Features of inhalant allergy on nasal endoscopy: a systematic review and meta-analysis.

BACKGROUND: Nasal endoscopy is increasingly accessible to ENT surgeons. The characteristics of the allergic upper airway are not well recognised. METHODOLOGY: MEDLINE (1946-2021), EMBASE (1974-2021), and the Cochrane Library were searched on 16th November 2021 to identify articles that reported endoscopic findings of patients with documented allergy who had undergone nasal endoscopy. The review followed the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. Meta-analysis was performed by pooling sensitivities and specificities using the hierarchical summary receiver operating characteristics model. RESULTS: A total of 4108 articles were identified, of which 15 manuscripts met the inclusion criteria. The included studies involved 4660 patients who had undergone nasal endoscopy. Middle turbinate (diffuse/polypoid) oedema (sensitivity 58.0%, specificity 84.5%), watery secretions (sensitivity 65.7%, specificity 76.5%), inferior turbinate hypertrophy (sensitivity 86.2%, specificity 32.2%), and unspecified turbinate hypertrophy (sensitivity 82.0%, specificity 42.9%) were identified as the features with the highest predictive value of inhalant allergy. CONCLUSIONS: Diffuse or polypoid oedema of the middle turbinate or watery secretions seen on nasal endoscopy can be a useful adjunct in the identification and diagnosis of inhalant allergy. These clinical features should be part of the diagnostic workup for patients that includes a clinical history and surrogate markers of allergic sensitisation from the skin and serum.

Intranasal corticosteroids do not affect intraocular pressure or lens opacity: a systematic review of controlled trials.

BACKGROUND: Intranasal corticosteroids (INCS) are prescribed for the long-term prophylactic treatment of inflammatory upper airway conditions. Although some systemic absorption can occur via topical routes, the clinical relevance is controversial. The effects of orally administered corticosteroids on intraocular pressure (IOP) and lens opacity (LO) are well established, but the impact of the INCS is less well defined. This study aims to systematically review the literature for evidence of adverse occular events with INCS use. METHODOLOGY: A systematic review of literature from Medline and Embase databases (January 1974 to 21st of November 2013) was performed. Using the PRISMA guidelines, all controlled clinical trials of patients using INCS, that reported original measures of IOP, LO, glaucoma or cataract incidences were included. Studies with adjuvant administration of oral, inhaled and intravenous steroids were excluded. RESULTS: 665 articles were retrieved with 137 were considered for full-text review. Of these, 116 (85%) were literature reviews and two were case reports. 19 studies (10 RCTs, 1 case-control, 8 case series) were included for the qualitative review, of which 18 reported data on IOP and 10 on cataract/LO. None (n=0) of the 10 RCT reporting data on glaucoma or IOP demonstrated changes in IOP compared to control. Also none (n=0) of the 6 RCTs reporting cataract or lens opacity demonstrated changes compared to control. CONCLUSION: Data from studies with low levels of bias, do not demonstrate a clinically relevant impact of INCS on neither ocular pressure, glaucoma, lens opacity nor cataract formation.

Modified Lund Mackay Postoperative Endoscopy Score for defining inflammatory burden in chronic rhinosinusitis.

OBJECTIVE: The Lund Mackay Postoperative Endoscopy Score (LMES) for chronic rhinosinusitis (CRS) is a poor measure of the patient experience. A proposed Modified Lund Mackay Postoperative Endoscopy Score (MLMES) aims to better describe the inflammatory burden in CRS. METHODS: A prospective study on CRS patients having endoscopic sinus surgery (ESS) was conducted. Endoscopy was recorded at the 6th and the 12th week post-op. The MLMES recorded changes in mucosa, mucus and purulence for each of the maxillary, ethmoid, sphenoid, frontal sinuses and olfactory fossa in post-ESS cavities. The correlation between MLMES and visual analogue scale of total rhinosinusitis symptoms, global anchor score of nasal function, Sino-Nasal Outcome Test 22 (SNOT-22) and nasal symptom score was analyzed. The inter-observer reliability, intra-observer reliability and correlation between the change in MLMES and in subjective measures were also investigated. RESULTS: Thirty patients were assessed. The MLMES significantly correlated with visual analogue scale, SNOT-22, global anchor and nasal symptom score. The change in MLMES correlated with the change in SNOT-22 and nasal symptom score. The inter-observer and intra-observer reliability were excellent. CONCLUSION: Objectives measurements for post-ESS patients can be reconsidered to represent the cumulative inflammatory burden of all sinuses. The proposed MLMES represents total sinus inflammatory burden and correlates well with patient reported outcome measures.

