those in serodiscordant relationships, and agreements to take risks were common. In the drug/sex economy, serostatus disclosure was uncommon and drug acquisition and use played a significant role in sexual risk taking. Our data emphasize a need to address the specific transmission risk contexts occurring among HIV-positive IDUs and to prioritize soc ial and interpersonal factors when promoting safer sexual norms among HIV-positive IDUs.

Kral AH, Lorvick J, Ciccarone D, Wenger L, Gee L, Martinez A, Edlin BR. HIV prevalence and risk behaviors among men who have sex with men and inject drugs in San Francisco. J Urban Health. 2005 Mar;82(1 Suppl 1):i43-50. Epub 2005 Feb 28.

The dual risks of male-to-male sex and drug injection have put men who have sex with men and inject drugs (MSM-IDU) at the forefront of the HIV epidemic, with the highest rates of infection among any risk group in the United.States. This study analyzes data collected from 357 MSM-IDU in San Francisco between 1998 and 2002 to examine how risk behaviors differ by HIV serostatus and self-identified sexual orientation and to assess medical and social service utilization among HIV-positive MSM-IDU. Twenty-eight percent of the sample tested HIV antibody positive. There was little difference in risk behaviors between HIV-negative and HIV-positive MSM-IDU. Thirty percent of HIV-positive MSM-IDU reported distributive syringe sharing, compared to 40% of HIV negatives. Among MSM-IDU who reported anal intercourse in past 6 months, 70% of positives and 66% of HIV negatives reported unprotected anal intercourse. HIV status varied greatly by self-identified sexual orientation: 46% among gay, 24% among bisexual, and 14% among heterosexual MSM-IDU. Heterosexual MSM-IDU were more likely than other MSM-IDU to be homeless and to trade sex for money or drugs. Gay MSM-IDU were more likely to have anal intercourse. Bisexual MSM-IDU were as likely as heterosexual MSM-IDU to have sex with women and as likely as gay-identified MSM-IDU to have anal intercourse. Among MSM-IDU who were HIV positive, 15% were currently on antiretroviral therapy and 18% were currently in drug treatment, and 87% reported using a syringe exchange program in the past 6 months. These findings have implications for the development of HIV interventions that target the diverse MSM-IDU population.

Minnis AM, Padian NS. Effectiveness of female controlled barrier methods in preventing sexually transmitted infections and HIV: current evidence and future research directions. Sex Transm Infect. 2005 Jun;81(3):193-200.

OBJECTIVES: To evaluate evidence for the effectiveness of female controlled physical and chemical barrier methods in preventing STI/HIV transmission, to examine recent reviews on microbicide development, and to highlight promising research directions. To discuss challenges in conducting effectiveness research and in translating results to public health intervention. METHODS: Systematic review of articles that examined the disease prevention effectiveness of at least one female controlled barrier method. Review of conference abstracts that presented clinical and preclinical microbicide data. RESULTS: Randomised controlled trials provide evidence that female condoms confer as much protection from STIs as male condoms. Observational studies suggest that the diaphragm protects against STI pathogens. Several microbicide effectiveness studies are under way and new directions, such as adaptation of therapeutic agents as preventive products, are being examined. Substantial attention is now given to product formul ation and novel delivery strategies. Combining microbicide products with different mechanisms of action as well as combining chemical and physical barriers will be necessary to maximise prevention effectiveness. CONCLUSIONS: Increased investment in the development and identification of female controlled barrier methods offers promise that additional products will be available in the years ahead. Generalizing trial results to a community setting, promoting products that may be less effective than male condoms, and bringing an effective product to scale introduce public health challenges that warrant attention. The need for female controlled barrier methods that provide women with the opportunity to take an active role in reducing their STI/HIV risk are urgently needed and constitute an essential tool to prevent continued spread of these infections.

Mulligan K, Anastos K, Justman J, Freeman R, Wichienkuer P, Robison E, Hessol NA. Fat distribution in HIV-infected women in the United States: DEXA substudy in the Women's Interagency HIV Study. J Acquir Immune Defic Syndr. 2005 Jan 1;38(1):18-22.

