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.

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.

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.

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.

Distribution of CD4+ T lymphocytes at diagnosis of acquired immunodeficiency syndrome-defining and other human immunodeficiency virus-related illnesses. The Adult and Adolescent Spectrum of HIV Disease Project Group.

BACKGROUND: Depletion of circulating CD4+ T lymphocytes among persons infected with the human immunodeficiency virus (HIV) is associated with increased risk for development of opportunistic, life-threatening diseases and death. METHODS: To describe the levels of CD4+ T lymphocytes at which acquired immunodeficiency syndrome (AIDS)-defining and other illnesses initially occur, we analyzed data from an ongoing survey of medical records of 18,062 HIV-infected patients who received medical care between January 1990 and August 1993 in more than 100 clinics, hospitals, and private practices in 10 US cities. We report the median and upper 80th percentile CD4+ T-lymphocyte counts at diagnosis. RESULTS: We found that AIDS-defining conditions first occurred in HIV-infected patients with CD4+ T-lymphocyte counts below 0.20 x 10(9)/L (200/microL) for 80% of diagnoses. Similarly, AIDS-defining diseases occurred at counts below 0.05 x 10(9)/L for 50% of diagnoses. Exceptions to both criteria were invasive cervical cancer and pulmonary tuberculosis. Non-AIDS-defining illnesses with which 80% of patients were diagnosed at CD4+ T-lymphocyte counts below 0.20 x 10(9)/L were bacterial sepsis and retinopathy (excluding cytomegalovirus). CONCLUSION: Our observations support the need for continued CD4+ cell count monitoring below a level of 0.20 x 10(9)/L as a guide to diagnosis and medical management of HIV-infected persons.

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.

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.

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.

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.

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.

Effects of antiretroviral therapy and opportunistic illness primary chemoprophylaxis on survival after AIDS diagnosis. Adult/Adolescent Spectrum of Disease Group.

OBJECTIVE: To examine the effects of antiretroviral therapy (ART) and opportunistic illness chemoprophylaxis on the survival of persons with AIDS and survival time based on year of AIDS diagnosis. DESIGN: Longitudinal medical record review. SETTING: Ninety-three hospitals and clinics in nine cities in the USA. PATIENTS: We observed 19,565 persons with AIDS from 1990 through January 1998. INTERVENTIONS: Prescribed use of antiretroviral monotherapy, dual- and triple-combination therapies, primary prophylaxis against Pneumocystis carinii pneumonia and Mycobacterium avium complex, and pneumococcal vaccine. MAIN OUTCOME MEASURES: Time from AIDS diagnosis to death in the presence and absence of ART. Survival curves were compared of AIDS cases diagnosed during 1990-1992 and 1993-1995. RESULTS: Triple ART had the greatest effect on the risk of death [relative risk (RR), 0.15; 95% confidence limit (CL), 0.12, 0.17], followed by dual ART (RR, 0.24; 95% CL, 0.22, 0.26), and monotherapy (RR, 0.38; 95% CL, 0.36, 0.40). Risk of death was decreased among persons receiving Pneumocystis carinii pneumonia prophylaxis (RR, 0.79; 95% CL, 0.70, 0.89) and Mycobacterium avium complex prophylaxis (RR, 0.76; 95% CL, 0.68, 0.86). Median survival increased from 31 months [95% confidence interval (CI), 30-32 months] for AIDS cases diagnosed during 1990-1992 to 35 months (95% CI, 35-38 months) for cases diagnosed during 1993-1995. CONCLUSIONS: The risk of death was decreased for persons receiving triple ART compared with persons receiving dual therapy and persons receiving monotherapy. Increased use of ART and improved ART regimens probably contributed to prolonged survival of persons whose diagnosis was made during 1993-1995 compared with persons whose diagnosis was made during 1990-1992.

Surveillance of AIDS-defining conditions in the United States. Adult/Adolescent Spectrum of HIV Disease Project Group.

