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Inverse correlation between CD8+ lymphocyte apoptosis and CD4+ cell counts during potent antiretroviral therapy in HIV patients.

OBJECTIVES: We have addressed the relationships between inhibition of CD4+ and CD8+ cell apoptosis and CD4+ cell recovery in HIV patients undergoing potent antiretroviral therapy (PART) by correlating apoptosis levels with virological and immunological parameters detected over a long-term period in HIV patients undergoing therapy. PATIENTS AND METHODS: Twenty-two HIV-1-infected patients undergoing PART were enrolled in a long-term, open longitudinal study. Data derived from 17 patients with successful response to therapy (TS; median time of follow-up 36 months, range 24-36 months) were used for correlation studies. Apoptosis was evaluated after short-term culture of peripheral blood lymphocytes by flow cytometry analysis of isolated nuclei or of annexin V/CD4, annexin V/CD8 double-stained cells. RESULTS: Sustained, noticeable levels of apoptosis inhibition in peripheral blood mononuclear cells were measured, in the long-term, in 16 of the 17 TS patients. Levels of total cell apoptosis correlated with levels of CD8+ apoptotic cells more significantly than with levels of CD4+ apoptotic cells. In addition, CD4+ cell counts were correlated inversely with levels of CD8+ apoptotic cells in a highly significant fashion, but not with levels of CD4+ apoptotic cells. CONCLUSIONS: Our data indicate that the increase of CD4+ lymphocytes in HIV patients, as a consequence of successful response to PART, may be related to changes in apoptosis level occurring in the CD8+, and not in the CD4+, cell compartment.

Adult↗

Correlation of immunologic status with high-resolution CT and distributions of pulmonary tuberculosis.

PURPOSE: To investigate the correlation of cluster of differentiation (CD)4 lymphocyte counts with high-resolution CT (HRCT) findings and distribution of pulmonary tuberculosis. MATERIAL AND METHODS: Thirty-seven bacteriologically proven pulmonary tuberculosis, clinically non-AIDS, patients underwent HRCT and CD4 lymphocyte counts in peripheral blood cells were obtained within 3 days after the CT examinations. Patients were categorized into four groups according to CD4 lymphocyte counts (A >800; B 800-500; C 500-200; D <200). HRCT findings analyzed were as follows: typical, atypical, and mixed findings of post-primary tuberculosis, common, uncommon, and mixed distribution, and number of lobes involved. RESULTS: CD4 lymphocyte counts correlated with the degree of the mixture of atypical CT findings (rho=0.565, p<0.001) and the degree of the mixture of uncommon distribution (rho=0.431, p<0.01). Number of involved lobes showed no statistically significant correlation (rho=0.209, p=0.21). CONCLUSION: In patients with low CD4 levels, atypical HRCT findings co-exist with typical findings, and uncommon sites are involved in addition to common sites.

Adult↗

Prevalence of measles antibodies in asymptomatic human immunodeficiency virus-infected adults.

One hundred five asymptomatic human immunodeficiency virus-seropositive adults were screened for measles antibody. Ages ranged from 21 to 59 years (mean, 35.7). CD4+ lymphocyte counts (range, 76-1137/mm3), percentage of CD4+ cells (6-42), CD4:CD8 ratio (0.08-1.3), measles antibody titers by EIA, and undocumented history of prior measles or immunization were obtained. Forty-six patients gave a history of measles but no immunization, 18 of immunization but no measles, 26 of immunization and measles, and 15 of neither measles nor vaccination. Only one patient (less than 1%) lacked levels of antibody considered protective. Neither the presence nor the level of antibody were predictable from patient age, history of measles or immunization, CD4+ lymphocyte count, percentage of CD4+ cells, or CD4:CD8 ratio. Nearly all subjects had antibody to measles, regardless of immunization or measles history. Whether these antibodies are truly protective is unknown.

Adult↗

CD4 T-cell count, viral load, and squamous intraepithelial lesions in women infected with the human immunodeficiency virus.