Surveys in HIV-infected men on antiretroviral therapy (ART) consistently demonstrate decreased levels of peripheral fat, with variable effects on central fat. This substudy of the Women's Interagency HIV Study was undertaken to examine fat distribution in a well-characterized cohort of HIV-positive and HIV-negative women in the United States. Whole-body dual-energy x-ray absorptiometry scanning with standardized regional analysis was performed in 271 nonpregnant women. Results were compared in the following groups: HIV negative (n = 88); and HIV positive on no ART (n = 70), highly active ART with a protease inhibitor (HAART/PI) (n = 48), or non-PI-containing HAART (n = 53). The groups were well matched with respect to race, with the majority of women coming from racial/ethnic minorities. The majority of both HIV-positive and HIV-negative women were overweight (body mass index [BMI] >/=25 kg/m), and many were obese (BMI >30 kg/m). Leg fat in both groups on HAART was significantly lower than in HIV-negative women (P = 0.01 and <0.0001 vs. HIV-negative for HAART/PI and HAART/no PI, respectively), whereas trunk fat was lower only in HAART/no PI (P = 0.0004 vs. HIV-negative). Thus, consistent with reports in men, lower levels of peripheral (leg) fat are seen in HIV-infected women on HAART, despite the high prevalence of obesity in this population.

Mulligan K, Zackin R, Clark RA, Alston-Smith B, Liu T, Sattler FR, Delvers TB, Currier JS; AIDS Clinical Trials Group 329 Study Team; National Institute of Allergy and Infectious Diseases Adult AIDS Clinical Trials Group. Effect of nandrolone decanoate therapy on weight and lean body mass in HIV-infected women with weight loss: A randomized, double-blind, placebo-controlled, multicenter trial. Arch Intern Med. 2005 Mar 14;165(5):578-85.

BACKGROUND: Weight loss is associated with accelerated mortality and disease progression in patients with human immunodeficiency virus (HIV) infection. Although studies have examined a variety of anabolic therapies in HIV-infected men, the safety and efficacy of such treatments in women have not been adequately studied. METHODS: In this randomized, double-blind, placebo-controlled, multicenter, phase I/II study, 38 HIV-infected women with documented weight loss of 5% or greater in the preceding year or a body mass index of less than 20 kg/m(2) were randomized to receive nandrolone decanoate (100 mg) or an equivalent volume of placebo every other week by intramuscular injection. Subjects received blinded treatment for 12 weeks, followed by open-label therapy for 12 weeks. Lean body mass and fat (bioelectrical impedance analysis) and weight were measured at baseline and at weeks 6, 12, 18, and 24. Biochemical assessments of safety (hematologic analyses, liver function tests, and sex hormone measurements) we re performed at these same time points. Clinical signs and symptoms were monitored biweekly. RESULTS: Subjects randomized to receive nandrolone had significant increases in weight and lean body mass during blinded treatment (4.6 kg [9.0%] and 3.5 kg [8.6%], respectively; P<.001 vs baseline and placebo in each case). Fat mass did not change statistically significantly in either group. Although there were no statistically significant differences between groups in biochemical measures, the number of grade 3 or greater toxicities, or reports of virilizing effects, a full assessment of safety cannot be made in a trial of this size. CONCLUSION: Nandrolone decanoate therapy may prove to be generally safe and beneficial in reversing weight loss and lean tissue loss in women with HIV infection and other chronic catabolic diseases.

Murphy E, Jacobson S, Franchini G, Taylor GP, Hanchard B, Morgan O, Lairmore M. International Retrovirology Association brings together scientists and clinicians to bridge discoveries about human T-lymphotropic viruses from the laboratory to clinical trials. Retrovirology. 2005 Mar 29;2(1):22.

Human T-lymphotropic virus type 1 (HTLV-1) and HTLV-2 were among the first human retroviruses discovered in the early 1980's. The International Retrovirology Association is an organized effort that fostered the efforts of scientists and clinicians to form interdisciplinary groups to study this group of retroviruses and their related diseases. The Association promotes excellent science, patient education, and fosters the training of young scientists to promote "bench-to-bedside" research. The International Conference on Human Retrovirology: HTLV and Related Viruses sponsored by the Association supports clinicians and researchers in the exchange of research findings and stimulation of new research directions. This years conference will be held from June 22 to 25, in Montego Bay, Jamaica http://www.htlvconference.org.jm/. Since its inception in 1988, these conferences have provided a highly interactive forum for the global community of HTLV scientists. This is of particular importance as HTLV research enters its third decade and a new generation of scientists takes over this important work. Many of the scientists attending the meeting will be from developing countries where HTLV is endemic, consistent with the history of international collaborations that have characterized HTLV research. The International Conference on Human Retrovirology provides a unique opportunity for researchers of all disciplines interested in HTLV infections to meet their peers and to address the questions facing clinicians and scientists who study retroviruses, like HTLV.

