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PubMed1996

[Study of comparative immunity of patients with M. tuberculosis and atypical Mycobacteria infection and infection by human immunodeficiency virus (HIV)].

The purpose of this retrospective study was to determine the basal immune status, in patients with human immunodeficiency virus (HIV) infection, who were affected from tuberculosis (TB) caused by Mycobacterium tuberculosis or atypical mycobacterium. In the current study, we report our experience with 280 patients diagnosed TB and HIV: fifty cases were eligible for enrollment at random with M. tuberculosis (group I) and we compare with 23 cases of atypical mycobacterias (group 2). When we analyze statistically both groups, we detected in group 2 the existence of a CD4 Lymphocytes count decrease and a mean IgA raised, opposite to group I (P < 0.0001). On other side, our investigation on survival showed that this was lower in atypical mycobacterias group (group 2) with a median time of survival of 10 months, opposite to 2,9 years in group I.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Clearance of Sendai virus by CD8+ T cells requires direct targeting to virus-infected epithelium.

Minimal numbers of CD8+ T cells are found in bronchoalveolar lavage (BAL) populations recovered from Sendai virus-infected mice that are homozygous (-/-) for a beta 2-microglobulin (beta 2-m) gene disruption. The prevalence of the CD8+ set was substantially increased in the pneumonic lungs of 8-12-week radiation chimeras made using substantially class I major histocompatibility complex (MHC) glycoprotein-negative beta 2-m (-/-) recipients and normal beta 2-m (+/+) bone marrow. Even so, the CD8+ (but not the CD4+) lymphocyte counts were still much lower than in the (+/+)-->(+/+) controls. The (+/+)-->(+/+) and (+/+)-->(-/-) chimeras cleared Sendai virus and potent virus-immune CD8+ cytotoxic T lymphocytes (CTL) specific for H-2Kb+viral nucleoprotein peptide were found in the BAL from both groups. However, following in vivo depletion of the CD4+ population, only the (+/+)-->(+/+) mice were able to deal with the infection. Similarly, adoptively transferred, H-2Kb-restricted CD8+ T cells from previously-primed (+/+) mice also failed to clear virus from the lungs of (+/+)-->(-/-) chimeras infected within 2 weeks of reconstitution with bone marrow, though they were effective in the (+/+)-->(+/+) controls. Sendai virus-immune CD8+ T cells are thus unable to eliminate virus-infected beta 2-m (-/-) lung epithelial cells that might be thought to be expressing very small amounts of either isolated class I heavy chain, or class I MHC glycoprotein that has bound beta 2-m derived from beta 2-m (+/+) T cells or macrophages present in the pneumonic lung. Furthermore, the CD8+ CTL that are being exposed to beta 2-m (+/+) stimulators in the BAL population cannot operate in some bystander mode to clear virus from respiratory epithelium.

Animals↗
PubMed1990

Quantitative analysis of human immunodeficiency virus type-1 DNA in asymptomatic carriers using the polymerase chain reaction.

A method for detecting human immunodeficiency virus type 1 (HIV-1) provirus DNA in lymphocytes with improved sensitivity and reproducibility was developed using the polymerase chain reaction (PCR). Amplified HIV-1 DNA was hybridized with a 32P-labeled probe and quantitated with a beta-scanner after electrophoresis. A linear relationship was obtained between the common logarithms of the counts detected and the number of HIV-1 DNA copies applied to the PCR. Detectability was from 3 copies/10(5) lymphocytes, and linearity was maintained from 10 to 10(3) copies. HIV-1 DNA was detected in all 9 asymptomatic carriers tested (18 to 2,857 copies/10(5) CD4+ T lymphocytes). The viral burden was inversely related to the CD4+ lymphocyte count, suggesting that quantitation of provirus levels may serve as a predictor of progress in early HIV infection.

Autoradiography↗
PubMed1993

[Results of zidovudine treatment of 9 vertically HIV infected children].

