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PubMed2004

Incidence of heparin-PF4 complex antibody formation and heparin-induced thrombocytopenia in acute coronary syndrome.

A multicenter prospective study on the rate of seroconversion of antibodies to heparin-PF4 complexes (heparin-induced thrombocytopenia [HIT] antibodies) during and after heparin treatment for 4 weeks was carried out in Japanese patients with acute coronary syndrome (ACS). A total of 254 ACS patients treated with heparin were enrolled consecutively from 12 facilities of cardiology. Two patients with preexisting HIT antibodies were excluded from the analysis. The total seroconversion rate for four weeks during and after heparin treatment was 8.7% (n=22, 95% confidence interval [CI]: 5.9-13.1), including values of 3.2% (n=8) at the end of heparin infusion and 5.5% (n=14) at 4 weeks. Among 22 seroconverted patients, four developed HIT and two of the four had the complication of thrombosis. The incidence of HIT was 1.6% (n=4, 95% CI: 0.04-3.1). The risk for thromboembolic development was higher in the seroconverted patients (odds ratio, 17.4, 95% CI: 5.2-58.4, p<0.0001) than nonconverted patients. An analysis of factors affecting the seroconversion rate was carried out. The seroconversion rate for ACS patients who underwent percutaneous coronary intervention (PCI; n=163) was 12.3%, significantly higher than the 2.3% in patients who did not undergo PCI (n=89), leading to an odds ratio of 6.1 (95% CI: 1.4-26.7, p=0.009). A significant odds ratio was obtained for each factor affecting the seroconversion: 3.5 (95% CI: 1.3-9.9, p=0.014) for more than 5 days of heparin infusion, 3.0 (95% CI: 1.2-7.6, p=0.035) for a thrombotic history and 2.7 (95% CI: 1.1-6.8, p=0.039) for hyperlipidemia. No other factor, including age or diabetes mellitus, contributed to the seroconversion. Therefore, PCI, duration of heparin treatment and thrombotic history facilitated the seroconversion in ACS patients. PCI patients treated for more than 5 days with heparin showed a maximal seroconversion rate of 18.3% (95% CI: 13.8-22.2). This high rate in PCI patients did not interact with age, type of underlying disease of unstable angina or myocardial infarction or thrombotic history. In conclusion, ACS patients demonstrating seroconversion are at risk of thromboembolic development due to the likelihood of immunomediated endothelial dysfunction. The increase in the rate of seroconversion in ACS patients would be affected by factors such as PCI with mechanical stress, longer duration of heparin treatment, thrombotic history and presence of hyperlipidemia. If PCI is undertaken with heparin anticoagulation for more than 5 days, seroconversion would easily occur, and the seroconverted patients could subsequently suffer from HIT.

Acute Disease↗
PubMed1991

Estimating the 1978-1990 and future spread of human immunodeficiency virus type 1 in subgroups of homosexual men.

The authors studied the historical spread of human immunodeficiency virus type 1 (HIV-1) infection in homosexual/bisexual men and projected its future spread in these men using data from an AIDS-free cohort recruited during late 1984 in Baltimore, Maryland; Chicago, Illinois; Los Angeles, California; and Pittsburgh, Pennsylvania. Dates of preentry seroconversion in HIV-1 seroprevalent men were estimated using study entry values of hematologic variables influenced by HIV-1 infection. The authors used survival methods incorporating truncation to determine numbers/dates of seroconversion for men with a pre-1984 AIDS diagnosis who were selectively excluded by design from the 1984 AIDS-free cohort. Overall, the annual seroconversion hazard rose progressively from 0.4% in 1978 to 13.8% in 1983, dropped to 4.6% in 1985, and remained relatively stable at 1.1-2.2% from 1986 to 1990. By January 1990, almost 46% of men who were seronegative in 1978 had seroconverted. The authors estimated historical rates of spread by city, age, education, and ethnicity to examine the effects of these factors in the early and continuing stages of the HIV-1 epidemic. There were striking differences among cities with respect to pre-1985 seroconversion rates but not with respect to post-1985 seroconversion rates. Age, education, and ethnicity were all associated with 1978-1990 seroconversion rates. Future seroconversion among homosexual men was predicted assuming that the "stabilized" 1986-1990 hazards (stratified by age) observed here will be representative of future rates. Truncated Kaplan-Meier methods gave the probability of a seronegative 20-year-old man's remaining seronegative in subsequent years. Such a man has a 20.2% chance of seroconverting before reaching the age of 25 years (a 4.4% yearly hazard). The annual hazard drops to 2.5% between 25 and 30 years, to about 1.5% between 30 and 45 years, and to 1.0% between 45 and 55 years. The overall probability of seroconversion prior to age 55 years is about 50%, with seroconversion still continuing at and after age 55. Given that this cohort consists of volunteers receiving extensive anti-HIV-1 transmission education, the future seroconversion rates of the general homosexual population may be even higher than those observed here.