Nemoto T, Operario D, Keatley J, Nguyen H, Sugano E. Promoting health for transgender women: Transgender Resources and Neighborhood Space (TRANS) program in San Francisco. Am J Public Health. 2005 Mar;95(3):382-4.

Transgender women are at high risk for HIV, substance abuse, and mental health problems. We describe a health promotion intervention program tailored to transgender women in San Francisco. The program creates a safe space for providing transgender-sensitive education about HIV risk reduction, substance abuse prevention, and general health promotion. Transgender health educators conduct workshops and make referrals to appropriate substance abuse treatment programs and other services in the community. Evaluation findings indicate that this community-tailored intervention may be an effective way to reach transgender women and reduce sexual risk behaviors, depression, and perceived barriers to substance abuse treatment.

Neuenburg JK, Cho TA, Nilsson A, Bredt BM, Hebert SJ, Grant RM, Price RW. T-cell activation and memory phenotypes in cerebrospinal fluid during HIV infection. J Acquir Immune Defic Syndr. 2005 May 1;39(1):16-22.

We characterized T cell phenotypes in 74 paired blood and cerebrospinal fluid (CSF) samples of HIV-infected and uninfected persons using four-color flow cytometry. CD4+ and CD8+ T cells subsets were further characterized by identifying activated/resting and memory/naive subsets in CSF and blood using the markers CD38/HLA-DR and CD45RA/CD62L, respectively. With and without HIV-infection, the proportion of CD4+ T cells and memory T cells among T cells in CSF was higher compared to blood. In HIV-infection, activated CD4+ and CD8+ T cells in CSF were more abundant than in uninfected controls. As expected, combination antiretroviral therapy (ART) reduced T cell activation in CSF and blood.

Novotny TE. HIV is not just a transitional problem. BMJ. 2005 Jul 23;331(7510):219. Comment on: BMJ. 2005 Jul 23;331(7510):216-9. BMJ. 2005 Jul 23;331(7510):220-3.

Parikh S, Gut J, Istvan E, Goldberg DE, Havlir DV, Rosenthal PJ. Antimalarial activity of human immunodeficiency virus type 1 protease inhibitors. Antimicrob Agents Chemother. 2005 Jul;49(7):2983-5.

Aspartic proteases play key roles in the biology of malaria parasites and human immunodeficiency virus type 1 (HIV-1). We tested the activity of seven HIV-1 protease inhibitors against cultured Plasmodium falciparum. All compounds inhibited the development of parasites at pharmacologically relevant concentrations. The most potent compound, lopinavir, was active against parasites (50% inhibitory concentration [IC50], 0.9 to 2.1 microM) at concentrations well below those achieved by ritonavir-boosted lopinavir therapy. Lopinavir also inhibited the P. falciparum aspartic protease plasmepsin II at a similar concentration (IC50, 2.7 microM). These findings suggest that use of HIV-1 protease inhibitors may offer clinically relevant antimalarial activity.

Retz MM, Sidhu SS, Blaveri E, Kerr SC, Dolganov GM, Lehmann J, Carroll P, Simko J, Waldman FM, Basbaum C. CXCR4 expression reflects tumor progression and regulates motility of bladder cancer cells. Int J Cancer. 2005 Mar 20;114(2):182-9.

Transitional cell carcinoma of the urinary bladder remains life threatening due to the high occurrence of metastases. Emerging evidence suggests that chemokines and their receptors play a critical role in tumor metastases. In our study, we performed a systematic analysis of the mRNA and protein expression levels of all 18 chemokine receptors in normal urothelium and bladder cancer. CXCR4 was the only chemokine receptor whose mRNA expression level was upregulated in bladder cancer cell lines as well as in invasive and locally advanced bladder cancer tissue samples (pT2-pT4). In contrast, superficial bladder tumors (pTa and pT1) displayed low CXCR4 expression levels and normal urothelial cells were negative for CXCR4. Immunohistochemistry of a bladder cancer tissue microarray (TMA) confirmed that a subgroup of invasive bladder cancers revealed a high CXCR4 protein expression, while superficial bladder tumors showed low immunoreactivity. To investigate the functional significance of CXCR4 expression, we perf ormed migration and invasion assays. Exposure of CXCR4-positive bladder cancer cells to CXCL12 in a Boyden chamber type assay provoked a significant increase in migration as well as invasion across a Matrigel barrier. Enhanced migration and invasion were inhibited by a CXCR4-specific blocking antibody. In contrast, normal urothelial cells did not respond to CXCL12 and lacked chemotactic migration. In conclusion, bladder cancer cells express CXCR4 progressively with advanced tumorigenesis and this receptor interacts with CXCL12 to mediate tumor chemotaxis and invasion through connective tissue. These properties identify CXCR4 as a potential target for the attenuation of bladder cancer metastases. (c) 2004 Wiley-Liss, Inc.