BACKGROUND: Recent studies have reported an increased incidence of squamous intraepithelial lesions in women infected with the human immunodeficiency virus (HIV). However, to the authors' knowledge there are scarce data regarding the relation between the CD4 T-lymphocyte count (CD4+), HIV viral load, and the development of cervical dysplasia as evidenced by cervicovaginal cytology. The objective of the current study was to examine the association between cervicovaginal smears (with and without squamous lesions) from HIV-infected women and their CD4+ counts and HIV viral load. METHODS: Two hundred ninety-six cervicovaginal smears from 108 HIV-infected women were reviewed and classified according to the Bethesda system. Abnormal cytologies (n = 74) were followed by colposcopy and/or biopsy. CD4+ counts and HIV viral loads were available at the time of the cytologic evaluation. Statistical analysis was performed using the Student t test and the Mann-Whitney U test. RESULTS: The control group (n = 222) had significantly higher CD4+ counts (378 vs. 246 cells/microL; P < 0.001) compared with the group with cervical lesions. There was no apparent difference between the CD4+ counts from women with low grade lesions and those from women with high grade lesions. The HIV viral load was significantly higher in patients with cytologic abnormalities than in those with negative Papanicolaou smears (P = 0.006). CONCLUSIONS: The degree of immunosuppression may contribute to the development of intraepithelial lesions in HIV-positive women, but once the lesion is established disease progression may not be affected by the CD4+ counts.

Adolescent↗

Analysis of BAL fluid in M. avium-intracellulare infection in individuals without predisposing lung disease.

The purpose of this study was to investigate the characteristics of pulmonary inflammation caused by Mycobacterium avium-intracellulare (MAI) in individuals with neither predisposing lung disease nor immunodeficiency. We reviewed the records of 20 patients with pulmonary MAI infection (including 19 female patients) whose past history and previous chest radiographs revealed no predisposing lung disease. We analysed the bronchoalveolar lavage fluid (BALF) from these 20 patients and from six normal female controls. The BALF was recovered directly from the relevant segment that was identified with chest-computed tomography. The BALF cell profiles showed significantly elevated counts for total cells, lymphocytes and neutrophils, but the macrophage cell count was not elevated. The CD4+ lymphocyte count and CD4+/CD8+ ratio were significantly increased compared with those in the controls. The lymphocytes demonstrated phenotypical evidence of activation, with increased expression of human leukocyte antigen-D-related antigen (HLA-DR). The tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and IL-8 concentrations were significantly increased. The neutrophil elastase concentration was also increased, and it was significantly correlated with the neutrophil cell count in the BALF. These findings suggest that the increased counts of activated CD4+ lymphocytes and neutrophils and the elevated concentrations of proinflammatory cytokines and neutrophil elastase appear to be common characteristics in Mycobacterium avium-intracellulare infection.

Bronchoalveolar Lavage Fluid↗

Combination therapy with stavudine and didanosine in children with advanced human immunodeficiency virus infection: pharmacokinetic properties, safety, and immunologic and virologic effects.

OBJECTIVES: To obtain preliminary information on the pharmacokinetic properties, tolerance, safety, and antiviral activity of combination therapy with stavudine and didanosine in children with advanced human immunodeficiency virus (HIV) infection. METHODS: Eight children (median age, 6.6 years; range, 2.8 to 12 years) with advanced HIV disease (median CD4 + lymphocyte count at baseline, 42 cells/ microL; range, 8 to 553 cells/microL) were treated with stavudine (2 mg/kg per day in two divided doses) and didanosine (180 mg/m2 per day in two divided doses) for 24 weeks. Seven children had histories of prior zidovudine therapy. All children had received stavudine alone for 19 to 33 months before the addition of didanosine to the treatment regimen. Children were assessed clinically and with laboratory studies at baseline, weekly through week 4 of combination therapy, and every 4 weeks thereafter. RESULTS: Analysis of stavudine and didanosine plasma half-life values, clearances, and area under the plasma concentration-versus-time curves revealed no obvious clinical pharmacokinetic interaction between the drugs through study week 12. Combination therapy was well tolerated, and there were no drug-associated clinical or laboratory adverse events. Signs and symptoms of peripheral neuropathy were not observed. All three children with baseline CD4 + lymphocyte counts greater than 50 cells/muL had greater than 20% increases in their counts within the first 12 weeks of therapy; CD4 + lymphocyte count increases were not observed in the other children. Plasma HIV RNA concentrations showed median declines of 0.88 log10 (range, -3.41 log10 to 0.31 log10) and 0.30 log10 (range, -0.63 log10 to 0.89 log10) at study weeks 12 and 24, respectively. CONCLUSIONS: Combination therapy with stavudine and didanosine was well tolerated and safe in this small group of children with advanced HIV disease. Plasma HIV RNA concentration declines suggest a favorable effect of therapy on virus load. These findings should be confirmed, and the regimen's clinical efficacy should be examined, in controlled studies of HIV-infected children with less-advanced disease.