BACKGROUND AND METHODS: Zidovudine has been shown to be an effective antiretroviral drug in the treatment of AIDS, AIDS-related complex and also symptomatic or asymptomatic HIV infection in adults. First studies concerning zidovudine therapy in children are now available. Since 1987 we take care of HIV-infected and -exposed children at our clinic in a multicenter study. In this report we present data of a 12 months treatment period with zidovudine of 9 perinatally infected children. At enrollment the children's age ranged from 5 months to 6.8 years. The drug was given orally as capsules or syrup at a dose of 10-17 mg/kg/d every 6-8 hours. RESULTS: Zidovudine was well tolerated. Only in one case we had to reduce the dosage for a longer period of time because of hematologic abnormalities. There were no other side effects. During the study 2 patients died before the scheduled treatment regimen could be completed. In 5 children we saw a clinical improvement like weight gain, decreased hepato- and/or splenomegaly, decreased lymphadenopathy and improvement in neurologic abnormalities. The CD4+ lymphocyte counts showed a transient increase. The in vitro mitogen induced proliferation also showed a transient improvement during the first months of treatment. The p24-antigen was detected in 7/9 children. No significant changes were observed over time. CONCLUSIONS: Zidovudine can be administered safety to children with HIV infection. It is well tolerated at a dose of 10-17 mg/kg/d given every 6-8 hours. In some children clinical improvement can be observed. The immunologic and virologic improvements are only transient.

AIDS-Related Opportunistic Infections↗
PubMed1993

Quantitative analysis of the human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocyte (CTL) response at different stages of HIV-1 infection: differential CTL responses to HIV-1 and Epstein-Barr virus in late disease.

Major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) are part of the cellular immune response to human persistent virus infections. Measurements of the frequency and specificity of human immunodeficiency virus type 1 (HIV-1)-specific CTL and their variation with time may indicate their relative importance in modulating the progression of HIV-1 infection. We have used limiting dilution analysis (LDA) to derive quantitative estimates of the frequency of HIV-1-specific CTL precursors in a cross-sectional study of 23 patients at different clinical stages of HIV-1 infection and to compare these with the frequency of CTL precursors specific for another persistent virus (Epstein-Barr virus [EBV]) in the same patients. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with autologous HIV-1-infected lymphoblasts and assayed for cytotoxicity in 51Cr release assays against autologous and MHC-mismatched lymphoblastoid B cells infected with recombinant vaccinia viruses expressing the three HIV-1 structural gene products. The frequency of MHC-restricted precursors was high in asymptomatic HIV-1-infected patients (env-specific CTL precursors up to 73/10(6) PBMC; gag-specific CTL precursors up to 488/10(6) PBMC), although the relative frequency against the different structural gene products varied from patient to patient. The HIV-1-specific CTL precursor frequency was reduced in patients who had more severe (< 400/microliters) CD4+ lymphocyte depletion, while in the majority of such patients the frequency of CTL precursors against EBV was maintained at levels observed in healthy controls. Direct CTL activity in unstimulated PBMC was observed in three of nine patients but no correlation was found between the presence of an activated CTL response and the magnitude of the CTL response detected after stimulation in LDA. Thus, CTL precursors were detected against all three HIV-1 structural gene products in patients with CD4+ lymphocyte counts > 400/microliters, at frequencies that are high compared with those reported for other persistent viruses. A CTL response directed against multiple protein antigens of HIV-1 may protect the patient against epitope variation. The fact that the EBV-specific CTL precursor frequencies were maintained in advanced HIV-1 infection suggests that there may be selective impairment of the HIV-1-specific CTL response associated with disease progression.

Adult↗
PubMed1991

Mycobacterium kansasii: a cause of treatable pulmonary disease associated with advanced human immunodeficiency virus (HIV) infection.

