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Pulmonary tuberculosis in HIV infection: radiographic appearance is related to CD4+ T-lymphocyte count.

SETTING: An adult HIV outpatient clinic in Cape Town, South Africa. OBJECTIVE: To investigate the relationship between the radiographic appearance of pulmonary tuberculosis (PTB) in HIV infected patients and CD4+ T-lymphocyte count. DESIGN: Pretreatment radiographs of 150 patients with newly diagnosed PTB were reviewed. CD4+ T-lymphocyte count was used as a marker of HIV disease progression. RESULTS: Upper zone infiltrate typical of PTB reactivation was present in 18 patients. This pattern was associated with early HIV infection (mean CD4+ T-cell count 389) and had 78% positive predictive value for identifying patients with > 200 CD4+ T-lymphocytes/microL. Pleural effusion was present in 32 patients and occurred over a wide intermediate range of CD4+ T-cell counts (mean 185). Lower or midzone infiltrates, adenopathy, interstitial pattern or normal radiograph occurred in 136 patients and were associated with advanced HIV disease (mean CD4+ T-cell count 105). These patterns had 84%, 89%, 89% and 100% positive predictive value, respectively, for identifying patients with < 200 CD4+ T-cell/microL. CONCLUSION: Pulmonary tuberculosis in African HIV-positive patients presents with a spectrum of radiographic abnormalities predictive of stage of HIV disease progression. In patients dually infected with HIV and PTB, chest radiographs are a useful adjunct to clinical staging.

Adolescent↗

Chlamydia pneumoniae infection in HIV-positive patients: prevalence and relationship with lipid profile.

OBJECTIVES: The aims of this study were to evaluate the prevalence and impact of Chlamydia pneumoniae infection in HIV-positive patients and to establish the relationship between C. pneumoniae infection and lipid profile. METHODS: Detection of C. pneumoniae was by polymerase chain reaction (PCR) on Peripheral Blood Mononuclear Cells (PBMCs) collected from 97 HIV-positive patients. Samples were collected after overnight fast in EDTA-treated tubes. On the same day, patients were also tested for routine chemistry, HIV viral load, CD3, CD8 and CD4 cell counts and lipid profile [cholesterol, high-density lipoproteins (HDLs), low-density lipoproteins (LDLs) and triglycerides]. RESULTS: The overall prevalence of C. pneumoniae was 39%. The prevalence of C. pneumoniae was inversely related to the CD4 lymphocyte count (P=0.03). In the naive group, C. pneumoniae-positive patients had both significantly higher HIV load (71 021+/-15 327 vs. 14 753+/-14 924 HIV-1 RNA copies/mL; P=0.03) and lower CD4 cell count (348.0+/-165.4 vs. 541.7+/-294.8; P=0.04) than C. pneumoniae-negative patients. Moreover, treatment-naive patients with C. pneumoniae infection had significantly higher mean levels of cholesterol (185.3+/-56.2 vs. 124.8+/-45.9 mg/dL; P=0.01), triglycerides (117.2+/-74.7 vs. 68+/-27.6 mg/dL; P=0.04) and LDL (122.4+/-60.1 vs. 55.6+/-58 mg/dL; P=0.05) than C. pneumoniae-negative patients. CONCLUSIONS: These data indicate that, in HIV-positive subjects, C. pneumoniae infection is relatively frequent and is associated with both low CD4 cell count and high HIV load. Furthermore, C. pneumoniae appears to be associated with hyperlipidaemia and might therefore represent a further risk factor for cardiovascolar disease in HIV-positive patients.

AIDS-Related Opportunistic Infections↗

Ocular findings in HIV-1 positive and HIV-1 negative participants in a rural population-based cohort in Uganda.

