Erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in sera of patients with HIV infection

Levels of erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured in sera of 28 HIV-seronegative heterosexual non-intravenous drug using controls, 57 HIV-seronegative and 42 HIV-seropositive asymptomatic intravenous drug users (IVDU) and 36 HIV-seronegative and 36 HIV-seropositive homosexuals, 79 patients with lymphadenopathy, 11 patients with AIDS-related complex (ARC) and 110 patients with AIDS. Serum erythropoietin levels were significantly elevated in HIV-seronegative and HIV-seropositive asymptomatic homosexuals and in patients with lymphadenopathy, ARC and AIDS when compared to controls. However, in asymptomatic HIV-seronegative and HIV-seropositive IVDU the erythropoietin levels were not significantly different from the control group. GM-CSF mean levels in both HIV-seronegative and HIV-seropositive IVDU were elevated compared with the level in controls, whereas the mean levels in both the HIV-seronegative and HIV-seropositive homosexuals were decreased relative to the level in controls. GM-CSF levels in patients with lymphadenopathy, ARC and AIDS were not significantly different from the control value. It appears that male homosexuals have mildly increased erythropoietin levels which rise substantially with the development of ARC and AIDS, which suggests that AIDS patients have intact capacity to produce erythropoietin. In contrast, GM-CSF levels are increased in association with IVDU but are not increased in association with HIV infection including ARC or AIDS. The difference in circulating levels of erythropoietin and GM-CSF may reflect the tissue sources of erythropoietin predominantly in the kidney and GM-CSF being a product of the immunological and inflammatory systems.     

Preferential recruitment of phagocytes into the lung of patients with advanced acquired immunodeficiency syndrome and tuberculosis

Limited data are available on the cellular and immunocytological characteristics of bronchoalveolar lavage (BAL) fluid in individuals infected with the human immunodeficiency virus (HIV) and pulmonary tuberculosis (TB). The immune host response against tuberculosis in early HIV-infection may differ from that in later stages of HIV disease, as is strongly suggested by different clinical and radiographic patterns. We studied the cellular elements in the lungs of 15 HIV-infected patients with advanced immunosuppression and pulmonary tuberculosis (TB/AIDS). The findings were compared with data from four other groups: 1) 15 HIV-seronegative patients with pulmonary TB; 2) 12 HIV-seropositive TB patients without previous AIDS-defining illnesses and with CD4+ >200 cells mm(-3); 3) five AIDS patients without pulmonary lesions; and 4) five healthy controls. BAL fluid and differential cell counts, as well as lymphocyte subsets, were determined. Despite a low CD4/CD8 ratio, the TB/AIDS group had a higher absolute number of CD8+ lymphocytes in the BAL fluid than the other groups. Alveolar macrophages and neutrophils were significantly increased in TB/AIDS patients compared to control groups. The number of eosinophils was increased in TB/HIV--patients but not in TB/AIDS patients. We conclude that tuberculosis in late stage HIV-infected patients has a distinct inflammatory cell profile, suggesting an enhanced compensatory mechanism that amplifies the unspecific inflammatory reaction.     

Differences in laboratory values in HIV infection by sex, race, and risk group.

OBJECTIVES: To determine differences in CD4+ and CD8+ lymphocyte values, beta 2-microglobulin (beta 2M), and HIV p24 antigenemia by sex and race among HIV-seropositive and HIV-seronegative injecting drug users (IDU), and to compare these values with those in homosexual men of equivalent status. DESIGN: Baseline values from a cohort of 206 HIV-seropositive and 173 HIV-seronegative IDU were compared with values from a cohort of 288 HIV-seropositive homosexual men and 176 HIV-seronegative controls, who were prospectively followed at 6-month intervals, to examine differences in laboratory values in HIV-infected individuals by sex, race, and risk group. METHODS: Among HIV-seropositives, we compared white and black IDU only (n = 167), and white male IDU (n = 38) with white homosexual men (n = 256). Laboratory values from the cohort of homosexual men at 24, 36 and 48 months of follow-up were compared with IDU values. RESULTS: HIV-infected female IDU had significantly higher CD4+ lymphocyte counts (P < 0.03) and percentages of CD4+ lymphocytes (P < 0.004) than male IDU, resulting in higher CD4:CD8 ratios (P < 0.002). White IDU had significantly higher serum beta 2M levels than black IDU (P < 0.02). Black female IDU were much less likely to be HIV p24-antigenemic (1%) than all other groups (P < 0.005). Compared with homosexual men, male IDU had significantly elevated beta 2M levels (0.58 mg/l higher). When controlled for CD4+ lymphocyte values as a surrogate for length of time HIV-infected, beta 2M and HIV p24 antigenemia differences persisted. CONCLUSIONS: These differences should be considered when HIV p24 antigen, CD4+ lymphocyte counts and beta 2M levels are used as surrogate markers in clinical trials and management of HIV disease.     

