Predictive markers of AIDS: a follow-up of lymphocyte subsets and HIV serology in a cohort of patients with lymphadenopathy

From 1982 to 1985, 89 HIV-1 seropositive men with persistent generalized lymphadenopathy (PGL) were enrolled into a prospective longitudinal study. In February 1988, after a mean observation time of 45 months, 23 patients had progressed to AIDS with opportunistic infection (AIDS/OI), 4 had developed Kaposi's sarcoma, 47 had developed HIV-related symptoms, 14 still had PGL as only symptom, and 1 was lost to follow-up. Patients with CD4 lymphocytes less than or equal to 0.40 x 10(9)/l as well as patients with HIV antigenaemia and those lacking antibodies to p24 all had a significantly higher risk of developing AIDS/OI within 30 months of observation than other patients. HIV antigen was present in 70% and antibodies to p24 were lacking in 61% of the patients at the time of AIDS/OI diagnosis. All but one (96%) of the AIDS/OI patients had CD4 numbers less than or equal to 0.20 x 10(9)/l at the same time. The estimated median time to AIDS/OI in patients with HIV antigenaemia was 21 months and in patients lacking p24 antibodies 27 months. In patients with CD4 numbers less than or equal to 0.20 and 0.40 x 10(9) cells/l the estimated median time to AIDS/OI was 14 months and longer than 30 months, respectively.     

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.     

Prognostic value of immunologic abnormalities and HIV antigenemia in asymptomatic HIV-infected individuals: proposal of immunologic staging

The prognostic value of various immunologic tests was investigated in 150 HIV-seropositive homosexual men, who were initially without HIV-related symptoms or AIDS and who were followed for a median of 12 months (range 3-28 months). The laboratory investigations included HIV antigen in serum, total lymphocyte count, T-helper (CD4) and T-cytotoxic/suppressor (CD8) counts, and lymphocyte transformation responses to the mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM), and to antigenic extracts from Candida albicans and cytomegalovirus. 24 individuals developed HIV-related symptoms or AIDS (11 cases). All parameters except the CD8 count were of prognostic value, but a multivariate analysis of symptom-free survival showed that HIV antigenemia, a CD4 count less than 0.5 x 10(9)/l, and relative response to PWM below 25% of controls contained all the prognostic information. Individuals abnormal at entry for these 3 variables had a theoretical 36 times as high hazard of developing symptoms within the observation period as had individuals with normal parameters. There was no significant covariation between HIV antigenemia on the one hand and CD4 count and response to PWM on the other. Although, the latter 2 variables covaried, each of them provided independent information, and both were used to classify the degree of the immunodeficiency in 3 stages: Im-0 with normal values, Im-1 with one, and Im-2 with both tests abnormal. Individuals in stage Im-2 had a 10 times increased risk of developing symptoms. The immunologic staging correlated significantly with the clinical grouping (CDC criteria). This staging improved in only 1, but deteriorated in half of 36 individuals observed for at least 18 months. Thus, the staging is likely to prove useful when attempts to arrest the immunodeficiency of HIV-infected individuals has to be monitored.     

HIV-seropositive thrombocytopenia: the action of zidovudine.

The action of zidovudine when administered to individuals with severe HIV thrombocytopenia was investigated. Four individuals with platelets less than 50 x 10(9)/l and CD4 cells greater than 200 x 10(6)/l were treated with 600 mg zidovudine per day for 6 weeks, no drug for 6 weeks, 1200 mg zidovudine per day for 6 weeks, then no drug for 6 weeks. Glycocalicin, a platelet protein which correlates inversely with platelet survival, was assayed before and after treatment. Glycocalicin indices were also measured in four additional individuals with HIV thrombocytopenia. Platelet counts rose 2.5-fold [95% confidence interval (Cl), 2.0-3.0)] for four subjects who received 600 mg zidovudine per day and 4.9-fold (95% Cl, 4.0-5.8) for three subjects receiving 1200 mg zidovudine per day. Platelet counts declined during drug-free intervals. Plasma glycocalicin indices were elevated in all with untreated HIV thrombocytopenia. Indices fell after zidovudine treatment in six of seven individuals, suggesting that zidovudine prolonged platelet survival. Analysis of 170 HIV-seropositive asymptomatic individuals [mean CD4 count 474 x x 10(6)/l, standard deviation (s.d.) 245 x 10(6)/l] revealed that 14 (8%) had less than 125 x 10(9)/l platelets but only 2 (1%) had less than 50 x 10(9)/l platelets. Platelet counts increased spontaneously in eight individuals with mild HIV thrombocytopenia among the 10 for whom repeat counts were available.     