OBJECTIVE: To assess the clinical features and response to therapy of Mycobacterium kansasii infection in patients with human immunodeficiency virus (HIV) infection. DESIGN: We reviewed the records of all patients with M. kansasii and HIV infection treated between January 1985 and June 1990. SETTING: The Johns Hopkins Hospital, Baltimore, Maryland. RESULTS: Nineteen patients with M. kansasii and HIV infection were identified; 14 patients had exclusive pulmonary infection, 3 patients had pulmonary and extrapulmonary infection, and 2 patients had exclusive extrapulmonary infection. At the time of diagnosis of M. kansasii infection, the median CD4+ lymphocyte count was 49 cells/microL (range, 0 to 198 cells/microL), and 16 of 19 patients had a previous diagnosis of the acquired immunodeficiency syndrome (AIDS). All 17 patients with pulmonary infection presented with fever and cough of at least 2 weeks duration. Chest radiographs showed either focal upper lobe infiltrates (n = 8) or diffuse interstitial infiltrates (n = 9); 9 patients also had thin-walled cavitary lesions. Nine patients with pulmonary M. kansasii infection were treated with antituberculosis chemotherapy, with resolution of fever and respiratory symptoms, improvement of radiographic infiltrates, and sputum conversion; 1 patient with M. kansasii osteomyelitis also responded to antituberculosis therapy. Autopsies done on 3 treated patients did not reveal any evidence of M. kansasii infection. Nine patients did not receive any antituberculosis chemotherapy; 2 untreated patients developed progressive cavitary pulmonary disease and died from M. kansasii pneumonia. CONCLUSIONS: Mycobacterium kansasii causes serious and potentially life-threatening pulmonary disease in patients with advanced HIV-related immunosuppression. In contrast to previous reports, our findings indicate that disease produced by M. kansasii in patients with HIV infection is responsive to antituberculosis chemotherapy.

Adult↗
PubMed2005

Pharmacokinetics of nevirapine in HIV-infected children receiving an adult fixed-dose combination of stavudine, lamivudine and nevirapine.

OBJECTIVE: To evaluate the steady state pharmacokinetics of nevirapine (NVP) in HIV-infected children receiving a fixed-dose combination of stavudine, lamivudine and NVP. METHODS: This cross-sectional study enrolled 34 children (18 girls) who had received GPO-VIR S30 (30 mg stavudine, 150 mg lamivudine and 200 mg NVP) for at least 8 weeks. Tablets were divided into quarter fractions (1/4, 1/2, 3/4 or 1 tablet) to attain the NVP dosages of 120-200 mg/m every 12 h. Plasma NVP levels were measured at predose, and at 2 and 6 h after drug administration. RESULTS: The median age was 8.4 years (range, 3-15). Median CD4 lymphocyte count and percentage at study entry was 576 x 10 cells/l and 20.25%, respectively. The median pharmacokinetics parameters were area under the curve at 12 h, 78.4 h x mug/ml; minimum plasma drug concentration, 5.98 microg/ml; plasma half-life, 25.5 h; apparent oral clearance, 0.079 l/kg per h; and volume of distribution, 2.95 l/kg. Only one child had a minimum plasma drug concentration < 3.4 microg/ml (2.57 microg/ml). Of the 13 children who received GPO-VIR as their first-line regimen, 12 had plasma HIV-1 RNA < 400 copies/ml at 6-18 months, with a median CD4 lymphocyte increase of 216 and 433 x 10 cells/l at 6 and 12 months of treatment, respectively. CONCLUSIONS: The administration of GPO-VIR S30 fixed-dose combination tablets in fractions or as a whole tablet to children resulted in appropriate NVP exposure and satisfactory virological and immunological benefit. This finding confirms the effectiveness of using a fixed-dose combination as a "transitional option" while waiting for a paediatric fixed-dose combination drug formulation.

Adolescent↗
PubMed1993

Lack of clinical utility of cytomegalovirus blood and urine cultures in patients with HIV infection.

OBJECTIVE: To determine the clinical significance of cytomegalovirus (CMV) blood and urine cultures in patients with human immunodeficiency virus (HIV) infection. DESIGN: Inception cohort of patients with HIV infection and CMV culture data. SETTING: Government referral-based research hospital. PATIENTS: A total of 322 HIV-infected patients who had a CMV blood culture and 293 HIV-infected patients who had a CMV urine culture within 7 days of a CD4 determination. MEASUREMENTS: Cytomegalovirus blood and urine culture results; circulating CD4 lymphocyte counts; pathologic or retinopathic findings of CMV disease. RESULTS: Nine of 26 patients (34.6%) with CMV viremia subsequently developed CMV end-organ disease compared with 11 of 74 (14.9%) patients without viremia, (difference, 19.7%; 95% CI, -0.3% to 39.7%). Fifteen of 47 patients (31.9%) with CMV viruria developed end-organ disease compared with 4 of 43 (9.3%) patients without viruria, (difference, 22.6%; CI, 6.7% to 38.5%). Cytomegalovirus culture positivity had poor predictive value for the subsequent development of end-organ disease (35% for viremia and 28% for viruria). Further, patients with proven end-organ disease were often not viremic (45%), but most were viruric (88%). Cytomegalovirus viremia did not correlate with the presence of either fever or weight loss in this patient group. Both blood culture positivity and urine culture positivity varied inversely with the CD4 count (P = 0.0001 for both associations). CONCLUSIONS: The likelihood that a blood or urine culture will be positive in a patient with HIV infection correlates better with immunologic status than with current or future clinical status. Although the absence of CMV viruria may suggest that CMV disease is not present, CMV blood and urine cultures have poor diagnostic and predictive value and therefore should be used primarily for research purposes or drug susceptibility testing and not for making clinical decisions.

