Walter Reed Stage Research Articles

Ventricle brain ratio in the clinical course of HIV infection

As part of the computerized tomographic assessment of an unselected group of 47 patients in different stages of HIV infection we determined the ventricle brain ratio (VBR) and the width of several cortical sulci. We compared the findings for subgroups of patients defined by their stage in the Walter Reed Staging Classification. There was a significant increase in VBR only in the subgroup of patients with manifest acquired immune deficiency syndrome (AIDS) (WR 6). The findings are discussed in connection with the question of the likelihood that dementia will develop even in stages of HIV-infection preceding AIDS.

Increased serum neopterin in patients with HIV-1 infection is correlated with reduced in vitro interleukin-2 production

Recently we have observed that the CD4+ T cell response of peripheral blood mononuclear cells (PBMC) to soluble antigens is the first to be lost in the course of HIV-1 infection followed by the loss of response to HLA alloantigens. In this study we compared serum neopterin concentrations of individuals with early stages of HIV-1 infection (stages WR1 and WR2, Walter Reed staging system) with in vitro interleukin-2 (IL-2) production of PBMC in response to stimulation with soluble antigens (influenza A virus and tetanus toxoid) and alloantigens. Neopterin concentrations were significantly higher in HIV-1-seropositive individuals who showed deficient IL-2 production in response to recall antigens only or to all of the stimuli tested in vitro, compared with HIV-1-seropositive individuals who exhibited no CD4+ T cell defects. No difference in serum neopterin concentrations was observed between the group that was functionally deficient to soluble antigens only versus those who were unresponsive to both types of stimuli. It appears that the selective loss of the MHC self-restricted CD4+ T cell function is associated with an increase in serum neopterin levels. Neopterin concentrations are an estimate of the activation status of macrophages. We conclude that defective in vitro production of lymphokines by T lymphocytes is associated with activated macrophages in vivo.

Increased drug reactions in HIV-1-positive patients: a possible explanation based on patterns of immune dysregulation seen in HIV-1 disease*

Drug reactions are common in HIV-1 disease, with the incidence having been reported to increase with increasing stage and with CD4+ T-cell counts below 200/microliters. However, there have been numerous reports of patients in which rechallenge, dosing changes or continued therapy have resulted in no recurrence or else clearing of the eruption. We followed 974 HIV-1-positive patients for 46 months as a part of a military study of HIV-1 disease. Within this group there were a total of 283 drug eruptions, with cutaneous manifestations in 201 patients in which clinical characteristics were noted and 86 patients in which cutaneous biopsies were performed. Serological evidence of reactivation or acute Epstein-Barr virus (EBV) or cytomegalovirus (CMV) infections were also noted, as well as peripheral eosinophilia. The incidence of drug eruptions significantly increased with increasing Walter Reed stage and decreasing CD4 counts and CD4/CD8 ratio, as well as with increasing age and in patients with increased numbers of other dermatological diagnoses. In addition, white patients had significantly more drug eruptions than did black. Serological or culture evidence of acute or reactivated EBV or CMV was significantly increased in patients with drug eruptions. The majority of the eruptions were maculopapular or morbilliform with a predominantly perivascular mononuclear cell infiltrate. HIV-1 positive patients have an increased incidence of drug reactions, the incidence having been reported to increase in patients with less than 200 CD4+ T cells/microliter. However, at very low T4 counts, especially those less than 25/microliter, and at a CD4/CD8 ratio of less than 0.10, the probability of reactions to trimethoprim-sulphamethoxazole (TMP-SMZ) is decreased in late-stage HIV-1 patients. Maculopapular or morbilliform eruptions are the most common clinical presentations, often accompanied by one or more of the following: fever, arthralgias, eosinophilia, and serum transaminase elevation. Histologically the majority of these eruptions show a perivascular mononuclear cell infiltrate, sometimes with focal interface changes and apoptotic, necrotic cells within the epidermis. Acute hypersensitivity reactions and toxic epidermal necrolysis (TEN) or Stevens-Johnson's syndrome (SJS) with diffuse epidermal apoptosis and necrosis have also been less commonly described. In a study of cutaneous manifestations in an HIV-1 positive military population, drug reactions were evaluated in terms of clinical features, histopathology, demographic features and laboratory findings.