Adult↗
PubMed1997

Early levels of CD4, neopterin, and beta 2-microglobulin indicate future disease progression.

Reduced CD4 T cell level and increased serum neopterin and beta 2-microglobulin levels, which reflect immunological activation and dysregulation, are three important markers of HIV disease. The aim in this study is to delineate more clearly the relation of activation to future CD4 values and disease progression. By analyzing a cohort of 198 seroconverters from the Multicenter AIDS Cohort Study with 9 years' follow-up, the dynamic changes and levels of these three markers and their interrelationships are explored. We observed that the levels of markers in the first year after seroconversion have a much stronger impact on the progression of the disease than the preseroconversion marker levels. The actual change during the year after seroconversion is not as important as the final level reached during that year. The early levels of markers after seroconversion appear to be good indicators of the subsequent course of disease as defined by CD4 level and slightly better than the quantitative changes following seroconversion or the changes in the period 1 to 2.5 years after seroconversion. To investigate the variation between subjects, the 198 seroconverters were stratified into three approximately equal-sized groups in 12 ways based on their pre- and postseroconversion levels and changes in the three markers. The group with the highest CD4 level within a year after seroconversion maintains the highest CD4 level 8 years after seroconversion. The group with the lowest level of neopterin or beta 2-microglobulin in this period has much higher future CD4 counts than the other two groups. The level of markers during the first year after seroconversion has a high predictive power for AIDS onset. Substantial differences in the hazards of AIDS are found between the groups with the highest and lowest CD4 count, neopterin, and beta 2-microglobulin following seroconversion. The three markers are generally correlated throughout the postseroconversion period but can provide distinct information. High current levels of neopterin or beta 2-microglobulin tend to be associated with low future CD4 count, while current levels of CD4 count have less association with future neopterin and beta 2-microglobulin levels.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Differences in the incidence of hepatitis B and human immunodeficiency virus infections among injecting drug users.

Both hepatitis B virus (HBV) and human immunodeficiency virus (HIV) type 1 seroconversions have been considered as outcome measures to evaluate the effectiveness of needle exchange programs. To assess the relationships between incident HBV and HIV infections among injecting drug users (IDUs), seroconversions were prospectively studied among a cohort of 240 HBV- and HIV- seronegative IDUs. The incidence of HBV seroconversion declined from 24.41/100 person-years in 1988 to 0 seroconversions in 1992. In contrast, HIV seroconversion rates varied little from the overall rate of 3.29/100 person-years. HBV seroconversion predicted subsequent HIV seroconversion among male IDUs (relative incidence [RI]= 4.23) but not among female IDUs (RI=0.86). Because of different transmission dynamics, HBV seroconversion probably has limited utility as a surrogate outcome measure for incident HIV. However, HBV seroconversion itself is an appropriate and important outcome measure for evaluation of prevention programs among IDUs.

Adult↗
PubMed2006

Outcomes of hepatitis B virus recurrence after liver transplantation.