Clinical parameters do not adequately predict outcome in necrotizing enterocolitis: a multi-institutional study.

OBJECTIVE: Necrotizing enterocolitis (NEC) remains a major cause of neonatal morbidity and mortality. Some infants recover uneventfully with medical therapy whereas others develop severe disease (that is, NEC requiring surgery or resulting in death). Repeated attempts to identify clinical parameters that would reliably identify infants with NEC most likely to progress to severe disease have been unsuccessful. We hypothesized that comprehensive prospective data collection at multiple centers would allow us to develop a model which would identify those babies at risk for progressive NEC. STUDY DESIGN: This prospective, observational study was conducted at six university children's hospitals. Study subjects were neonates with suspected or confirmed NEC. Comprehensive maternal and newborn histories were collected at the time of enrollment, and newborn clinical data were collected prospectively, thereafter. Multivariate logistic regression analysis was used to develop a predictive model of risk factors for progression. RESULT: Of 455 neonates analyzed, 192 (42%) progressed to severe disease, and 263 (58%) advanced to full feedings without operation. The vast majority of the variables studied proved not to be associated with progression to severe disease. A total of 12 independent predictors for progression were identified, including only 3 not previously described: having a teenaged mother (odds ratio, OR, 3.14; 95% confidence interval, CI, 1.45 to 6.96), receiving cardiac compressions and/or resuscitative drugs at birth (OR, 2.51; 95% CI, 1.17 to 5.48), and having never received enteral feeding before diagnosis (OR, 2.41; 95% CI, 1.08 to 5.52). CONCLUSION: Our hypothesis proved false. Rigorous prospective data collection of a sufficient number of patients did not allow us to create a model sufficiently predictive of progressive NEC to be clinically useful. It appears increasingly likely that further analysis of clinical parameters alone will not lead to a significant improvement in our understanding of NEC. We believe that future studies must focus on advanced biologic parameters in conjunction with clinical findings.

Excess salmonellosis in women in the United States: 1968-2000.

We describe recent epidemiological changes in salmonellosis. Linking 1968-2000 National Salmonella Surveillance System to census data, we calculated population-based age- and sex-stratified rates of non-urinary salmonellosis for the top 30 non-typhoidal serotypes. Using 1996-1997, 1998-1999, and 2000-2001 population-based FoodNet surveys, we compared reported diarrhoea, medical visits, and stool cultures. Despite an overall female-to-male incidence rate ratio (FMRR) of 0.99, the sex-specific burden of salmonellosis varied by age (<5 years FMRR 0.92; 5-19 years 0.85; 20-39 years 1.09; 40-59 years 1.23, and 60 years 1.08) and serotype (FMRR range 0.87 for Mississippi to 1.25 for Senftenberg). Serotype-specific FMRRs and median age (range 2 years for Derby to 29 years for Senftenberg) were related (correlation 0.76, P<0.0001). Recently, the relative burden of salmonellosis in women has increased. FoodNet data suggest that this change is real rather than due to differential reporting. Excess salmonellosis in women may reflect differences in exposure or biological susceptibility.

A prospective, randomized clinical trial of universal WBC reduction.

BACKGROUND: Recipient exposure to allogeneic donor WBCs results in transfusion complications for selected populations of recipients. Whether or not WBC reduction should be universally applied is highly controversial. STUDY DESIGN AND METHODS: In a general hospital, a randomized, controlled clinical trial of conversion to universal WBC reduction was conducted. Patients (11%) with established medical indications for WBC-reduced blood were not eligible. All other patients who required transfusion were assigned at random to receive either unmodified blood components or stored WBC-reduced RBCs and platelets. Analysis for each patient was restricted to the first hospitalization. RESULTS: All eligible patients (n = 2780) were enrolled. Three specified primary outcome measures were not different between the two groups: 1) in-hospital mortality (8.5% control; 9.0% WBC-reduced; OR, 0.94 [95% CI, 0.72-1.22]; p = 0.64); 2) hospital length of stay (LOS) after transfusion (median number of days, 6.4 for control and 6.3 for WBC-reduced; p = 0.21); and 3) total hospital costs (median, $19,500 for control and $19,200 for WBC-reduced, p = 0.24). Secondary outcomes (intensive care LOS, postoperative LOS, antibiotic usage, and readmission rate) were not different between the two groups. Subgroup analysis based on patient age, sex, amount of blood transfused, or category of surgical procedure showed no effect of WBC reduction. Patients who received WBC-reduced blood had a lower incidence of febrile reactions (p = 0.06). CONCLUSION: A beneficial effect of conversion from selective to universal WBC reduction was not demonstrated.