Antiviral Agents↗

Lack of efficacy of low dose oral interferon alfa in symptomatic HIV-1 infection: a randomised, double blind, placebo controlled trial.

BACKGROUND: Interferon alfa (IFN-alpha) exhibits dose related in vitro activity against human immunodeficiency virus (HIV), with complete inhibition of HIV replication at IFN-alpha concentrations > or = 256 IU/ml. In mid-1990, Kenyan investigators reported that oral administration of an extremely low dose (150 IU/day) of natural human (nHu) IFN-alpha resulted in complete alleviation of AIDS related complex and AIDS symptoms and resolution of opportunistic infections without additional treatment. Moreover, loss of HIV antibody seropositivity was reported in approximately 10% of treated patients. Subsequent small studies failed to substantiate these spectacular claims, but controversy on the efficacy of this treatment persisted. METHODS: We studied 559 adult Ugandan patients with WHO stage 2-4 HIV infection and a Karnofsky performance score of more than 50, who had not received any drugs with antiretroviral activity in the previous 3 months. The patients were randomly assigned in a double blind fashion either to 150 IU oral nHuIFN-alpha/day or placebo. The duration of treatment was extended from 28 weeks to 60 weeks 9 months after enrollment had started. At that time 112 subjects had already received 28 weeks of treatment and been discontinued from the study. RESULTS: Both study groups were comparable with respect to all baseline characteristics studied, except that the nHuIFN-alpha group had slightly lower absolute CD4+ lymphocyte counts (median 60.7 x 10(6)/l) than the placebo group (median 85.3 x 10(6)/l) (p = 0.033). Therefore, all analyses were adjusted for CD4+ lymphocyte counts at entry. In both treatment groups there was relentless progression of HIV disease. Subjects treated with nHuIFN-alpha and placebo had similar mortality, disease progression rates, decline of CD4+ lymphocyte counts and Karnofsky performance scores, and prevalence of symptoms. No patient reverted to HIV-1 seronegative antibody status. Serious adverse events were not seen. Quality control of the study medication documented that the active drug indeed contained IFN-alpha activity. CONCLUSIONS: The current large, randomised, double blind, placebo controlled study did not show any benefit from oral treatment with 150 IU nHuIFN-alpha/day in a population of African patients with symptomatic HIV infection.

Acquired Immunodeficiency Syndrome↗

Study of prevalence, severity, and etiological factors associated with acute pancreatitis in patients infected with human immunodeficiency virus.

OBJECTIVES: Patients with the human immunodeficiency virus (HIV) disease can develop pancreatic gland inflammation from HIV infection and related causes, or from factors totally independent of it. The incidence and severity acute pancreatitis in patients with HIV diseases and the frequency of associated etiological factors have not been examined in any detail. The purpose of this study was to (a) determine the prevalence of acute pancreatitis, (b) evaluate severity of pancreatic gland inflammation, (c) identify commonly associated etiological factors with acute pancreatitis, and (d) examine the relationship between CD4 lymphocyte counts and serum pancreatic enzyme levels (amylase and lipase) in patients with HIV disease. METHODS: We examined the medical records of 321 patients with HIV disease seen at Sinai Hospital of Baltimore between July of 1993 to June of 1994. Data collected from these records included clinical, laboratory, and radiologic features of pancreatitis, staging of HIV disease, risk factors, CD4 lymphocyte counts, medications associated with the presence of opportunistic infections, Kaposi's sarcoma, and lymphoma. RESULTS: From 321 patients with HIV disease, 45 patients developed at least one episode of acute pancreatitis as defined by clinical and laboratory criteria during the 1-yr period. A statistically significant negative correlation was found between serum pancreatic enzyme level and the number of CD4 lymphocytes (r = -0.15, p < 0.05 for serum amylase; r = -0.2, p < 0.05 for serum lipase). Furthermore, patients with asymptomatic HIV infection or CD4 lymphocyte count >500 mm3 did not develop asymptomatic hyperamylasemia or acute pancreatitis. Furthermore, the presence of gallstones, active injection drug use, pentamidine therapy, Pneumocystis carinii, Mycobacterium avium intracellulare correlated significantly (p < 0.001) with the diagnosis of acute pancreatitis. CONCLUSIONS: A detailed review of medical records of patients with HIV disease seen in a community hospital in 1 yr (1993-1994) suggests a high incidence (14%) of mild to moderately severe acute pancreatitis. In this group of patients, pancreatic gland inflammation is commonly associated with gallstones, intravenous drug abuse, pentamidine intake, and Pneumocystis carinii and Mycobacterium avium intracellulare infections. In addition, marked reduction in CD4 lymphocyte count is associated with increase in serum pancreatic enzyme levels (amylase, lipase activity) suggesting pancreatic gland inflammation or altered pancreatic enzyme turnover.