Adult↗
PubMed1993

Pentoxifylline decreases tumor necrosis factor expression and serum triglycerides in people with AIDS. NIAID AIDS Clinical Trials Group.

Tumor necrosis factor-alpha (TNF)-cachectin increases the expression of the human immunodeficiency virus (HIV), reverses the therapeutic efficacy of zidovudine (ZDV), and may contribute to the wasting syndrome. Pentoxifylline (Trental) decreases TNF activity; in cell culture, it decreases HIV replication and down-regulates expression of the HIV long terminal repeat (LTR). Therefore, pentoxifylline was administered to 25 patients with advanced AIDS in this AIDS Clinical Trial Group study (ACTG #160), the goal of which was to investigate the ability of the drug to decrease TNF expression and HIV replication in this patient population. One patient discontinued drug treatment because of toxicity. Data were analyzed on the 17 patients who completed the 8-week study treatment with pentoxifylline, 400 mg, thrice daily. The median pretreatment CD4+ lymphocyte count was 32 cells/mm3. Fasting serum triglycerides, which have previously been shown to correlate with levels of interferon-alpha and/or TNF, fell on average by 66 mg/dl (p = 0.06). TNF mRNA levels in peripheral blood mononuclear cells fell in 10 of 16 patients (p = 0.02). HIV load decreased and increased significantly in four and one patients, respectively, but did not change in the group as a whole. This study demonstrates the safety of pentoxifylline in AIDS patients and its ability to decrease triglycerides and TNF mRNA levels.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Serum total and specific IgE levels in children infected with human immunodeficiency virus.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with polyclonal B-cell activation, and elevated IgE levels are found in infected adults. Chronic nasal symptoms, sinusitis, and otitis media are particularly common in children infected with HIV. The possible allergic cause of nasal symptoms in children infected with HIV has not been explored. OBJECTIVE: The study was designed to evaluate the relationship between HIV infection and IgE levels in a group of children infected with HIV. METHODS: Total serum IgE was measured by enzyme immunoassay and compared with values for age-matched normal subjects. Specific IgE was determined by RAST test to Dermatophagoides pteronyssinus, American cockroach, Bahia grass, short ragweed, cat, and oak. Lymphocyte subpopulations were determined by standard flow cytometry. RESULTS: Fifty-seven total IgE and 342 specific IgE levels were determined from 29 infected children (19 girls and 10 boys; ages, 7 to 150 months; mean age, 49 months). Initial IgE levels of 29 subjects ranged from 1.4 to 787.6 IU/ml (mean = 123.4 +/- 34.4 IU/ml). Nine of 29 (31%) subjects had initial IgE levels greater than two standard deviations higher than age-matched normal subjects. No patients had detectable specific IgE to any of the six aeroallergens. There was no correlation, as determined by linear regression analysis, between IgE levels and absolute CD4 number or CD4:CD8. CONCLUSION: Elevated total but not specific IgE is common in children infected with HIV and does not correlated with absolute CD4 lymphocyte count, suggesting that the elevated IgE level reflects a somewhat independent polyclonal activation of B-lymphocytes.

Adolescent↗
PubMed1992

Primary prophylaxis with fluconazole against systemic fungal infections in HIV-positive patients.

