The association of clinical conditions and serologic tests with CD4+ lymphocyte counts in HIV-infected subjects without AIDS.

Early intervention guidelines in HIV infection require knowledge of CD4+ lymphocyte count; however, CD4+ determinations require special laboratory procedures and may not be readily available in all situations. Using data from 207 HIV-seropositive homosexual men without AIDS, we evaluated the association of difference clinical conditions or serologic tests with CD4+ count. Men with conditions including seborrheic dermatitis, hairy leukoplakia, oral candidiasis and chronic diarrhea, and men with beta2-microglobulin levels greater than or equal to 4.0 mg/l had significantly lower CD4+ counts. However, the probability that a subject with such parameters had less than 200 x 10(6)/l CD4+ cells was limited (25-63%). Although the probability that a subject with such parameters had less than 500 x 10(6)/l CD4+ cells was better (76-88%), the probability that a person without these parameters had greater than or equal to 500 x 10(6)/l CD4+ cells was only 45-50%. Clinical and serologic parameters may provide important prognostic information, but cannot be used to reliably determine the level of CD4+ cells.     

Long-term safety and efficacy of zidovudine in patients with advanced human immunodeficiency virus disease. Zidovudine Epidemiology Study Group.

An epidemiologic study was initiated in 1987 to evaluate the long-term safety and efficacy of zidovudine in patients with advanced human immunodeficiency virus disease. Data from 886 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and CD4+ lymphocyte count less than 0.25 x 10(9)/L are reported. Eighteen-month survival was 67% for the cohort. Pretreatment factors associated with increased survival time included index diagnosis of AIDS-related complex, hematocrit of 0.35 or greater, CD4+ lymphocyte count of 0.15 x 10(9)/L or greater, high functional status, and time from diagnosis of AIDS to treatment of less than 60 days. By proportional hazards analysis, development of serious anemia was the most significant factor associated with early death. Receiving zidovudine for a high proportion of time significantly improved chances of survival even if anemia developed. Serious leukopenia occurring in 37% and serious anemia occurring in 32% of patients. Nonhematologic adverse events were uncommon and no previously unreported adverse events were seen.     

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.     

Impact of tuberculosis on the course of HIV-infected patients with a high initial CD4 lymphocyte count.

OBJECTIVE: To assess the influence of tuberculosis (TB) on the progression of human immunodeficiency virus (HIV) infection in patients without immunological impairment. MATERIAL AND METHODS: In an observational study of retrospective cohorts, the evolution of 28 HIV-infected patients with TB and a CD4 lymphocyte count >500 x 10(6) cells/l was compared with 56 HIV-infected patients without TB. Each case was paired with two controls by CD4 lymphocyte count (+/-50 x 10(6)/l) and date of starting follow-up (+/-6 months). The progression of HIV infection was evaluated as: 1) immunological progression: time to CD4 lymphocyte count <200 x 10(6)/l; 2) clinical progression: time to development of acquired immune-deficiency syndrome (AIDS), excluding TB; 3) survival; and 4) global disease progression: time to the first defined event in 1, 2 and/or 3. The times to these events were estimated using Kaplan Meier curves. RESULTS: There were no significant differences between the cohorts for age, sex and risk group. Faster immunological impairment (RR 2.94; 95%CI 1.46-8.6; P < 0.01), greater progression to AIDS (RR 4.01; 95%CI 1.66-9.69; P < 0.01), lower survival (RR 3.89; 95%CI 1.53-9.87; P < 0.05) and higher global disease progression (RR 2.82; 95%CI 1.57-5.09; P < 0.01) were found in the cohort of TB patients. These associations were still significant after adjustment for CD4 lymphocyte counts. CONCLUSION: The diagnosis of TB in HIV-infected patients with a high initial CD4 lymphocyte count (>500 x 10(6)/l) was related to greater progression to AIDS and shorter survival.     