PURPOSE: To report the ocular findings in HIV-1 seropositive individuals and HIV-negative controls in a population-based cohort in rural Uganda. METHODS: Participants were examined by an ophthalmologist, who was unaware of their HIV-status. RESULTS: 238 participants were examined, 43 were HIV-1 prevalent cases (infected prior to 1990); 62 were HIV-1 incident cases and 133 were HIV-negative controls. Eleven of the HIV-positive participants had AIDS, and a further 8 had a CD4 count of less than 200 cells/mm3. Bilateral low vision was recorded in 9 participants and cataracts were the main cause of bilateral low vision. The mean intra-ocular pressure (IOP) was 12.6 mm Hg, and no association was found between IOP and CD4 lymphocyte count. Although significantly more HIV positives had some sign of intraocular inflammation compared to the negatives (p = 0.02) there was no significant linear trend in the HIV positives with decreasing CD4 count. Overall, 11 (26%) prevalent, 6 (10%) incident cases and 8 (6%) HIV-negatives controls had some evidence of intraocular inflammation, however, only one person had reduced visual acuity attributable to these lesions. Punctate epithelial erosions and keratic precipitates in the anterior chamber were seen significantly more frequently in HIV-positives compared to the HIV-negative controls. Cotton wool spots were not seen. CONCLUSIONS: A substantial proportion of HIV-infected persons had ocular findings which may have been attributable to their infection, however in only one case did this result in reduced visual acuity. Although the ocular complications of AIDS seem to comprise a large extra element in the work load of tertiary care hospitals dealing with eye problems, on a population basis such cases are infrequent.

Adult↗

Specificity of binding of HIV-1 anti-p24 antibodies to CD4+ lymphocytes from HIV-infected subjects.

The clinical utility of a flow cytometric assay (FCA) for intracellular HIV p24 antigen was evaluated in a group of HIV-1-infected subjects. A previously described method, p24-FCA (1), was modified to minimize nonspecific staining and to include irrelevant isotype-matched control antibodies. Blood mononuclear cells from 32 HIV-1 seropositive subjects and 14 HIV-1 seronegative controls were examined. In HIV-1 seropositive individuals, the proportion of CD4+ lymphocytes that bound the p24 monoclonal and the isotype control antibodies were not different. The frequency of cells binding p24 antibodies increased with declining CD4 counts and was highest in patients with low CD4+ lymphocyte counts. Although results of p24-FCA do reflect disease progression, the high nonspecific binding of monoclonal antibodies in infected subjects obscures specific p24 binding and precludes its use as an accurate measure of infection within single cells.

Antibody Specificity↗

Human immunodeficiency virus infection and hepatitis C pathology.

To investigate the possible influence of human immunodeficiency virus (HIV) infection on hepatitis C virus-related liver disease, liver morphology was evaluated in 160 HBsAg-negative patients with chronic hepatitis C, including 68 HIV-positive and 92 HIV-negative cases. No differences were detected in the severity of necro-inflammatory hepatic lesions between HIV-negative and HIV-positive patients when the CD4+ lymphocytes count exceeded 400 cells/mm3. In contrast, HIV-positive patients with CD4+ lymphocytes below 400 cells/mm3 showed a significantly lower grade of portal inflammation and piecemeal necrosis. These results suggest that liver lesions in hepatitis C may largely depend on immunomediated mechanisms.

Adult↗

Clinical and laboratory findings of disseminated Mycobacterium avium complex infection (DMAC) in a pair matched case-control study.

A pair matched case/control study was conducted from January 1991 to 30 June 1992 in order to define clinical and laboratory findings associated with DMAC infection in AIDS patients. Since DMAC infection is usually associated with advanced immunodeficiency, and therefore also with other opportunistic illnesses, in addition to the number of CD4+ lymphocytes, cases and controls were matched using the following criteria: date of AIDS diagnosis and antiretroviral therapy, number and severity of associated opportunistic infections and, whenever possible, type of Pneumocystis carinii prophylaxis, age and gender, in this order of relevance. Cases (defined as patients presenting at least one positive culture for MAC at a normally sterile site) and controls presented CD4+ lymphocyte counts below 50 cel/mm3. A significantly higher prevalence of general, digestive and respiratory signs, increased LDH levels, low hemoglobin levels and CD4+ cell counts were recorded for cases when compared to controls. Increases in gammaGT and alkaline phosphatase levels seen in cases were also recorded for controls. In conclusion, the strategy we used for selecting controls allowed us to detect laboratory findings associated to DMAC infection not found in other advanced immunosupressed AIDS patients without DMAC.

AIDS-Related Opportunistic Infections↗

First human trial of a DNA-based vaccine for treatment of human immunodeficiency virus type 1 infection: safety and host response.