Differences in difficulty adjudicating clinical events in patients with advanced HIV disease.

Adjudication of clinical events is often used as a quality assurance method in clinical research. During the design of the Viral Activation Transfusion Study (a clinical trial in patients with advanced HIV disease), a set of study endpoints was defined (primarily AIDS-defining conditions), criteria for confirmation of each event type were developed, and an adjudication procedure was established. The adjudication process included 1) an initial review of documentation of each event by two independent reviewers, 2) the opportunity to request additional information, 3) a second review either of additional documentation or of cases in which there was disagreement on first review, and 4) the consultation of a third reviewer if there was still disagreement. Overall, of 288 reported endpoints, 30% required additional documentation or more than one review, and 16% were not confirmed at the end of the adjudication process. However, these percentages varied widely over different types of events. For example, of 30 reported nonophthalmalogic cytomegalovirus events, 37% required additional documentation and 40% were not confirmed. In contrast, every one of 17 reported Pneumocystis cariini pneumonias were confirmed with no requirement for additional documentation. The results can be used to help design endpoint documentation and adjudication procedures for other studies, thereby improving data quality and reducing costs.

WBC reduction in RBC concentrates by prestorage filtration: multicenter experience.

BACKGROUND: As universal leukocyte (WBC) reduction (ULR) is being considered as a new standard, few data are available on the performance of WBC-reduction filtration in routine practice. The performance of WBC-reduction in RBCs, using varied filtration practices, in meeting the current FDA requirement (<5 x 10(6)), Council of Europe (EC) recommendation, the proposed FDA requirement (<1 x 10(6)), and a more stringent proposal (<5 x 10(5)) for residual WBCs per RBC unit was assessed and compared. STUDY DESIGN AND METHODS: Participating facilities were the 11 sites of the Viral Activation Transfusion Study (VATS), a prospective study of the impact of transfusion with and without WBC-reduction on survival and HIV viral load in HIV-1-infected patients. Patients randomly assigned to undergo WBC reduction were required to receive RBCs < or =14 days old that had undergone prestorage (within 72 hours of collection) WBC-reduction filtration by a method devised to achieve a postfiltration WBC count of <5 x 10(6). Residual WBC quantitation was performed by PCR in the central VATS laboratory by using frozen WBC-reduced RBC samples obtained at issue for transfusion. RESULTS: A total of 1869 WBC-reduced RBC units were studied. Filtration practices varied within and between sites. There were significant differences in mean residual WBC counts at the 11 sites (p<0.001). Among the WBC-reduced RBC units, 0.8 percent exceeded 5 x 10(6) WBCs per unit, 8.3 percent exceeded 1 x 10(6) WBCs per unit, and 14.3 percent exceeded 5 x 10(5) WBCs per unit. CONCLUSION: Residual WBCs in WBC-reduced RBC units vary within and between sites. WBC reduction was successful, in that over 99 percent and 91 percent of VATS WBC-reduced RBC units met US and EC thresholds, respectively. However, the small but measurable failure rate indicates that not every unit will meet these guidelines.

Highly active antiretroviral therapy decreases mortality and morbidity in patients with advanced HIV disease.