Zidovudine treatment of AIDS and ARC in Denmark 1987

In 1987, a total of 138 Danish patients (94 AIDS and 44 ARC) received treatment with zidovudine, a total observation period of 572 treatment months. 15 AIDS and 1 ARC patient died after a median of 70 days (range 2-295). In the ARC group 4 patients developed AIDS (3 Pneumocystis carinii pneumonia, 1 Kaposi's sarcoma). Among the AIDS patients 38 new opportunistic infections were reported. 24 of these opportunistic infections occurred within 6 weeks after treatment initiation. 79 patients were observed for more than 3 months, 25 of these had their daily dose zidovudine reduced, usually from 1,200 mg to 600 mg, 9 others were temporarily off drug. HIV antigen was analyzed in serum samples from 93 patients. Of these, 28 (52%) of 54 initially HIV antigen-positive became antigen-negative, 7 (18%) of 39 initially HIV antigen-negative became antigen-positive within the first 8 weeks of zidovudine treatment. In 57 patients the total count of CD4+ cells were evaluated. A significant increase in the number of CD4+ cells was observed during treatment. In nearly all patients an increase in MCV and a decrease in neutrophil count was observed. 44 of the patients received a total of 307 blood transfusions on 94 occasions and 19 (14%) patients required multiple transfusions. The mortality among the AIDS patients was significantly lower compared to historical controls. In our experience zidovudine treatment is reasonably well tolerated and the side effects are manageable.     

Improvement of HIV-specific immunity in HIV-infected twins treated with highly active antiretroviral therapy, interleukin 2, and syngeneic adoptively transferred cells.

Five HIV-seropositive twins were treated with HAART and given cycles of treatment consisting of adoptive cellular therapy from their HIV-seronegative identical twins followed by a 5-day course of intravenous IL-2. Changes in absolute and percent CD4(+) and CD8(+) cell count were monitored and compared with changes in these parameters occurring in seven age-, sex-, and disease stage-matched HIV-infected patients treated with HAART alone. Increase in the magnitude and breadth of HIV-specific immune responses was monitored in three twin subjects who received multiple treatment cycles. Absolute and percent CD4(+) cell counts rose dramatically and to significantly higher levels in the recipient twins than in control subjects treated with HAART only. The subjects who received multiple cycles of treatment developed new and increased levels of HIV-specific activated and memory cytotoxic T lymphocyte responses, and interferon gamma-secreting effector cells. Treatment consisting of HAART, adoptive cellular therapy, and IL-2 was superior to treatment with HAART alone for improving absolute and percent CD4(+) cell counts and inducing new, or increasing the magnitude of, HIV-specific immune responses in HIV infected patients.     

Striking inverse association of IgG-anti-Fab gamma antibodies and CD4 cell counts in patients with acquired immunodeficiency syndrome (AIDS)/AIDS-related complex.

The contribution of autoimmune phenomena to the pathogenesis of acquired immunodeficiency syndrome (AIDS) is poorly understood. We investigated the relationship between IgG-anti-Fab gamma autoantibodies and the main immunologic feature of AIDS, the decrease of CD4+ helper lymphocytes. Sera of 33 human immunodeficiency virus (HIV) infected (HIV+) hemophilia patients with AIDS/AIDS-related complex (ARC), 57 HIV+ patients without AIDS/ARC, 23 HIV-negative (HIV-) patients, and 76 healthy controls were tested for antibody activity against the Fab region of IgG. Patients with AIDS/ARC had significantly higher IgG-anti-Fab gamma activity than HIV+ patients without AIDS/ARC, HIV- patients, or controls (P less than .0001). A striking inverse association was found between IgG-anti-Fab gamma and CD4+ cell counts (r = -.69; P less than 10(-6)). Sequential testing in 16 AIDS/ARC patients showed that an increase in the IgG-anti-Fab gamma activity was invariably accompanied by a decrease in the CD4+ cell count. IgG-anti-Fab gamma antibodies may play an important role in the immunopathogenesis of AIDS.     