OBJECTIVE: To investigate the efficacy of fluconazole prophylaxis against systemic fungal infections in HIV-positive patients. DESIGN: Open label treatment compared with historical controls. SETTING: Patients were seen at the Parkland Memorial Hospital HIV Clinic, Dallas, Texas, USA between 1 March 1990 and 28 February 1991. PATIENTS, PARTICIPANTS: Three hundred and thirty-seven historical controls were followed for 157 patient-years, and 329 fluconazole-treated patients for 145 patient-years. INTERVENTIONS: Fluconazole (100 mg daily) was administered to all patients with CD4 lymphocyte counts less than 68 x 10(6)/l seen at our HIV clinic after 1 March 1990. MAIN OUTCOME MEASURES: Lysis-centrifugation blood cultures were recorded monthly for all patients during both study periods. RESULTS: Twenty infections (16 cryptococcosis, four histoplasmosis) occurred in 337 historical reference control patients (product-limit 1-year incidence, 7.5 +/- 2.0/year). Four infections (one cryptococcosis, three histoplasmosis) occurred in the treated patient group (product-limit 1-year incidence, 1.8 +/- 0.9/year). CONCLUSIONS: Fluconazole warrants further evaluation for prophylaxis against systemic fungal infections in HIV-positive patients.

Adult↗
PubMed2005

Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010.

The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy results in significant improvement in clinical outcome for individuals with non-HIV-associated aggressive B-cell lymphoma. To assess the potential risks and benefits of the addition of rituximab to CHOP for HIV-associated non-Hodgkin lymphoma (HIV-NHL) 150 patients receiving CHOP for HIV-NHL were randomized (2:1) to receive 375 mg/m(2) rituximab with each chemotherapy cycle (n = 99) or no immunotherapy (n = 50) in a multicenter phase 3 trial. The complete response rate (CR + CRu) was 57.6% for R-CHOP and 47% for CHOP (P = .147). With a median follow-up of 137 weeks, time to progression, progression-free survival, and overall survival times were 125, 45, and 139 weeks, respectively, for R-CHOP and 85, 38, and 110 weeks, respectively, for CHOP (P = not significant, all comparisons). Treatment-related infectious deaths occurred in 14% of patients receiving R-CHOP compared with 2% in the chemotherapy-alone group (P = .035). Of these deaths, 60% occurred in patients with CD4 counts less than 50/mm(3). Progression-free survival was significantly influenced by CD4(+) count (P < .001) and International Prognostic Index score (P = .022), but not bcl-2 status. The addition of rituximab to CHOP in patients with HIV-NHL may be associated with improved tumor responses. However, these benefits may be offset by an increase in infectious deaths, particularly in those individuals with CD4(+) lymphocyte counts less than 50/mm(3).

Adult↗
PubMed1996

Serum ferritin levels in normal and HIV-1 infected pregnant women.

Between May, 1994 and May, 1995 serum ferritin concentrations were measured in 74 pregnant women who were HIV-1 positive (17 with CD4 cell counts below 200 cells/uL) and in 148 HIV-1 negative pregnant controls in first trimester of gestation to determine if a high level of serum ferritin is present in pregnant women with HIV-1 infection. Comparisons were made between groups stratified by CD4 cell counts. Pregnant women with HIV-1 infection had 92% higher mean serum ferritin levels (112.8 versus 58.8 ug/L, p < 0.005) compared to controls, whereas the mean maternal age, parity, gestational age, haemoglobin levels and body mass index at entry into the study did not differ significantly between the control and HIV-1 infection groups. The serum ferritin levels inversely correlated with the percentage of CD4 lymphocytes, CD4 cell counts and the CD4/CD8 ratio. This study suggests that serum ferritin levels can also be used as an immunological marker in HIV-1 infected pregnant women.

Biomarkers↗
PubMed1996

[Colony-stimulating factors and HIV-related neoplasms].

OBJECTIVE: it is analyzed a group of patients with HIV related malignancy treated with myelosuppressive therapy with granulocyte colony stimulating factor (G-CSF) to study the efficacy of hematopoietic growth factors in these subjects. PATIENTS AND METHODS: it was studied the clinical and hematological evolution of 20 patients with HIV related malignancy treated with standard dose of chemotherapy and 5 micrograms/Kg/day of G-CSF starting 24 hours after the completion of chemotherapy administration. It was done an epidemiological study and was determined haemoglobin level, and the number of leukocytes, monocytes, neutrophils, lymphocytes, CD4+ lymphocytes and platelets before and after the chemotherapy administration. RESULTS: all of the patients were men with mean age of 37 +/- 2 years. The mean of lymphocyte CD4+ count was 17 x 10(6)/l and the tumor was the first aids manifestation in 50% of the subjects. The mean days of hospitalization was 14 +/- 3 days. As the result of the G-CSF administration, the leucocyte and the neutrophil count was statistically elevated (p < 0.01) and the platelets, the lymphocytes and the monocytes were not statistically elevated. Only one patient had a severe adverse reaction. Seventeen patients (85%) are dead, but only in 3 the cause was an infectious disease. CONCLUSION: the use of G-CSF prophylactically can elevate the neutrophil count and avoid the apparition of febrile neutropenia in patients with HIV related malignancies.