Decreased CD7 expression in cutaneous infiltrates of HIV-1+ patients. Military Medical Consortium for the Advancement of Retroviral Research (MMCARR).

CD7 is an early T-cell marker that has been used in the diagnosis of stem cell leukemias. Loss of expression of CD7 with a battery of other mature T-cell markers has also been used as one criteria in the diagnosis cutaneous T-cell lymphomas. More recently, CD7-negative T cells have been shown to be a normal population of T cells in the peripheral blood and the skin, and may represent a mature T-cell population with a different pattern of maturation and activation. In addition, in HIV-1 disease expansion of CD7-negative T cells has been found in the peripheral blood. We evaluated the number of CD7-negative T cells in skin infiltrates to determine whether there was an increase of CD7-negative T cells. We studied T-cell markers including CD3, CD4, CD7, CD8, CD20, CD29, and HLA-DR on cutaneous biopsy material from inflammatory dermatoses in 57 patients with HIV-1 disease in Walter Reed stages (WR) 1-6, and in 14 HIV-1-negative patients WR0. The inflammatory infiltrates showed a moderate to marked decrease in CD7 expression on CD3+ T cells in benign inflammatory infiltrates of the majority of HIV-1+ patients. The majority of HIV-1-negative patients showed no decrease in CD7 expression, although 5 of 14 showed a moderate decrease and 1 of 14 showed a marked decrease. Although the nature of CD7- T cells has not been clearly defined, this population of mature T cells appears to have distinct immunologic properties as well as a trophism for skin. Better characterization of these T cells, as well as factors that promote their maturation and activation, may give clues to the high incidence as well as the pathogenesis of skin disease in HIV-1+ patients.

Metronidazole for Eosinophilic Pustular Folliculitis in Human Immunodeficiency Virus Type 1-Positive Patients

Eosinophilic pustular folliculitis (EPF) of Ofuji presents as coalescing papulopustular plaques with central clearing and postinflammatory hyperpigmentation, occurring in otherwise healthy adults. 1 In patients who are human immunodeficiency virus type 1-positive (HIV + ), EPF occurs as pruritic, discrete erythematous urticarial follicular papules, usually distributed over the head and neck areas, sometimes with extension to the proximal aspect of the upper extremities and the upper aspect of the trunk, and may be a separate disorder. 2 In previous reports and in our patients this condition tends to occur in late-stage disease, Walter Reed stages 5 and 6, with CD4 counts of less than 0.25 to 0.30×10 9 /L. 2 The eruption tends to be chronic and resistant to therapy, and although the majority of our patients have moderate-to-severe pruritus, they do not develop sepsis or other systemic symptoms that are directly related to EPF. Demodex, Tinea, Pityrosporum, and Staphylococcus aureus have

Malignant Lymphoma of Soft Tissue in an HIV-1+ Patient: A Rare Site for Primary Malignant Lymphoma with Implications for Treatment

Soft tissue lymphomas are rare; however, the only large reported series has indicated that soft tissue lymphomas may have a better prognosis than similar-grade tumors found at other sites, and even high-grade lesions may respond to local therapies. We present a human immunodeficiency virus type 1 (HIV-1)-positive, Walter Reed stage VI black male with a documented high-grade soft tissue non-Hodgkin's lymphoma with no other evidence of tumor on complete systemic evaluation. Although extranodal lymphomas are common in HIV-1 disease, we are aware of no other reports of a soft tissue lymphoma in an HIV-1-positive patient. A significant percentage of soft tissue lymphomas in the general population, even when they are high grade, responds to local therapies including surgical excision and radiation. Thus, confirmation of this diagnosis in HIV-1 disease may be important, because these patients frequently develop fatal opportunistic infections and tolerate chemotherapy poorly, especially in late stages of disease.

Primary anaplastic large cell (KI-1 positive) lymphoma of the mandible as the initial manifestation of acquired immunodeficiency syndrome in a pediatric patient

A case of an anaplastic large-cell lymphoma with Ki-1 immunohistochemical reactivity presenting in the mandible of a 12-year-old girl with Walter Reed Stage 6 human immunodeficiency virus infection is described.