Continued CD4 cell count increases in HIV-infected adults experiencing 4 years of viral suppression on antiretroviral therapy

OBJECTIVE: To determine the extent to which HIV-infected patients, including those with advanced immunodeficiency, can reverse peripheral CD4 T-cell depletion while maintaining long-term viral suppression on highly active antiretroviral therapy. DESIGN: Cohort study. PARTICIPANTS: Four-hundred and twenty-three HIV-infected patients who initiated HAART prior to 1998 and achieved a viral load 1000 copies/ml. MAIN OUTCOME MEASURE: CD4 count changes. RESULTS: Among patients who maintained plasma HIV RNA levels /= 350 x 10(6)/l, respectively (all gains were significantly greater than zero; P < 0.05). Among those with a pre-therapy CD4 count of < 50 x 10(6)/l, 88% achieved a CD4 cell count of >/= 200 x 10(6)/l and 59% achieved a count of >/= 350 x 10(6)/l by year 4. Factors associated with increased CD4 cell count gains from month 3 to year 4 included lower pre-therapy CD4 cell count, younger age, female sex, and infrequent low-level viremia (versus sustained undetectable viremia). CONCLUSIONS: Most patients who achieve and maintain viral suppression on HAART continue to experience CD4 T-cell gains through 4 years of therapy. The immune system's capacity for CD4 T lymphocyte restoration is not limited by low pre-therapy CD4 counts.     

CD4+ cells and CD4+ percent as risk markers for Pneumocystis carinii pneumonia (PCP): implications for primary PCP prophylaxis.

The incidence of Pneumocystis carinii pneumonia (PCP) during 2 years in HIV-infected patients with less than or equal to 100 x 10(6)/l CD4+ cells, less than or equal to 200 x 10(6)/l CD4+ cells and less than 20% CD4+ cells of total T lymphocytes were compared. The relative PCP risk in 57 patients with less than or equal to 100 CD4+ cells was more than twice higher than in 120 patients with less than or equal to 200 CD4+ cells. The latter had almost twice higher relative PCP risk than 271 patients with less than or equal to 20% CD4+ cells. Only 3/56 patients who acquired PCP had greater than 200 CD4+ cells and 15/56 patients had greater than 100 CD4+ cells. Centers for Disease Control (CDC) recommends primary PCP prophylaxis in HIV-infected patients when the number of CD4+ cells is less than 200 x 10(6)/l or when the CD4+ is less than 20. On the basis of the presented data we suggest that primary prophylaxis is considered only when CD4+ cells fall below 200 x 10(6)/l.     

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)     

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.     

Changes in the spectrum of AIDS-defining conditions and decrease in CD4+ lymphocyte counts at AIDS manifestation in Germany from 1986 to 1991.

OBJECTIVES: Analysis of changes in the spectrum of AIDS-defining conditions and their correlation with CD4+ lymphocyte counts in different risk groups associated with HIV transmission. METHODS: Review of data from all adult AIDS cases reported in Germany between 1986 and 1991. RESULTS: Among AIDS cases diagnosed between 1986 and 1991, the proportion of cases with lymphoma and wasting syndrome increased, while the proportion of Kaposi's sarcoma decreased. Homosexual men, but not intravenous drug users, showed a decrease in the proportion of cases in Pneumocystis carinii pneumonia and an increase in the proportions with toxoplasmosis and cytomegalovirus infection. The median CD4+ lymphocyte count at time of AIDS diagnosis decreased from 73 x 10(6)/l in 1986 (25 and 75 percentiles, 28 and 212) to 47 x 10(6)/l in 1990 (25 and 75 percentiles, 20 and 120; P less than 0.01). This decrease was the result of reduced CD4+ lymphocyte counts of individuals presenting with opportunistic infections; there was no corresponding change for individuals with non-infectious AIDS-defining conditions. CONCLUSIONS: AIDS diagnosis is now occurring at a later time in the natural history of HIV infection than in 1986, and the relative frequency of specific AIDS-defining conditions has changed. Most pronounced is a decrease of Pneumocystis carinii pneumonia. Changes in the natural history of HIV infection due to therapeutic and prophylactic interventions must be considered when interpreting epidemiological data in the course of the AIDS epidemic. These changes also have implications for the planning and execution of medical care.     

Immune activation markers and AIDS prognosis.

Four assays for serum levels of cellular products of immune activation were examined as prognostic markers for AIDS in a prospective study of asymptomatic HIV-seropositive homosexual men. Baseline serum values of beta 2-microglobulin (beta 2M), neopterin, soluble CD8 (sCD8), and soluble interleukin-2 receptor (sIL-2R) for 185 men were examined univariately and multivariately as predictors of AIDS during 36 months of follow-up. Thirty-three cases of AIDS (18%) were diagnosed during the follow-up period. All four assays correlated highly with each other (r = 0.48-0.63), and all four were good univariate predictors of AIDS and comparable to CD4 lymphocyte count. beta 2M, neopterin, and sCD8 predicted AIDS independently of both CD4 count and HIV p24 antigen or p24 antibody in multivariate analysis. Within the range of CD4 count 200-499 x 10(6) cells/l, an immune activation marker used in combination with an assay for p24 antigen identifies those at 3-6% risk of AIDS over 36 months (low risk on both assays) and those at 63-86% risk (high risk on both assays). These results can be used to guide physicians and patients making decisions about treating asymptomatic HIV infection with zidovudine in individuals with CD4 lymphocyte count of 200-499 x 10(6) cells/l.     