Adult↗
PubMed2005

[Recurrent strongyloidiasis as an indicator of HTLV-1 infection].

HISTORY AND CLINICAL FINDINGS: A 53-year-old West African man presented two years after a travel to Guinea because of severe headache, neck stiffnes, fever and pruritus. The patient had been in orthopedical treatment for the last five months. INVESTIGATIONS: Stool microscopy revealed a high number of Strongyloides stercoralis larvae. Hematology, biochemistry and all other parasitology results were normal. HIV-1/2 testing was negative and CD4+-lymphocyte count was normal. Concomitant infection by Human T Cell lymphotropic virus type 1 (HTLV-1) was confirmed by serology and PCR. The phylogenetic analysis confirmed African origin of the virus. TREATMENT: The infection responded to a five-day course of albendazol at 400 mg/d but during the following five years repeat recrudescences were observed inspite of high-dosage and prolonged antiparasitic treatments. Eventually, eradication of the infection was achieved by a four day course of ivermectin 0.2 mg/kg/d. CONCLUSIONS: Although both strongyloidiasis and HTLV-1 infections occur most frequently in tropical areas, these may also be observed in temperate regions. Suppression of the immune system by HTLV-1 differs from that by HIV. CD4+-lymphocytes were rarely decreased. Prolonged treatment with ivermectin in a dosage exceeding the current recommendations may be required in HTLV-1 infected patients and was well tolerated. The unusual presentation of the infection with muscular symptoms contributed to the delay of the diagnosis. HTLV-1 positive patients must be monitored for years. They and their partners must be instructed how to prevent transmission of the virus.

Albendazole↗
PubMed1990

Major histocompatibility complex genes influence the outcome of HIV infection. Ancestral haplotypes with C4 null alleles explain diverse HLA associations.

Several alleles at multiple HLA loci have been found to be associated with infection with human immunodeficiency virus (HIV): HLA A1; B8, B35; Cw7, Cw4; DR1, DR3 and DQ1, are associated with particular disease manifestations and/or disease progression. Furthermore, in a pilot study we have shown an increase in the frequency of C4 null alleles and suggested that all the reported HLA alleles could reflect association with a limited number of ancestral haplotypes (AHs). On this occasion, we studied 122 Caucasoid patients classified according to Centers for Disease Control (CDC) criteria. The control group consisted of 67 seronegative homosexual or bisexual males at risk of developing HIV infection. C4 null alleles were unequivocally present in 58% of patients in CDC IV compared with 33% of the seronegative subjects (chi 2 = 5.65, p less than 0.05). Furthermore, C4 null alleles could be excluded in only 8% and 16% of CDC III and IV, respectively, but in 30% of the seronegative subjects. An increased frequency of three AHs largely accounted for the increases in C4 null and HLA alleles. To examine the role of specific AHs we undertook a longitudinal analysis of a subgroup of 26 patients who seroconverted under observation. Seventeen of these patients were followed for 32 to 63 months. All seven patients with the 8.1 AH (A1, CW7, B8, BfS, C4AQ0, C4B1, DR3, DQ2) developed low CD4 lymphocyte counts (less than 450 x 10(6)/l) compared with only 2 of 10 patients without this haplotype (p less than 0.002). All three deaths occurred in patients with the 8.1 AH. The acquired immunodeficiency syndrome developed in three further cases with either 8.1- or B35-bearing (35.x) haplotypes. Sequential CD4/8 ratios showed an early and progressive decline in individuals with 8.1 or 35.x. Since the 8.1 and 35.x AHs contain deletions of the central major histocompatibility complex (MHC) genes, we suggest that the genes affecting HIV infection and progression are within the central MHC region.

Alleles↗
PubMed1993

Impact of the 1993 revision of the AIDS case definition on the prevalence of AIDS in a clinical setting.

