Salmonella Persistence within the Peripheral Lymph Nodes of Cattle following Experimental Inoculation.

Utilizing a transdermal method of inoculation developed in our laboratory, the duration of infection of Salmonella in the peripheral lymph nodes of steers was examined. Thirty-six Holstein steers (mean body weight of 137 kg) were inoculated with Salmonella Montevideo (day 0) on each lower leg and both sides of the back and abdomen. Calves were euthanized beginning at 6 h and subsequently on each of days 1, 2, 4, 7, 9, 11, 14, and 21 postinoculation (four animals each time). The subiliac, popliteal, and superficial cervical (prescapular) lymph nodes were collected and cultured (quantitatively and qualitatively) for the challenge strain of Salmonella. The challenge strain was detected via direct culture within the lymph nodes at 6 h postinoculation and on each subsequent necropsy date. Salmonella levels in lymph node were 0.8 to 1.8 log CFU/g. Lymph nodes were generally positive after enrichment culture throughout the experiment. Salmonella elimination appeared to begin approximately 14 days postinoculation. However, elimination was not completed by day 21; therefore, a second experiment was conducted identical to the first except that the time from inoculation to necropsy was extended. Salmonella was recovered via direct culture on each of the necropsy days, and results in general were similar to those of experiment I, except that on days 20, 24, and 28 isolates from serogroups C2 and E1 were identified in addition to the inoculation strain C1 in multiple animals. The data from both experiments indicate that after a single inoculation event, Salmonella would be completely cleared by approximately 28 days. Further research with expanded times between inoculation and necropsy is required for verification.

Evidence supporting vertical transmission of Salmonella in dairy cattle.

We set out to investigate whether Salmonella enterica could be recovered from various tissues of viable neonatal calves immediately following parturition. Eleven samples were aseptically collected from each of 20 calves and consisted of both left and right subiliac and prescapular lymph nodes (LN), mesenteric LN, spleen and liver, as well as intestinal tissue (including luminal contents) from the small intestine, caecum, spiral colon and rectum. In addition, a faecal sample was collected from 19 of the dams. Salmonella was recovered from at least one sample from 10 of the 20 neonates. Across all calves, Salmonella was recovered from 12·7% of all samples and from LN in particular, Salmonella was recovered from 10·0%, 5·0%, and 5·0% of subiliac, prescapular, and mesenteric LN, respectively. Within calves, Salmonella was recovered from 0% to 73% of samples and across tissues, estimates of Salmonella prevalence were greatest in the caecum (30%) but was never recovered from the right pre-scapular LN. These data provide evidence of vertical transmission from a dam to her fetus such that viable calves are born already infected and thereby not requiring faecal-oral exposure for transmission. This new knowledge ought to challenge - or at least add to - existing paradigms of Salmonella transmission dynamics within cattle herds.

Investigation into Possible Differences in Salmonella Prevalence in the Peripheral Lymph Nodes of Cattle Derived from Distinct Production Systems and of Different Breed Types.

Previous research demonstrated significant variation in the prevalence of Salmonella in peripheral lymph nodes (LNs) of feedlot cattle and cull cows, with greater prevalence in feedlot cattle. Therefore, we performed experiments to investigate whether these differences in Salmonella prevalence in subiliac LNs are due to, or influenced by, breed, which in many respects is a proxy for the production system in which the animal is derived. Holstein steers are a by-product of dairy systems, and beef steers are an intended product of commercial beef operations. For the first experiment, Holstein and beef steers originating from the same feedlot and harvested on the same day were sampled. Of the 467 Holstein and 462 beef cattle LNs collected, 62.1% of Holstein and 59.7% of beef cattle samples harbored Salmonella (P = 0.46; qualitative culture), with 51.2 and 48.9% of samples containing quantifiable concentrations (P = 0.49), respectively. The concentration of Salmonella within the LN followed a decreasing trend over the collection period (May to October), averaging 1.4 log CFU/g of LN for both Holstein and beef cattle samples (P = 0.78). In a second experiment, we compared 100% Brahman cattle to their beef cattle counterparts, as we hypothesized that the resistance of Brahman cattle to insects may reduce Salmonella transmission via biting insects. Of the 42 Brahman and 31 beef cattle LNs collected, the concentration of Salmonella within the LN averaged 3.0 log CFU/g for Brahman cattle and 2.9 log CFU/g for beef cattle samples (P = 0.30). Using qualitative culture, we recovered Salmonella from 100% of LNs from Brahman cattle and 97% of beef cattle samples (P = 0.25). Results of this research indicate that the differences observed are not due to breed and are likely a function of age, immune function, or other factors yet to be identified. Understanding which cattle are more likely to harbor Salmonella within LNs will aid in targeting both pre- and postharvest intervention strategies.