Bioelectrical Impedance Analysis as a Predictor of Survival in Patients with Human Immunodeficiency Virus Infection

In patients with AIDS, short-term survival has been related to body weight, body composition, and serum nutritional parameters, but their prognostic impact at earlier stages of the HIV infection is not known. With an individual follow-up period of 1,000 days, we investigated the prognostic relevance of electrical tissue conductivity [resistance R, reactance Xc, phase angle alpha, extracellular mass (ECM), body cell mass (BCM)] measured by bioelectrical impedance analysis, of the CD4+ cell count, and of serum parameters indicating malnutrition in 75 HIV-infected male patients at Walter Reed stages 3-5. After initial recording, 29 patients (38.7%) died from AIDS during this period. Among 12 parameters estimated with a semiparametric Cox regression model adjusted for therapy (pentamidine, azidothymidine), the phase angle alpha (parameter estimate: -1.043, 95% confidence interval of -0.61 to -1.47; p < or = 0.0001), the ECM/BCM ratio, Xc, BCM, serum cholesterol, number of CD4+ cells, and serum albumin had significant prognostic influence on survival, whereas age, body weight, body mass index, resistance, serum protein, and serum triglycerides did not. In a model with four covariates (CD4+ cells, phase angle, pentamidine, azidothymidine), the prognostic impact of the CD4+ cell count (parameter estimate: -0.549) was lower compared with the phase angle alpha (parameter estimate: -0.799; p < or = 0.0001) and did not gain statistical significance (p = 0.0626). The phase angle alpha was the best single predictive factor for survival among all 12 parameters (comparison of the respective Cox models with the likelihood ratio test).(ABSTRACT TRUNCATED AT 250 WORDS)

Cutaneous thrombosis in human immunodeficiency virus type 1-positive patients and cytomegalovirus viremia

In a group of over 900 patients infected with human immunodeficiency virus type 1 (HIV-1) who underwent follow-up for cutaneous disease, we have seen 17 patients in whom evidence of thrombotic disease developed ( Table ). The majority of patients have presented with peripheral thrombophlebitis or strokes as their presenting thrombotic incident; however, we have seen two patients whose first sign of a hypercoagulable state was digital infarcts (Table) ( Figure 1 ). The case reports of the two patients with cutaneous infarction illustrate this serious complication of HIV-1 infection. Report of Cases.Case 1. A 28-year-old HIV-1-positive Walter Reed stage 6 (last CD4 count, 0.09 × 10 9 /L 1 year before) black man presented with acute onset of multiple digital infarcts of both upper extremities (Figure 1). The patient had had periodic low-grade fevers for over 4 months. Multiple blood cultures for bacteria, mycobacteria, and fungi were all negative. Coagulation studies included the following

Cutaneous findings in HIV-1-positive patients: A 42-month prospective study

Cutaneous disease is common in patients infected with HIV-1. The aim of our study was to identify cutaneous markers associated with HIV-1 infection and disease progression as measured by Walter Reed (WR) stage. For 42 months we have observed 912 HIV-1-positive patients in all WR stages. All patients had an extensive past and present medical history taken as well as a complete physical examination, periodic visits, and appropriate diagnostic procedures. Increasing dryness of the skin and seborrheic dermatitis are early findings in a large percentage of patients in WR stage 1; the occurrence and severity of both conditions increase with disease progression. Tinea infections, condylomata acuminata, and verrucae are seen early, but with disease progression, although there is no clear increase in occurrence, these infections become more diffuse and resistant to treatment. Flares in acne vulgaris and folliculitis show a peak occurrence in early and mid-stage disease with a decreased occurrence in late-stage disease. Herpes simplex infections, oral candidiasis, molluscum contagiosum, Staphylococcus aureus infections, and oral hairy leukoplakia show a marked increase in occurrence with advanced disease. Conditions that have a statistically significant association with disease progression as measured by a change in a stage include drug eruptions, seborrheic dermatitis, oral candidiasis, oral hairy leukoplakia, molluscum contagiosum, herpes zoster, and hyperpigmentation (nail, oral, skin). The most frequent and persistent cutaneous disorders were asteatosis (with or without asteatotic eczema) and seborrheic dermatitis. Conditions that were associated with a change in WR stage include drug eruptions, seborrheic dermatitis, oral candidiasis, oral hairy leukoplakia, molluscum contagiosum, herpes zoster, and hyperpigmentation. In addition to Kaposi's sarcoma, patients with HIV-1 disease have an increased potential for the development of both cutaneous epithelial and probably melanocytic malignancies. Epithelial tumors were seen in patients in all stages of disease.