A longitudinal study of immunological status in Chinese haemophiliacs: importance of the heat viral inactivation of factor concentrates. I. Immunological associations with the consumption of factor concentrates

Summary . Twenty-four of 117 cases of haemophilia A (20.5%) and none of 18 cases of haemophilia B reported in this study had an antibody to the human immuno-deficiency virus (HIV). Both groups of patients showed similar immunological alterations. HIV-seropositive haemophilia A patients had an increased CD8 cell count and a similarly decreased CD4/CD8 ratio as compared to HIV-seronegative haemophilia A patients. Multiple regression analysis for the association of CD4/CD8 ratio with HIV infection status and dosage of plasma products in haemophilia A and B patients, respectively, revealed that there was a significant negative association of ln(CD4/CD8) with dosage of factor VlII concentrates (P = 0.0435) and factor IX concentrates (P = O.O028), respectively. N o association occurred between CD4/CD8 ratio and HIV infection as well as dosage of other plasma products. These data indicate that the immunological abnormalities of our haemophilia A and B patients in their early years were primarily caused by various viral infections and/or a suppressive effect of allogeneic protein through infusion of factor concentrates and not caused simply by HIV infection.     

Reduction of IFN-gamma and IL-2 production by peripheral lymphocytes of HIV-exposed seronegative subjects.

OBJECTIVES: In order to evaluate the role played by cytokine profile as a co-factor involved in the resistance to HIV infection in couples serodiscordant for HIV, we studied HIV-seronegative subjects with multiple unprotected sexual exposures. DESIGN AND METHODS: Twenty-one HIV-exposed seronegative subjects (HEPS), their 21 HIV-seropositive partners and 10 HIV-seronegative unexposed individuals were studied for T helper (Th) types 1-2 cell pattern and CCR5 receptor. RESULTS: Twelve out of 21 HIV-seropositive partners of HEPS showed a CD4 cell count below 200 lymphocytes/microl. HIV strains were isolated from peripheral blood mononuclear cells (PBMC) in 17 patients (81%): seven subjects with syncytium-inducing strains and 10 with non-syncytium-inducing isolates. Low Th1 cytokine production and high levels of IL-4 were detected in HIV-seropositive subjects. A significant reduction of IL-2 and IFN-gamma expression in the CD4 and CD8 cells of HEPS was found compared with HIV-seronegative unexposed individuals. Similar levels of low IL-4 were present in both HEPS and controls. The partial deletion of a single allele (wild type/delta32) of CCR5 was found in only one HEPS. CONCLUSION: The downregulated Th1 profile we observed in HEPS could be related to a cellular anergy state with a protective role in the transmission rate of HIV. Low levels of IL-2 and IFN-gamma could be involved in a low-grade activation state of CD4 lymphocytes. A decrease of IFN-gamma levels could render macrophage cells incapable of antigen presentation, thus resulting in a reduction of the cell-to-cell spread of infection.     

Enhanced antibody responses to Epstein-Barr virus in HIV-infected homosexual men

We investigated the association between human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) infections in 593 homosexual men. The status of EBV infection in this group was evaluated based on serological evidence of EBV-specific antibody responses. The geometric mean titers (GMT) of antibody to EBV capsid antigen (EBV-VCA) (1:154) and EBV early antigen (EA) (1:16) in 141 HIV-seropositive men were significantly higher than respective titers in 452 HIV seronegative men (1:95 and 1:12). Antibody titers to EBV were higher in HIV-infected men with lymphadenopathy than in asymptomatic HIV-seropositive men. However, these correlation were less evident in patients with AIDS-related complex. Elevated antibody titers to EBV were found to be independent of levels of total serum IgG. Cytomegalovirus (CMV) antibody titers were also found to be significantly increased among HIV-seropositive men, independent of total IgG. Antibody titers to EBV were not correlated with those to CMV in either HIV-seronegative or HIV-seropositive men. Subjects without evidence of HIV infection, but who had high antibody titers to EBV-VCA and EBV-EA, had elevated mean numbers of CD3+, CD4+, and CD8+ cells, and lower levels of CD4+/CD8+ cell ratios compared to subjects with low EBV-antibody titers. This study suggests that the elevated levels of circulating antibodies against EBV in homosexual men are associated with loss of control of latent EBV due to HIV infection.     