BACKGROUND: Mortality and morbidity related to AIDS have decreased among HIV-infected patients taking highly active anti-retroviral therapy (HAART), but previous studies may have been confounded by other changes in treatment. OBJECTIVE: To assess the benefit of HAART in patients with advanced AIDS and anemia. DESIGN: Prospective, multicenter cohort study. SETTING: The Viral Activation Transfusion Study (VATS), with enrollment from August 1995 through July 1998 and follow-up through June 1999. PATIENTS: 528 HIV-infected patients with cytomegalovirus (CMV) seropositivity or disease who were receiving a first red blood cell transfusion for anemia. MEASUREMENTS: In a person-year analysis of follow-up before and after initiation of HAART, Poisson regression was used to calculate crude rate ratios and rate ratios adjusted for CD4 count, HIV RNA level, calendar period, time on study, sex, ethnicity, and injection drug use. RESULTS: At baseline, patients had a median CD4(+) lymphocyte count of 0.015 x 10(9) cell/L, median plasma HIV RNA level of 4.8 log(10) copies/mL, and median hemoglobin concentration of 73 g/L. Use of HAART increased from 1% of active patients in January 1996 to 79% of active patients in January 1999. The crude death rate was 0.24 event/person-year among patients taking HAART and 0.88 event/person-year among those not taking HAART (rate ratio, 0.26; adjusted rate ratio, 0.38; P < 0.001 for both comparisons). Rates of non-CMV disease were 0.15 event/ person-year after HAART and 0.45 event/person-year before HAART (crude rate ratio, 0.34 [ P < 0.001]; adjusted rate ratio, 0.66 [ P < 0.05]). Rates of CMV disease were 0.10 event/person-year after HAART and 0.25 before HAART (crude rate ratio, 0.42 [ P < 0.01]; adjusted rate ratio, 1.01 [ P > 0.2]). Results were similar in patients with baseline CD4(+) lymphocyte counts less than 0.010 x 10(9) cells/L. CONCLUSIONS: The data support an independent reduction in mortality and opportunistic events attributable to HAART, even in patients with very advanced HIV disease. However, patients with CMV infection or disease may not have a reduction in new CMV events due to HAART.

Survival of transfused donor white blood cells in HIV-infected recipients.

The appearance and expansion of donor white blood cells in a recipient after transfusion has many potential biologic ramifications. Although patients with HIV infection are ostensibly at high risk for microchimerism, transfusion-associated graft-versus-host disease (TA-GVHD) is rare. The purpose of this study was to search for sustained microchimerism in such patients. Blood samples were collected from 93 HIV-infected women (a subset from the Viral Activation Transfusion Study, an NHLBI multicenter randomized trial comparing leukoreduced versus unmodified red blood cell [RBC] transfusions) before and after transfusions from male donors. Donor lymphocytes were detected in posttransfusion specimens using a quantitative Y-chromosome-specific polymerase chain reaction (PCR) assay, and donor-specific human leukocyte antigen (HLA) alleles were identified with allele-specific PCR primers and probes. Five of 47 subjects randomized to receive nonleukoreduced RBCs had detectable male lymphocytes 1 to 2 weeks after transfusion, but no subject had detectable male cells more than 4 weeks after a transfusion. In 4 subjects studied, donor-specific HLA haplotypes were detected in posttransfusion specimens, consistent with one or more donors' cells. None of 46 subjects randomized to receive leukoreduced RBCs had detectable male lymphocytes in the month after transfusion. Development of sustained microchimerism after transfusion in HIV-infected patients is rare; HIV-infected patients do not appear to be at risk for TA-GVHD.

Are serum hormones associated with the risk of prostate cancer? Prospective results from the Massachusetts Male Aging Study.

OBJECTIVES: To determine whether prediagnostic serum hormones are predictive of prostate cancer risk in a sample of men 40 to 70 years old at baseline. METHODS: Seventeen serum hormones, including androgens, estrogens, and adrenal and pituitary hormones, were measured at baseline (1987 to 1989) and used to predict incident prostate cancer by follow-up (1995 to 1997) using data from the Massachusetts Male Aging Study, a prospective, population-based random sample. RESULTS: Seventy men (4%) of 1576 were diagnosed with prostate cancer between the baseline and follow-up periods (approximately 8 years). None of the hormones were associated with prostate cancer risk except for androstanediol glucuronide (AAG), which exhibited a nonlinear, inverse relationship with prostate cancer (P <0.003) when age, body mass index, alcohol use, dihydrotestosterone, and total prostate-specific antigen were controlled for. Men in the second, third, and fourth quartiles of AAG relative to the first were less likely to be diagnosed with prostate cancer, although only the comparison of the second versus the first achieved statistical significance (odds ratio 0.2, 99% confidence interval 0.04 to 0.6). No dose-response relationships were observed. CONCLUSIONS: The lack of association with most hormones and the nonlinear association with AAG calls into question whether serum hormones collected during midlife are risk factors for prostate cancer.