A DNA-based vaccine containing human immunodeficiency virus type 1 (HIV-1) env and rev genes was tested for safety and host immune response in 15 asymptomatic HIV-infected patients who were not using antiviral drugs and who had CD4+ lymphocyte counts of > or = 500 per microliter of blood. Successive groups received three doses of vaccine (30, 100, or 300 microg) at 10-week intervals in a dose-escalation trial. Vaccine administration induced no local or systemic reactions, and no laboratory abnormalities were detected. Specifically, no patient developed anti-DNA antibody or muscle enzyme elevations. No consistent change occurred in CD4 or CD8 lymphocyte counts or in plasma HIV concentration. Antibody against gp120 increased in individual patients in the 100- and 300-/microg groups. Some increases were noted in cytotoxic T lymphocyte activity against gp160-bearing targets and in lymphocyte proliferative activity. The safety and potential immunogenicity of an HIV-directed DNA-based vaccine was demonstrated, a finding that should encourage further studies.

AIDS Vaccines↗

Correlation coefficient estimation involving a left censored laboratory assay variable.

When assessing a correlation between two exposure or biological marker variables, one sometimes encounters the problem of indeterminate values for one of the variables due to an assay detection limit. In this event, investigators often report correlation coefficients computed after removing the pairs involving non-detectable values, or after substituting some small constant for those values. These ad hoc practices can lead to bias in both point and confidence interval estimates of the true correlation coefficient. To address this issue, we consider two parametric techniques for estimating the correlation in the presence of left censoring for one of the variables. The first is a maximum likelihood approach, and the second is an adaptation of multiple imputation motivated primarily by potential benefits in confidence interval coverage. Both of the estimators studied reduce to the standard Pearson's correlation coefficient in the event of no censoring, and hence are valid in cases where this measure would be appropriate for the complete data. We assess these approaches empirically and contrast them with ad hoc methods for estimating the correlation between cervicovaginal human immunodeficiency virus (HIV) viral load measurements and CD4+ lymphocyte counts from HIV positive women enrolled in a clinical trial conducted in Bangkok, Thailand.

Anti-HIV Agents↗

Improvement of symptomatic human immunodeficiency virus-related lymphoid interstitial pneumonia in patients receiving highly active antiretroviral therapy.

To analyze the impact of highly active antiretroviral therapy on lymphoid interstitial pneumonia (LIP), we reviewed the medical files of 5 human immunodeficiency virus (HIV)-infected patients in whom LIP was diagnosed during 1996-2001 who had never previously received antiretroviral treatment. Patients were mildly immunosuppressed at the time of diagnosis of LIP but had high plasma HIV loads and marked circulating and pulmonary CD8 hyperlymphocytosis. All patients improved clinically, radiologically, and functionally; improvement was accompanied by a drastic reduction in the virus load and an increase in the CD4 lymphocyte count.

AIDS-Related Opportunistic Infections↗

Impact of protease inhibitor therapy on HIV-related oropharyngeal candidiasis.

OBJECTIVE: To determine the relationship between antiretroviral therapy and changes in prevalence and amount of oropharyngeal candidiasis (OPC) and skin test reactivity for delayed type hypersensitivity. DESIGN: Observational cohort. SETTING: University-based public hospital AIDS clinic. PATIENTS: Adults with advanced HIV infection who had been taking nucleoside transcriptase inhibitor drugs but had not taken a protease inhibitor and who started antiretroviral treatment with ritonavir. MAIN OUTCOME MEASURES: OPC lesions score, oral candidal colonization, oral candidal quantification, skin test reactivity for delayed type hypersensitivity (purified protein derivative, candidal and streptokinase antigens), plasma HIV RNA and CD4 cell count at weeks 8, 16 and 48 weeks. RESULTS: In the 99 patients who entered the study, there was a significant reduction in the HIV plasma RNA (mean log decrease from baseline at 48 weeks 0.88) and a significant increase in CD4 cell counts (mean CD4 cell increase from baseline at 48 weeks 128 x 10(6) cells/l). Only 17% of patients had < 200 copies/ml HIV RNA at 48 weeks. There were significant decreases in the prevalence of OPC lesions (31% at baseline to 1% at 48 weeks; P < 0.001), and in oral candidal loads [2226 to 811 colony-forming units (CFU)/ml; P = 0.0171]. The percentage of patients with at least one positive skin test increased significantly (6 to 28%; P < 0.05). Patients whose CD4 lymphocyte count was > 200 x 10(6) cells/l at 48 weeks had significantly lower oral candidal loads and were more likely to have a positive skin test than patients whose CD4 cell count was < 200 x 10(6) cells/l. CONCLUSION: In patients with advanced HIV infection, antiretroviral treatment including a protease inhibitor has a positive impact in the natural history of OPC. This positive impact appears to be correlated with a better immunological function and occurs despite continuous HIV replication.

