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Biomedical subjects

P S Sullivan

Publications and source records attributed to P S Sullivan.

At least 19 recordsLinked to original sources

Low prevalence of antiretroviral resistance among persons recently infected with human immunodeficiency virus in two US cities.

Resistance testing for treatment-naïve, recently HIV-infected persons is not currently recommended; its clinical value will depend on the prevalence of resistance-associated mutations among recently infected persons. To estimate this prevalence, specimens were collected during 1997-1999 in Seattle and Los Angeles from drug-naïve, recently HIV-infected persons. HIV-1 protease and reverse transcriptase (RT) RNA sequences were amplified from plasma by RT-polymerase chain reaction (RT-PCR), sequenced, and analysed. Of 69 patients, five (7%) had resistance-associated mutations: three (4%) had primary mutations associated with resistance to nucleoside reverse transcriptase inhibitors (NRTI) or non-nucleoside-RTIs, and three patients (4%) had secondary NRTI mutations. No primary mutation associated with resistance to protease inhibitors was observed. Mean age of the five persons with resistance-associated mutations (38 years) was higher than that of the 64 persons without resistance-associated mutations (31 years, P=0.04). The findings suggest that the prevalence of resistance-associated mutations among persons recently infected with HIV in these cities is low.

Adolescent↗

Evaluation of United States-licensed human immunodeficiency virus immunoassays for detection of group M viral variants.

Six Food and Drug Administration (FDA)-licensed human immunodeficiency virus type 1 (HIV-1) and HIV-1/2 immunoassays, including five enzyme immunoassays and one rapid test, were challenged with up to 250 serum samples collected from various global sites. The serum samples were from individuals known to be infected with variants of HIV-1 including group M subtypes A, B, B', C, D, E, F, and G and group O. All immunoassays detected the vast majority of samples tested. Three samples produced low signal over cutoff values in one or more tests: a clade B sample, an untypeable sample with a low antibody titer, and a group O sample. It is concluded that HIV-1 immunoassays used in the United States are capable of detecting most HIV-1 group M variants.

AIDS Serodiagnosis↗

Effect of influenza vaccination on disease progression among HIV-infected persons.

OBJECTIVE: To describe the effect of influenza vaccination on long-term change in CD4 count and HIV RNA level, and on progression to AIDS or death. DESIGN AND SETTING: A longitudinal medical record review set in 113 medical clinics in 10 United States cities. PATIENTS: A total of 36,050 HIV-infected persons aged > or = 13 years in care for HIV infection. MAIN OUTCOME MEASURES: Change in CD4 count and HIV RNA level at follow-up (3-12 months after vaccination); hazard ratios (HR) for association of influenza vaccine with progression from baseline CD4 or HIV RNA level to AIDS and to death. RESULTS: The median CD4 count among all persons decreased 28 cells/year during follow-up, with no difference in change in CD4 count between the 8007 (40%) vaccinated (median = 6 months, vaccine to follow-up CD4 count) and the 11,794 unvaccinated persons. In a viral load subanalysis, median HIV RNA level decreased 90 copies/ml per year among all persons during follow-up; decreases were not different between vaccinated and unvaccinated persons (median = 7 months, vaccine to follow-up HIV RNA level determination). Influenza vaccination was weakly associated with decreased risk of progression to clinical AIDS [HR 0.93; 95% confidence interval (CI), 0.87-0.99], but not associated with time to death (HR, 0.97; CI, 0.93-1.01). CONCLUSIONS: No negative long-term effect of influenza vaccination on CD4 counts, HIV RNA levels, or progression to AIDS or death was found in this HIV-infected population. These data suggest that physicians should not withhold influenza vaccine because of concerns about long-term detrimental effects of increased viral replication.

Acquired Immunodeficiency Syndrome↗

Aspergillosis among people infected with human immunodeficiency virus: incidence and survival. Adult and Adolescent Spectrum of HIV Disease Project.

