HIV-positive Donors Research Articles

The TRAIL of Helpless CD8+T Cells in HIV Infection

Our understanding of how CD4(+) T cells can regulate CD8(+) T cell responses in HIV infection is still incomplete. Recent evidence obtained in mice suggests that CD4(+) T cell help is required for efficient CD8(+) T cell-mediated immunity in chronic infection: CD8(+) T cells primed in the absence of such help release the TNF-related apoptosis-inducing ligand TRAIL and undergo apoptosis. Using a novel ELISPOT assay, in the present study we show that CD8(+) T cells are also a source of the antigen-specific TRAIL response in HIV-infected patients with CD4(+) T cell counts below 200. In patients with CD4(+) T cell counts above 200 TRAIL was not detectable. Accordingly, antigens to which patients have likely been exposed when CD4(+) T cell levels were high (e.g., influenza, CMV, and EBV) did not induce TRAIL. Within the HIV-positive donor population with low CD4(+) T cell counts a dissociation of the interferon-gamma (IFN-gamma) and TRAIL response to different HIV peptide epitopes was detectable suggesting impaired immunity to antigens that triggered TRAIL in the absence of IFN-gamma. Our findings emphasize that "helpless" CD8(+) T cells, i.e., cells that have been primed in the absence of CD4(+) T cell help, may play a crucial role in HIV infection. A "helpless" phenotype may impair CD8(+) T cell control of HIV and other infections and possibly contribute to the depletion of CD4(+) T cells via apoptosis. Immunizations and infections in this "helpless" state might result in ineffective CD8(+) T cell responses.

Impaired Naive and Memory B-Cell Responsiveness to TLR9 Stimulation in Human Immunodeficiency Virus Infection

Toll-like receptor 9 (TLR9) agonists such as unmethylated bacterial CpG DNAs activate B lymphocytes directly, potentially influencing their function and homeostasis. To assess B-cell responsiveness to TLR9 agonists in human immunodeficiency virus (HIV) disease, we examined the ability of naive and memory B cells to proliferation and to increase surface expression of CD80 in response to CpG oligonucleotides (ODN). CpG ODN induced expression of CD80 similarly in B cells from HIV-infected persons and from healthy controls. In contrast, proliferation responses to CpG ODN were markedly impaired in both naive and memory B-cell subsets from HIV-infected persons. Naive B-cell proliferation defects were related to plasma HIV RNA and, among memory B cells, to the frequencies of CD21-negative cells. Importantly, TLR9 mRNA levels were significantly diminished in freshly prepared naive B cells and especially so in memory B cells from HIV-positive viremic donors, suggesting a possible underlying mechanism for the observed functional impairments. Dose-response studies indicated that optimal induction of CD80 expression was achieved with much lower concentrations of CpG ODN than optimal induction of proliferation. We propose that the relatively low threshold of activation that is required for CD80 induction by CpG ODN might explain the preservation of this response in B cells from HIV-infected persons despite diminished TLR9 expression. Impaired responsiveness to TLR9 agonists may contribute to defects in humoral immunity in HIV infection.

Uniquely South African: time to consider offering HIV-positive donor kidneys to HIV-infected renal failure patients?

Kidney transplantation has been established as the most effective form of renal replacement therapy from a cost and quality of life perspective in the developed world.

Sequence analysis of gag and env genes of HIV type 1 circulating in former blood donors of Fuyang city, Anhui province

