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Markers in HIV associated tuberculosis in Kenya.

Tuberculosis is one of the most frequent opportunistic infections in HIV-infected patients in developing countries. In some instances, manifestations of pulmonary tuberculosis precede all other HIV related signs and symptoms because of the high virulence of M. tuberculosis. In order to characterise the interaction between these two pathogens, clinical and immunological parameters in pulmonary tuberculosis patients with and without HIV infection were compared. Amongst newly diagnosed pulmonary tuberculosis patients the association of some of these changes with the clinical outcome were evaluated. Of these, 44% were co-infected with HIV. Pulmonary tuberculosis patients with HIV-1 presented more frequently with lymphadenopathy and diarrhoea than those without HIV-1. Peripheral blood CD4+ counts were significantly lower in patients with pulmonary tuberculosis with HIV-1 than those with pulmonary tuberculosis alone, P= 0.0292. Low CD4+ lymphocyte counts, lymphadenopathy and BCG scar absence could serve as indicators of HIV-1 infection in pulmonary tuberculosis (PTB) patients.

Journal Article↗

Age-adjusted CD4+ lymphocyte parameters in healthy children at risk for infection with the human immunodeficiency virus. The Military Pediatric HIV Consortium.

Values for CD4+ lymphocytes are reported to vary by age. We evaluated an ethnically diverse population of healthy children at risk for human immunodeficiency virus infection to establish normal ranges for age-adjusted CD4+ lymphocyte parameters. We identified a threshold of approximately 30% CD4+ lymphocytes which corresponded to a 5th percentile for all ages. It is important that no significant differences in absolute CD4+ lymphocyte counts on the basis of ethnic group were found.

Age Factors↗

Clinical and laboratory correlates of Pneumocystis carinii pneumonia in children infected with HIV.

The case histories of 27 children with Pneumocystis carinii pneumonia (PCP) who were followed up in the AIDS Program at the Children's Hospital of New Jersey, Newark, are reviewed. The mean and median age at PCP diagnosis were 10.8 and 7.7 months, respectively. All of the children had other clinical evidence of infection with the human immunodeficiency virus that was documented prior to the diagnosis of PCP or found at the time of PCP diagnosis. Most patients who presented to the hospital were acutely ill, and complications of treatment occurred in 70%. Overall, 89% of the patients died and 70% survived for less than 6 months after diagnosis of PCP. Median survival after the diagnosis of PCP was only 2.0 months and the median life span of children with PCP was only 14.4 months. Only 40% of children with PCP had CD4 lymphocyte counts at or below the threshold for institution of PCP prophylaxis in adults of 200 x 10(6) cells/L (200 cells/mm3).

CD4-Positive T-Lymphocytes↗

Reference intervals of CD3, CD4, CD8, CD4/CD8, and absolute CD4 values in Asian and Non-Asian populations.

A study to determine reference intervals in normal Asian and non-Asian populations for CD3 (T cells), CD4 (T helper/inducer cells), CD8 (T suppressor/cytotoxic cells), and for the CD4/CD8 ratio and absolute CD4 lymphocyte count was performed. Coulter Clone/Cytostat reagents were used. The samples were lysed using the Coulter Q-Prep and analyzed on the Coulter Profile II flow cytometer. The Asian population appeared to have a lower mean percentage of CD3 and CD4 cells, a lower CD4/CD8 ratio, and lower absolute CD4 lymphocytes. These findings indicate that race should be a consideration in determining reference intervals for immunophenotyping for CD3, CD4, and CD8.

Adult↗

Ocular manifestations in HIV-seropositive patients.

A total of 153 patients with human immunodeficiency virus (HIV) infection underwent complete ophthalmologic examinations for the presence of any eye pathology. We wanted to show a correlation between such pathology and total CD4+ lymphocyte count, believed to be an indicator of immunologic status. The most frequently encountered lesions were cotton-wool patches, vascular congestion, hemorrhages, chorioretinitis, segmental vasculitis, and pallid papilla. Almost all of the patients with ocular anomalies also had a CD4+ count of less than 200 cells/mm3 suggesting that ocular lesions have a negative prognostic significance even in asymptomatic patients who present with a severe impairment of their immune system.

AIDS-Related Complex↗

Painful gingivitis may be an early sign of infection with the human immunodeficiency virus.