HIV prevalence, immunosuppression, and drug resistance in patients with tuberculosis in an area endemic for AIDS.

From October 1987 to June 1988, we attempted to determine the prevalence of HIV infection among patients hospitalized with tuberculosis and the extent of immunosuppression among those tuberculosis patients infected with HIV. Of 178 consecutive patients, 18-65 years of age, who were hospitalized with newly diagnosed, previously untreated tuberculosis, 46% (82 out of 178) had clinical or serological evidence of HIV infection, 30% (54 out of 178) were HIV-seronegative, and 24% (42 out of 178) could not be assessed for the presence of HIV infection. Among the HIV-seropositive patients without an AIDS-defining diagnosis by non-tuberculous criteria, the median CD4 lymphocyte (CD4) count was 133 x 10(6) cells/l (range: 11-677 x 10(6]; among the HIV-seronegative patients, the median CD4 count was 613 x 10(6) cells/l (range: 238-1614 x 10(6); P less than 0.001). Among the HIV-seropositive patients, those with disseminated tuberculosis (median CD4 = 79 x 10(6) cells/l) and those with pulmonary tuberculosis who had radiographic evidence of mediastinal or hilar adenopathy (median CD4 = 45 x 10(6) cells/l) had the most severe CD4 depletion, whereas those with localized extrapulmonary tuberculosis (median CD4 = 242 x 10(6) cells/l) and those with pulmonary tuberculosis without adenopathy (median CD4 = 299 x 10(6) cells/l) were less severely immunosuppressed. Of the 178 patients, 6% (11 out of 178) were infected with strains of Mycobacterium tuberculosis resistant to both isoniazid and rifampin.     

Human immunodeficiency virus infection in tuberculosis patients

Human immunodeficiency virus (HIV) serology was performed in non-Asian-born patients 18-65 years old with newly diagnosed tuberculosis at a county tuberculosis clinic, and demographic and clinical features of HIV-seropositive and HIV-seronegative patients were compared. Sixty of 128 eligible patients agreed to participate, of whom 17 (28%) were seropositive. Risk of HIV was associated with homosexual contact, intravenous drug use, or both; however, 4 (24%) of the 17 seropositives denied risk behaviors. Significantly more blacks (48%) than whites (10%) or Latinos (20%) were HIV-seropositive (P less than .01). Site of disease, tuberculin reactivity, response to therapy, drug toxicity, and relapse did not differ significantly between groups. HIV-seropositive patients had significantly lower median CD4+ cell counts (326/mm3, range 23-742/mm3, vs. 929/mm3, range 145-2962/mm3, P less than .0005) and median CD4+:CD8+ ratios (0.50, range 0.14-1.07 vs. 1.54, range 0.35-4.36, P less than .0001). HIV infection is associated with clinically typical tuberculosis and HIV screening of tuberculosis patients is recommended in areas where HIV is endemic.     

Mortality in HIV-seropositive versus -seronegative persons in the era of highly active antiretroviral therapy: implications for when to initiate therapy