OBJECTIVE: To examine the reporting of AIDS-defining illnesses using two national surveillance systems. METHODS: Comparison of AIDS indicator diseases reported to the national AIDS reporting system (ARS) for AIDS cases diagnosed from January 1990-December 1992 among individuals aged > 13 years in 10 metropolitan areas, with that observed in the Adult/Adolescent Spectrum of HIV Disease (ASD) project, a surveillance project that monitors the clinical diagnoses of HIV-infected individuals receiving medical care. RESULTS: In the 10 metropolitan areas, 39,265 individuals with AIDS were reported to ARS, and 5969 with AIDS had medical record reviews as part of ASD. At initial AIDS diagnosis, the number of indicator diseases reported to ARS was almost identical to the number observed in ASD (mean number of diagnoses, ARS 1.3; ASD 1.2). However, ASD recorded a greater number of diagnoses over time than ARS (mean number of indicator diagnoses > 12 months after initial diagnosis, ASD 2.3; ARS 1.4). Conditions that typically occur late in the course of AIDS such as Mycobacterium avium infection and cytomegalovirus disease, were more frequently recorded by ASD than by ARS. CONCLUSION: ARS provides complete, population-based information on the frequency of AIDS-defining conditions at initial diagnosis. However, specialized surveillance projects such as ASD are needed to accurately describe subsequent AIDS-defining conditions.

Toxoplasmic encephalitis in HIV-infected persons: risk factors and trends. The Adult/Adolescent Spectrum of Disease Group.

OBJECTIVE: To evaluate the incidence of and risk factors for toxoplasmic encephalitis among HIV-infected persons. DESIGN: Medical facility-based prospective medical record reviews of consecutive patients. METHODS: We analysed data collected from January 1990 through August 1995 in more than 90 inpatient and outpatient medical facilities in nine US cities. Incidence was calculated as cases per 100 person-years and risk ratios (RR) for annual incidence were calculated using proportional hazards regression while controlling for city, sex, race, age, county of birth, HIV exposure mode, and prior prescription of trimethoprim-sulfamethoxazole (TMP-SMX). RESULTS: The incidence of TE was 4.0 cases per 100 person-years among persons with a CD4+ T-lymphocyte count of < 100 x 10(6)/l. In multivariate analysis, among the nine cities the annual incidence of toxoplasmosis was significantly lower only in Denver [RR, 0.3; 95% confidence interval (CI), 0.1-0.7; referent city, Seattle]. Persons prescribed TMP-SMX were half as likely to develop toxoplasmic encephalitis as those who were not (RR, 0.5; 95% CI, 0.4-0.7). Of the 4173 persons with AIDS (1987 Centers for Disease Control and Prevention definition) who died during the study period, 267 (6.4%) had toxoplasmic encephalitis in the course of HIV disease. CONCLUSIONS: Toxoplasmic encephalitis in HIV-infected persons varies by geographic area in the United States. TMP-SMX reduces the risk for toxoplasmic encephalitis.

Survival prognosis of HIV-infected patients.

Previous studies of survival after a diagnosis of acquired immunodeficiency syndrome (AIDS) have reported variation in temporal trends in association with age, gender, race, mode of transmission, lymphadenopathy, antiretroviral therapy, and presence of specific opportunistic infections at diagnosis. We used a logistic regression model to assess the effect of these factors while controlling for other potential predictors of time from initial CD4 cell count to death in 839 HIV-infected patients at a public hospital in Atlanta, Georgia. Our study found that a CD4 level of < 200 cells/microliters [odds ratio (OR) = 1.71; 95% confidence interval (CI) of 1.58, 1.85] and the presence of an AIDS-indicating condition (initial diagnosis OR = 2.50 and CI of 1.93, 3.24; diagnosis of a second AIDS condition OR = 3.02 and CI of 2.08, 4.40) are independently predictive of survival in HIV-infected persons. Furthermore, specific clinical manifestations of AIDS vary in their contribution to progression from diagnosis of AIDS to death. Therefore, changes in survival of AIDS patients must take into account changes over time in the relative frequency of specific AIDS-indicating diagnoses.

Estimation of the temporal probability of human immunodeficiency virus (HIV) dementia after risk stratification for HIV-infected persons.