To determine the subtype and analyze the genetic characteristics of the HIV-1 predominantly circulating in the former blood donors of Fuyang city, Anhui province. Whole blood samples were collected from 294 HIV-positive former blood donors of Fuyang city, 157 males and 137 females, aged 42 +/- 8. The fragments of HIV-1 env and gag genes were amplified by nested-PCR from the whole blood samples and thereafter sequenced. The env and gag sequences derived from 244 and 245 HIV infected individuals respectively were analyzed by using MEGA software, and related researches were also done according to the disease progression of the HIV infected individuals. Phylogenetic trees showed that both the env and gag strains were clustered with the Thailand B reference strains. The internal nucleotide distances of the env and gag genes were 9.11% and 3.59% respectively. The nucleotide distances of both env and gag genes significantly increased as the CD4 T-cell counts decreased or as the viral load rose (both P < 0.001). The V3 loop tip motifs were dramatically dominated by GPGQ in the long-time non-progressors, and by GPGR in the slow progressors (P = 0.038). The predominant strains circulating in the HIV-1 infected former blood donors of Fuyang city are of the Thailand B clade. Low CD4 T-cell count and high viral load are associated with the increase of genetic distances among viral isolates. The V3 loop tip motif changes from GPGQ to GPGR along with the progression of disease.

Blood transfusion services in countries that joined the EU in the last years: Czech Republic

The Czech Republic is a country in the middle of Europe with 10·3 million inhabitants and 80 000 km2. It became a European Union (EU) member in 2004. Blood transfusion service is disperse, hospital based. Blood is collected mostly from voluntary non‐remunerated blood donors and the country is self‐sufficient in blood components and plasma for fractionation. Predeposit autologeous programme is popular and covers around 4·5% of red cells needs. Donor population is stable and relatively safe. Total of 21 HIV positive donors have been detected during last 20 years, the incidence of hepatitis in blood donors is decreasing being below 0·10 pro mille for hepatitis B virus and below 0·20 pro mille for hepatitis C virus in 2005. European standards have been accepted and implemented during last 15 years; safety (quality) and general availability being the priorities. Donor selection, blood collection, processing and testing comply with EU directives. Producers of blood components (blood establishments) are under control of the state authority (State Institute for Drug Control). Recommendations based on expert opinion are available for clinical use of blood. Adverse effects of treatment are followed and investigated. Costs of blood components and plasma products are covered by general health insurance.

Risk factors for human immunodeficiency virus infection among blood donors in Sao Paulo, Brazil, and their relevance to current donor deferral criteria

The objective of this study was to investigate risk factors of human immunodeficiency virus (HIV)-seropositive blood donors in Brazil and to determine if current donor deferral criteria are appropriate. Demographic and behavioral data among cases with confirmed HIV seropositivity (n = 272) were compared with those who had a false-positive serology (n = 468) between January 1999 and December 2003 in a case-control analysis with logistic regression. Risk factors that should have resulted in predonation deferral were reported by 48.9 percent of HIV-positive and 9.4 percent of false-positive donors. In multivariate analysis, male cases were significantly more likely to report male-male sex (adjusted odds ratio [AOR], 26.2; 95% confidence interval [CI], 7.8-87.4), a previous sexually transmitted disease diagnosis (AOR, 3.2; 95% CI, 1.5-6.9), exchanging money for sex (AOR, 2.1; 95% CI, 1.0-4.2), and at least two partners in the past 12 months (AOR, 2.3; 95% CI, 1.4-3.6). HIV-positive male donors were also more likely to be reactive for the presence of hepatitis C virus antibody (AOR, 4.0; 95% CI, 1.3-12.0) and hepatitis B virus core antibody (AOR, 3.8; 95% CI, 1.9-7.7). Female cases were more likely to report an intravenous drug user partner (AOR, 12.4; 95% CI, 1.3-120.2), a sexual partner with multiple sex partners or who had a history of sex with a sex worker (AOR, 13.0; 95% CI, 2.7-63.2), and at least two partners in the past 12 months (AOR, 2.2; 95% CI, 1.0-5.3). A substantial number of HIV-infected donors reported a risk factor that could have been identified in the predonation screening. Male-male sexual behavior was still the strongest determinant of HIV status in the studied population.

Progression to WHO criteria for antiretroviral therapy in a 7-year cohort of adult HIV-1 seroconverters in Abidjan, Côte d'Ivoire.