The spectrum of HIV-1-related disease among outpatients in New York City.

OBJECTIVES: To define the spectrum of HIV-1-related disease in New York City (NYC) and to determine how the clinical spectrum of illness differs in various populations. DESIGN AND METHODS: The medical records of the 2983 HIV-infected individuals who had received care through 1989 at four hospital outpatient clinics and two private physicians' offices were reviewed retrospectively. RESULTS: Sixty-one per cent of the study patients and 48% of patients seen in 1989 had AIDS. HIV-infected women were significantly less likely to have AIDS and CD4 lymphocyte counts less than 200 x 10(6)/l than men. For every 100 AIDS patients seen in 1989, there were 88 non-AIDS patients with CD4 counts less than 500 x 10(6)/l, of whom 41 had CD4 counts less than 200 x 10(6)/l; thus, in addition to an estimated 16,425 individuals living with AIDS in NYC, we estimate that there are at least 14,454 HIV-infected individuals without AIDS with CD4 counts less than 500 x 10(6)/l, of whom 6734 have CD4 counts less than 200 x 10(6)/l. Men who have sex with men were significantly more likely to have Kaposi's sarcoma, cytomegalovirus disease and retinitis, cryptosporidiosis and lymphoma, and significantly less likely to have Pneumocystis carinii pneumonia, esophageal candidiasis, extrapulmonary tuberculosis (TB) and bacterial pneumonia than intravenous drug users. Whites were significantly less likely to have pulmonary TB than Hispanics, non-Haitian and Haitian blacks, toxoplasmosis than Hispanics and Haitian blacks, and salmonella septicemia than non-Haitian blacks. The frequencies of most diagnoses did not differ by sex; gynecologic diseases were recorded infrequently in the medical records of women in this study. CONCLUSIONS: These data indicate that there are more than 30,000 HIV-infected adults living in NYC with significant immunosuppression, that an increasing proportion of AIDS cases in NYC will occur among women, and that the spectrum of HIV-related disease varies markedly in different populations.     

Correlation between CD4 cell counts and cellular and plasma viral load in HIV-1-seropositive individuals.

We conducted a study of 152 HIV-1-seropositive individuals in order to evaluate the possible correlations between the isolation of HIV from peripheral blood mononuclear cells or from plasma and CD4 cell counts. HIV was isolated from only 36% of plasma samples, and the isolation rate was closely related to CD4 cell counts, increasing gradually from 0% in subjects with greater than 800 x 10(6)/l CD4 cells to 88% in those with less than 100 x 10(6)/l CD4 cells. In contrast, HIV was isolated from 92% of cell samples (99% in subjects with less than 900 x 10(6)/l CD4 cells, 46% in those with CD4 counts greater than or equal to 900 x 10(6)/l). Since most cell samples were positive, a scoring method was designed to quantify the cellular viral load. The results obtained demonstrated that the cellular viral load was closely related to CD4 counts. We also found that the cellular viral load was higher in subjects with either positive plasma isolation or positive p24 antigenaemia. The measurement of the cellular viral load by this scoring method appears to be useful for the management of HIV-seropositive individuals and for the evaluation of therapeutic trials.     

Lung CD4 lymphocytes predict survival in asymptomatic HIV infection

BACKGROUND: Plasma viral load and blood CD4 counts are accepted indicators of severity of illness in patients with HIV-1. Lung CD4 counts have not been evaluated in asymptomatic HIV-1 patients as indicators of disease severity. OBJECTIVE: To determine if lung lymphocyte counts in asymptomatic subjects with HIV compare with plasma viral loads and blood CD4 counts in predicting survival. DESIGN: Retrospective, cross-sectional analysis. SETTING: Midwestern urban community, December 1996 to August 1998. PARTICIPANTS: HIV-seropositive subjects (n = 95) without AIDS-related pulmonary complications. MEASUREMENTS: Plasma viral load, blood hemoglobin and blood lymphocyte subtypes, lung lymphocyte subtypes from BAL, body mass index, and mortality. RESULTS: Eight of the 95 subjects (8.4%) had died at the 4-year follow-up. Lung CD4 counts were significantly related to mortality by univariable analysis (2.5 x 10(3)/mL vs 0.9 x 10(3)/mL, median values for survivors vs nonsurvivors, respectively, p = 0.010). Modeling using exact methods further showed lung CD4 counts to be a significant predictor of survival after individually adjusting for potential confounders, including plasma viral load and blood CD4 count. CONCLUSIONS: Lung CD4 counts in patients with HIV-1 infection may provide an independent predictor of survival.     