Cataloguing of Potential HIV Susceptibility Factors during the Menstrual Cycle of Pig-Tailed Macaques by Using a Systems Biology Approach.

UNLABELLED: Our earlier studies with pig-tailed macaques demonstrated various simian-human immunodeficiency virus (SHIV) susceptibilities during the menstrual cycle, likely caused by cyclic variations in immune responses in the female genital tract. There is concern that high-dose, long-lasting, injectable progestin-based contraception could mimic the high-progesterone luteal phase and predispose women to human immunodeficiency type 1 (HIV-1) acquisition and transmission. In this study, we adopted a systems biology approach employing proteomics (tandem mass spectrometry), transcriptomics (RNA microarray hybridization), and other specific protein assays (enzyme-linked immunosorbent assays and multiplex chemokine and cytokine measurements) to characterize the effects of hormonal changes on the expression of innate factors and secreted proteins in the macaque vagina. Several antiviral factors and pathways (including acute-phase response signaling and complement system) were overexpressed in the follicular phase. Conversely, during the luteal phase there were factors overexpressed (including moesins, syndecans, and integrins, among others) that could play direct or indirect roles in enhancing HIV-1 infection. Thus, our study showed that specific pathways and proteins or genes might work in tandem to regulate innate immunity, thus fostering further investigation and future design of approaches to help counter HIV-1 acquisition in the female genital tract. IMPORTANCE: HIV infection in women is poorly understood. High levels of the hormone progesterone may make women more vulnerable to infection. This could be the case during the menstrual cycle, when using hormone-based birth control, or during pregnancy. The biological basis for increased HIV vulnerability is not known. We used an animal model with high risk for infection during periods of high progesterone. Genital secretions and tissues during the menstrual cycle were studied. Our goal was to identify biological factors upregulated at high progesterone levels, and we indeed show an upregulation of genes and proteins which enhance the ability of HIV to infect when progesterone is high. In contrast, during low-progesterone periods, we found more HIV inhibitory factors. This study contributes to our understanding of mechanisms that may regulate HIV infection in females under hormonal influences. Such knowledge is needed for the development of novel prevention strategies.

Oral salmonella challenge and subsequent uptake by the peripheral lymph nodes in calves.

Previous attempts to infect peripheral lymph nodes (PLNs) with Salmonella via oral inoculation have been inconsistent. Therefore, we performed a series of experiments to determine whether multiple exposures to an oral challenge would result in Salmonella-positive PLN in cattle. In each of three experiments, calves were inoculated with Salmonella Montevideo. In the first experiment, calves were challenged with either no Salmonella (control), a single oral dose (∼10(10); PCON), or 10 consecutive doses in water (∼10(3); WAT). The positive control treatment resulted in an increase (P < 0.05) in the percentage of Salmonella-positive PLNs, compared with the WAT-treated and control animals. Experiments 2 and 3 were designed to additionally determine if the stress associated with feed and water deprivation influences the systemic spread of Salmonella from the gastrointestinal tract to PLNs. Following 14 days of oral inoculation (average 7.1 × 10(4) CFU/day) in experiment 1, Salmonella was recovered from one subiliac and one superficial cervical lymph node of calves that were deprived of feed and water (72 h). No treatment differences (P > 0.05) were observed between control and deprived calves. Based on the poor recovery of Salmonella from the PLNs in WAT-challenged calves in experiments 1 and 2, a higher challenge dose (average 1.2 × 10(7) CFU) was used in experiment 3. The increased dose resulted in the recovery of the challenge strain of Salmonella from the PLNs (70.8 and 75.0% of control and deprived calves, respectively). However, no treatment differences (P > 0.05) were observed between control and deprived calves. Results of this research demonstrated that a substantial oral challenge is required to produce Salmonella-positive PLNs. However, as the challenge periods examined herein were considerably shorter compared with the normal time spent by cattle in feedlots, increased exposure time to lower doses may produce the same effect observed in experiment 3.