The introduction of high doses of hepatitis B immune globulin (HBIG) and lamivudine for liver transplantation (OLT) prophylaxis has reduced the risk of hepatitis B recurrence and improved the survival of patients transplanted for hepatitis B virus (HBV)-related liver disease. But, posttransplant prophylaxis strategies to treat the recurrence of HBV have not yet been standardized. We analyzed 23 patients with HBV recurrence among 340 HBV-associated liver transplants performed from September 1996 to April 2004 (6.7%). Nine patients underwent deceased donor OLT and 14, living donor OLT. Mean follow-up was 37 months. Seroconversion after recurrence was observed in 6 of 23 patients (26%). Mean time to HBV recurrence tended to be shorter among the seroconversion (+) patients compared to seroconversion (-) patients (10 months vs 19.7 months; P = .062). Seroconversion rate after HBIG and lamivudine combination therapy for patients with HBV recurrence was 37.5% and time to seroconversion after HBV recurrence was 1.7 months. Seroconversion was best achieved when the pretransplant HBV DNA level was high and HBeAg was positive. Also, seroconversion rate was increased when HBV DNA level was low and the alanine transferase level high at the time of recurrence and when the time to recurrence after transplantation was short. Seroconversion after HBV recurrence, which was observed in 26%, may be increased in selected cases. Accordingly, aggressive treatment should be undertaken after HBV recurrence.

Antiviral Agents↗
PubMed1997

Pre-AIDS mortality from natural causes associated with HIV disease progression: evidence from the European Seroconverter Study among injecting drug users.

OBJECTIVES: To study differences in pre-AIDS mortality between European cohorts of injecting drug users (IDU) and to evaluate whether pre-AIDS mortality increased with time since HIV seroconversion and decreasing CD4 count. METHODS: The study population consisted of 664 IDU with documented intervals of HIV seroconversion from eight cohort studies. Differences in pre-AIDS mortality were studied between European sites; an evaluation of whether pre-AIDS mortality increased with time since HIV seroconversion and decreasing CD4 count was carried out using Poisson regression. RESULTS: One hundred and seven IDU died, of whom 57 did not have AIDS. Pre-AIDS causes of death were overdose/suicide (49%), natural causes such as bacterial infections/cirrhosis (40%), and unintentional injuries/unknown (11%). Considering pre-AIDS death and AIDS as competing risks, 14.7% were expected to have died without AIDS and 17.3% to have developed AIDS at 7 years from seroconversion. No statistically significant differences in pre-AIDS mortality were found between European regions, men and women, age categories and calendar time periods. Overall pre-AIDS mortality did not increase with time since seroconversion, but did increase with decreasing CD4 count. Evaluating cause-specific mortality, only pre-AIDS mortality from natural causes appeared to be associated with time since seroconversion as well as immunosuppression. For natural causes, the death rate per 100 person-years was 0.13 the first 2 years after seroconversion, 0.73 in years 2-4 [risk relative (RR) to years 0-2, 5.6], 1.83 in years 4-6 (RR, 14.0) and 1.54 for > or = 6 years (RR, 11.7). This rate was 0 for a CD4 cell count > or = 500 x 10(6)/l, 1.06 for 200-500 x 10(6)/l and 4.06 for < 200 x 10(6)/l (RR versus > or = 200 x 10(6)/l, 7.0). In multivariate analysis, both CD4 count and time since seroconversion appeared to be independently associated with death from natural causes; CD4 count appeared to be the strongest predictor (adjusted RR, 5.9). CONCLUSIONS: A high pre-AIDS mortality rate was observed among IDU. No significant differences were observed across European sites. Pre-AIDS mortality from natural causes but not from overdose and suicide was associated with HIV disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV.