Anecdotal reports have suggested that painful gingivitis may be associated with infection due to the human immunodeficiency virus (HIV). Twenty patients who presented to the emergency department with a chief complaint of gum pain were evaluated for HIV infection, CD4/CD8 T lymphocyte profiles, complete blood cell counts and differentials, and lymphocyte function (response to mitogenic stimulation). Seven of the 20 patients (35%) were seropositive for HIV. Three of the seven HIV-seropositive patients were unaware of their HIV infection until tested in this study (with use of an ELISA and western blotting). The HIV-seropositive patients were significantly older than the HIV-seronegative patients (31.4 +/- 3 years and 24 +/- 1 year, respectively). Two of the seven HIV-seropositive patients presented with severe CD4 lymphocyte depletion. The other five HIV-seropositive patients presented with CD4 lymphocyte counts of 473 +/- 155 (mean +/- SE). Regardless of HIV serological status, all patients demonstrated a severely depressed mitogenic response when compared with control subjects. There were no remarkable differences in complete blood cell counts and differentials within each serological group. Significant differences, however, were noted when CD4/CD8 lymphocyte counts and ratios were measured. Identification of clinical presentations, such as painful gingivitis, that reflect an early stage of HIV infection could aid in the timing of therapy and prevention of the spread of HIV infection.

Adult↗

HIV infection, cigarette smoking and CD4+ T-lymphocyte counts: preliminary results from the San Francisco Men's Health Study.

The effect of cigarette smoking on CD4+ T lymphocytes was investigated in the San Francisco Men's Health Study cohort. The cohort was established by probability sampling in 1984 to study infection with HIV. Smoking showed an association with increased CD4+ cell counts in all men but the effect was attenuated in HIV-seropositive men (85 cells/microliter difference in median counts, non-smokers compared with smokers) compared with HIV-seronegative men (230 cells/microliter difference in median counts). The positive dose response between packs smoked per day and CD4+ counts observed in uninfected men was substantially reduced in infected men (slope 87 versus 27 cells/microliter). Analysis of data from HIV seroconverters suggest that smokers' counts fall faster than non-smokers' following infection, and that response to smoking becomes less pronounced soon after infection. This report demonstrates that those who monitor CD4+ cell counts in HIV-infected individuals for clinical and/or research purposes should also consider smoking status.

Adult↗

The role of non-viral load surrogate markers in HIV-positive patient monitoring during antiviral treatment.

Monitoring the efficacy of highly active antiretroviral treatment (HAART) is crucial if disease progression and the emergence of viral mutants are to be avoided. Classical viral load monitoring is too expensive for large-scale use in resource-limited settings. Three alternative measures, CD4 count, total lymphocyte count (TLC) and haemoglobin, were evaluated as surrogate markers of treatment success (viral load below detection level) among 710 HIV-positive patients who started HAART in an HIV treatment centre in Belgium. TLC correlated well with changes in CD4 counts during HAART, but an increase in TLC alone was a poor predictor of treatment success. A combination of increases in both haemoglobin levels and TLC proved a reliable predictor of successful treatment outcome comparable to the increase in CD4 count, but its specificity and sensitivity were low.

Adult↗

[Clinical characteristics of patients with AIDS treated at the Infectious Disease Clinic, Medical Academy, in Wrocław during the years 1989-1990].

In the period 1989-1990 15 patients with various stages of HIV infection were treated. Among them were: 8 (53.3%) i.v. drug users, 6 (40%) homo- and bisexual men, and 1 (6.1%) woman with post-transfusion infection. The undertaken medical and laboratory examination, on the basis of CDC/WHO criteria, revealed: 6 patients with PGL, 6-with IV A stage, 1-IVB, 1-IVd and 1-IVE. The group of homo and bisexual men had lover CD4 lymphocyte counts than other patients. From our group only 7 patients were treated unsuccessfully with Retrovir (600 mg daily/6 months) but without side effects. Three patients died to this day.

Acquired Immunodeficiency Syndrome↗

Hepatitis C virus infection in patients infected with the human immunodeficiency virus.