Factors influencing outcome of treatment with zidovudine of patients with AIDS in Australia. The Australian Zidovudine Study Group

In a multicentre study of zidovudine therapy in Australia commencing in June 1987, 308 homosexual or bisexual men with AIDS started on zidovudine by 30 June 1988. Using follow-up data collected through 31 December 1988, the outcome of the first 18 months of zidovudine therapy in these patients has been analysed in terms of efficacy, expressed as survival and as time to development of a new AIDS-defining condition, and in terms of safety, expressed as toxicity. Median survival from time of diagnosis of AIDS was 124 weeks, significantly longer (P less than 0.001, logrank statistic) than the median survival of 44 weeks in historical controls representing AIDS patients prior to the availability of zidovudine therapy. Median survival time from starting zidovudine has not been reached in these patients, while 172 (56%) developed new AIDS-defining conditions, with median time to progression of 48 weeks. Anaemia requiring transfusion was experienced by 155 patients (50%). Significant differences (P less than 0.01, logrank statistic) in survival were found in favour of patients who commenced zidovudine therapy (Dx-zidovudine time) within 12 weeks of diagnosis and had baseline Karnofsky scores greater than or equal to 80, haemoglobin greater than or equal to 11 g/dl, CD4+ cell counts greater than or equal to 50 x 10(6)/l. Therapy-related significant differences (P less than 0.01, logrank statistic) in survival were found in favour of patients with no weight loss and who received the full zidovudine dose (1.2g) during the first 52 weeks of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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.     

Incidence and natural history of Mycobacterium avium-complex infections in patients with advanced human immunodeficiency virus disease treated with zidovudine. The Zidovudine Epidemiology Study Group.

To determine the incidence and natural history of Mycobacterium avium-complex infections in persons with advanced human immunodeficiency virus (HIV) infection, we studied a multicenter cohort of 1,020 persons with acquired immunodeficiency syndrome (AIDS) or the AIDS-related complex (ARC) and CD4 cell count < 0.250 x 10(9)/L initially treated with zidovudine between April 1987 and April 1988. M. avium-complex infections developed in 123 (12%) patients during follow-up, with a 2-yr actuarial risk of 19%. Patients with an initial diagnosis of Pneumocystis carinii pneumonia were more likely to develop M. avium-complex infections than patients with an initial diagnosis of another opportunistic disease or of ARC (p = 0.002). Individuals developing M. avium-complex infections had lower baseline CD4 cell counts, hematocrits, lymphocyte counts, and total white blood cell counts than those who did not develop M. avium-complex infection. During follow-up, individuals who developed M. avium-complex infections were more likely to have severe anemia, to experience zidovudine dose reductions, and to die than were patients without M. avium-complex (p < 0.001). By proportional hazards analysis, a baseline CD4 cell count < 0.100 x 10(9)/L, development of severe anemia, P. carinii pneumonia during follow-up, and zidovudine dose interruption were significantly associated with subsequently developing M. avium-complex infection. A proportional hazards analysis of survival showed that M. avium-complex infection, severe anemia, zidovudine dose interruption, occurrence of an opportunistic infection, CD4 cell count < 0.100 x 10(9)/L, baseline AIDS diagnosis, and transfusion independently predicted an increased risk of death.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognostic value of an elevated CD8 lymphocyte count in HIV infection. Results of a prospective study of 152 asymptomatic HIV-positive individuals.

OBJECTIVE: To evaluate the prognostic value of an elevated CD8 lymphocyte count in the early stages of HIV infection. DESIGN: A prospective study ongoing since January 1986. METHODS: One hundred and fifty-two asymptomatic HIV-positive individuals with a CD4 lymphocyte count > 400 x 10(6)/l at enrollment were included. Disease progression was defined as a CD4 count < 200 x 10(6)/l. RESULTS: During the follow-up period, CD4 count decreased in 33 individuals; CD8 count increased to > 1500 x 10(6)/l in 38 individuals and doubled in 35. The risk of a decreasing CD4 count was estimated to be 1.7-fold higher, although not significantly so, after the elevation of the CD8 count to > 1500 x 10(6)/l than before or in the absence of such an increase. However, this predictive value disappeared when five baseline parameters found to predict the outcome (neopterin, beta 2-microglobulin, p24 antigen, anti-p18 antibody and immunoglobulin A) were adjusted. CONCLUSION: Elevated CD8 count appears to be a weak marker for disease progression.     