AIDS-Related Opportunistic Infections↗

Acquired immunodeficiency syndrome-related oral and/or cutaneous histoplasmosis: a descriptive and comparative study of 21 cases in French Guiana.

BACKGROUND: Oral or cutaneous acquired immunodeficiency syndrome (AIDS)-related histoplasmosis is a rare presentation of disseminated histoplasmosis. OBJECTIVE: To describe this clinical presentation and to compare it with other forms of AIDS-related disseminated histoplasmosis. METHODS: A cross-sectional study of patients with AIDS-related disseminated histoplasmosis was performed. CD4 counts and survival were compared between patients with oral or cutaneous histoplasmosis and patients with nonmucocutaneous disseminated histoplasmosis. RESULTS: The mean CD4 lymphocyte count was lower in patients with mucocutaneous lesions than in patients with nonmucocutaneous disseminated histoplasmosis (29 vs. 72/mm3, P = 0.002). The proportion of survivors 1 month after diagnosis did not differ significantly between the two groups (13/21 vs. 32/45, P = 0.4). At 6 months, the proportion of survivors was significantly lower for patients with mucocutaneous lesions (6/21 vs. 22/39, P = 0.03). CONCLUSIONS: These results suggest that mucocutaneous lesions occur at a later stage of human immunodeficiency virus infection, but are not, in themselves, associated with a higher level of mortality. The excess mortality at 6 months reflects deaths from other complications of severe immunodepression. This study confirms the polymorphism of mucocutaneous lesions, emphasizing the need for systematic testing for Histoplasma in all cases of mucocutaneous lesions in AIDS patients.

AIDS-Related Opportunistic Infections↗

On the use of auxiliary data to estimate the survival function and its variance: an application to acquired immunodeficiency syndrome.

Prospective studies have as their goal the estimation of the survival function when the time to the specified event may be censored due to loss to follow-up or to the termination of the study before the event of interest occurs. In such a study, information about an auxiliary event, correlated to the event of interest, is often available. An example of such an auxiliary event in cancer studies is remission or relapse. A stochastic model was proposed by Lagakos, which utilizes this type of information in the analysis of survival studies [1]. The primary objective of using an auxiliary information is to improve the estimation of survival. This article proposes a method to estimate the variance of the estimator of the survival function S(t) for the model including such auxiliary information. Thus, we compute for different situations the relative efficiency of the estimator of S(t) using the stochastic model to the estimator of S(t) using only survival data. The method is applied to data from a prospective study of 379 HIV-seropositive homosexual men, of whom 31 developed AIDS. In our example, the auxiliary event is defined by the level of CD4 lymphocyte counts using distinct threshold values, for instance 200 cells/mm3, while the event of interest is the time to development of AIDS.

Acquired Immunodeficiency Syndrome↗

Serologic confirmation of HIV infection.

As the number of patients with Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS) increases, it is important for eye care practitioners to become familiar with the serologic testing used in testing for HIV infection. These tests include: HIV-ELISA (enzyme linked immunosorbent assay), HIV-Western Blot, PCR (polymerase chain reaction) gene amplification, p24 core antigen assay, Beta 2-microglobulin levels, and CD4 lymphocyte counts. This Symposium discusses the aforementioned serologic tests and their uses in the diagnosis and management of HIV infection.

AIDS Serodiagnosis↗

Acinetobacter infections in patients with human immunodeficiency virus infection: microbiological and clinical epidemiology.