Validation of Post-Acidification p24 Antigen as a Prognostic Marker for HIV Disease Progression

The HIV p24 antigen has demonstrated predictive value for HIV disease progression independent of CD4 count. An acidification procedure has resulted in 40–70 percent p24 antigen positivity across HIV clinical stages, although the predictive value of post-acidification p24 antigen for disease progression has not been fully validated. We hypothesized that there would be significant differences in p24 antigen positivity between matched cohorts of rapid progressors (RP) and slow progressors (SP). Seven hundred sixteen people enrolled in the USAF HIV Natural History Study were stratified according to the slope of CD4 change over time. RP were defined as people in the fastest 15 percent of CD4 decline who also progressed at least 2 Walter Reed (WR) stages. SP were defined as people in the slowest 15 percent of CD4 decline who did not progress more than 1 WR stage. Twenty-five RP were matched to 25 SP based on initial CD4 count (median CD4 RP=750, SP=720), WR stage, age, and duration of follow-up (RP=1086 das, SP=1126 days) with no significant differences between groups. Ten/25(40 percent) of the RP and 2/25(8 percent) of the SP were p24 antigen positive by the acidification assay (p=0.018). Using the standard assay, 6/25(24 percent) of RP and 1/25(4 percent) of SP were p24 antigen positive RP and SP. p24 antigen as detected with the acidification assay was predictive ffor HIV rapid progressors when compared to slow progressors in early stage HIV patients even when controllong for initial CD4 count, age, and duration of follow-up.

Early detection of distal symmetrical polyneuropathy during HIV infection by paired stimulation of sural nerve

In 203 HIV infected patients in various clinical stages neurological examination, paired stimulation (LPSS), nerve conduction velocity (NCVS) and amplitude (AMPS) of the sural nerve, distal latency (DLP), nerve conduction velocity (NCVP), amplitude (AMPP) and F waves of the peroneal nerve were recorded. Neurological examination revealed symptoms and clinical of polyneuropathy in 67 (33%) (WR 1–6) of the patients. LPSS after paired stimulation was abnormal in 25.5%, NCVS in 14.2%, AMPS in 9.8%, NCVP in 11.8%, DLP in 11.2%, AMPP in 5.9% and FWP in 14.6%. Our findings indicate a high incidence of peripheral nerve system involvement during HIV infection. In 11.5% of all patients only LPSS proved polyneuropathy. Neurophysiological results from HIV infected patients with symptoms and clinical signs of polyneuropathy were statistically significantly different from HIV infected patients without symptoms and clinical signs of polyneuropathy. The delay of LPSS represents the most sensitive neurophysiological indicator of polyneuropathy during HIV infection and announces the onset of peripheral nerve disease even in early stages of infection, according to Walter Reed staging classification 1 and 2 (approx. 20%).

Staphylococcus aureus carriage and HIV-1 disease: association with increased mucocutaneous infections as well as deep soft-tissue infections and sepsis

Cutaneous colonization by<i>Staphylococcus aureus</i>has been found to be significantly increased in patients infected with the human immunodeficiency virus (HIV-1). The incidence of<i>S aureu</i>s carriage was shown to stay relatively constant with disease progression, Walter Reed (WR) stage 1 through 6.¹ <i>Staphylococcus aureus</i>sepsis, deep soft-tissue infections, and pneumonia have all been frequently reported in patients with advancing HIV-1 disease, and<i>S aureus</i>infections, often undiagnosed premortem, were seen in greater than 50% of the patients from one autopsy study.²Trauma, intravenous catheters (peripheral and central lines), intravenous drug abuse, and lymphedema are considered to be risk factors. As part of a study on the natural history of cutaneous disease in HIV-1 disease, patients were followed up prospectively to determine if there was a correlation with infection by<i>S aureus</i>and the stage of disease. <h3>Patients and Methods.</h3> A total of 646 HIV-1—positive patients were