Riley ED, Bangsberg DR, Guzman D, Perry S, Moss AR. Antiretroviral therapy, hepatitis C virus, and AIDS mortality among San Francisco's homeless and marginally housed. J Acquir Immune Defic Syndr. 2005 Feb 1;38(2):191-5.

Mortality has declined in most HIV-infected populations yet remains high among those with barriers to accessing antiretroviral (ARV) therapy. We sought to determine predictors of death in a group of HIV-infected homeless persons in San Francisco. Between 1996 and 2002, quarterly interviews and blood draws were conducted. Hazards of death were compared by number of months of the prior 6 months that an individual took any ARV, drug use, hepatitis C virus (HCV) status, and housing status. Among 330 participants, 65% were HCV-seropositive at baseline, 85% received ARV during the study period, and there were 57 deaths (5.3 per 100 person-years). Compared with 0 of the prior 6 months on therapy, the risk of death was not significantly reduced for individuals on 1 to 5 months of therapy (hazard ratio [HR]=0.82, 95% confidence interval [CI]: 0.43-1.57), but the risk of death was reduced 62% for those on ARV therapy for 6 months (HR=0.38, CI: 0.19-0.76). Housing status and HCV status were not significant predictor s of death. HIV is the major cause of death in this population, whereas the impact of HCV infection seems to be minimal. Sustained ARV treatment significantly reduces the risk of death among the homeless.

Riley ED, Moss AR, Clark RA, Monk SL, Bangsberg DR. Cash benefits are associated with lower risk behavior among the homeless and marginally housed in San Francisco. J Urban Health. 2005 Mar;82(1):142-50. Epub 2005 Feb 28.

To address the widespread debate about the role of public assistance to the urban poor, the authors determined characteristics of individuals receiving cash assistance and explored the link between cash subsidies and risk behavior. From 1999 to 2000, a representative sample of homeless and marginally housed (HMH) adults living in San Francisco was recruited and interviewed about subsidies, shelter, jail, and drug use. Among 1,156 adults, 87% were ever homeless, 22% currently injected drugs, and 14% were HIV positive. Sixty percent of participants reported that most of their income came from subsidies [mostly subsidized (MS)]. The MS had lower odds of receiving any income from selling drugs or trading sex. Adjusting for HIV infection, the MS had higher odds of sleeping in a hotel [odds ratio (OR) = 2.39] or shelter (OR = 1.61) compared to the street. The MS had lower odds of injection drug use (OR = 0.69) and recent incarceration (OR = O.77). Among San Francisco's homeless, being MS was positively associat ed with having shelter and negatively associated with injection drug use and incarceration. These data suggest that government subsidies are associated with positive health behaviors among the urban poor.

Spudich SS, Huang W, Nilsson AC, Petropoulos CJ, Liegler TJ, Whitcomb JM, Price RW. HIV-1 chemokine coreceptor utilization in paired cerebrospinal fluid and plasma samples: A survey of subjects with viremia. J Infect Dis. 2005 Mar 15;191(6):890-8. Epub 2005 Feb 9.

BACKGROUND: Chemokine receptors serve as coreceptors for human immunodeficiency virus type 1 (HIV-1) entry, influence cell tropism, and may critically determine central nervous system infection pathogenesis. Using an in vitro functional entry assay, we examined utilization of 2 principal coreceptors in cerebrospinal fluid (CSF) and plasma in 46 subjects. METHODS: Paired CSF and plasma samples were selected from subjects with a range of CD4 T cell counts. Amplified populations of env sequences were characterized as using CCR5 (R5), CXCR4 (X4), or both receptors (R5+X4). Individual clones derived from 3 subjects were analyzed for viral tropism and phylogeny. RESULTS: CSF and plasma pairs were mainly concordant for R5 (36/46) or R5+X4 (5/46) viruses. However, 5 pairs were discordant, 2 of which had the R5+X4 phenotype in CSF despite having the R5 phenotype in plasma. Although R5+X4 tropism was associated with advanced immunodeficiency, all 4 subjects with acquired immunodeficiency syndrome dementia complex h ad R5 tropism in CSF. Clones derived from R5+X4-tropic populations revealed mixtures of R5 and X4 viruses and viruses able to utilize either coreceptor, suggesting both virus exchange between compartments and autonomous CSF virus evolution. CONCLUSIONS: Although R5 viruses predominate in the CSF, HIV-1 populations able to utilize CXCR4 are also present. Discordant tropism in CSF and plasma may have implications for R5 inhibitor therapy.