Virologic and immunologic values allowing safe deferral of antiretroviral therapy

OBJECTIVE: To determine how long highly active antiretroviral therapy can be deferred in HIV-1 infected persons. DESIGN: Observational cohort study of HIV-1 infected men at four academic centers in the USA. OUTCOME: Progression to clinical AIDS or to CD4 cell counts < 200 x 10(6)/l in the absence of antiretroviral therapy among HIV-1 infected men. RESULTS: No participant with a CD4 cell count between 201 x 10(6) and 350 x 10(6)/l and having < 20 000 copies/ml of HIV RNA progressed to clinical AIDS within 1 year. In men with > 350 x 10(6) CD4 cells/l and < 60 000 copies of HIV RNA/ml there were also no instances of progression to clinical AIDS within 1 year. No participant with < 10 000 copies HIV RNA/ml and between 201 x 10(6) and 350 x 10(6) CD4 cells/l had a decrease in CD4 cells to < 200 x 10(6)/l within 1 year. In men with baseline CD4 cell counts > 350 x 10(6)/l and HIV RNA < 30 000 copies/ml, only 3% had a decrease in CD4 cell count to < 200 x 10(6)/l within 1 year. CONCLUSION: This analysis supports recommendations to defer therapy in HIV-1 infected individuals with CD4 cell counts > 350 x 10(6)/l and HIV RNA < 60 000 copies/ml and in persons with CD4 cell counts between 201 x 10(6) and 350 x 10(6)/l and < 20 000 copies/ml HIV RNA. Up to 79% of persons with > 350 x 10(6) CD4 cells/l and 29% with CD4 cell counts between 201 x 10(6) and 350 x 10(6)/l may, with close monitoring, safely defer therapy.     

Bacteriuria in men infected with HIV-1 is related to their immune status (CD4+ cell count).

OBJECTIVE: Reports from the United States that urinary tract infections (UTI) are more common in homosexual than in heterosexual men have not been confirmed in Europe. The occurrence of several UTI in men infected with HIV-1 has been recorded in The Netherlands. We therefore analysed the relationship between the presence of bacteriuria and the immune status (CD4+ cell count) in these HIV-1-infected patients. DESIGN: Urinary cultures were obtained prospectively for 2 years, during the first visit and every 6 months thereafter, when signs and symptoms of UTI occurred and when patients had fever of unknown origin. CD4+ cell counts were measured at the same time. SETTING: The study was performed at the University Hospital, Utrecht, The Netherlands. PATIENTS, PARTICIPANTS: One hundred and thirty HIV-1-infected men attended our hospital. Data from 98 were analysed. Eighty-nine (91%) of these men were either homo- or bisexual. MAIN OUTCOME MEASURES: Positive urinary culture. RESULTS: Group 1 (CD4+ cell count less than 200 x 10(6)/l) consisted of 47 patients; 30% had at least one period of bacteriuria, with 21 episodes. Group 2 (CD4+ cell count 200-500 x 10(6)/l) consisted of 27 patients; 11% had at least one period of bacteriuria, with five episodes. We did not find bacteriuria in the 24 patients in group 3 (CD4+ cell count greater than 500 x 10(6)/l). The rate of bacteriuria per patient-month, 4 (group 1) versus 2 (group 2), differed significantly (P less than 0.001). A significant relationship between CD4+ cell count and bacteriuria was found (P = 0.00003); no relationship, however, was found with anal intercourse, hospitalization, Karnofsky score, follow-up, or age. CONCLUSION: We conclude that men infected with HIV and presenting with a CD4+ cell count less than 200 x 10(6)/l are at increased risk for bacteriuria.     

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.     