Evaluation of the World Health Organization staging system for HIV infection and disease in Ethiopia: association between clinical stages and laboratory markers

OBJECTIVE: To study the association between the clinical axis of the World Health Organization (WHO) staging system of HIV infection and disease and laboratory markers in HIV-infected Ethiopians. DESIGN: Cross-sectional study. METHODS: Clinical manifestations and stage of HIV-positive individuals participating in a cohort study of HIV infection progression, and of HIV-positive patients hospitalized with suspicion of AIDS, were compared to CD4+ T-cell count and viral load. RESULTS: Of the 86 HIV-positive participants of the cohort study, 53 (62%), 16 (19%), 16 (19%), and one (1.2%) were in stage 1, 2, 3 and 4, respectively. Minor weight loss (n = 15) and pulmonary tuberculosis (n = 9) were the most commonly diagnosed conditions among the 38 (44%) symptomatic HIV-positive individuals. Although 23 (27%) HIV-positive participants had CD4+ T-cell counts less than 200 x 10(6)/l, only one was in clinical stage 4. Among 79 hospitalized HIV-positive patients, 15 (19%) and 64 (81%) were in stage 3 and 4, respectively. The majority (83.5%) had CD4+ T-cell counts < 200 x 10(6)/l. Individuals at stage 3 had lower CD4+ T-cell counts and higher viral loads when seen in hospital as compared to cohort participants (P = 0.06 and 0.008, respectively). When grouping the two study populations, the median CD4+ T-cell count decreased (337, 262, 225, 126, and 78 x 10(6)/l, P< 0.01), and the median viral load increased (4.08, 3.89, 4.47, 5.65, and 5.65 log10 copies/ml, P < 0.01), with increasing clinical stage of HIV infection (1, 2, 3 cohort, 3 hospital, and 4, respectively). Median CD4+ T-cell counts were remarkably low in HIV-negative participants (749 x 10(6)/l), and in HIV-positive participants at stage 1 and 2 (337 and 262 x 10(6)/l, respectively). CONCLUSIONS: There was a good correlation between WHO clinical stages and biological markers. CD4+ T-cell counts were low in Ethiopians, particularly during early stages of HIV-1 infection, and preliminary reference values at different stages of HIV-1 infection were determined. In HIV-infected Ethiopians, lymphocyte counts less than 1,000 x 10(6)/l in non-hospitalized individuals, and less than 2,000 x 10(6)/l in hospitalized patients, had high positive predictive value, but low sensitivity, in identifying subjects with low CD4+ T-cell counts (< 200 x 10(6)/l) who would benefit from chemoprophylaxis of opportunistic infections. The on-going longitudinal study will be useful to confirm the prognostic value of the WHO staging system.     

Splenectomy is safe and effective in human immunodeficiency virus- related immune thrombocytopenia [see comments]

Sixty-eight patients, followed in a prospective cohort study of 185 human immunodeficiency virus (HIV)-infected patients with severe immune thrombocytopenia (platelets < 50 x 10(9)/L), underwent splenectomy, 2 to 41 months (median: 10 months) after immune thrombocytopenic purpura (ITP) was diagnosed. The mean platelet count increased from 18 x 10(9)/L to 223 x 10(9)/L with a persistent increase in 56 (82%). It also led to a significant increase of the mean CD4 cell count from 475 x 10(6)/L to 725 x 10(6)/L within a mean delay of 10 months. In the whole cohort, with a mean follow-up of 63 months (range, 6 to 126), the 5-year estimated rate for progression to acquired immunodeficiency syndrome (AIDS) was 23% (95% confidence interval [CI], 15% to 31%) and the AIDS-free survival was 69% (95% CI, 61% to 77%). To investigate the potential impact of splenectomy, a Cox's multiple regression model was used; as splenectomy was not randomly assigned, it was incorporated as a time-dependent covariate. After adjustment on the CD4 cell count, no statistically significant differences were observed between the splenectomized and the nonsplenectomized patients: AIDS progression rate (P = 0.23), survival (P = 0.64) and AIDS-free survival (P = 0.72) were not influenced by splenectomy. Splenectomy is both effective and safe in the treatment of severe, refractory ITP associated with HIV infection.     