AIDS-Related Opportunistic Infections↗

[Validity of an ELISA test for CD4+ T lymphocyte count and validity of total lymphocyte count in the assessment of immunodeficiency status in HIV infection].

A newly available commercial ELISA (TRAx CD4, T Cell Diagnostics USA) for enumerating CD4+ T lymphocytes has been evaluated with blood samples of 105 HIV seropositive and 6 seronegative subjects. Results from the flow cytometric analysis were used as reference. The sensitivity and specificity of the ELISA to identify HIV seropositive subjects having less than 200 CD4+ T lymphocytes/microliters were assessed and studied using the ROC curve. The reproducibility of the ELISA test was analyzed on 40 samples. The results of the ELISA correlated well with these of the flow cytometric analysis (r = 0.79, p < 0.001). However, the ELISA test tends to overestimate the true CD4 count in HIV seropositives. This overestimation could not be explained by the aspecific contribution of monocytic CD4. The threshold for identifying HIV seropositive subjects with less than 200 CD4+ T lymphocytes with a maximum sensitivity and specificity was determined with ROC curve and equalled 400 cell equivalents with the ELISA (sensitivity and specificity were equal to 80%) and 1,450 lymphocytes/microliters with the total absolute lymphocyte count (sensitivity and specificity were equal to 75%). Using this curve, a threshold of 300 cell equivalents for the ELISA test and of 1,100 lymphocytes/microliters for the absolute lymphocyte count was shown to maximize the specificity (> 95%) without a significant loss of sensitivity.

CD4-Positive T-Lymphocytes↗

Kaposi's sarcoma in HIV infection: impact on opportunistic infections and survival.

OBJECTIVE: To determine the effect of Kaposi's sarcoma on survival of HIV-infected patients. METHODS: Retrospective cohort study to compare the survival of 241 HIV-infected homosexual patients with Kaposi's sarcoma (cases) with that of 241 HIV-infected homosexual patients without Kaposi's sarcoma (control subjects) but with a similar level of immunosuppression (measured by the absolute CD4+ lymphocyte count). RESULTS: Cases and control subjects were similar in age, occurrence of previous opportunistic infections, and the use of antiretroviral therapy. The mean CD4+ lymphocyte counts were similar for cases and control subjects (185 x 10(6) versus 184 x 10(6)/l, respectively). Cases had a higher incidence of opportunistic infections (5.95 versus 3.88 infections, respectively, per 100 person-months of observation) and a greater number of infections typical of late-stage HIV infection. Cases had a shorter overall survival than did control subjects (P=0.0025). Kaposi's sarcoma was associated with an increased risk of death (odds ratio, 1.28), even when adjusting for age, previous opportunistic infection, baseline CD4+ lymphocyte count, and antiretroviral therapy. CONCLUSION: Kaposi's sarcoma appears to accelerate the clinical course of HIV infection. Opportunistic infections develop earlier and more often in patients with the disease than in control subjects. Survival was significantly shorter in patients with Kaposi's sarcoma.

AIDS-Related Opportunistic Infections↗

Quantitative DNA proviral detection in HIV-1 patients treated with antiretroviral therapy.