The prevalence and characteristics of hepatitis C virus (HCV) infection in 226 patients who were seropositive for human immunodeficiency virus (HIV) were determined. Antibody to HCV (anti-HCV) was detected by enzyme immunoassay (EIA), and positive results were confirmed by a neutralization EIA or recombinant immunoblot assay. The prevalence of anti-HCV was 8%. Intravenous drug use was the most common risk factor for HCV infection (61.1% of patients), and 52.4% of intravenous drug users were seropositive for anti-HCV (HCV+). Only 16.7% of HCV+ patients had AIDS, as compared with 37.4% of anti-HCV-seronegative (HCV-) patients (P = .04). The prevalence of hepatitis B virus markers in patients with and without anti-HCV was similar. The CD4+ lymphocyte counts were higher for HCV+ patients than for HCV- patients (P = .001), and the prevalence of anti-HCV decreased in parallel with CD4+ counts. Elevated liver function test values were more common for HCV+ patients than for HCV- patients (61.1% vs. 26.0%; P < .01), but abnormalities were usually slight (< 2-fold elevation in values). HCV viremia was detected by the polymerase chain reaction in 88.2% of HCV+ patients. Despite the coexistence of HIV and HCV infection, liver disease appeared to be mild, and HCV infection did not appear to increase the severity of HIV infection. Serological tests for HCV appear to underestimate the prevalence of HCV infection in patients with advanced HIV infection or AIDS.

Adult↗

Acute human immunodeficiency virus syndrome in an adolescent.

Acute human immunodeficiency virus (HIV) seroconversion illness is a difficult diagnosis to make because of its nonspecific and protean manifestations. We present such a case in an adolescent. A 15-year-old boy presented with a 5-day history of fever, sore throat, vomiting, and diarrhea. The patient also reported a nonproductive cough, coryza, and fatigue. The patient's only risk factor for HIV infection was a history of unprotected intercourse with 5 girls. Physical examination was significant for fever, exudative tonsillopharyngitis, shotty cervical lymphadenopathy, and palpable purpura on both feet. Laboratory studies demonstrated lymphopenia and mild thrombocytopenia. Hemoglobin, serum creatinine, and urinalysis were normal. The following day, the patient remained febrile. Physical examination revealed oral ulcerations, conjunctivitis, and erythematous papules on the thorax; the purpura was unchanged. Serologies for hepatitis B, syphilis, HIV, and Epstein-Barr virus were negative. Bacterial cultures of blood and stool and viral cultures of throat and conjunctiva showed no pathogens. Coagulation profile and liver enzymes were normal. Within 1 week, all symptoms had resolved. The platelet count normalized. Repeat HIV serology was positive, as was HIV DNA polymerase chain reaction. Subsequent HIV viral load was 350 000, and the CD4 lymphocyte count was 351/mm3. HIV is the seventh leading cause of death among people aged 15 to 24 in the United States, and up to half of all new infections occur in adolescents. Our patient presented with many of the typical signs and symptoms of acute HIV infection: fever, fatigue, rash, pharyngitis, lymphadenopathy, oral ulcers, emesis, and diarrhea. Other symptoms commonly reported include headache, myalgias, arthralgias, aseptic meningitis, peripheral neuropathy, thrush, weight loss, night sweats, and genital ulcers. Common seroconversion laboratory findings include leukopenia, thrombocytopenia, and elevated transaminases. The suspicion of acute HIV illness should prompt virologic and serologic analysis. Initial serology is usually negative. Diagnosis therefore depends on direct detection of the virus, by assay of viral load (HIV RNA), DNA polymerase chain reaction, or p24 antigen. Both false-positive and false-negative results for these tests have been reported, further complicating early diagnosis. Pediatricians should play an active role in identifying HIV-infected patients. Our case, the first report of acute HIV illness in an adolescent, emphasizes that clinicians should consider acute HIV seroconversion in the appropriate setting. Recognition of acute HIV syndrome is especially important for improving prognosis and limiting transmission. It is imperative that we maintain a high index of suspicion as primary care physicians for adolescents who present with a viral syndrome and appropriate risk factors.

AIDS Serodiagnosis↗

Enhanced basophil releasability in subjects infected with human immunodeficiency virus.