BACKGROUND: The optimal time to initiate highly active antiretroviral therapy (HAART) remains unclear. METHODS: Five hundred eighty-three human immunodeficiency virus (HIV)-seropositive and 920 HIV-seronegative injection drug users (IDUs) were followed from 1997 to 2000. HIV-seropositive participants were categorized according to receipt of HAART (either initiated or switched to HAART) and initial CD4 cell count. Survival analysis that included delayed-entry and Cox proportional-hazards models was used to evaluate the effect of HAART, with adjustments for factors associated with access to HAART. RESULTS: Compared with HIV-seronegative participants, overall survival was similar in HIV-seropositive participants who received HAART at >350 CD4 cells/microL, but mortality was higher both in participants with >350 CD4 cells/microL who did not receive HAART and in participants who received HAART at 200-350 CD4 cells/microL (mortality rates, 19.9, 24.0, 43.0, and 50.5/1000 person-years, respectively). In proportional-hazards models in which HIV-seronegative participants were the reference group and in which age, sex, race, frequency of drug use, substance-abuse treatment, and health-care utilization were adjusted for, hazard ratios were 1.01 (95% confidence interval [CI], 0.41-2.45), 2.28 (95% CI, 1.38-3.78), and 2.09 (95% CI, 1.07-4.10) for the latter 3 groups. In HIV-seropositive participants, HAART significantly improved survival when initiated at CD4 cell counts < 200 cells/microL. CONCLUSIONS: Survival of HIV-seropositive participants receiving HAART approximated that of HIV-seronegative participants only when therapy was given at CD4 cell counts > 350 cells/microL. These data, restricted to IDUs, suggest initiating or switching to HAART at higher CD4 cell levels than are currently recommended.     

The chest roentgenogram in pulmonary tuberculosis patients seropositive for human immunodeficiency virus type 1

To determine the impact that co-infection with HIV has on the radiographic presentation of pulmonary tuberculosis, we examined the chest roentgenograms obtained before treatment in 225 HIV-tested adult Haitians with bacillary (smear or culture or both) positive pulmonary tuberculosis. There were 67 HIV-seropositive and 158 HIV-seronegative patients. Intrathoracic adenopathy alone was more common and parenchymal infiltrates less common in HIV-seropositive patients (p less than 0.05). Although a parenchymal infiltrate was less likely to be cavitating in the HIV-seropositive group (p less than 0.05) when cavitary parenchymal disease was present, HIV seropositivity did not affect the number of cavities (single or multiple) or the size of the largest cavity. Patients with AIDS were significantly more likely to have a chest radiographic pattern consistent with primary tuberculosis (80 percent) than HIV-seropositive patients without AIDS (30 percent), and the latter were significantly more likely to have such a pattern than HIV-seronegative patients (11 percent) (p less than 0.05). The HIV-seropositive patients were equally infectious, regardless of the pattern of disease (primary vs postprimary). Even though pulmonary tuberculosis in an HIV-seropositive adult probably results from reactivation of dormant foci or reinfection, the pattern on the chest roentgenogram often suggests primary disease, especially if the patient has AIDS.     

Detection of opportunistic and non-opportunistic intestinal parasites and liver flukes in HIV-positive and HIV-negative subjects

We assessed the frequency and distribution of infection with opportunistic and non-opportunistic intestinal parasites and the liver fluke, Opisthorchis viverrini, in HIV-seropositive and HIV-seronegative subjects. Age- and sex-matched HIV-seropositive (n = 78) and HIV-seronegative patients (n = 78) from two hospitals in Khon Kaen Province, Thailand, participated in this study from November 1998 to August 2000. These subjects were divided according to the presence of diarrhea and CD4 counts. A single stool sample was obtained and analyzed by using specific techniques. Opisthorchis viverrini, was the most common parasite (19.2%) in each group. The prevalence rates of Cryptosporidium spp (11.5%) and Strongyloides stercoralis (17.9%) in the HIV-seropositive group were significantly (p < 0.05) higher than those in the HIV-seronegative group (1.0% for Cryptosporidium spp and 7.7% for S. stercoralis infections). The prevalences of these two parasites were 28% for Cryptosporidium spp and 20% for S. stercoralis in HIV-seropositives with diarrhea and CD4 counts lower than 100 cells/mm3, and were higher compared with patients without diarrhea or with high CD4 counts. These results suggest that infection with these parasites increases during HIV infection. The epidemiological distribution of Cryptosporidium and S. stercoralis may have implications for AIDS-related diseases.     