Correlates of change in cytomegalovirus viremia in patients with advanced human immunodeficiency virus infection who require transfusion.

The Viral Activation Transfusion Study compared leukocyte-reduced to unfiltered red blood cell transfusions in human immunodeficiency virus (HIV)- and cytomegalovirus (CMV)-coinfected patients. Relationships between serially measured plasma CMV load and clinical and laboratory outcomes over a median of 12 months were examined in 511 subjects. At baseline, subjects had a median of 15 CD4(+) cells/mm(3), 25% had CMV disease, and 21.5% were viremic. No relationship was found between changes in CMV viremia and changes in HIV RNA. Increased CMV viremia was associated with a concomitant fall in Karnofsky score. Highly active antiretroviral therapy (HAART) led to a decrease in CMV viremia after a 90-day delay. After adjustment for HIV load and CD4(+) cell count, CMV viremia remained associated with an increased risk of CMV disease (relative hazard, 5.78). In late-stage HIV-infected patients, CMV viremia was associated with lower functional status and increased risk of CMV disease. HAART suppressed CMV viremia only after a delay of several months.

Leukocyte-reduced red blood cell transfusions in patients with anemia and human immunodeficiency virus infection: the Viral Activation Transfusion Study: a randomized controlled trial.

CONTEXT: Allogeneic blood transfusions have immunomodulatory effects and have been associated with activation of human immunodeficiency virus (HIV) and cytomegalovirus (CMV) in vitro and of HIV in small pilot studies. Retrospective studies suggest that transfusions adversely affect the clinical course of HIV. Data in selected non-HIV-infected patients requiring blood transfusion have suggested clinical benefit with leukocyte-reduced red blood cells (RBCs). OBJECTIVE: To compare the effects of leukoreduced and unmodified RBC transfusions on survival, complications of acquired immunodeficiency syndrome, and relevant laboratory markers in HIV-infected patients. DESIGN AND SETTING: Double-blind randomized controlled trial conducted in 11 US academic medical centers from July 1995 through June 1999, with a median follow-up of 12 months (24 months in survivors). PATIENTS: A total of 531 persons infected with HIV and CMV, aged 14 years or older, who required transfusions for anemia; 259 received leukoreduced transfusions and 262 received unmodified transfusions (10 did not receive the planned transfusion). MAIN OUTCOME MEASURES: Survival and change in plasma HIV RNA level 7 days after transfusion, compared by type of transfusion. RESULTS: At entry, the groups were similar in demographic, clinical, and relevant laboratory characteristics. A total of 3864 RBC units were transfused. Two hundred eighty-nine deaths occurred (151 with leukoreduced transfusion; 138 with unmodified transfusion); median survival was 13.0 and 20.5 months, respectively (relative hazard [RH], 1.20; 95% confidence interval [CI], 0.95-1.51; log-rank P =.12). Analyses adjusted for prognostic factors suggested possible worse survival with leukoreduction (RH, 1.35; 95% CI, 1.06-1.72). There was no difference in time to new opportunistic event/death or frequency of transfusion reactions. No changes in plasma HIV RNA level were seen in either group at days 7, 14, 21, or 28, even in patients not taking antiretroviral drugs. There were no differences in trends between groups in CMV DNA, CD4 cell counts, activated (CD38% or human leukocyte antigen-DR) CD8 cell counts, or plasma cytokine levels. CONCLUSIONS: We found no evidence of HIV, CMV, or cytokine activation following blood transfusion in patients with advanced HIV infection. Leukoreduction provided no clinical benefit in these patients. These data demonstrate the importance of conducting controlled studies of effects of leukoreduction in different patient populations, since smaller studies in other patient populations have suggested leukoreduction may be beneficial.

Qualitative and quantitative PCR measures of cytomegalovirus in patients with advanced HIV infection who require transfusions.