Impact of pulmonary tuberculosis on survival of HIV-infected adults: a prospective epidemiologic study in Uganda

BACKGROUND: Retrospective cohort studies of tuberculosis suggest that active tuberculosis accelerates the progression of HIV infection. The validity of these findings has been questioned because of their retrospective design, diverse study populations, variable compliance with anti-tuberculous therapy and use of anti-retroviral medication. To assess the impact of tuberculosis on survival in HIV infection we performed a prospective study among HIV-infected Ugandan adults with and without tuberculosis. METHODS: In a prospective cohort study, 230 patients with HIV-associated tuberculosis and 442 HIV-infected subjects without tuberculosis were followed for a mean duration of 19 months for survival. To assess changes in viral load over 1 year, 20 pairs of tuberculosis cases and controls were selected and matched according to baseline CD4 lymphocyte count, age, sex and tuberculin skin test status. RESULTS: During the follow-up period, 63 out of of 230 tuberculosis cases (28%) died compared with 85 out of 442 controls (19%), with a crude risk ratio of 1.4 [95% confidence interval (CI), 1.07-1.87]. Most deaths occurred in patients with CD4 lymphocyte counts < 200 x 10(6) cells/l at baseline (n = 99) and occurred with similar frequency in the tuberculosis cases (46%) and the controls (44%). When the CD4 lymphocyte count was > 200 x 10(6)/l, however, the relative risk of death in HIV-associated tuberculosis was 2.1 (95% CI, 1.27-3.62) compared with subjects without tuberculosis. For subjects with a CD4 lymphocyte count > 200 x 10(6)/l, the 1-year survival proportion was slightly lower in the cases than in the controls (0.91 versus 0.96), but by 2 years the survival proportion was significantly lower in the cases than in the controls (0.84 versus 0.91; P < 0.02; log-rank test). For subjects with a CD4 lymphocyte count of 200 x 10(6) cells/l or fewer, the survival proportion at 1 year for the controls was lower than cases (0.59 versus 0.64), but this difference was not statistically significant (P = 0.53; logrank test). After adjusting for age, sex, tuberculin skin test status, CD4 lymphocyte count, and history of HIV-related infections, the overall relative hazard for death associated with tuberculosis was 1.81 (95% CI, 1.24-2.65). In a nested Cox regression model, the relative hazard for death was 3.0 (95% CI, 1.62-5.63) for subjects with CD4 lymphocyte counts > 200 x 10(6)/l and 1.5 (95% CI, 0.99-2.40) for subjects with a CD4 lymphocyte count of 200 x 10(6)/l or fewer. CONCLUSION: The findings from this prospective study indicate that active tuberculosis exerts its greatest effect on survival in the early stages of HIV infection, when there is a reserve capacity of the host immune response. These observations provide a theoretical basis for the treatment of latent tuberculous infection in HIV-infected persons.     

Intensive chemotherapy regimen (LMB86) for St Jude stage IV AIDS-related Burkitt lymphoma/leukemia: a prospective study

Prognosis of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma has improved since the introduction of highly active antiretroviral therapy. Burkitt lymphomas (BLs) still have poor outcome in patients with bone marrow (BM) or central nervous system (CNS) involvement when treated with standard-dose chemotherapy. We have prospectively evaluated the LMB86 regimen in 63 human immunodeficiency virus (HIV)-infected patients with stage IV (BM and/or CNS involvement) BL consecutively recruited between November 1992 and January 2006. At BL diagnosis, the median CD4 cell count was 239 x 10(6)/L (range, 16-1188 x 10(6)/L). BM and CNS involvement were present in 55 (80%) and 48 (76%) patients, respectively. Forty-four patients (70%) achieved complete response. Seven treatment-related deaths occurred and all patients experienced severe BM toxicity. With a median follow-up of 66 months (range, 6-165 months), 11 patients relapsed. The estimate 2-year overall survival and disease-free survival were 47.1% (95% CI, 34-59.1) and 67.8% (95% CI, 51-80), respectively. We identified 2 poor prognosis factors: low CD4 count and ECOG more than 2. Patients with 0 or 1 factor had good outcome (2-year survival: 60%) contrasting with patients with 2 factors (2-year survival: 12%). We conclude that LMB86 regimen is highly effective in advanced HIV-related BL and should be proposed for patients with CD4 count higher than 200 x 10(6)/L or ECOG of 2 or less.     