Class-specific antibody response to pneumococcal capsular polysaccharides in men infected with human immunodeficiency virus type 1

We characterized the effect of infection with human immunodeficiency virus type 1 (HIV) on levels of total immunoglobulins and pneumococcal vaccine-specific immunoglobulins in 28 heterosexual and 25 homosexual men seronegative for HIV; 27 asymptomatic, seropositive homosexual men; and 21 patients with AIDS. Total serum IgG levels were increased in both HIV-seropositive groups compared with the HIV-seronegative men (P less than .001). Total IgM levels, however, were elevated only in the asymptomatic, HIV-seropositive men (P less than .08); total IgA levels were elevated only in the patients with AIDS (P less than .05). Vaccine-specific serum IgG, IgM, and IgA significantly increased over baseline three and six weeks after immunization in all groups (P less than .05). Responses to vaccine among the HIV-seronegative groups were similar but were greater for all antibody classes than were responses among the HIV-seropositive groups (P less than .05).     

Natural history of advanced HIV disease in patients treated with zidovudine. The Zidovudine Epidemiology Study Group.

OBJECTIVE: To describe the natural history of advanced HIV disease in patients treated with zidovudine. DESIGN: Longitudinal, observational study. SETTING: Twelve academic and community-based sites. PATIENTS, PARTICIPANTS: Eight hundred and sixty-three patients with AIDS or AIDS-related complex (ARC) with a CD4+ lymphocyte count less than 250 x 10(6)/l, who first received zidovudine between 15 April 1987 and 14 April 1988. MAIN OUTCOME MEASURES: Survival, progression to AIDS and first development of specific opportunistic illness. RESULTS: Median survival after initiation of zidovudine therapy ranged from greater than 900 days in patients with a baseline CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 560 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/1. Other factors associated significantly with poorer survival were diagnosis of AIDS (versus ARC), baseline age greater than or equal to 40 years, hematocrit less than 35%, and diminished functional status. In patients with ARC at enrollment, median time of progression to AIDS ranged from 810 days in patients with a CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 310 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/l. Rates of development of specific opportunistic infections or neoplasms and HIV encephalopathy were determined for different baseline CD4+ lymphocyte count ranges. Myelosuppression was significantly more common in patients with CD4+ lymphocyte counts greater than or equal to 100 x 10(6)/l. Sixty-five per cent of patients with a CD4+ lymphocyte count greater than or equal to 100 x 10(6)/l and 51% with a CD4+ lymphocyte count less than 100 x 10(6)/l continued to receive zidovudine 2 years after starting therapy. CONCLUSIONS: We describe the natural history of a cohort of patients treated with zidovudine for advanced HIV disease. These CD4+ lymphocyte count-stratified estimates of disease progression should provide prognostic information useful in the clinical management of advanced disease and the design of future studies.     

HIV infection in patients with tuberculosis in Kinshasa, Zaire

To better define the interrelationship of infection with human immunodeficiency virus (HIV) and tuberculosis (TB), we conducted three HIV serosurveys of inpatients and outpatients with confirmed or suspected TB in Kinshasa, Zaire. HIV seroprevalence in hospitalized sanatorium patients did not change significantly in serosurveys conducted in 1985 and 1987 (92/231 [40%] versus 85/234 [36%]). These proportions were significantly higher than the 17% HIV seroprevalence observed in a 1987 serosurvey of 509 consecutive patients with an initial diagnosis of pulmonary TB seen at an outpatient TB diagnostic center in Kinshasa (p less than 0.001). HIV seroprevalence was higher in sanatorium patients with extrapulmonary TB (22/46 [48%]) and suspected pulmonary TB (60/132 [45%]) than in patients with bacteriologically confirmed pulmonary TB (94/287 [33%]) (p less than 0.02). Mycobacterium sputum isolation rates were similar in HIV-seropositive (28/34 [82%]) and HIV-seronegative patients (135/159 [85%]). All isolates were Mycobacterium tuberculosis. Eighteen (21%) of 84 HIV-seropositive sanatorium patients in 1987, who were followed for two months after admission, had died, compared with 11 (9%) of 128 HIV-seronegative patients (p less than 0.01). However, clearance rates of acid-fast bacilli from sputum after standard therapy were equally good in HIV-seropositive and HIV-seronegative survivors. With the growing AIDS problem, the serious TB burden in sub-Saharan Africa may become even more onerous and may critically overload the stressed African health care systems.     