Aspergillosis is a life-threatening fungal infection in immunocompromised people, including people infected with human immunodeficiency virus (HIV). We determined the incidence of aspergillosis among HIV-infected people and survival after aspergillosis diagnosis by use of a national HIV surveillance database. Among 35,252 HIV-infected patients, the incidence of aspergillosis was 3.5 cases per 1000 person-years (p-y; 95% confidence interval [CI], 3.0-4.0 per 1000 p-y). Incidence was higher among people aged > or =35 years (4.1 per 1000 p-y, 95% CI, 3. 5-4.8), among people with CD4 counts of 50-99 cells/mm(3) (5.1 per 1000 p-y, 95% CI, 2.8-7.3), or CD4 counts of <50 cells/mm(3) (10.2 per 1000 p-y, 95% CI, 8.0-12.2), versus people with CD4 counts of >200 cells/mm(3), people with > or =1 acquired immune deficiency syndrome-defining opportunistic illness (8.6 per 1000 p-y, 95% CI, 7.4-9.9), and people who were prescribed at least one medication associated with neutropenia (27.7 per 1000 p-y, 95% CI, 21.0-34.3). Median survival time after diagnosis of aspergillosis was 3 months, and 26% survived for > or =1 year. These findings suggest that aspergillosis is uncommon, occurs especially among severely immunosuppressed or leukopenic HIV-infected people, and is associated with poor survival.

AIDS-Related Opportunistic Infections↗

Epidemiology of thrombosis in HIV-infected individuals. The Adult/Adolescent Spectrum of HIV Disease Project.

OBJECTIVE: To describe the incidence of clinically recognized thrombosis and associated factors among individuals infected with HIV. DESIGN: A longitudinal medical record review. SETTING: Over 100 medical clinics in nine US cities. PATIENTS: A total of 42 935 individuals aged 13 years or older with HIV infection, observed for an average of 2.4 years. MAIN OUTCOME MEASURES: The incidence of thrombosis among HIV-infected individuals; adjusted odds ratios for factors associated with thrombosis. RESULTS: The incidence of thrombosis among HIV-infected individuals was 2.6/1000 person-years (PY). Factors significantly associated with thrombosis included: age of 45 or more years (adjusted odds ratio [AOR], 1.9; 95% confidence interval [CI], 1.4-2.7); a diagnosis of cytomegalovirus disease or retinitis (AOR, 1.9; CI, 1.2-2.9), or other AIDS-defining opportunistic illness (AOR, 1.5; CI, 1.1-2.2); hospitalization (AOR, 3.3; CI, 2.5-4.4); and the prescription of megestrol acetate (AOR, 2.0; CI 1.3-2.9) or indinavir (AOR, 2.4; CI 1.4-4.3). The prescription of other protease inhibitors, sex, race, and mode of HIV exposure were not associated with thrombosis. CONCLUSION: Among HIV-infected individuals, clinically detected thrombosis is more common in those who have opportunistic illnesses, for whom megestrol acetate or indinavir have been prescribed, who have been hospitalized, and who are aged 45 years or older. Physicians should be aware of the risks of thrombosis in order to promote the early identification and appropriate treatment or prophylaxis. Further study is needed to characterize the association between indinavir and thrombosis.

Adolescent↗

Genetic factors associated with thrombosis in pregnancy in a United States population.

OBJECTIVE: Polymorphisms in the genes for factor V (factor V Leiden), prothrombin, methylenetetrahydrofolate reductase, and angiotensin-converting enzyme have been associated with the occurrence of venous thrombosis. The objective of this study was to determine the relationships of these polymorphisms to thrombosis during pregnancy. STUDY DESIGN: This case-control study included 41 case patients with venous thrombosis during pregnancy and 76 control subjects matched for hospital and for race (white vs black) who had a normal pregnancy. RESULTS: Among white subjects, mutations in the genes for factor V and prothrombin were associated with increased risks of venous thrombosis during pregnancy (factor V: odds ratio, 18.3; 95% confidence interval, 2.7-432; P =.001; prothrombin: odds ratio infinity; 95% lower confidence limit, 1.7; P =.01). No black subject had either of these two mutations. For both black and white subjects the D/D genotype of the gene for angiotensin-converting enzyme entailed increased risk compared with the other genotypes (odds ratio, 2.7; 95% confidence interval, 1.2-6.3; P =.02). The polymorphism in the gene for methylenetetrahydrofolate reductase was unrelated to thrombosis during pregnancy among both blacks and whites. CONCLUSION: Women who had thrombotic complications during pregnancy demonstrated an increased prevalence of genetic mutations related to coagulation. The additional risk of thrombosis during pregnancy associated with such genetic mutations can be substantial.