OBJECTIVE: To determine the impact of the 1993 revision of the Centers for Disease Control and Prevention (CDC) AIDS surveillance case definition on the prevalence of AIDS. DESIGN: Review of prospectively collected baseline clinical and demographic data on HIV-infected patients presenting for care between December 1988 and May 1991. SETTING: The HIV Clinic of the Johns Hopkins Hospital, an urban, primary care institution. MAIN OUTCOME MEASURE: Diagnosis of AIDS by the 1987 (specific indicator diseases) or the 1993 (indicator diseases, pulmonary tuberculosis, recurrent bacterial pneumonia, cervical carcinoma, or CD4 lymphocyte count < 200 x 10(6)/l) CDC case definition. RESULTS: Of 955 patients evaluated, 122 (13%) had AIDS by the 1987 case definition at presentation. An additional 126 (13%) met the 1993 but not the 1987 case definition. Patients meeting only the 1993 case definition were more likely to be female [28 versus 14%; odds ratio (OR), 2.4; 95% confidence interval (CI), 1.2-3.0; P = 0.01] and intravenous drug users (40 versus 26%; OR, 2.0; 95% CI, 1.1-3.3; P = 0.02) than patients meeting the 1987 case definition. Fifty-five per cent of patients meeting only the 1993 case definition were asymptomatic, and 7% (nine patients) had new indicator diseases but CD4 counts > 200 x 10(6)/l. Median time to progression from a diagnosis of AIDS by the 1993 case definition to diagnosis by the 1987 case definition was 435 days. Patients with AIDS by the 1987 case definition had a median survival of 594 days from presentation (2-year survival, 42%), while median survival time for patients with AIDS by the 1993 case definition only was 947 days (2-year survival, 60%; P < 0.005). CONCLUSIONS: The proposed 1993 revision of the AIDS surveillance case definition would double the number of prevalent AIDS cases, with significant increases in the proportion of cases who are female, intravenous drug users, or asymptomatic. Survival of patients meeting the 1993 case definition is significantly longer than that of patients meeting the 1987 case definition. The new AIDS case definition will have a major impact both on AIDS surveillance and on medical and social service programs that use diagnosis of AIDS as a criterion for eligibility for services.

AIDS-Related Opportunistic Infections↗
PubMed1991

A multicenter trial of oral zidovudine in children with advanced human immunodeficiency virus disease. The Protocol 043 Study Group.

BACKGROUND AND METHODS: Zidovudine has been shown to be an effective antiretroviral treatment in adults with human immunodeficiency virus (HIV) infection. We examined the safety of zidovudine and the tolerance of and therapeutic response to the drug in 88 children with advanced HIV disease. During a 24-week outpatient trial, zidovudine (180 mg per square meter of body-surface area per dose) was given by mouth every six hours and serial measurements were made of clinical, immunologic, and virologic indexes. Children who completed 24 weeks of treatment were permitted to continue receiving zidovudine. RESULTS: Of the 88 children (mean age, 3.9 years; range, 4 months to 11 years), 61 completed the initial 24-week trial, and 49 continued to receive zidovudine for up to 90 weeks (median follow-up, 56 weeks). The patients generally tolerated zidovudine well. One or more episodes of hematologic toxicity occurred in 54 children (61 percent)--anemia (hemoglobin level, less than 75 g per liter) in 23 children (26 percent) and neutropenia (neutrophil count, less than 0.75 x 10(9) per liter) in 42 (48 percent). Many of these abnormalities resolved spontaneously, but 30 children required transfusions or a modification of the dose of zidovudine. Only three children had to stop receiving the drug because of hematologic toxicity. Kaplan-Meier analysis demonstrated that the probability of survival was 0.89 after 24 weeks and 0.79 after 52 weeks. There was marked improvement in weight gain, cognitive function (mainly in children less than 3 years old), serum and cerebrospinal fluid concentrations of p24 antigen, and the proportion of cerebrospinal fluid cultures negative for HIV. CD4+ lymphocyte counts (mean at base line, 0.263 x 10(9) per liter) improved during the first 12 weeks, although the improvement was not sustained through the 24th week. CONCLUSIONS: Zidovudine in a dose of 180 mg per square meter every six hours can be safely administered to children with advanced HIV disease. The resultant clinical, immunologic, and virologic improvements in children are similar to those reported with zidovudine in adults.

Acquired Immunodeficiency Syndrome↗