To estimate the probability of reaching the criteria for starting highly active antiretroviral therapy (HAART) in a prospective cohort of adult HIV-1 seroconverters in Abidjan, Côte d'Ivoire. We recruited participants from HIV-positive donors at the blood bank of Abidjan for whom the delay since the estimated date of seroconversion (midpoint between last negative and first positive HIV-1 test) was < 36 months. Participants were offered early trimethoprim-sulfamethoxazole (cotrimoxazole) prophylaxis, twice-yearly measurement of CD4 count and we made standardized records of morbidity. We used the Kaplan-Meier method to estimate the probability of reaching the criteria for starting HAART according to WHO 2006 guidelines. 217 adults (77 women (35%)) were followed up during 668 person-years (PY). The most frequent diseases recorded were mild bacterial diseases (6.0 per 100 PY), malaria (3.6/100 PY), herpes zoster (3.4/100 PY), severe bacterial diseases (3.1/100 PY) and tuberculosis (2.1/100 PY). The probability of reaching the WHO 2006 criteria for HAART initiation was estimated at 0.09, 0.16, 0.24, 0.36 and 0.44 at 1, 2, 3, 4 and 5 years, respectively. Our data underline the incidence of the early HIV morbidity in an Ivorian adult population and provide support for HIV testing to be made more readily available and for early follow-up of HIV-infected adults in West Africa.

Preliminary evidence of efficacy from an open label trial of a therapeutic AIDS vaccine derived from the blood of HIV-positive donors

Two earlier reported studies indicated the beneficial clinical effects of THIVAC, a therapeutic HIV vaccine derived from the blood of HIV-positive donors. However, in those studies no stringent statistical analysis to support the beneficial clinical outcome was attempted. This report retrospectively analyses the effect of the therapy on the CD4 counts in 272 treated individuals who had at least one pair of T-cell tests carried out before and during treatment. Except for the earliest time point (median 25 days of treatment) when p = 0.11, the mean increase in CD4 counts was statistically significant at every discrete time point with peak at 112 days when p = 0.0000000000005. Despite the open label nature of this study, the results appear highly significant, supporting unequivocally the beneficial effects of THIVAC as a safe and promising immunotherapeutic modality for treating HIV.

Prevalence of HIV positive blood donors among screened volunteers who satisfied the criteria for blood donation in a semi-urban Nigeria population

Two thousand five hundred and thirty two (2,532) males, aged 25 – 50 years potential blood donors were randomly selected from the total number of volunteer blood donors who satisfied the initial screening criteria for donating blood, and were screened for HIV using Immunocomb II (HIV 1 and 2 Bispot) and Recombigen HIV-1/HIV-2RTD. Results from the study reveal that this procedure of screening volunteer donors by initial criteria alone does not fully eliminate all HIV positive donors. The prevalence of HIV positive donors among the screened volunteers who satisfied the criteria for blood donation was 0.87%. Keywords: Prevalence, blood donor, hiv positive and semi urban population

Rapid deterioration of HIV co-infected patients waiting for liver transplantation is not predicted by MELD