Hierarchical pattern of mucosal candida infections in HIV-seropositive women

PURPOSE: Candida is the most common cause of opportunistic mucosal infections in human immunodeficiency virus (HIV)-positive women. We had observed an apparent correlation between the severity of immunodeficiency and the site of mucosal candida infection. The current study was designed to determine whether significant correlations existed between the sites of mucosal candida infection and the degree of immunodeficiency, as determined by subsets of lymphocyte populations. PATIENTS AND METHODS: The subjects in this study are 66 HIV-seropositive women evaluated by members of the Brown University Acquired Immunodeficiency Syndrome (AIDS) Program during the 3-year period, September 1, 1986, through August 30, 1989. All patients had thorough clinical evaluations and relevant laboratory studies at defined intervals. All patients with CD4 lymphocyte counts below 0.2 X 10(9)/L received zidovudine therapy as soon as it became available. After July 1988, all patients with CD4 counts below 0.2 X 10(9)/L received prophylaxis against Pneumocystis carinii pneumonia. All patients were counseled about HIV infection, its modes of transmission, and the early symptoms of opportunistic infections. RESULTS: The longitudinal data demonstrated that candida often infected vaginal mucosa when there was no significant reduction in CD4 lymphocyte counts. Candida infection of the oropharyngeal mucosa was associated with highly significant reductions in CD4 lymphocyte counts. Esophageal candidiasis occurred only with advanced immunodeficiency associated with CD4 counts below 0.1 X 10(9)/L. CONCLUSIONS: Candida mucosal infections occur in a hierarchical pattern in women with HIV infection. Determination of the basis for the differences in susceptibility to candida of the vaginal, oropharyngeal, and esophageal mucosal surfaces will require further studies.     

HIV/AIDS患者机会性感染特点分析

目的探讨HIV／MDS患者机会性感染疾病谱及其与CD4^＋及CD8^＋T细胞间的关系,从而为临床防治机会性感染提供依据。方法对北京佑安医院感染科2002—2005年收治的181例HIV／AIDS患者的临床资料进行回顾性分析。结果181例患者中,有104例发生了机会性感染,部分患者同时有多种机会性感染。本组最常见的机会性感染是口腔念珠菌感染（52．9％）,其他依次为卡氏肺孢子菌肺炎（PCP）（31．7％）、结核（21．2％）、食管或肠道真菌感染（15．4％）、疱疹病毒感染（12．5％）及肺部感染（6．7％）等;各种机会性感染中,结核组与PCP组间CD4／CD8比值差异具有统计学意义;按同时伴有机会性感染的种类数分组,机会性感染各组的平均CD4^＋、CD8^＋T细胞计数及CD4／CD8比值均显著低于无机会性感染组;随着机会性感染种类的增加,CD4^＋T细胞数逐渐降低,CD4／CD8比值亦逐渐降低。结论HIV／MDS患者机会性感染多见于消化和呼吸系统,发生频率与CD4^＋T细胞计数及CD4／CD8比值有着非常密切的关系,CD4^＋T细胞计数小于200个／μl、CD4／CD8比值小于0．20,机会性感染明显增加,且随着病情进展同时发生多种机会性感染的几率也明显增加,此可作为开展机会性感染预防的参照指标。     

Incidence and natural history of cytomegalovirus disease in patients with advanced human immunodeficiency virus disease treated with zidovudine. The Zidovudine Epidemiology Study Group.