The amount of proviral DNA in peripheral blood mononuclear cells (PBMCs) from 93 HIV-1 seropositive patients on long-lasting antiretroviral therapy was measured by the SYBR green real-time PCR technique. Variable levels of proviral DNA, ranging from 14 to 1847 copies of HIV-1 DNA per 10(6) PBMC were found, without a significant correlation between proviral load and plasma HIV-1 RNA levels or CD4(+) lymphocyte counts. To investigate the possible role of HIV-1 DNA levels as prognostic markers in clinical practice, the amount of proviral DNA and peripheral blood CD4(+) lymphocyte counts were further evaluated after 5 months of continued therapy in 32 patients who maintained a persistently undetectable viremia throughout the observation period. Interestingly, a clear-cut decrease (> or =0.5 log) in proviral DNA levels was significantly associated with a definite increase in CD4(+) lymphocyte counts. Even though plasma HIV-1 RNA levels remain the basic parameter to monitor both the intensity of viral replication and the efficacy of therapeutic interventions, the results obtained in our study seem to indicate that measuring proviral DNA levels could represent an adjunct prognostic marker, especially useful in patients whose HIV-1 RNA levels drop below detectable limits.

Anti-HIV Agents↗

Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa.

BACKGROUND: A community-based antiretroviral therapy (ART) programme was established in 2001 in a South African township to explore the operational issues involved in providing ART in the public sector in resource-limited settings and demonstrate the feasibility of such a service. METHODS: Data was analysed on a cohort of patients with symptomatic HIV disease and a CD4 lymphocyte count < 200 x 10 cells/l. The programme used standardized protocols (using generic medicines whenever possible), a team-approach to clinical care and a patient-centred approach to promote adherence. RESULTS: Two-hundred and eighty-seven adults naive to prior ART were followed for a median duration of 13.9 months. The median CD4 lymphocyte count was 43 x 10 cells/l at initiation of treatment, and the mean log10 HIV RNA was 5.18 copies/ml. The HIV RNA level was undetectable (< 400 copies/ml) in 88.1, 89.2, 84.2, 75.0 and 69.7% of patients at 3, 6, 12, 18 and 24 months respectively. The cumulative probability of remaining alive was 86.3% at 24 months on treatment for all patients, 91.4% for those with a baseline CD4 lymphocyte count > or =50 x 10 cells/l, and 81.8% for those with a baseline CD4 lymphocyte count < 50 x 10 cells/l. The cumulative probability of changing a single antiretroviral drug by 24 months was 15.1% due to adverse events or contraindications, and 8.4% due to adverse events alone. CONCLUSIONS: ART can be provided in resource-limited settings with good patient retention and clinical outcomes. With responsible implementation, ART is a key component of a comprehensive response to the epidemic in those communities most affected by HIV.

Adult↗

A mathematical model and CD4+ lymphocyte dynamics in HIV infection.

The paper presents a model of CD4 + lymphocyte dynamics in HIV-infected persons. The model incorporates a feedback mechanism regulating the production of T lymphocytes and simulates the dynamics of CD8 + lymphocytes, whose production is assumed to be closely linked to that of CD4 + cells. Because CD4 + lymphocyte counts are a good prognostic indicator of HIV infection, the model was used to simulate such therapeutic interventions as chemotherapy and active and passive immunization. The model also simulated the therapeutic administration of anti-CD8 antibodies; this intervention was assumed to activate T-cell production by activating a feedback mechanism blocked by the high numbers of CD8 + lymphocytes present in HIV-infected persons. The character and implications of the model are discussed in the context of other mathematical models used in HIV infection.

CD4 Lymphocyte Count↗

Progressive human immunodeficiency virus-specific immune recovery with prolonged viral suppression.

The degree of immune recovery achievable with anti-human immunodeficiency virus (HIV) therapy remains to be established. The effects of potent antiretroviral therapy, including ritonavir and saquinavir, on immune function were studied for a prolonged period in 41 patients. After 96 weeks, 88% of patients had plasma HIV RNA levels below the limit of quantitation. There were continuous increases in CD4 lymphocyte counts and in CD4:CD8 ratios over time. About half the patients developed lymphoproliferative responses to HIV p24 antigen, and nearly all developed responses to phytohemagglutinin. This occurred in parallel with increases in interleukin-12 production and expression of CD28 on CD8 lymphocytes, despite potential antiproliferative effects of protease inhibitors. Transient increases in virus load were temporally associated with loss of proliferative responses. The improved immune function, including HIV-specific immunity in many subjects, demonstrates the potential reversibility of HIV-induced immunodeficiency and does not identify a limit to immune recovery.