Cellular and humoral immunity in various cohorts of male homosexuals in relation to infection with human immunodeficiency virus

The relationship between infection with human immunodeficiency virus (HIV) and various immunological parameters was studied in: (a) healthy controls; (b) homosexual individuals from the AIDS risk group without anti-HIV antibodies; (c) idem, but with anti-HIV antibodies; (d) patients with persistent generalized lymphadenopathy (PGL); (e) patients with AIDS-related syndrome; (f) patients with AIDS and opportunistic infections. In each group, consisting of 15-20 individuals, the following parameters were studied: absolute numbers of CD4+ and CD8+ cells; ratio CD4+/CD8+; cellular immune responses as measured in vivo by delayed-type hypersensitivity (DTH) and in vitro; and antibody response in vivo after immunization with a low dose of keyhole limpet haemocyanin. Healthy HIV antibody-positive individuals and patients with persistent generalized lymphadenopathy already showed a decreased CD4+/CD8+ ratio, mainly due to an increase in the number of CD8+ cells. The ratio in the AIDS-related syndrome and AIDS groups was even lower, but this was now due to low numbers of CD4+ cells while the number of CD8+ cells was normal. The lymphocyte proliferative response was low in the HIV antibody-positive group, normal in the group with persistent generalized lymphadenopathy and profoundly decreased in the AIDS-related syndrome and AIDS groups. DTH was enhanced in the PGL group and diminished in both ARC and AIDS. Compared to healthy controls, the antibody response upon immunization with a low dose of keyhole limpet haemocyanin was depressed (although not absent) in all groups studied, even in HIV antibody-negative homosexuals. In the HIV antibody-positive group, the severity of the impairment of the various parameters of immunocompetence was not related to the presence of HIV antigenaemia.     

Bacteremic pneumococcal pneumonia in HIV-seropositive and HIV-seronegative adults.

STUDY OBJECTIVES: To compare the demographic, clinical, laboratory, and microbiological data, and the hospital course and outcome of HIV-seropositive and HIV-seronegative adults with bacteremic pneumococcal pneumonia. DESIGN: Retrospective observation study conducted over a 2-year period. SETTING: Academic teaching hospital attached to the University of the Witwatersrand, Johannesburg, South Africa. PATIENTS: Consecutive patients with bacteremic pneumococcal pneumonia were identified on the basis of positive blood culture results. INTERVENTIONS: All available demographic, clinical, routine laboratory, radiographic, and microbiological data were recorded retrospectively for each of the patients, and the combined data for the HIV-seropositive patients were compared with those of the HIV-seronegative patients. MEASUREMENT AND RESULTS: A total of 112 patients (31 HIV-seropositive and 81 HIV-seronegative patients) were entered into the study. The HIV-seropositive patients were significantly younger than the HIV-seronegative patients (32.8 vs 39.6 years old) and had lower admission hemoglobin (11.8 vs 13.4 g/dL), WBC count (10.3 vs 14.3 x 10(9)/L), serum albumin (31 vs 36 g/L), sodium (129 vs 132 mmol/L), and potassium (3.0 vs 3.5 mmol/L), respectively. Although the HIV-seropositive patients appeared to have more multilobar pulmonary consolidation on the chest radiograph than the HIV-seronegative patients (60% vs 34%), this did not quite reach statistical significance. In addition, the HIV-seropositive patients had significantly more infections (48.4% vs 20.8%) with pneumococcal serogroups/serotypes (serogroups 6, 19, 23, and serotype 14) that are found more commonly in children, and they also had more penicillin-resistant isolates (13% vs 2.5%) than the HIV-seronegative patients, respectively. Similarly, it was noted that when these data were analyzed according to gender (irrespective of HIV status), women had significantly more infections than men (47% vs 21%) with serogroups/serotypes that are usually found in children, more penicillin-resistant isolates (15% vs 1%), and more co-trimoxazole-resistant isolates (21% vs 5%), respectively. There were no differences noted in any of the other parameters, including initial APACHE (acute physiology and chronic health evaluation) II score, PaO2/fraction of inspired oxygen ratio, duration of temperature, duration of IV therapy, duration of hospitalization, complications, and outcome, when comparing HIV-seropositive and HIV-seronegative patients. Two patients in each group died. CONCLUSIONS: The clinical features of bacteremic pneumococcal pneumonia are similar in HIV-seropositive and HIV-seronegative patients. Although differences are noted in various laboratory and microbiological parameters, they do not appear to have an impact on outcome.