Spontaneous histamine release and basophil response to IgE-dependent (anti-IgE) and IgE-independent (formyl-methionine peptide, calcium ionophore A23187) stimuli were evaluated in 15 patients with acquired immunodeficiency syndrome (AIDS), 8 with AIDS related complex (ARC), 7 with lymphadenopathy syndrome (LAS), 11 seropositive asymptomatic subjects, 10 human immunodeficiency virus (HIV)-seronegative drug addicts, and 20 normal subjects. Both spontaneous histamine release and anti-IgE-induced histamine release were significantly increased in HIV-infected subjects, in comparison with seronegative drug addicts and normal controls. Basophil response to anti-IgE was higher in AIDS/ARC patients than in seropositive asymptomatic subjects and LAS patients, although the difference was not statistically significant. When basophils were challenged with 0.1 microM formyl-methionine peptide, a significantly increased histamine secretion was found in HIV-infected subjects; conversely, at the higher formyl-methionine peptide concentration (10 microM), as well as at all calcium ionophore A23187 concentrations, histamine release was similar in all the studied groups. No correlation was found among anti-IgE-induced histamine release, total lymphocyte counts, CD4+ and CD8+ T cell counts, and total serum IgE levels. These findings indicate that infection with HIV is associated with an increased basophil releasability. This could be of some relevance in the increased incidence of allergic manifestations and adverse drug reactions observed in AIDS patients.

AIDS-Related Complex↗

Clinical programs for clinical research on AIDS: description of a randomized prospective study of clindamycin versus pyrimethamine for prevention of Toxoplasma gondii infection.

The risk of toxoplasmic encephalitis complicating AIDS appears largely limited to those HIV-infected patients with serologic evidence of past Toxoplasma gondii infection and low CD4 lymphocyte counts. The Community Programs for Clinical Research on AIDS has initiated a randomized, placebo-controlled trial to determine if clindamycin or pyrimethamine prophylactic regimens are effective and safe in preventing toxoplasmic encephalitis.

Acquired Immunodeficiency Syndrome↗

Asymptomatic women at high risk of vertical HIV-1 transmission to their fetuses.

OBJECTIVE: To identify how reliably CD4+ (helper) lymphocyte count and p24 antigenaemia can predict mother-to-infant transmission of human immunodeficiency virus type 1 (HIV-1). DESIGN: Prospective study. SETTING: University of Turin Center for Intravenous Drug Users (IVDU) and/or HIV-1 seropositive pregnant women. SUBJECTS: Twenty-nine infants born to asymptomatic seropositive women from November 1985 to June 1991. RESULTS: Seven children (24%) developed symptomatic infection, while 22 healthy seronegative children at the age of 18 months were considered uninfected. A CD4+ lymphocyte count persistently < 500/mm3 during pregnancy was associated significantly with the child's infection status with a relative risk (RR) of 11.4. (CI 1.58-82.05). A marked association (RR 13.6) (CI 1.93-95.72) was similarly detected between maternal antigenaemia and the risk of the child being infected. In a multivariate logistic analysis, crude and adjusted odds ratios (OR) of transmission were 27.0 (95% CI 2.5-291.2) and 35.6 (1.1-1159) for low CD4+ counts; 64 (3.2-1261) and 51.6 (2.5-1058) for p24 antigenaemia. CONCLUSIONS: Asymptomatic HIV positive women with a CD4+ count below 500/mm3 or p24 antigenaemia are about ten times as likely to transmit the virus to their children. CD4+ lymphocytes decrease during pregnancy and a low CD4+ cell count early in pregnancy remains low up to delivery. Therefore knowledge that they have a low CD4+ lymphocyte count early in pregnancy may help women to decide whether or not to continue their pregnancy.

Adult↗

Protein levels of interleukin-12 p70 holomer, its p40 chain and interferon-gamma during advancing HIV infection.

BACKGROUND: a switch from T helper 1 (TH1) to T helper 2 (TH2)-like cytokine production has been proposed for progressive HIV infection. OBJECTIVE: to study whether this hypothesis is reflected by altered IL-12 and IFN-gamma serum levels in HIV patients. METHODS: we measured serum levels of IL-12 p40 and p70 and IFN-gamma in 90 HIV seropositive patients at differing disease stages and in 10 healthy controls by radioimmunoassays. These cytokines were compared to established surrogate markers of immunodeficiency. RESULTS: IFN-gamma, as well as IL-12 p40 and p70, levels were significantly increased in HIV patients compared to controls. However, IFN-gamma and IL-12 showed no significant variations with progressive stages of immunodeficiency. IFN-gamma levels showed a significant positive correlation to the progression marker beta2-microglobulin and correlated negatively with CD4+ lymphocyte counts. In addition, IFN-gamma concentrations were related to sTNF-R p55 and p75 serum levels. Interestingly. IFN-gamma was related to IL-12 only with respect to p40, but not to p70. CONCLUSIONS: although our data do not necessarily reflect cytokine secretion at the single cell level or the cytokine milieu in the lymphoid microenvironment, our results from peripheral blood fail to demonstrate progressively decreased IL-12 and IFN-gamma serum levels in HIV infected patients.