Anti-HIV Agents↗

High prevalence of cervical squamous cell abnormalities among HIV-infected women with immunological AIDS-defining illnesses.

AIM: To assess the results of Pap smear at postpartum scheduled visit, especially the prevalence of squamous cell abnormalities including association with CD4(+) T-lymphocyte count (CD4(+) count) levels at delivery among HIV-infected women between the years 1996 and 2004. METHODS: As part of the research and implementation programs of short course antiretroviral regimens for the prevention of mother to child perinatal HIV transmission in HIV-infected pregnant women delivered at Siriraj hospital, CD4(+) count at delivery and Pap smear at postpartum were evaluated. RESULTS: Among 636 women, 13.3% had squamous cell abnormalities. Seventy-seven cases (90.6%) of squamous cell abnormalities were low grade squamous intraepithelial lesions. The prevalence of squamous epithelial cell abnormalities detected by Pap smear, was higher in women whose CD4(+) count at delivery was < 200 cells/microL than in women whose CD4(+) count at delivery was > or = 200 cells/microL, with a significant difference (21.2%vs 12.2%). CONCLUSIONS: All HIV-infected pregnant women should be evaluated for clinical and immunological status during the antepartum period. Pelvic examination and Pap smear should be considered as a part of this evaluation. They should receive comprehensive health-care services that continue after pregnancy, including postpartum gynecologic examination and Pap smear. Women with normal cervical cytological findings but low CD4(+) count should be offered an antenatal Pap smear and long-term follow-up including a 6-monthly Pap smear.

CD4 Lymphocyte Count↗

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.

Adolescent↗

Medication costs associated with the care of HIV-infected patients.

The treatment costs for human immunodeficiency virus (HIV)-infected patients continue to rise as patients survive longer because of advances in antiretroviral therapy and effective chemoprophylaxis. Medication costs per patient increase in proportion to progressive immunodeficiency. We retrospectively studied medication costs for 196 HIV-infected patients with stratification by CD4-lymphocyte count. Medication costs per patient-month were correlated with CD4-lymphocyte count (linear regression, r = -.53, P < 0.01), with higher costs associated with lower CD4 counts. The medication cost for patients with CD4 counts < 100 cells/mm3 averaged $1043 per month. Medication costs per patient increase with the development of each new opportunistic infection or other AIDS-associated condition. Costs can be expected to increase as new therapeutic agents are introduced, as treatment is initiated at earlier stages of HIV infection, and as more patients survive to the point of severe CD4-lymphocyte depletion.

Anti-Infective Agents↗

Application of the World Health Organization system for HIV infection in a cohort of homosexual men in developing a prognostically meaningful staging system.

OBJECTIVE: Validation of a modified version of the recently proposed World Health Organization (WHO) staging system for HIV infection and disease in a cohort of homosexual men. METHODS: Five hundred and thirty HIV-positive men followed for a median of 51 months (range, 1-98 months) were eligible for analysis. Subjects were classified into stages at their first seropositive visit and at all subsequent visits. RESULTS: As of 1 April 1991, 136 subjects (26%) had progressed to stage IV of the modified WHO system on the basis of their CD4 lymphocyte counts, and 78 subjects (15%) had died. Kaplan-Meier estimates for progression to stage IV from stages I, II and III were 52.8 +/- 7.5% over 6.6 years, 58.1 +/- 7.1% over 5.9 years and 66.5 +/- 9.7% over 5.7 years (log-rank P = 0.0001). Estimated median times to stage IV were 6.4, 5.3 and 3.8 years from stages I, II and III, respectively. Estimated median times to death were 10.9, 8.2, 6.3 and 1.7 years from stages I to IV, respectively. Results remained unchanged when CD4 lymphocyte count was replaced with lymphocyte count in the laboratory axis of the staging system. CONCLUSIONS: The proposed staging scheme, based on the WHO system, provides a prognostically meaningful classification for HIV infection in a cohort of homosexual men. Furthermore, the use of absolute lymphocyte count as a valid alternative for CD4 lymphocyte count has implications for the applicability of this system in many parts of the world where diagnostic resources are limited.

CD4-Positive T-Lymphocytes↗