The Viral Activation Transfusion Study (VATS) was a randomized trial that compared leukocyte-reduced transfusions with unfiltered red blood cell transfusions in HIV and cytomegalovirus (CMV) antibody-positive patients with anemia who were undergoing their first blood transfusion. The relations of the baseline qualitative and quantitative polymerase chain reaction (PCR) measures of plasma CMV viremia, HIV RNA, CD4(+) cell counts, and quality of life in these study subjects were examined. The 511 study subjects had a median CD4(+) cell count equal to 15 cells/mm3, and 110 (21.5%) had CMV viremia by qualitative assay. In multivariate models, frequency of positive qualitative CMV increased with decreasing CD4(+) cell counts (p =.04 trend), higher HIV RNA (p <.001), and a history of CMV disease (p <.001). Quantitative CMV PCR were performed on the 110 qualitative assay-positive study subjects. Median CMV viral load was 1780 copies/ml. In multivariate regression models, lower CD4(+) cell count (p =.03), and a history of CMV disease (p <.001) correlated with the level of CMV load. HIV RNA load and CMV load were not correlated. A lower Karnofsky score was associated with both the presence and quantity of CMV DNA.

Family history and the risk of prostate cancer.

OBJECTIVES: Several studies have identified prostate cancer family history as a risk factor for prostate cancer incidence, typically associated with a twofold to fourfold increase in risk. A family history of breast cancer has also been implicated. We investigated the associations between prostate cancer incidence and family histories of prostate and breast cancer, controlling for possible confounding due to environmental factors. METHODS: Data from the random sample-based Massachusetts Male Aging Study cohort (1987 to 1997) were used. Incidence rates were calculated as the number of cases per person-year of follow-up. Covariates were adjusted for using Poisson regression. RESULTS: Among 1149 men with an average of 8.7 person-years of follow-up, 57 were diagnosed with prostate cancer, 110 men reported a prostate cancer family history, and 157 reported a breast cancer family history. The age-adjusted relative risk (RR) of prostate cancer incidence associated with prostate cancer family history was 3.29 (95% confidence interval [CI] 1.82 to 5.94). No evidence of heterogeneity was found across age levels (P = 0.83). Additional adjusting for environmental factors such as smoking, alcohol use, body mass index, physical activity, education, sexually transmitted disease history, diet, and hormone levels yielded a slightly higher RR (3.78, 95% CI 1.96 to 7.28). No association with a family history of breast cancer was evident (RR = 1.18, 95% CI 0.51 to 2.43). CONCLUSIONS: We found an association between prostate cancer incidence and a family history of prostate cancer, independent of environmental factors. No association with a family history of breast cancer was evident.

Failure of neonatal clomipramine treatment to alter forced swim immobility: chronic treadmill or activity-wheel running and imipramine.

We examined whether chronic running on a treadmill or activity wheel would attenuate the increased swim immobility that has been reported after neonatal clomipramine (CLI) treatment. Male Sprague-Dawley pups (N = 60) were injected with the monoamine reuptake inhibitor clomipramine hydrochloride (40 mg/kg per day i.p.) from 8 to 21 days of age. Another group (N = 12) received saline vehicle. At age 4 weeks, the CLI pups were randomly assigned to experimental conditions: (1) sedentary; (2) 24-h access to an activity wheel; (3) sedentary that received the antidepressant drug imipramine hydrochloride (10 mg/kg twice daily) during the last 10 days of the experiment; (4) activity wheel + imipramine; (5) treadmill running (30 m/min for 1 h at 0 degrees incline, 6 days/week). At age 16 weeks, rats underwent the Porsolt swim test 48 h after the last imipramine injection and/or the last exercise session. The increase in swim immobility among CLI-treated rats was small (one quarter of SD) and not statistically significant (p>0.10). The results are not consistent with our previous finding of antidepressant-like effects of activity-wheel running based on brain noradrenergic adaptations and enhanced male copulatory performance after neonatal CLI treatment. The lack of change in swim performance after clomipramine questions the generalizability of the CLI model of depression and the validity of the forced swim test as a behavioral measure of depression when it is used after neonatal CLI injection or chronic activity-wheel running.

Interventions to prevent vertical transmission of HIV-1: effect on viral detection rate in early infant samples.