Data were analyzed from a multicenter observational cohort study of 1002 persons with AIDS or AIDS-related complex (ARC) and total CD4 cell count < 0.25 x 10(9)/L treated with zidovudine between April 1987 and April 1988. Cytomegalovirus (CMV) disease developed in 109 patients (10.9%), with a 2-year actuarial risk of 15%. Manifestations included retinitis (93 patients), esophagitis (10), colitis (8), gastritis (1), hepatitis (1), and encephalitis (1). The probability of CMV disease at 2 years for patients with initial counts < 0.1 x 10(9)/L was 21.4%, compared with 10.3% for patients with initial counts > or = 0.1 x 10(9)/L (P < .001). By proportional hazards analysis, baseline CD4 cell count < 0.1 x 10(9)/L, enrollment diagnosis of AIDS, and homosexuality were significantly associated with subsequently developing CMV disease. Median survival after diagnosis of CMV disease was 173 days, and CMV was an independent predictor of death. CMV contributes to AIDS-related morbidity and mortality. As new anti-CMV drugs become available, prophylaxis should be targeted at individuals with CD4 cell counts < 0.1 x 10(9)/L.     

Yogurt containing probiotic Lactobacillus rhamnosus GR-1 and L. reuteri RC-14 helps resolve moderate diarrhea and increases CD4 count in HIV/AIDS patients

HIV/AIDS is changing the human landscape in sub-Saharan Africa. Relatively few patients receive antiretroviral therapy, and many suffer from debilitating diarrhea that affects their quality of life. Given the track record of probiotics to alleviate diarrhea, conventional yogurt fermented with Lactobacillus delbruekii var bulgaricus and Streptococcus thermophilus was supplemented with probiotic Lactobacillus rhamnosus GR-1 and L. reuteri RC-14. Twenty-four HIV/AIDS adult female patients (18 to 44 y) with clinical signs of moderate diarrhea, CD4 counts over 200, and not receiving antiretrovirals or dietary supplements, consumed either 100 mL supplemented or unsupplemented yogurt per day for 15 days. Hematologic profiles, CD4 cell counts, and quality of life was evaluated at baseline, 15 and 30 days postprobiotic-yogurt feeding. There was no significant alteration in the hematologic parameters of both groups before and after the probiotic-yogurt feeding. The probiotic yogurt group at baseline, 15 and 30 days had a mean WBC count of 5.8+/-0.76 x 10(9)/L, 6.0+/-1.02 x 10(9)/L, and 5.4+/-0.14 x 10(9)/L, respectively. However, the mean CD4 cell count remained the same or increased at 15 and 30 days in 11/12 probiotic-treated subjects compared to 3/12 in the control. Diarrhea, flatulence, and nausea resolved in 12/12 probiotic-treated subjects within 2 days, compared to 2/12 receiving yogurt for 15 days. This is the first study to show the benefits of probiotic yogurt on quality of life of women in Nigeria with HIV/AIDS, and suggests that perhaps a simple fermented food can provide some relief in the management of the AIDS epidemic in Africa.     

Appearance of predictors of disease progression in relation to the development of AIDS

To study the natural history of HIV-1 infection in relation to serological and immunological profiles, 199 asymptomatic HIV-1-antibody (HIV-1-core-antibody)-seropositive and 76 seroconverted homosexual men were followed prospectively for 39 months. AIDS was diagnosed in 38 men. The AIDS attack rate was 20.8% after 39 months. The AIDS attack rate in the HIV-I-core-antibody positives was 12.1, versus 30.1% in the HIV-1-core-antibody negatives (P less than 0.001), and it was 13.3% in the HIV-1-antigen (HIV-1-Ag) negatives versus 53.9% in the HIV-1-Ag positives (P less than 0.001). The AIDS attack rate after 39 months was 10.9% in men with counts greater than or equal to 0.5 x 10(9)/l and 49.9% in those with CD4+ lymphocyte counts less than 0.5 x 10(9)/l. AIDS attack rates after 30 months in the same cohort have been previously reported [1], and were as follows: 6.8% in the core-antibody positives versus 35.7% in the core-antibody negatives. 6.9% in the HIV-1-Ag negatives versus 43.9% in the HIV-1-Ag positives, and 6.1% in those with CD4+ lymphocyte counts greater than or equal to 0.5 versus 51.9% in those with CD4+ lymphocyte counts less than 0.5 x 10(9)/l. The disappearance of core antibody, the appearance of antigen and the occurrence of low CD4+ lymphocyte counts preceded AIDS by a mean (s.d.) of 21.3 (8.9), 17.7 (8.8) and 15.7 (8.9) months, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human immunodeficiency virus infection in Haemophiliacs in Taiwan: the importance of CD4 lymphocyte count in the progression to acquired immunodeficiency syndrome