Ten-year trends in CD4 cell counts at HIV and AIDS diagnosis in a London HIV clinic

OBJECTIVE: To examine temporal trends (1986-1996) in the CD4 cell count at first HIV-1 positive test and initial AIDS diagnosis, and the influence of selected patient characteristics and treatment factors on these trends. DESIGN: A retrospective clinic-based study. SETTING: Three hospital-based clinics in West London. PATIENTS: A group of 5921 adult HIV-1-seropositive persons and 2835 reported patients with AIDS over a 10-year period from 1 January 1986 to 1 October 1996. METHODS: The CD4 cell count at HIV diagnosis (CD4HIV) was defined as the nearest CD4 cell count to within 2 months of HIV diagnosis; and the CD4 cell count at AIDS diagnosis (CD4AIDS) as the last CD4 cell count in the two months prior to the development of AIDS. Simple and multiple linear regression analysis were used to examine the influence of selected covariates on CD4HIV and CD4AIDS. RESULTS: The percentage of patients with an available CD4HIV and CD4AIDS increased from less than 5% in 1987 to 53% and 40%, respectively, in 1990, and 79% and 48%, respectively, in 1996. Patients with a missing CD4HIV or CD4AIDS were younger and less likely to have received antiretroviral therapy or prophylaxis for Pneumocystis carinii pneumonia (PCP). There was no significant change in CD4HIV over a 10-year period (median 334 x 10(6) cells/l), but a lower CD4HIV was associated with older age at presentation and injecting drug use. There was a delay in the onset of clinical AIDS, with a fall in the median CD4AIDS value from 99 x 10(6) cells/l prior to 1987, to 58 x 10(6) cells/l in 1990, 68 x 10(6) cells/l in 1994 and 60 x 10(6) cells/l in 1996; this decline in onset was seen for PCP as well as for cytomegalovirus and atypical mycobacterial infections. At all time periods, a lower CD4AIDS was associated with combined use of antiretroviral therapy and PCP prophylaxis. After adjustment for use of antiretroviral therapy and PCP prophylaxis prior to AIDS diagnosis, year of diagnosis was no longer associated with CD4AIDS. There was a significant trend towards an improved survival following AIDS diagnosis from 20.1 months prior to 1988, to 20.3 months (1989-1990), 21.0 months (1991-1992) and 22.1 (1993-1994) (P < 0.0005). CONCLUSIONS: The observed decline in CD4AIDS value was related to the introduction of antiretroviral therapy in 1988, and PCP prophylaxis in 1989. Temporal changes in the CD4 cell count at HIV and AIDS diagnosis among different demographic groups can provide insights into the changing natural history of the HIV epidemic and access to medical care. We recommend monitoring of the CD4 cell count at new HIV and AIDS diagnosis and at initiation of antiretroviral therapy as additional measures in national HIV/AIDS surveillance.     

Zidovudine in patients with human immunodeficiency virus (HIV) infection and Kaposi sarcoma. A phase II randomized, placebo-controlled trial

STUDY OBJECTIVE: To evaluate the toxicity, effects on immune function, antitumor effects, antiretroviral effects, and pharmacokinetics of zidovudine therapy in patients with early human immunodeficiency virus (HIV) infection and Kaposi sarcoma. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: National Institutes of Health, a referral-based research institution (single site). PATIENTS: Physician-referred volunteer patients with HIV infection, Kaposi sarcoma, CD4+ lymphocyte counts greater than 0.2 x 10(9)/L, and no systemic symptoms or history of opportunistic infection. Of 41 patients enrolled, 4 had not met all entry criteria and were therefore not evaluable. INTERVENTIONS: Patients were randomized to one of four treatment groups for an initial 12-week treatment period: oral placebo (9 patients); zidovudine, 250 mg orally every 4 hours (9 patients); zidovudine, 0.5 mg/kg body weight intravenously every 4 hours (9 patients); and zidovudine, 2.5 mg/kg intravenously every 4 hours (10 patients). After at least 12 weeks of therapy at their assigned dose, patients were treated with oral zidovudine, generally 250 mg every 4 hours, with a mean 42-week follow-up. MEASUREMENTS AND MAIN RESULTS: Anemia and granulocytopenia were the major toxicities. Significant increases in platelet counts and declines in serum HIV antigen and IgG and IgM levels occurred in treated patients. Treated patients were more likely than those on placebo to clear HIV from the cerebrospinal fluid. There were no differences in tumor progression or CD4+ or CD8+ lymphocyte counts among the groups. CONCLUSIONS: Zidovudine was well tolerated and had antiretroviral activity in patients with early HIV infection and Kaposi sarcoma but it had no significant effect on the extent of Kaposi sarcoma or on immune function.