HAART therapy has significantly decreased the morbidity and mortality associated with HIV infection and. as a result, people infected with HIV are no longer dying from progression of HIV to AIDS. Unfortunately, an increasing number of co-infected patients are dying from complications of liver failure. Liver disease is now the leading cause of death for HIVpositive patients co-infected with hepatitis C and a major cause of death for HIV/HBV co-infected patients.1 As a result of the increasing demand for liver transplantation inHIV-positive people and recognition of improved survival associated with HAART, a number of transplant centers are proceeding with liver transplantation in selected patients with well-controlled HIV. Multiple small studies in the era of HAART suggest that patient and graft survival rates are similar to those in HIV-negative recipients.2-10 It is on this background that Ragni et al.11 in this issue of Liver Transplantation demonstrate significantly shorter pretransplantation survival in HIV-positive patients listed for liver transplantation compared with HIV-negative subjects, despite equivalent Model for End-Stage Liver Disease (MELD) scores at the time of listing. Furthermore, the shortened pretransplantation survival times were primarily associated with death related to infection/sepsis in a subset of the HIV-positive candidates. Ragni et al.’s findings are highly relevant, in that this is the first documentation of a more rapid demise of the co-infected HIV liver transplant candidates that has been observed on waiting lists at an increasing number of transplant centers. The parameters that have proven to be predictive for poor outcome in the MELD system (INR, bilirubin, and creatinine) failed to predict the poorer outcome in the subset of HIV-positive patients who succumbed to infection/sepsis. CD4 counts at the time of listing were also unable to distinguish the subset of HIV-positive patients with poor outcomes. The higher incidence of sepsis-related death inHIV-positive people with liver insufficiency as compared to their HIV-negative counterparts on the liver transplant waiting list could be predicted on the basis of the multiple immunologic and metabolic insults present in the coinfected patient with liver insufficiency. In addition to the impaired detoxification capacity of the damaged liver, the co-infected patient is further compromised by the immune defects associated with HIV as well as the hepatotoxicity of several of the antiretroviral agents comprising HAART. Therefore, the documentation of increased sepsis/infections leading to decreased cumulative survival rates of HIV co-infected candidates on liver transplant waiting lists should come as no surprise. However, the issue of what can be done to improve the survival of the HIV co-infected liver transplant candidate remains unresolved. Ragni et al. stress the importance of early referral of the HIV co-infected patient, and the importance of this cannot be underestimated. There are multiple barriers that can delay the evaluation process leading to activation as an acceptable candidate, and Ragni et al.’s report makes it clear that this group of patients cannot afford these delays. It should be emphasized that these patients must meet the same standards as all liver transplant recipients, including a prolonged period of abstinence from alcohol and narcotics, sufficient rehabilitation, and demonstration of social support. Since HIV positivity is still perceived as a contraindication to transplantation by a significant percentage of the medical community, these issues have not been adequately dealt with by the time of referral. The problems with late referral are further exacerbated by the inherent complexity in caring for HIV/HBV and HIV/HCV coinfected patients. Many of these patients are disenfranchised from essential medical care as a result of poor insurance coverage. Even when appropriate medical consultation is obtained, the hepatologist will defer to the HIV specialist, the HIV specialist defers back to the

Expression of a novel cytokine, IL-4delta2, in HIV and HIV–tuberculosis co-infection

Correcting the Th2 shift in HIV/AIDS represents a potential intervention strategy. However data on interleukin (IL)-4 expression in HIV or AIDS are un-interpretable because of failure to distinguish between IL-4 and its splice variant and natural antagonist, IL-4delta2. To determine Th1 [interferon (IFN)-gamma], IL-4delta2 and Th2 (IL-4) expression in whole blood and lung lavage from healthy volunteers and in HIV or HIV-tuberculosis (TB) co-infection. Cross-sectional with prospective cohort. Expression of IL-4delta2, IL-4 and IFN-gamma were determined by quantitative real-time PCR, using unstimulated cells from whole blood and lung lavage, in 20 HIV-TB (pulmonary) co-infected patients, 20 matched HIV-positive controls and 20 HIV-negative healthy volunteers. Results were correlated with plasma viral load, CD4 cell counts, radiological scores and response to anti-TB treatment. Compared to HIV negative donors, stable HIV-positive donors did not have increased levels of mRNA encoding IL-4, IL-4delta2 or IFN-gamma in blood or lavage. By contrast, the HIV-TB co-infected donors had increased IL-4 and IFN-gamma in both compartments. However the antagonist, IL-4delta2 was increased only in lavage. Consequently the dominant form was IL-4delta2 in lavage, but IL-4 itself in blood. The lung IL-4/IFN-gamma ratio correlated with radiological disease extent. With anti-TB treatment, IL-4 levels did not change whilst IL-4delta2 levels increased significantly. IL-4 and its natural antagonist, IL-4delta2 and are not upregulated in the absence of opportunistic infection. However in HIV-TB co-infection both cytokines increase in lung, but only IL-4 in the periphery. Further studies are required to determine if IL-4 facilitates systemic HIV progression.