Van der Straten A, Kang MS, Posner SF, Kamba M, Chipato T, Padian NS. Predictors of diaphragm use as a potential sexually transmitted disease/HIV prevention method in Zimbabwe. Sex Transm Dis. 2005 Jan;32(1):64-71.

BACKGROUND: Women who are the most vulnerable to sexually transmitted diseases/HIV are often unable to consistently use condoms. One potential alternative method currently under investigation is the diaphragm. GOALS: The goals of this study were to assess diaphragm uptake and use over time in Zimbabwe and to identify factors associated with self-reported consistent diaphragm use. STUDY: Women attending family planning clinics who were inconsistent condom users received a diaphragm intervention and were followed for 6 months. RESULTS: Of the 186 participants, 99% ever reported using the diaphragm, and, at study exit, 96% had used it in the previous 2 months. Consistent diaphragm use since the previous visit was reported by 13% to 16% of the women, and in multivariate regression analysis, it was significantly associated with never using condoms (adjusted odds ratio, 24.08; 95% confidence interval, 6.71-86.34). Other factors included discreet use, preferring diaphragms to condoms, timing of insertion, domest ic violence, and contraception. CONCLUSION: Diaphragms were well accepted among women at risk for sexually transmitted diseases/HIV.

Wilkins K, Dolev JC, Turner R, LeBoit PE, Berger TG, Maurer TA. Approach to the treatment of cutaneous malignancy in HIV-infected patients. Dermatol Ther. 2005 Jan-Feb;18(1):77-86.

Patients infected with human immunodeficiency virus (HIV) have an increased risk of developing skin cancers. These at-risk patients may have atypical presentations and/or altered clinical courses. This article will review and discuss management issues for the following malignancies: lymphomas, malignant melanoma, basal cell carcinoma, squamous cell carcinoma, and Kaposi's sarcoma.

Wilson LS, Moskowitz JT, Acree M, Heyman MB, Harmatz P, Ferrando SJ, Folkman S. The economic burden of home care for children with HIV and other chronic illnesses. Am J Public Health. 2005 Aug;95(8):1445-52. Epub 2005 Jun 28.

OBJECTIVES: We compared types, amounts, and costs of home care for children with HIV and chronic illnesses, controlling for the basic care needs of healthy children to determine the economic burden of caring for and home care of chronically ill children. METHODS: Caregivers of 97 HIV-positive children, 101 children with a chronic illness, and 102 healthy children were surveyed regarding amounts of paid and unpaid care provided. Caregiving value was determined according to national hourly earnings and a market replacement method. RESULTS: Chronically ill children required significantly more care time than HIV-positive children (7.8 vs 3.9 hours per day). Paid care accounted for 8% to 16% of care time. Annual costs were $9300 per HIV-positive child and $25 900 per chronically ill child. Estimated national annual costs are $86.5 million for HIV-positive children and $155 to $279 billion for chronically ill children. CONCLUSIONS: Informal caregiving represents a substantial economic value to society. The tota l care burden among chronically ill children is higher than that among children with HIV.

Zheng YH, Peterlin BM. Intracellular immunity to HIV-1: Newly defined retroviral battles inside infected cells. Retrovirology. 2005 Apr 13;2(1):25.

Studies of the human immunodeficiency virus type 1 (HIV-1) continue to enrich eukaryotic biology and immunology. Recent advances have defined factors that function after viral entry and prevent the replication of proviruses in the infected cell. Some of these attack directly viral structures whereas others edit viral genetic material during reverse transcription. Together, they provide strong and immediate intracellular immunity against incoming pathogens. These processes also offer a tantalizing glimpse at basic cellular mechanisms that might restrict the movement of mobile genetic elements and protect the genome.

Zheng YH, Lovsin N, Peterlin BM. Newly identified host factors modulate HIV replication. Immunol Lett. 2005 Mar 15;97(2):225-34. Epub 2005 Jan 13.


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