Plane of nutrition influences the performance, innate leukocyte responses, and resistance to an oral Salmonella enterica serotype Typhimurium challenge in Jersey calves.

Two experiments investigated how plane of nutrition influences performance, leukocyte responses, and resistance to an oral Salmonella enterica serotype Typhimurium challenge. In experiment 1, 46 (2±1 d of age) calves were randomly assigned to 2 diets: a low (LPN; n=23) and high plane of nutrition (HPN; n=23). The LPN calves were fed 409 g/d of dry matter (DM) of a 20% crude protein and 20% fat milk replacer, whereas HPN calves were fed 610 and 735 g/d of DM of a 28% crude protein and 25% fat milk replacer during wk 1 and 2 to 6, respectively. In experiment 2, 20 bull calves (LPN; n=11 and HPN; n=9) were orally challenged on d 80 with 1.5×10(7) cfu of Salmonella Typhimurium (ATCC #14028). The HPN calves had a greater incidence (87.5 vs. 45.5%) and duration of days with high fecal scores (5.5 vs. 3.5 d). The LPN calves had greater neutrophil surface expression of L-selectin on d 7, 21, and 42. Following the Salmonella Typhimurium challenge, calf starter DM intake was greater among the HPN calves. The percentage of neutrophils producing an oxidative burst was also greater among HPN calves on d 1 to 5 after the challenge. Similarly, the intensity of the oxidative burst tended to be greater among the HPN calves on d 2 and 3 postchallenge. The secretion of tumor necrosis factor-α from whole-blood cultures stimulated with lipopolysaccharide tended to be greater on d 1 and was greater on d 5 and 6 among HPN calves. The median ranks of haptoglobin concentrations were greater and plasma zinc concentrations tended to be decreased among LPN calves. These data indicate that feeding a HPN to Jersey calves improved average daily gain and feed efficiency, but increased the incidence of high fecal scores during the first few weeks of life; however, the HPN Jersey calves may be more resistant to Salmonella Typhimurium after weaning.

Improved performance and heightened neutrophil responses during the neonatal and weaning periods among outdoor group-housed Holstein calves.

The objective was to determine if outdoor group housing of Holstein calves influences metabolic status, leukocyte responses, and behavior compared with individually housed calves. Forty-nine Holstein heifer calves (2 ± 1 d of age) were randomly assigned to 1 of 2 treatments: individually housed (G1; n = 22) or group housed [3 calves per pen (G3); n = 27]. The space allowances per calf were 4.8 and 7.0m(2) for G1 and G3, respectively. All calves were offered an identical plane of milk replacer nutrition (747 and 1,010 g of DM/d of a 28% CP:20% fat milk replacer from wk 1 to 2 and wk 3 to 6, respectively). Weaning was initiated during wk 7 by removing the p.m. feeding and calves were completely weaned when they consumed 900 g of calf starter/d (as fed) for 2 consecutive days after d 54. At d 90, calves were commingled into random outdoor groups of 5 calves per pen. Peripheral blood was collected during the neonatal (d 3, 10, and 21), weaning (d 46, 48, and 54), and commingling periods (d 90, 93, and 98) and was analyzed for neutrophil oxidative burst (OB) capacity when cocultured with Escherichia coli, neutrophil surface L-selectin protein expression, and whole-blood secretion of tumor necrosis factor-α when cocultured with lipopolysaccharide. Starter intake was greater for G3 during the postweaning period (wk 8 to 12). Average daily gain was greater for G3 than G1 from d 54 to 68 and tended to be greater after commingling from d 113 to 133. During the neonatal period, G3 calves had more activated neutrophils, as evidenced by increased neutrophil L-selectin protein expression and a tendency for increased percentage of neutrophils producing an OB than G1 calves. During weaning, G3 calves continued to have more activated neutrophils with increased L-selectin expression on d 46 and 48 and a greater OB intensity throughout the period. No differences were observed among leukocyte responses between treatments at d 93 and 98. Outdoor group-housed Holstein calves had improved performance and heightened neutrophil responses compared with individually housed calves.