Black People↗

Human immunodeficiency virus (HIV) subtype surveillance of African-born persons at risk for group O and group N HIV infections in the United States.

A population-based surveillance registry was used to identify human immunodeficiency virus (HIV)-infected persons in the United States at increased risk for group O and group N infections (those born in or near African countries where group O infection has been reported). Of 155 eligible subjects, 37 gave samples. By phylogenetic and serologic analysis, 32 were infected with group M (16 with subtype A, 5 with B, 7 with C, and 1 each with subtypes D, F2, G, and recombinant A/J) and 2 with group O but none with group N virus. For 3, samples could not be typed by serology or amplified by polymerase chain reaction using group M-, O-, or N-specific primers. In the United States, group O HIV infection is uncommon; no case of group N infection was found. African-born persons may have HIV strains typical of their birth country. Ongoing subtype surveillance may allow early identification of novel or emerging HIV strains.

Adult↗

Persistently negative HIV-1 antibody enzyme immunoassay screening results for patients with HIV-1 infection and AIDS: serologic, clinical, and virologic results. Seronegative AIDS Clinical Study Group.

OBJECTIVE: To describe persons with HIV infection and AIDS but with persistently negative HIV antibody enzyme immunoassay (EIA) results. DESIGN: Surveillance for persons meeting a case definition for HIV-1-seronegative AIDS. SETTING: United States and Canada. PATIENTS: A total of eight patients with seronegative AIDS identified from July 1995 through September 1997. MAIN OUTCOME MEASURES: Clinical history of HIV disease, history of HIV test results, and CD4 cell counts from medical record review; results of testing with a panel of EIA for antibodies to HIV-1, and HIV-1 p24 antigen; and viral subtype. RESULTS: Negative HIV EIA results occurred at CD4 cell counts of 0-230 x 10(6)/l, and at HIV RNA concentrations of 105,000-7,943,000 copies/ml. Using a panel of HIV EIA on sera from three patients, none of the HIV EIA detected infection with HIV-1, and signal-to-cut-off ratios were < or = 0.8 or all test kits evaluated. Sera from five patients showed weak reactivity in some HIV EIA, but were non-reactive in other HIV EIA. All patients were infected with HIV-1 subtype B. CONCLUSIONS: Rarely, results of EIA tests for antibodies to HIV-1 may be persistently negative in some HIV-1 subtype B-infected persons with AIDS. Physicians treating patients with illnesses or CD4 cell counts suggestive of HIV infection, but for whom results of HIV EIA are negative, should consider p24 antigen, nucleic acid amplification, or viral culture testing to document the presence of HIV.

Acquired Immunodeficiency Syndrome↗

Viral and immunologic examination of human immunodeficiency virus type 1-infected, persistently seronegative persons.

Persons who were human immunodeficiency virus type 1 (HIV-1)-infected but who remained persistently seronegative (HIPS) on HIV-1 antibody tests were examined through AIDS case surveillance. Six such individuals (HIPS-1 to -4, -7, and -9) were examined to determine whether their persistent seronegativity was attributable to immune dysfunction or infection with atypical HIV. Of the 6, 4 had antibody titers to at least 1 other common pathogen. In vitro stimulation of peripheral blood mononuclear cells from HIPS-4 and HIPS-7 with pokeweed mitogen or phosphorothioate oligodeoxynucleotide (direct B cell mitogen) did not produce HIV-1-specific antibody. Reconstitution experiments with recombinant interleukin (rIL)-4 and rIL-12 also had no impact on antibody production. Virus isolates from HIPS-4 and -9 were R5X4-tropic, whereas HIPS-7 was CCR5-tropic only. Sequence analysis of long terminal repeat, p24, and env gp41 did not reveal any specific mutation, and phylogenetic analysis confirmed that all 6 virus specimens were HIV-1 subtype B. These data suggest that the lack of a detectable antibody response in these patients may be the result of immune dysfunction.

Amino Acid Sequence↗

Bordetella bronchiseptica infection in human immunodeficiency virus-infected patients.