Ex Vivo Modeling of Oral HIV Transmission in Human Palatine Tonsil

The majority of newly acquired HIV infections are believed to occur following transmission of virus infectivity across mucosal surfaces, although many mechanistic details still remain unresolved. We have used human ex vivo organ cultures and primary cell populations to analyze the cellular and molecular basis for mucosal HIV transmission. By using human palatine tonsil from routine tonsillectomies and semen from HIV-positive donors, we have created an experimental equivalent to oral HIV transmission. HIV infection was readily transferred into tonsillar lymphocytes, but this transmission into lymphocytes was dramatically reduced when the exposed lymphocyte populations were protected by intact mucosal surfaces. In this study, we consider the impact that leukocyte activation and morphological aberrations in surface structure may have on susceptibility to primary HIV infection and introduce novel time-lapse confocal microscopy procedures that begin to reveal the dynamic complexity associated with cell-mediated HIV transmission.

Behavior Assessment of Blood Donors Facing the Risk of HIV Infection, Abidjan, Côte D'Ivoire, 2001-2002

Despite precautions taken to guarantee blood safety, in the National Blood Transfusion Center (CNTS) of Abidjan, about 30 regular blood donors are detected with HIV seroconversion each year, two-thirds of them men. A survey through face-to-face interviews was carried out at the CNTS of Abidjan from September 2001 to March 2002 among HIV-positive and HIV-negative regular blood donors, informed about their serologic status. HIV-negative regular blood donors informed about their serologic status since a median time of 67 months (n = 50) disclosed more risky behaviors such as multiple sexual partners (68%) than HIV-positive blood donors informed about their status (n = 112) since a median time of 35 months (41%) (P < 0.001). Condoms were systematically used by 17% of HIV-negative blood donors and 55% of HIV-positive blood donors (P < 0.001). Enhanced counseling and awareness could reduce in the future the number of cases of seroconversion among regular blood donors and improve their subsequent behavior. Blood donors who have unprotected sex with partners of unknown HIV serologic status and especially with casual partners are strongly exposed to HIV transmission and should be discouraged to continue giving blood, after adequate counseling.

HIV-1 Subtype C Drug-Resistance Background among ARV-Naive Adults in Botswana

Current HIV-1 antiretroviral (ARV) drug resistance knowledge is limited to HIV-1 subtype B (HIV-1B). We addressed whether unique genetic and phenotypic properties of HIV-1 subtype C (HIV-1C), southern Africa's most prevalent subtype, may foment earlier and/or distinct resistance mutations. Population-level HIV-1C genotypes were evaluated with respect to drug resistance prevalence before Botswana's public ARV treatment programme began. Viruses were genotyped from 11 representative districts of northern and southern Botswana, and consensus sequences from these 71 individuals and 51 previously reported sequences from HIV-positive blood donors were constructed. Phylogenetic analysis classified all 71 sequences but one, which exhibited pol gene mosaicism, as HIV-1C. The protease and reverse transcriptase coding region had no detectable known primary mutations associated with HIV-1B protease inhibitor (PI) drug resistance. Secondary mutations associated with PI drug resistance were found in all sequences. Several HIV-1C-specific polymorphic sites were found across the pol gene. Northern and southern Botswana viral sequences showed no significant differences from each other. Population genotyping shows that, without countrywide ARV treatment, HIV-1C-infected Batswana harbour virtually no primary mutations known to confer resistance to the three major HIV-1B ARV drug classes. Some secondary PI mutations and polymorphic sites in the protease enzyme necessitate continuous population monitoring, particularly after introduction of countrywide ARV treatment in Botswana. Although its PI resistance development rate and kinetics are not known, our data may suggest increased susceptibility and readiness of HIV-1C to develop resistance under drug pressure when the PI class of drugs is used.