BACKGROUND: We evaluated the role of complications caused by Acinetobacter spp. in the setting of HIV infection. METHODS: Clinical records of 1,923 consecutive HIV-infected patients hospitalized in a 9-year period were retrospectively reviewed, in order to identify all cases of Acinetobacter spp. complications, and to assess their occurrence and outcome according to several epidemiological, clinical and laboratory parameters. RESULTS: Ten patients out of 1,923 (0.52%) developed Acinetobacter spp. infections: sepsis in four cases, urinary tract infection in three, pneumonia in two and septicaemic pneumonia in the remaining patient. All patients were severely immunocompromised, as shown by a mean CD4+ lymphocyte count of 122 cells/microl and a frequent prior diagnosis of AIDS. As opposed to other infections, septicaemia was associated with a significantly lower CD4+ cell count and a more frequent occurrence of neutropenia. Hospital-acquired Acinetobacter spp. infections were significantly more frequent than community-acquired ones, and prevailingly involved patients with AIDS and leucopenia, being responsible for frequent blood dissemination. Antimicrobial, corticosteroid and cotrimoxazole treatment were frequently carried out during the month preceding disease onset. Antibiotic susceptibility studies proved the complete resistance of microbial isolates to ampicillin and cephalothin and poor sensitivity to second-generation cephalosporins and gentamicin, while greater susceptibility was shown to ceftazidime, netilmicin and amikacin, followed by piperacillin, cotrimoxazole and quinolones. Appropriate antimicrobial treatment led to clinical and microbiological cure in all cases, with no related mortality or relapses. CONCLUSIONS: Since only 23 episodes of HIV-associated Acinetobacter spp. infections have been described to date in 11 different reports (nine cases of bacteraemia, eight of pneumonia, two of urinary tract involvement, one of intravenous access device infection, one of meningitis and two with unspecified localization), our series represents the largest one dealing with HIV-associated Acinetobacter spp. infections. According to our experience, Acinetobacter spp. may be responsible for appreciable morbidity among patients with HIV infection, above all when a low CD4+ cell count, neutropenia and hospitalization are present. Clinicians and microbiologists who work in the field of HIV infection should consider the potential pathogenic role of Acinetobacter spp. organisms even in the absence of some presumed risk factors, because of the relationship between these infections and immunodeficiency, hospitalization, other infectious complications, prior antibiotic and steroid treatment and extended antimicrobial resistance patterns.

Acinetobacter↗

[Dilated cardiomyopathy in HIV infection].

The HIV-positive patient with dilated cardiomyopathy was described. Possible causes of heart failure in HIV infection was discussed. To achieve subclinical heart failure diagnosis authors suggest to perform echocardiography as a routine procedure in HIV-positive patients with low CD4 lymphocytes count and who have been infected for long time or when their disease becomes more advanced.

Adult↗

The value of serum albumin in pretreatment assessment and monitoring of therapy in HIV/AIDS patients.

OBJECTIVES: We sought to examine the utility of serum albumin measurement in staging AIDS and monitoring patients' response to therapy. METHODS: The possible importance of serum albumin measurement in assessing AIDS stage and in monitoring the response to highly active antiretroviral therapy using CD4 cell count and body weight as parameters was examined in 185 consecutive HIV-infected, therapy-naïve individuals who were recruited for antiretroviral therapy at the university of Ilorin Teaching Hospital. The regimen included lamivudine, stavudine and nevirapine. The diagnosis of AIDS was established through a combination of clinical features and HIV seropositivity using two different enzyme-linked immunosorbent assay techniques. Serum albumin level was determined by the Bromocresol green method, while the CD4 lymphocyte count was obtained using the Dynal T4 count method. Body weight was measured in kilograms with light clothes on. RESULTS: There were significant positive correlations between pretreatment albumin and both pretreatment CD4 cell count and pretreatment weight, and between post-treatment albumin and both post-treatment weight and post-treatment CD4 cell count up to a count of 700 cells/microL. There were also significant positive correlations between increase in serum albumin and both increase in body weight and duration of treatment. CONCLUSIONS: We conclude that, in developing countries where many patients may not be able to afford to pay for CD4 cell counts and viral load tests, which are the traditional markers for HIV disease, serum albumin would be a very useful surrogate test for predicting severity of HIV infection and for clinical monitoring of response to antiretroviral therapy.

Adult↗