From July 1984 to December 1996, we tested and studied 303 haeophilic patients for the infection of the human immunodeficiency virus (HIV). Among the 261 Haemophilia A patients 44 were HIV positive (16.9%), while none of the Haemophilia B patients was HIV positive. The mean age of the 44 HIV-seropositive patients in 1984 was 20.6 years (2–37 years). Seven who had known seroconversion dates and 29 whose first seropositive dates were known seroconverted before 1986. Acquired immunodeficiency syndrome (AIDS) has developed in 16 patients, nine of whom presented with Pneumocystis carinii pneumonia, three with tuberculosis infection, and 13 had died. The Kaplan–Meier estimate of the progression rate to AIDS after the date of first seropositive test is about 30% at the 10th year. The median survival time after development of AIDS obtained from the Kaplan–Meier estimate of the survival curve was 11.7 months. Statistical analysis for the covariate effects on the risk of developing AIDS by the Cox proportional hazards model revealed that there was a statistically significant negative association of the risk for progression to AIDS with the logarithm of initial CD4 cell counts ( P  = 0.027) and the rate of decline of CD4 cell counts ( P  = 0.040), but not with age ( P  = 0.650). In conclusion, the clinical characteristics of AIDS Haemophiliacs in Taiwan were not different from that observed in western countries. Low initial CD4 cell count and sharp decline in CD4 cell counts, but not age, increased the risk of progression to AIDS.     

CD4+ and CD8+ lymphocytes and HIV RNA in HIV infection: high baseline counts and in particular rapid decrease of CD8+ lymphocytes predict AIDS

OBJECTIVE: To study the progression of HIV infection in relation to immunological and virological variables with emphasis on the role of CD8+ lymphocytes. DESIGN: Prospective follow-up from October 1991 of patients observed for at least 18 months allowing nucleoside analogue monotherapy. Peripheral CD4+ and CD8+ lymphocyte counts, HIV RNA, and soluble CD8 were analysed by statistics allowing the evaluation of serial data, avoiding time points with concurrent infections. SETTING: Tertiary university clinic. PATIENTS: Forty-nine patients were followed for 52.6 months, baseline CD4+ count of 300 x 10(6)/l, sample interval of 5.9 months (medians). MAIN OUTCOME MEASURES: AIDS, death, and CDC groups B- or C-related events. RESULTS: AIDS developed in 28% of patients. Baseline CD8+ counts above the median were significantly associated with AIDS development; the best Cox model included CD8+ cells and the log10RNA/CD4 ratio. A decline in CD8+ counts relative to baseline most significantly predicted AIDS, along with higher baseline RNA and actual CD4+ counts of less than 200 x 10(6)/l. Levels of soluble CD8 in the blood relative to total CD8+ cells significantly increased in patients developing AIDS. Death occurred in 16% of the patients, and was only predicted by high CD8+ cell counts at baseline. CDC B- and C-related events occurred in 35% of the patients and were best predicted by high baseline CD8+ counts and high RNA levels. CONCLUSIONS: The serial quantitation of CD8+ lymphocytes gave highly significant predictive information on the natural progression of HIV infection in patients with moderate to severe immune deficiency. Our data suggest that the hyperactivation of CD8+ lymphocytes is an important factor leading to a numerical decrease of CD8+ lymphocytes in progressive HIV infection.     

The natural history of human immunodeficiency virus infection in a haemophilic cohort

112 haemophilic patients infected with HIV were followed up with clinical and laboratory assessment between 1 December 1979 and 30 November 1988. Sixty-six (59%) of the patients developed HIV-related clinical symptoms and 22 (20%) developed AIDS. Twenty (18%) of the patients developed p24 antigenaemia. Amongst the 59 patients whose date of seroconversion could be estimated the calculated 8-year cumulative incidence of AIDS was 40% (symptoms 73%). For the whole cohort of 112 patients, the median slope of linear regression of the absolute T4 lymphocyte count was steeper for those with AIDS (-0.113 x 10(9)/l per year) than for those without AIDS (-0.054 x 10(9)/l per year) (P less than 0.02). While 15 cases of AIDS developed during 58 patient-years of follow up after falling below a T4 lymphocyte count of 0.2 x 10(9)/l, only two cases occurred during 450 patient-years before reaching this count. Thus the decline of the T4 lymphocyte count to 0.2 x 10(9)/l may be an appropriate additional end-point for the assessment of new treatments for asymptomatic patients infected with HIV.