Impaired Monocyte Maturation in Response to CpG Oligodeoxynucleotide Is Related to Viral RNA Levels in Human Immunodeficiency Virus Disease and Is at Least Partially Mediated by Deficiencies in Alpha/Beta Interferon Responsiveness and Production

The biological activity of CpG oligodeoxynucleotide 2216 (ODN2216), a Toll-like receptor 9 agonist, was investigated with monocytes from human immunodeficiency virus (HIV)-negative and HIV-positive (HIV+) donors. Exposure of peripheral blood mononuclear cells to CpG ODN2216 led to decreased expression of the monocyte marker CD14 and increased expression of the dendritic cell marker CD83, as well as increased expression of HLA-DR, CD40, CD80, and CD86 among the monocytes. Several features of the CpG ODN-induced maturation were diminished in monocytes from HIV+ donors, and these deficiencies were related to increased viremia but not to CD4 cell counts. Alpha interferon (IFN-alpha) was implicated as at least a partial mediator of the CpG ODN-induced monocyte maturation. Reduced production of IFN-alpha in response to CpG ODN and reduced frequencies of plasmacytoid dendritic cells, the principal IFN-alpha-producing cell type in peripheral blood, were observed in peripheral blood mononuclear cells from HIV+ donors. These deficiencies also were related to levels of plasma HIV RNA. Responses of monocytes from HIV+ donors to direct stimulation with IFN-alpha also were partially impaired. Thus, reduced production of IFN-alpha and reduced IFN-alpha responsiveness may contribute to diminished functional responses to CpG ODN in HIV disease. Application of CpG ODNs in HIV disease for adjuvant or immunoregulatory purposes may be particularly useful for HIV+ donors without high-level viremia.

ＨＩＶ感染献血者の高危険性行為に関する調査と血液の安全性確保対策

HIV-infected voluntary blood donors have increased to more than 80 a year in the last 5 years. There are concerns that blood donation is being used for HIV testing by persons with high-risk behaviors, whose blood in the window period might result in HIV infection of recipients.A questionnaire was sent to 366 AIDS Care Core Hospitals, asking them to report the number of consultation by and characteristics of HIV-positive blood donors found by testing donations over the last 3 years. There were 185 HIV-positive donors reported, 158 (85%) of whom were male. Only 22 donors sought testing (12%), which increased to 13% over the last 5 years compared to 8% in previous years (not significant). However, 132 donors (71%) had high-risk behaviors including men who have sex with men (MSM: 57%) and multiple heterosexual partners (15%), but no intravenous drug users. Among the male donors, irrespective of whether they agreed to, denied or were undecided about donation for the purpose of HIV testing, MSM were the highest in each group (90%, 59%, and 77%, respectively), showing a remarkable increase to 71% over the last 5 years compared to 55% in 1993-1997 and 27% in 1986-1992. In addition, the fact that most infected donors did not approve of donation for the purpose of testing but revealed high-risk behavior once consulted a doctor in the hospitals shows a clear contradiction to their attitude at donation, at which time they ignored notices against donations for HIV testing or by those with high-risk behaviors before, at the time of, and after donation. Therefore, it should be considered that most but not all HIV-positive donors, particularly MSM, donated in order to obtain a HIV test.To ensure safety, it is recommended that MSM should be denied donating blood, and that donor recruitment should be focused on repeat donors, since HIV infection rates in first-time donors were three times higher than those in repeat donors.

Phase II placebo-controlled study of V-1 Immunitor as a therapeutic modality for treatment of HIV