We developed a scheme using routinely available data to estimate the risk of human immunodeficiency virus (HIV) dementia in HIV-infected persons over time. We performed a longitudinal review of medical records from more than 100 medical facilities in 11 U.S. cities. A total of 19,462 HIV-infected persons without history of dementia enrolled in a multi-institution survey. The main outcome measure was the development of HIV dementia (1987 case definition) during the median follow-up period of 17 months (range, 1 to 72 months). Of 19,462 HIV-infected persons, HIV dementia developed in 880 persons (4.5%; 2.6% per person-year). The strongest predictors of HIV dementia were CD4+ T-lymphocyte count, anemia, and AIDS-defining infections or cancer. The 2-year probability of HIV dementia was highest for persons who had a CD4+ T-lymphocyte count of fewer than 100 cells/microL and an AIDS-defining illness or anemia or both (18.6 to 24.9%). Intermediate risk was observed in persons with CD4+ T-lymphocyte count of 100 to 199 cells/microL and an AIDS-defining illness or anemia or both or in persons with a CD4+ T-lymphocyte count of fewer than 100 cells/microL but without another risk factor (2-year probability, 10.4 to 15.2%). The 2-year probability that HIV dementia would develop was lowest (1.0%) for persons with CD4+ T-lymphocyte count of more than 200 cells/microL and no other risk factors. Risk stratification using routine clinical information provides information that may prove useful in patient care decisions.

Pregnancy rates among women infected with human immunodeficiency virus. Adult/Adolescent HIV Spectrum of Disease Project Group.

OBJECTIVE: To examine pregnancy rates among women infected with human immunodeficiency virus (HIV). METHODS: We used data from an ongoing survey of medical records of 3915 women who were 15-44 years of age, infected with HIV, and who received care between January 1990 and August 1994 in more than 90 clinics, hospitals, and private practices in 11 United States cities. RESULTS: At enrollment, 570 (14%) of these women were pregnant. Pregnancy rates at entry varied significantly (P < .05) by age in years (15-19 [47%], 20-24 [30%], 25-29 [18%]; 30-34 [11%]; 35-39 [5%]; 40-44 [2%]); clinical status (with AIDS opportunistic illness [3%], without AIDS opportunistic illness [17%]; and race-ethnicity (white [12%], black [17%], Hispanic [8%], Asian [0%], Native American [30%]) but not by mode of exposure (injecting drug use [10%], heterosexual contact [15%], and blood transfusion [12%]). After enrollment, 5.8% of women became pregnant each year. New pregnancies were significantly less likely to occur among women with an AIDS opportunistic illness (adjusted rate ratio 0.4, 95% confidence interval [CI] 0.2-0.6), and significantly more likely to occur among women who were less than 25 years of age (adjusted rate ratio 8.3, 95% CI 5.3-13.2) and who were black (adjusted rate ratio 1.6, 95% CI 1.2-2.1). Among women who were pregnant at enrollment or during observation, 12% were pregnant more than once. CONCLUSIONS: High rates of pregnancy at entry to medical care among HIV-infected women stress the importance of counseling and voluntary testing as routine obstetric-gynecologic practice. In some groups, rates of new pregnancies remain high; standard HIV care for women should include family planning services and assurance that if a woman chooses to practice contraception, contraceptives will be available and affordable.

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.

Long wave ultraviolet radiation stimulates arachidonic acid release and cyclooxygenase activity in mammalian cells in culture.

Human fibroblasts and mouse C3H 10T1/2 cells in culture were prelabeled with [3H]arachidonic acid and exposed to UVA radiation. Cells released labeled arachidonate metabolites into medium in a dose-dependent fashion (5-20 J cm-2). The time course of release appeared biphasic with peak responses occurring immediately and at 2 h post irradiation. Release of radiolabel was oxygen and calcium ion dependent and was inhibited by the addition of phenylglyoxal, indomethacin, and dibucaine to the medium. High performance liquid chromatographic examination of medium extracts revealed UVA stimulation of cyclooxygenase metabolism of [3H]arachidonic acid and specifically, prostaglandin E2 production by cells in culture. Furthermore, UVA stimulated a dose-dependent release of membrane incorporated [3H]choline from cells in culture. Paper chromatographic analysis of the medium provided evidence that choline release from the membrane was predominantly accompanied by release of phosphorylcholine with some glycerophosphorylcholine suggesting indirectly that the major pathway for UVA-stimulated arachidonic acid release was via phospholipase C and diacylglycerol lipase enzyme systems.