Use of a wave reverberation technique to infer the density compression of shocked liquid deuterium to 75 GPa.

A novel approach was developed to probe density compression of liquid deuterium (L-D2) along the principal Hugoniot. Relative transit times of shock waves reverberating within the sample are shown to be sensitive to the compression due to the first shock. This technique has proven to be more sensitive than the conventional method of inferring density from the shock and mass velocity, at least in this high-pressure regime. Results in the range of 22-75 GPa indicate an approximately fourfold density compression, and provide data to differentiate between proposed theories for hydrogen and its isotopes.

Double Z-pinch hohlraum drive with excellent temperature balance for symmetric inertial confinement fusion capsule implosions.

A double Z pinch driving a cylindrical secondary hohlraum from each end has been developed which can indirectly drive intertial confinement fusion capsule implosions with time-averaged radiation fields uniform to 2%-4%. 2D time-dependent view factor and 2D radiation hydrodynamic simulations using the measured primary hohlraum temperatures show that capsule convergence ratios of at least 10 with average distortions from sphericity of /r200 MJ.

Equation of state measurements in liquid deuterium to 70 GPa.

Using intense magnetic pressure, a method was developed to launch flyer plates to velocities in excess of 20 km/s. This technique was used to perform plate-impact, shock wave experiments on cryogenic liquid deuterium ( L-D(2)) to examine its high-pressure equation of state. Using an impedance matching method, Hugoniot measurements were obtained in the pressure range of 30-70 GPa. The results of these experiments disagree with previously reported Hugoniot measurements of L-D(2) in the pressure range above approximately 40 GPa, but are in good agreement with first principles, ab initio models for hydrogen and its isotopes.

Viral load as an independent risk factor for opportunistic infections in HIV-infected adults and adolescents.

OBJECTIVE: We investigated whether HIV plasma RNA (viral load; VL) predicts risk for opportunistic infections (OI) in HIV-infected persons, independent of CD4 lymphocyte count and other factors that might affect disease outcome. METHODS: Among persons who had initiated antiretroviral therapy (ART), we studied the risk for OI following a VL measurement in the Centers for Disease Control and Prevention Adult and Adolescent Spectrum of HIV Disease (ASD) Project, a medical record review study of HIV-infected persons in 11 US cities. Analysis was limited to persons who had initiated ART and who had VL data, primarily from the period 1996-1999. Persons were considered at risk for OI for 1 to 6 months after a given VL; risk for OI was assessed using a Poisson multiple regression model controlling for CD4 lymphocyte count, ART, and other variables potentially associated with development of OI: history of AIDS OI, age, sex, race, HIV risk category, OI prophylaxis, and calendar year. RESULTS: Although decreasing CD4 count was the strongest predictor of risk for OI [relative risk (RR), 13.3 for persons with CD4 lymphocyte count < 50 x 10(6)/l compared with persons with CD4 lymphocyte count > or = 500 x 10(6)/l], increasing VL was independently associated with increased risk [RR, 1.6, 1.9, 2.7, and 3.5 for VL of 7000-19 999, 20 000-54 999, 55 000-149 999, and > or = 150 000 copies/ml (by reverse transcription-PCR), respectively, compared with VL < 400]. Similar results were obtained when the risk period was reduced to 5, 4, 3, and 2 months after VL measurement. CONCLUSIONS: VL is an independent risk factor for OI and should be considered in special situations, such as in decisions to discontinue primary or secondary OI prophylaxis after CD4 lymphocyte counts have increased in response to ART.

Risk factors for and trends in gonorrhea incidence among persons infected with HIV in the United States.