V-1 Immunitor (V1) is an oral AIDS vaccine containing heat- and chemically-inactivated viral antigens derived from pooled blood of HIV-positive donors. V1 has a pending status as an investigational drug but is currently marketed as a dietary supplement. Earlier published, uncontrolled studies of V1 demonstrated body weight gain, increase in T-lymphocyte numbers, decrease in viral load, and improved survival of end-stage AIDS patients. In order to substantiate prior observations we have undertaken a placebo-controlled phase II clinical trial involving 47 antiviral therapy naive, asymptomatic individuals who had over 350 mm(3) CD4 T-cells (mean/median 538/480) at study entry. Both placebo and treatment arms were identical demographically and by every clinical parameter measured at baseline. At the end of 6-month follow-up 29 volunteers who received V1 b.i.d. had gained on average 43 CD4 T-cells (540 versus 583). This gain was statistically significant (p=0.01) while changes in T-cell numbers in placebo group failed to reach the significance threshold (p=0.33). The clinical potential of V1 is further supported by an elevation in CD4/CD8 ratio among V1 recipients and decline in CD4/CD8 ratio in patients on placebo (0.575 versus 0.524; p=0.02). The average weight gain among patients on V1 was 1.8 kg while placebo group lost 0.5 kg. These results suggest that V1 may delay or reverse the disease progression without any concurrent toxicity and support our prior open-label studies indicating that V1 confers clinical benefit. A phase III clinical study is required to confirm these findings and to allow us to seek license for V1 as a therapeutic AIDS vaccine.

Serological findings amongst first-time blood donors in Yaoundé, Cameroon: is safe donation a reality or a myth?

Blood safety remains an issue of major concern in transfusion medicine in developing countries where national blood transfusion services and policies, appropriate infrastructure, trained personnel and financial resources are lacking. This is aggravated by the predominance of family and replacement, rather than regular benevolent, nonremunerated donors. Thus, in order to identify and encourage healthy, regular and benevolent nonremunerated donors, consenting first-time blood donors in the Yaoundé University Teaching Hospital were screened for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), hepatitis C virus (HCV), human T-cell lymphotropic virus-I (HTLV-I) and syphilis using standard methods. Of 252 first-time donors recruited, 66 (26.2%) were positive for at least one of the infections screened. There were 7.9% positive for HIV, 10.7% for HBSAg, 4.8% for HCV and 9.1 and 1.6%, respectively, for syphilis and HTLV-I. About 30% of the 66 infected persons had co-infections. HIV-positive donors had a significantly increased risk of being positive for antibodies to syphilis (OR = 7.27; 95% CI = 2.23-23.51; P = 0.0007), not observed for HBV, HCV and HTLV-I. These results suggest that blood transfusion is still very unsafe in this community and that it is imperative that emphasis be laid on donor education. Furthermore, donors with a history of sexually transmitted infections should be totally excluded from all donations.

Investigation of eye splash and needlestick incidents from an HIV-positive donor on an intensive care unit using root cause analysis.

Two doctors working on a busy intensive care unit sustained injuries whilst removing a chest drain from an HIV-positive patient. One doctor had a needlestick injury into his finger whilst the other sustained an eyesplash when the chest drain was pulled out. Following Department of Health format 'Doing less harm', a root cause and human factor analysis of the incident was carried out. The aim was to explore the underlying issues. Training, cultural and organizational issues were exposed, and are now being addressed. This approach has led to a far more effective dialogue with the National Health Trust concerned than was previously experienced, and there is early evidence of progress on important aspects of health and safety management at organizational level. Lack of health and safety training of doctors at undergraduate and postgraduate level needs to be addressed.

Correlates of nontransmission in US women at high risk of human immunodeficiency virus type 1 infection through sexual exposure.

Seventeen women who were persistently uninfected by human immunodeficiency virus type 1 (HIV-1), despite repeated sexual exposure, and 12 of their HIV-positive male partners were studied for antiviral correlates of non-transmission. Thirteen women had > or = 1 immune response in the form of CD8 cell noncytotoxic HIV-1 suppressive activity, proliferative CD4 cell response to HIV antigens, CD8 cell production of macrophage inflammatory protein-1 beta, or ELISPOT assay for HIV-1-specific interferon-gamma secretion. The male HIV-positive partners without AIDS had extremely high CD8 cell counts. All 8 male partners evaluated showed CD8 cell-related cytotoxic HIV suppressive activity. Reduced CD4 cell susceptibility to infection, neutralizing antibody, single-cell cytokine production, and local antibody in the women played no apparent protective role. These observations suggest that the primary protective factor is CD8 cell activity in both the HIV-positive donor and the HIV-negative partner. These findings have substantial implications for vaccine development.