Adult↗

Clinical and microbiological survey of Serratia marcescens infection during HIV disease.

Clinical charts of 2,398 consecutive HIV-infected patients hospitalized over an 8-year period were reviewed retrospectively to identify all cases of Serratia infection and to evaluate the occurrence and outcome of these cases according to several epidemiological. clinical, and laboratory parameters. Seventeen of 2,398 (0.71%) patients developed Serratia marcescens infections: nine had septicaemia, six had pneumonia, one had a lymph node abscess, and one had cellulitis. All patients were severely immunocompromised, as evidenced by a mean CD4+ lymphocyte count of < 70 cells/microl and a frequent diagnosis of AIDS (13 patients). When compared with other disease localizations, septicaemia was related to a significantly lower CD4+ cell count and a more frequent occurrence of neutropaenia. Antibiotic, corticosteroid, or cotrimoxazole treatment was frequently carried out during the month preceding disease onset. Hospital-acquired Serratia spp. infection was more frequent than community-acquired infection and was significantly related to AIDS, neutropaenia, and sepsis. Antimicrobial sensitivity testing showed complete resistance to ampicillin and cephalothin but elevated susceptibility to ureidopenicillins, second- and third-generation cephalosporins, aminoglycosides, quinolones, and cotrimoxazole. An appropriate antimicrobial treatment attained clinical and microbiological cure in all cases, in absence of related mortality or relapses. Since only 13 episodes of HIV-associated Serratia spp. infection have been described until now in nine different reports (7 patients with pneumonia, 3 with sepsis, 1 with endophthalmitis, 1 with perifolliculitis, and 1 with cholecystitis), our series represents the largest one dealing with Serratia marcescens infection during HIV disease. Serratia marcescens may be responsible for appreciable morbidity among patients with HIV disease, especially when a low CD4 + cell count, neutropaenia, and hospitalization are present. The clinician and the microbiologist facing a severely immunocompromised HIV-infected patient with a suspected bacterial disease should consider the Serratia spp. organisms. In fact, a rapid diagnosis and an adequate and timely treatment can avoid disease relapses and mortality.

AIDS-Related Opportunistic Infections↗

Impact of stressful life events, depression, social support, coping, and cortisol on progression to AIDS.

OBJECTIVE: This study examined prospectively the effects of stressful events, depressive symptoms, social support, coping methods, and cortisol levels on progression of HIV-1 infection. METHOD: Eighty-two homosexual men with HIV type-1 infection without AIDS or symptoms at baseline were studied every 6 months for up to 7. 5 years. Men were recruited from rural and urban areas in North Carolina, and none was using antiretroviral medications at entry. Disease progression was defined as CD4(+) lymphocyte count <200/microl or the presence of an AIDS indicator condition. RESULTS: Cox regression models with time-dependent covariates were used adjusting for race, baseline CD4(+) count and viral load, and cumulative average antiretroviral medications. Faster progression to AIDS was associated with higher cumulative average stressful life events, coping by means of denial, and higher serum cortisol as well as with lower cumulative average satisfaction with social support. Other background (e.g., age, education) and health habit variables (e.g., tobacco use, risky sexual behavior) did not significantly predict disease progression. The risk of AIDS was approximately doubled for every 1.5-unit decrease in cumulative average support satisfaction and for every cumulative average increase of one severe stressor, one unit of denial, and 5 mg/dl of cortisol. CONCLUSIONS: Further research is needed to determine if treatments based on these findings might alter the clinical course of HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

AIDS in Edinburgh drug users: observations on the epidemic and implications for its future management.

We are now witnessing the anticipated explosion of cases of AIDS resulting from the epidemic of HIV infection among Edinburgh drug users in the first half of the last decade. We expect the number of new cases of AIDS to continue to increase, although the rate at which they do so may be mitigated by intervention which slows the rate of progression to AIDS. There is evidence that current management of patients may postpone a diagnosis of AIDS until later in the natural history of HIV infection when immunity is very low as manifested by CD4+ lymphocyte counts. Health care planners need to provide resources for an increasing number of HIV-infected persons who have not yet fulfilled the definition of AIDS but who nevertheless require extensive resources both in the community and in hospital.

Acquired Immunodeficiency Syndrome↗