Legionnaires' Disease in Human Immunodeficiency Virus-Infected Patients: Eight Cases and Review

Despite being a well-known pathogen for immunocompromised patients, Legionella pneumophila has infrequently been described in persons with infection due to human immunodeficiency virus (HIV). Since 1986, we have identified eight cases of legionella pneumonia among seven HIV-infected persons enrolled in the HIV Natural History Study of the U.S. Air Force. The median CD4+ T cell count for these patients was 83/mm3; 50% of the cases occurred in persons for whom AIDS was previously diagnosed, and five of the cases were nosocomial. Six of the patients had coexistent pulmonary infections. None of the cases occurred among persons receiving prophylactic therapy with trimethoprim-sulfamethoxazole. Therapeutically, all patients appeared to respond well to standard antilegionella therapy or high doses of trimethoprim-sulfamethoxazole. Overall, these seven patients represent 1.7% of the patients with late-stage HIV infection (Walter Reed stage 5 or 6) in this cohort. L. pneumophila, although remaining an uncommon pathogen for HIV-infected patients, may produce serious disease in this population. HIV-infected persons should be considered at risk for legionnaires' disease, particularly in institutions where potable water supplies have become contaminated.

Hypereosinophilia Secondary to Immunodysregulation in Patients With HIV-1 Disease

We have seen eight patients positive for human immunodeficiency virus type 1 (HIV-1) with marked peripheral eosinophilia, lasting 4 months or longer, in which no causal agent was identified. In addition, we have seen a progressive increase in peripheral eosinophilia and a similar increase in tissue eosinophilia in our patient population that is associated with increasing Walter Reed stage (<b>Figure 1</b>).¹ <h3>Materials and Methods.</h3> All patients with markedly elevated eosinophil levels (over 20% of the total white blood cell count) (<b>Table</b>) had regular complete blood cell counts obtained over a 30-month period. Urinalysis, liver and renal function tests, and multiple serologic tests for infectious organisms were administered for all patients. In some cases, tests for connective tissue disease, chest roentgenograms, electrocardiograms, multiple stool samples, bone marrow aspirates, and biopsy specimens were performed or obtained. A battery of special stains (periodic acid-Schiff, Gomori methenamine silver, Brown and Hoppes, Ziehl-Neelsen, and

Absence of Seroconversion of HIV-1 Antibody in Seroreactive Individuals-Reply

In Reply. —We concur with Tenenbaum et al that our results do not, and cannot, absolutely rule out the possibility that seroreversion of HIV antibody status may occur. Our conclusion is therefore that if seroreversion occurs, it is exceedingly rare, and certainly far less common than errors that may occur in the testing process. Tenenbaum et al question how frequently HIV-reactive adults are tested in the military health care system. Our standard policy is for patients to be restaged, using the Walter Reed Staging Classification, every 6 months.1Generally, antibody tests are repeated in the evaluation of early-stage patients, but less commonly in patients who have progressed to the acquired immunodeficiency syndrome (AIDS). Our potential seroreverters did not have a greater number of antibody tests because they demonstrated significant progression of disease, with four dying from complications of AIDS. Our most recent potential seroreverter, patient 6, had five antibody

Frequency of cells positive for HIV-1 p24 antigen assessed by flow cytometry

Markers of HIV disease progression such as soluble p24 antigen detection and CD4 lymphocyte depletion are most useful in the later stages of HIV disease and are relatively insensitive as therapeutic monitors. Flow cytometric detection of HIV-1 replication in CD4 lymphocytes was evaluated for use as a marker in predicting disease progression earlier in the course of HIV disease. To determine whether the number of HIV-1-infected CD4 cells, as measured by p24 antigen detection, can be correlated with disease progression, we used flow cytometry to detect intracellular HIV-1 p24 in CD4 lymphocytes from HIV-1-seropositive subjects at all stages of HIV disease. Mononuclear cells from HIV-1-seropositive subjects and uninfected control subjects were permeabilized and stained with anti-HIV-1 p24 monoclonal antibodies. The cells were then stained with a fluorescein isothiocyanate-conjugated goat antimurine immunoglobulin G followed by a phycoerythrin-conjugated monoclonal anti-CD4 antibody. The percentage of p24-positive CD4 lymphocytes was compared with absolute CD4 counts, soluble p24 detection and Walter Reed classification. CD4 lymphocyte absolute counts and the percentage of CD4 lymphocytes declined as the Walter Reed classification indicated disease progression. The mean percentage of p24 antigen-positive CD4 lymphocytes increased with disease progression. Only 30% of Walter Reed stage 6 subjects were soluble p24 antigen-positive, whereas 68% were cellular p24 antigen-positive. The percentage of p24 antigen-positive CD4 lymphocytes increased as HIV disease progressed. Flow cytometric quantitation of p24 antigen-positive CD4 cells is a useful method of monitoring in vivo HIV replication and disease progression.