BACKGROUND: Cross-sectional studies suggest an association between bacterial vaginosis (BV) and HIV-1 infection. However, an assessment of a temporal effect was not possible. OBJECTIVES: To determine the association of BV and other disturbances of vaginal flora with HIV seroconversion among pregnant and postnatal women in Malawi, Africa. DESIGN: Longitudinal follow-up of pregnant and postpartum women. METHODS: Women attending their first antenatal care visit were screened for HIV after counselling and obtaining informed consent. HIV-seronegative women were enrolled and followed during pregnancy and after delivery. These women were again tested for HIV at delivery and at 6-monthly visits postnatally. Clinical examinations and collection of laboratory specimens (for BV and sexually transmitted diseases) were conducted at screening and at the postnatal 6-monthly visits. The diagnosis of BV was based on clinical criteria. Associations of BV and other risk factors with HIV seroconversion, were examined using contingency tables and multiple logistic regression analyses on antenatal data, and Kaplan-Meier proportional hazards analyses on postnatal data. RESULTS: Among 1196 HIV-seronegative women who were followed antenatally for a median of 3.4 months, 27 women seroconverted by time of delivery. Postnatally, 97 seroconversions occurred among 1169 seronegative women who were followed for a median of 2.5 years. Bacterial vaginosis was significantly associated with antenatal HIV seroconversion (adjusted odds ratio = 3.7) and postnatal HIV seroconversion (adjusted rate ratio = 2.3). There was a significant trend of increased risk of HIV seroconversion with increasing severity of vaginal disturbance among both antenatal and postnatal women. The approximate attributable risk of BV alone was 23% for antenatal HIV seroconversions and 14% for postnatal seroconversions. CONCLUSIONS: This prospective study suggests that progressively greater disturbances of vaginal flora, increase HIV acquisition during pregnancy and postnatally. The screening and treating of women with BV could restore normal flora and reduce their susceptibility to HIV.

Cohort Studies↗
PubMed1998

The impact of chronic hepatitis C virus infection on HIV disease and progression in intravenous drug users.

OBJECTIVE: It is unclear whether co-infection with hepatitis C virus (HCV) can influence HIV related morbidity or mortality, either by accelerating HIV-related disease progression, or by contributing to end stage liver disease. The aim of this study was to examine the effect of HCV infection on the severity and progression of HIV disease in a cohort of Edinburgh intravenous drug users (IDUs). METHODS: In 240 (47%) out of 508 patients in the Edinburgh IDU cohort both HIV seroconversion dates and anti-HCV serology were available. Demographic variables and HIV-related progression between anti-HCV positive and anti-HCV negative groups were compared. Parameters assessed included clinical endpoints (time of development of significant symptoms attributable to HIV (CDC stage IV), time of development of AIDS, and time of death) and immunological endpoints (time of CD4+ counts dropping below 200/mm3, 100/mm3 and 50/mm3). RESULTS: Two hundred and two out of 240 patients (84%) had positive anti-HCV serology. There was no significant difference in the frequency of clinical and immunological endpoints between the anti-HCV positive and negative groups. Progression analysis from HIV seroconversion to HIV related clinical endpoints indicated that anti-HCV serology was not a significant factor influencing the rate of HIV progression (relative risks (RR) for anti-HCV positive group: seroconversion to CDC IV, 1.01; seroconversion to AIDS, 1.05; seroconversion to death, 0.90). Likewise, HCV serostatus did not significantly affect progression to immunological endpoints (RR for anti-HCV positive group: seroconversion to CD4+ < 200/mm3, 1.04; seroconversion to CD4+ < 100/mm3, 1.13; seroconversion to CD4+ < 50/mm3, 0.97. Overall mortality from end stage liver failure was 4% in HCV-seropositive patients without AIDS. This suggests that HCV has had a clinically (though not statistically) significant impact on overall survival in this cohort. CONCLUSIONS: This study demonstrates that HCV co-infection does not influence the rate of progression to either clinical or immunological endpoints in our population of HIV-infected drug users. Further data are required to assess the effect of HIV on thge progression of HCV-related liver disease.

Adult↗