Bordetella bronchiseptica is a pleomorphic gram-negative coccobacillus that commonly causes respiratory tract infections in dogs. We identified nine human immunodeficiency virus (HIV)-infected persons with culture-confirmed B. bronchiseptica infections (eight respiratory tract and one disseminated infection). The respiratory illnesses ranged in severity from mild upper respiratory tract infection to pneumonia. All nine patients had had at least one AIDS-defining condition before the B. bronchiseptica infection. Two patients had household contact with dogs before their illnesses, and one had household contact with cats. Infection due to B. bronchiseptica is uncommon in HIV-infected persons. Additional data are needed to fully define the spectrum of disease due to B. bronchiseptica infections and to evaluate the possibility that this infection may be acquired from pets. Treatment of B. bronchiseptica infection should be tailored to the patient and should be based on the results of susceptibility testing.

AIDS-Related Opportunistic Infections↗

Geographic differences in noninjection and injection substance use among HIV-seropositive men who have sex with men: western United States versus other regions. Supplement to HIV/AIDS Surveillance Study Group.

To study the prevalence of and factors associated with the use of alcohol and nonprescription drugs by HIV-seropositive men who have sex with men (MSM) and to describe variations in alcohol and nonprescription drug use by geographic region, we analyzed data from a multistate, population- and facility-based interview study conducted in 12 U.S. states and metropolitan areas. Among 9735 MSM with HIV infection or AIDS who completed a 45-minute interview, nearly one third reported possible alcohol abuse. Large proportions of MSM also reported the use of marijuana (51%), noninjected cocaine (31%), and crack cocaine (16%) in the 5 years before the interview. Smaller proportions of MSM reported ever having injected cocaine (13%), stimulants (8%), and heroin (8%). Results of logistic regression indicated that in the 5 years before interview, white MSM were significantly (p < .01) more likely than referent (mostly Hispanic) MSM to report use of hallucinogens, marijuana, nitrites, noninjected amphetamines, and diazepam; black MSM were significantly more likely than referent MSM to report use of noninjected crack cocaine. Use of injected stimulants was significantly associated with white race versus referent MSM, and residing in the West versus East. The prevalence of alcohol and drug use among HIV-seropositive MSM is high, and prevalences and types of substance use differ by region and racial/ethnic group. To prevent HIV transmission in this population, health departments and community-based organizations must understand the unique local patterns of substance use to develop effective substance abuse prevention and treatment programs.

Adult↗

Epidemiology of anemia in human immunodeficiency virus (HIV)-infected persons: results from the multistate adult and adolescent spectrum of HIV disease surveillance project.

To study the incidence of, the factors associated with, and the effect on survival of anemia in human immunodeficiency virus (HIV)-infected persons, we analyzed data from the longitudinal medical record reviews of 32,867 HIV-infected persons who received medical care from January 1990 through August 1996 in clinics, hospitals, and private medical practices in nine United States cities. We calculated the 1-year incidence of anemia (a hemoglobin level of <10 g/dL or a physician diagnosis of anemia); the adjusted odds ratios showing excess risk of anemia associated with demographic factors, prescribed therapies, and concurrent diseases; the risk of death for patients who developed anemia compared with risk for patients who did not develop anemia; and, of patients who did develop anemia, the risk of death for those who did not recover from anemia compared with the risk for those who did recover. The 1-year incidence of anemia was 36.9% for persons with one or more acquired immunodeficiency syndrome (AIDS)-defining opportunistic illnesses (clinical AIDS), 12.1% for patients with a CD4 count of less than 200 cells/micron or CD4 percentage of <14 but not clinical AIDS (immunologic AIDS), and 3.2% for persons without clinical or immunologic AIDS. Of anemia diagnoses, 22% were identified by physicians as drug related. Incidence of anemia was associated with clinical AIDS, immunologic AIDS, neutropenia, thrombocytopenia, bacterial septicemia, black race, female sex, prescription of zidovudine, fluconazole, and ganciclovir, and lack of prescription of trimethoprim-sulfamethoxazole. The increased risk of death associated with anemia differed by first CD4 count: for patients with a CD4 count of >/=200 cells/microL at the beginning of the survival analysis, the risk of death was 148% (99% confidence interval [CI], 114 to 188) greater for those who developed anemia; for patients whose first CD4 count was <200 cells/microL, the risk of death was 56% (99% CI, 43 to 71) greater for those in whom anemia developed. For persons in whom anemia developed, the risk of death was 170% (99% CI, 132 to 203) greater for persons who did not recover from anemia compared with those who did recover. Anemia is a frequent complication of HIV infection, and its incidence is associated with progression of HIV disease, prescription of certain chemotherapeutics, black race, and female sex. Anemia, particularly anemia that does not resolve, is associated with shorter survival of HIV-infected patients.