OBJECTIVE: To determine the risk factors for and trends in gonorrhea infections among HIV-infected persons. DESIGN: Longitudinal review of medical records of HIV-infected patients. METHODS: We analyzed data about HIV-infected patients obtained from 1991 to 1998 in over 100 facilities participating in the Adult/Adolescent Spectrum of HIV Disease Project. RESULTS: The overall incidence of gonorrhea was 9.5 cases per 1000 person--years. Factors associated with higher gonorrhea incidence (P < 0.01) included younger age, male--male sex, black race, HIV infection without AIDS (namely AIDS-defining opportunistic illness or CD4 cell count < 200 x 10(6) cells/l), and recent recreational use of injection or non-injection drugs. There was an increase in the trend among men who have sex with men (P < 0.01) and a decrease in the trend among patients with heterosexual contact as their HIV exposure risk (P < 0.01). Among injection drug users there was no significant trend from 1991 to 1996, but there was an increase in gonorrhea incidence from 6.6 cases/1000 person-years in 1997 to 16.3 cases/1000 person--years in 1998. CONCLUSIONS: Following HIV diagnosis, some individuals continue to practice risky sexual behaviors which result in gonorrhea and may transmit HIV. The increase in the trend in gonorrhea incidence among HIV-infected men who have sex with men is of particular concern because it suggests an increase in risky sexual behaviors. These findings indicate a need for effective HIV prevention strategies that involve reducing risky sexual behaviors in HIV-infected persons.

Survival of patients with AIDS, after diagnosis of Pneumocystis carinii pneumonia, in the United States.

To examine survival after diagnosis of Pneumocystis carinii pneumonia (PCP) and factors associated with early death (during the month of or the month after diagnosis of PCP), data were analyzed from the Adult and Adolescent Spectrum HIV Disease project. Among 4412 patients with 5222 episodes of PCP during follow-up (1992-1998), survival at >1 month after diagnosis was 82%, and survival at > or =12 months after diagnosis was 47%; 12-month survival increased from 40% in 1992-1993 to 63% in 1996-1998. By multiple logistic regression analysis, early death was associated with history of PCP (odds ratio [OR], 1.4), age 45-59 years (OR, 1.9) or > or =60 years (OR, 3.7), and CD4 cell count of 0-24 cells/microL (< or =5 months before PCP; OR, 1.8) or 25-49 cells/microL (OR, 1.4) (P<.05). Concurrent prescription of combination antiretroviral therapy (OR, 0.2) and other antiretroviral therapy (OR, 0.4) was associated with surviving the early period. This study shows improved survival after diagnosis of PCP in recent years, despite emergence of antibiotic-resistant mutant P. carinii strains.

Pneumococcal disease among human immunodeficiency virus-infected persons: incidence, risk factors, and impact of vaccination.

To determine the factors associated with pneumococcal disease (pneumococcal pneumonia or invasive disease) and the impact of pneumococcal vaccine in HIV-infected persons, we analyzed patient data collected by the Adult and Adolescent Spectrum of HIV Disease Project for person-time between January 1990 and December 1998. Among 39,086 persons with 71,116 person-years (py) of observation, 585 episodes of pneumococcal disease were diagnosed (incidence, 8.2 episodes per 1000 py). Factors associated with an increased risk for pneumococcal disease (P < .05) included injection drug use (adjusted relative risk [RR], 1.5) and blood transfusion (RR, 2.0) as the mode of HIV transmission (referent, male-male sex); black race/ethnicity (RR, 1.5; referent, white race); history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic illness (RR, 2.1); a CD4(+) cell count of 200-499 cells/microL (RR, 2.5) or < 200 cells/microL (RR, 3.7; referent, CD4(+) cell count of > or = 500 cells/microL); and alcoholism (RR, 2.0). Factors associated with a decreased risk included prescription of antiretroviral therapy (RR for monotherapy, 0.6; for dual therapy, 0.7; for triple therapy, 0.5) and pneumococcal vaccination (RR for persons vaccinated at a CD4(+) cell count of > or = 500 cells/microL, 0.5). We recommend that pneumococcal vaccine be given to HIV-infected persons before profound immunosuppression has occurred.

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.

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.

HIV-associated tuberculosis in the era of highly active antiretroviral therapy. The Adult/Adolescent Spectrum of HIV Disease Group.