OBJECTIVE: To determine whether mode of delivery or the use of maternal or neonatal antiretroviral prophylaxis influence the age when HIV-1 can first be detected in infected infants, particularly the probability of detection at birth. METHODS: In a collaboration between four multicentre studies, data on 422 HIV-1 infected infants who were assessed by HIV-1 DNA PCR or cell culture before 14 days of age were analysed. Weibull mixture models were used to estimate the cumulative proportion of infants with detectable levels of HIV-1 according to use of maternal/neonatal antiretroviral therapy (mainly zidovudine monotherapy) and mode of delivery. RESULTS: HIV-1 was detected in 162 infants (38%) when they were first tested, at a median age of 2 days. At birth, it was estimated that 36% [95% confidence interval (CI), 31-41%] of infants have levels of virus that can be detected by DNA PCR or cell culture. This percentage was not associated with either mode of delivery (35% for vaginal delivery versus 40% for cesarean section delivery; P = 0.4) or the use of maternal or neonatal antiretroviral prophylaxis. Among infants with undetectable levels of HIV-1 at birth, the median time to viral detectability was estimated to be 14.8 days (95% CI, 12.9-16.8 days). This time was increased by 15% (95% CI, -11 to 48%; P = 0.3) among infants who were exposed to antiretroviral therapy postnatally compared with infants who were not exposed. No effect was observed for mode of delivery. CONCLUSIONS: The outcome of an early virological test for HIV-1 is thought to be related directly to the timing of transmission and cesarean section delivery primarily reduces the risk of intrapartum transmission. The absence of an association between mode of delivery and viral detectability at birth was therefore unexpected. There was no evidence that foetal or neonatal exposure to prophylactic zidovudine delays substantially the diagnosis of infection, although this cannot be inferred for combination antiretroviral therapy.

Plasma human immunodeficiency virus (HIV) type 1 RNA load in men and women with advanced HIV-1 disease.

Several studies of patients infected with human immunodeficiency virus (HIV) type 1 have suggested that women have lower plasma HIV-1 RNA levels than men, even when controlling for CD4 T cell levels. A cross-sectional analysis was performed in 494 patients (21% of whom were women) who enrolled in a prospective study of anemic HIV-1-infected patients requiring transfusion. The median CD4 T cell count and plasma HIV-1 RNA levels were 15 cells/microL and 4.83 log(10) copies/mL (67,350 copies/mL), respectively. In unadjusted analyses, women had slightly higher mean log HIV-1 RNA titers than men (0.19 log(10) higher copies/mL; 95% confidence interval, -0.05 to 0.44; P=.11). Adjustment for CD4 T cell count, race or ethnicity, injection drug use, and age yielded a smaller sex difference (0.13 log(10) copies/mL higher in women; P=.28). In this population of patients with very advanced HIV disease, there is no evidence that women have lower HIV-1 RNA levels than men.

'Modeling' relationships among HIV-1 replication, immune activation and CD4+ T-cell losses using adjusted correlative analyses.

OBJECTIVE: To model the relationships among HIV-1 replication, immune activation and CD4+ T-cell losses in HIV-1 infection. METHODS: Cross-sectional analysis of baseline data from the Viral Activation by Transfusion Study. Comparisons of unadjusted and adjusted correlative analyses to establish models for mechanisms of cell loss in AIDS. RESULTS: Using these analyses, significant correlations were found among plasma levels of tumor necrosis factor alpha (TNFalpha) and its type two receptor (TNFrII), interleukin-6 (IL-6), beta2-microglobulin, expression of CD38 and HLA-DR on CD8+ T lymphocytes and plasma levels of HIV-1 RNA. When correlations among these indices were adjusted for possible intermediary correlations, the relationship between HIV-1 RNA levels and all plasma markers of immune activation could be accounted for by the correlation between plasma HIV-1 RNA and plasma TNFrII levels. In addition, the negative correlations that both HIV-1 RNA levels and TNFrII levels had with CD4+ T-cell counts were partially accounted for by the correlations of HIV-1 RNA and TNFrII with CD38 expression on CD8+ T cells. In persons with advanced disease (CD4+ T cells < 50 x 10(6)/l) IL-6 levels were inversely correlated with CD4+ T-cell counts. CONCLUSIONS: This analysis is consistent with a model wherein HIV-1 replication induces TNFalpha expression that induces multiple other indices of immune activation. In this model, HIV-1 replication and TNFalpha expression induce CD4+ T-cell losses at least in part through mechanisms reflected in heightened CD38 expression.