AIDS-Related Opportunistic Infections↗

Surveillance for thrombocytopenia in persons infected with HIV: results from the multistate Adult and Adolescent Spectrum of Disease Project.

Thrombocytopenia in persons infected with HIV is prevalent and has numerous causes. To study the occurrence, associations, and effect on survival of thrombocytopenia in HIV-infected persons, we used surveillance data from a longitudinal survey of the medical records of 30,214 HIV-infected patients who received medical care from January 1990 through August 1996 in more than 100 medical clinics in 10 U.S. cities. Thrombocytopenia was defined as a physician diagnosis of thrombocytopenia or a platelet count of < 50,000 platelets/ microliter. Analysis of associations of thrombocytopenia was conducted using logistic regression. In HIV+ patients, the 1-year incidence [corrected] of thrombocytopenia was 8.7% in persons with one or more AIDS-defining opportunistic illnesses (clinical AIDS), 3.1% in patients with a CD4 count < 200 cells/mm3 but not clinical AIDS (immunologic AIDS), and 1.7% in persons without clinical or immunologic AIDS. The incidence of thrombocytopenia was associated with clinical AIDS (adjusted odds ratio [AOR] 2.2; 99% confidence interval [CI] 1.7-3.0), immunologic AIDS (AOR 1.5, CI 1.0-2.1), history of injecting drug use (AOR 1.4, CI 1.0-1.9), anemia (AOR 5.0, CI 3.8-6.7), lymphoma (AOR 3.7, CI 1.3-10.6), and black race (AOR 0.7, CI 0.5-0.9). After controlling for anemia, clinical AIDS, CD4 count, neutropenia, antiretroviral therapy, and Pneumocystis carinii pneumonia prophylaxis, thrombocytopenia was significantly associated with decreased survival (risk ratio 1.7; 95% CI, 1.6-1.8). Thrombocytopenia in HIV-infected persons is an important clinical condition associated with shorter survival.

AIDS-Related Opportunistic Infections↗

Changes in AIDS incidence for men who have sex with men, United States 1990-1995.

OBJECTIVES: To describe changes in AIDS incidence for men who have sex with men (MSM) from 1990 to 1995, by demographic and geographic groups. METHODS: We examined national AIDS surveillance data reported up to 30 September 1996, for men who received AIDS diagnoses in the years 1990-1995 and whose only reported risk behavior was sex with men. We evaluated trends in AIDS rates by estimating the incidence of clinical AIDS (AIDS defined by opportunistic illnesses), and report clinical AIDS incidence rates for MSM (AIDS rates) and proportional change in rates from 1990 to 1995. RESULTS: Clinical AIDS rates (MSM per 100,000 men per year) increased by 12% from 25.5% in 1990 to 28.5% in 1995. Significant variations in AIDS rates and 5-year changes in AIDS rates were observed in various subgroups of MSM. Five-year increases in AIDS rates were highest for American-Indian/Alaskan native (53%), black (45%), and Hispanic (23%) MSM; the only decrease occurred for white MSM (-2%). Incidence for black MSM increased from twofold (in 1990) to threefold (in 1995) the rate for white MSM. Large increases in AIDS rates were observed for MSM in rural areas (34%) and areas with 50,000 to 249,999 residents (34%) and for MSM aged over 60 years (32%). CONCLUSIONS: The high national AIDS rate for MSM continued to rise, but more slowly than earlier in the epidemic. Racial/ethnic minority MSM had consistently large increases in AIDS rates; AIDS rates decreased only slightly for white MSM. The AIDS epidemic among MSM is not homogenous, and AIDS rates continue to increase for minority MSM, and MSM living in rural areas. HIV prevention remains a high priority for all MSM, especially black and Hispanic MSM.