Delayed-Type Hypersensitivity Skin Testing Predicts Progression to AIDS in HIV-infected Patients

To evaluate the prognostic significance of cutaneous delayed-type hypersensitivity (DTH) skin testing in persons infected with HIV. Cohort study. United States Air Force (USAF) Medical Center. Consecutive sample of 889 HIV-infected USAF personnel or dependents undergoing their first staging evaluation from 1985 through August 1990 in the USAF HIV Natural History Study. All patients were evaluated with DTH skin testing including purified protein derivative and four control skin test antigens: mumps, candida, tetanus toxoid, and trichophyton. In addition, all patients underwent CD4+ T-cell surface marker determinations. The relation between DTH skin test response at first evaluation and progression to Walter Reed stage 6 (presence of an AIDS-defining opportunistic infection) was evaluated using Kaplan-Meier survival analysis. Patients with more than 400 CD4+ T cells/mm3 are more likely than those having fewer than 400 CD4+ T cells per mm3 to respond to at least one (94% compared with 67%, P < 0.001) or at least two (86% compared with 45%, P < 0.001) DTH skin tests. Mean CD4 counts are lower for anergic compared with nonanergic patients and for patients responding to a single control skin test compared with those responding to two or more skin tests (P < 0.05). The DTH skin test response at first evaluation was also found to predict progression to AIDS; the relative risk at 5 years of follow-up was 2.5 (95% CI, 1.2 to 5.2) for anergy compared with a single positive skin test and 3.0 (CI, 1.4 to 6.2) for a single compared with two or more skin test responses. The DTH skin test response at first evaluation was a predictor of progression (P < 0.001) when controlling for initial CD4 count and Walter Reed stage in a Cox proportional hazards regression analysis. The DTH skin test response, a functional measure of cellular immunity, is an independent predictor of progression to AIDS in persons with HIV.

Clinical features of inflammatory dermatoses in human immunodeficiency virus type 1 disease and their correlation with Walter Reed stage

As part of a military study of the natural history of human immunodeficiency virus type 1 (HIV-1) disease, all patients entered in the study were examined for cutaneous changes associated with HIV-1 infection. Our purpose was to characterize and record the types of inflammatory dermatoses in a large number of HIV-1-infected patients to determine whether there was a correlation with the stage of disease. The clinical findings in each case were compared with the results of cultures and biopsy specimens and correlated with Walter Reed stage. Most of the inflammatory dermatoses were maculopapular eruptions often with prominent follicular involvement, and in some there was a lichenoid component. With increasing Walter Reed stage, many eruptions become papulosquamous, some with psoriasiform scale and some with a hypertrophic lichenoid appearance. Although most of the inflammatory eruptions were nonspecific clinically, most cases showed features resembling those in graft-versus-host disease.

Histopathologic and immunohistochemical findings associated with inflammatory dermatoses in human immunodeficiency virus type 1 disease and their correlation with Walter Reed stage

Cutaneous lesions are common in patients with human immunodeficiency virus type 1 (HIV-1) infection. In many cases they are nonspecific inflammatory dermatoses. Our goal was to determine whether features of these inflammatory dermatoses were characteristic of HIV-1 infection and whether the changes correlated with the stage of disease. Biopsy specimens of inflammatory dermatoses from 176 HIV-1-infected patients in all Walter Reed stages were reviewed and the changes were compared with each WR stage. The changes found were nonspecific but were suggestive of features described in graft-versus-host disease and became more prominent in late-stage disease. A correlation was found between the changes and the stage of disease, and the findings add support to prior reports that at least some of the changes in HIV-1 infection may be autoimmune in origin.