OBJECTIVE: To determine the effect of highly active antiretroviral therapy (HAART) on the risk of tuberculosis (TB) among persons infected with the human immunodeficiency virus (HIV), and to examine trends in TB. METHODS: For the risk factor analysis, we examined data from the Adult/Adolescent Spectrum of HIV Disease (ASD) project from January 1996 through June 1998. ASD is an observational cohort study conducted in over 100 clinics and hospitals in 11 US cities. Poisson regression was used to model the incidence of TB while controlling for HIV-exposure mode, race, country of birth, CD4 count, TB preventive therapy, and half-year of diagnosis. We also examined trends in TB incidence January 1992 to June 1998. RESULTS: During the risk factor analysis period, 80 cases of TB occurred in 16,032 person-years (5.0 cases/1000 person-years). In multivariate analysis, the risk of TB was much lower among persons prescribed HAART (RR = 0.2, 95%CI 0.1-0.5, P < 0.001), and also lower among persons prescribed other antiretroviral therapy (RR = 0.6, 95% CI 0.4-1.0, P = 0.05), than the risk in persons not prescribed antiretroviral therapy. In addition, TB rates declined from January 1992 to June 1998 (P < 0.001). CONCLUSION: Widespread use of HAART reduced the risk for TB and may help bring about further declines in TB among persons infected with HIV.

Incidence and trends in Kaposi's sarcoma in the era of effective antiretroviral therapy.

OBJECTIVE: To evaluate the impact of antiretroviral and antiherpesvirus therapies on the incidence of KS and assess trends in incidence of Kaposi's sarcoma (KS) in a large multicenter HIV/AIDS surveillance system between 1990 and 1998. METHODS: Incidence was calculated per 100 person-years (py); the effects of therapies on risk for KS were calculated by using multivariate Poisson regression controlling for gender, race/ethnicity, age, HIV exposure mode, CD4+ cell count, and calendar year. Antiretroviral therapy was defined as monotherapy, dual therapy, or triple therapy (95% of triple therapy regimens contained a protease inhibitor). Acyclovir, ganciclovir, and foscarnet were the antiherpesvirus therapies evaluated. RESULTS: There were 37,303 HIV-infected people in the study contributing 70,238 py. Those prescribed triple antiretroviral therapy had a 50% reduction in the incidence of KS (95% confidence interval, 20%-70%) compared with those who were not prescribed antiretroviral therapy and there was a reduction in risk for KS among persons prescribed foscarnet (p =.05). Overall, KS incidence declined an estimated 8.8% per year (observed incidence 4. 1 per 100 py in 1990 to 0.7 per 100 py in 1998; p <.001). CONCLUSION: Incidence of KS is declining in this large U.S. population and may continue to decline as new, more effective antiretroviral agents are developed and used widely.

Entamoeba histolytica/Entamoeba dispar infections in human immunodeficiency virus-infected patients in the United States.

We describe the incidence of and laboratory and clinical characteristics associated with Entamoeba histolytica/Entamoeba dispar infection diagnosed in human immunodeficiency virus (HIV)-infected persons enrolled in the Adult and Adolescent Spectrum of HIV Disease Project. From 1 January 1990 to 1 January 1998 (82, 518 person-years of follow-up), 111 patients (98% men) were diagnosed with E. histolytica/E. dispar infection. Among HIV-infected patients in the United States, the incidence of diagnosed E. histolytica disease is low (13.5 cases per 10,000 person-years [95% confidence interval, 7.7-22.2], with diagnosis most common in those patients exposed to HIV through male-male sex.

Risk for preventable opportunistic infections in persons with AIDS after antiretroviral therapy increases CD4+ T lymphocyte counts above prophylaxis thresholds.

To determine incidence and risk for preventable opportunistic infections (Pneumocystis carinii pneumonia [PCP] and disseminated Mycobacterium avium-complex [MAC] infection) in persons whose CD4(+) T lymphocyte counts had increased by >/=100 cells/microL to exceed the threshold of risk and in persons whose CD4(+) counts had never dropped below the threshold of risk, we analyzed data collected during the period 1990-1998 in the Adult/Adolescent Spectrum of HIV (Human Immunodeficiency Virus) Disease Project. Using a counting-process formulation of the Cox model, we analyzed observation time in these 2 groups for persons who were prescribed antiretroviral therapy but not prophylaxis. The incidences of the infections were low for patients whose CD4(+) count rose above the threshold of risk (PCP, 0.6 cases per 100 person-years [PY]; MAC, 1. 0 cases per 100 PY) and not higher than in persons whose CD4(+) counts had not decreased below these thresholds, which suggests that discontinuation of primary prophylaxis for opportunistic infections may be considered for some patients.