Acquired Immunodeficiency Syndrome↗

Determination of the lifespan of erythrocytes from greyhounds, using an in vitro biotinylation technique.

OBJECTIVE: To determine the RBC lifespan of Greyhounds, using an in vitro labeling technique. DESIGN: RBC from dogs were labeled with NHS-biotin and their disappearance measured over time to determine RBC lifespan. SAMPLE POPULATION: 5 Greyhounds that had been vaccinated against distemper, adenovirus 1 and 2 infections, parainfluenza, leptospirosis, parvovirus, and coronavirus infections, Bordetella bronchiseptica infection, and rabies the previous year; 3 sexually intact 14-month-old Beagles served as controls. PROCEDURE: After venipuncture for CBC, catheters were inserted in the cephalic vein of each dog. Butorphanol was then administered to achieve mild sedation and analgesia, and glycopyrrolate was administered to ensure maintenance of adequate heart rate during phlebotomy. Dogs were positioned in lateral recumbency; blood was removed via jugular venipuncture, using a standard laboratory donor blood bag containing citrate-phosphate-dextrose solution. Blood was transferred aseptically into sterile polystyrene containers and NHS-biotin was added. After incubation, the labeled RBC were reinfused into the dogs and the blood was allowed to recirculate for 1 hour before the first postinfusion sample was taken. At frequent intervals, blood to be analyzed was taken by jugular venipuncture, and the percentage of labeled cells was determined by flow cytometry. RESULTS: The mean RBC lifespan of non-Greyhounds was significantly longer than that of Greyhounds (104.3 +/- 2.2 days vs 53.6 +/- 6.5 days; P = 0.001). A negative linear correlation was also found between age of the Greyhounds and their RBC lifespan (P = 0.01, R2 = 0.91). CONCLUSIONS: The shorter RBC lifespan of the Greyhounds may explain the finding of macrocytosis reported in earlier work. The reason for the shorter RBC lifespan in Greyhounds may be caused by differences in Greyhound RBC membrane structure or accelerated RBC removal from the circulation.

Animals↗

Successful determination of platelet lifespan in C3H mice by in vivo biotinylation.

Mice are frequently used as test animals in blood platelet research studies, but safe and convenient methods are not available to easily assess lifespan. Therefore we have improved an existing method for measuring platelet lifespan by determining the disappearance of biotin-labeled platelets from the circulation of mice with immunofluorescence and flow cytometry. In vivo labeling of platelets with Sulfo-NHS-Biotin, a water-soluble moiety, was used as a direct method for labeling the entire platelet population by direct infusion into mice. Platelet samples were collected daily, washed, labeled with a fluorescent detection agent, and analyzed by flow cytometry to measure the percentage of biotinylated cells. This method allowed a rapid determination of murine platelet lifespan without requiring radioactive labels. Using this method, we have estimated that the platelet lifespan in C3H male mice is approximately 4.8 days.

Affinity Labels↗

Association of mean platelet volume and bone marrow megakaryocytopoiesis in thrombocytopenic dogs: 60 cases (1984-1993).

Medical records of 60 thrombocytopenic dogs in which platelet volume analysis was performed between 1984 and 1993 were reviewed. Information collected from the records included signalment, mean platelet volume, the clinical pathologist's assessment of the adequacy of the megakaryocyte population in the bone marrow, and the causes of thrombocytopenia. In all dogs, the bone marrow aspirate had been collected within 48 hours of platelet volume analysis. Sensitivity and specificity of using platelet volume analysis (mean volume < or = 12.00 microns 3 vs mean volume > 12.00 microns 3) as a test for bone marrow megakaryocyte response (adequate vs inadequate) in thrombocytopenic dogs was determined. Sensitivity was 88%, specificity was 80%, predictive value of a positive test was 96%, and predictive value of a negative test was 57%. Results suggested that megathrombocytosis in a thrombocytopenic dog was a good predictor of adequate bone marrow response (normal or hyperplastic bone marrow megakaryocyte population); however, a mean platelet volume < or = 12.00 microns 3 in thrombocytopenic dogs was not strongly predictive of inadequate bone marrow response.

Animals↗