Immune complex transfer enzyme immunoassay for antibody IgM to HIV-1 p17 antigen

The immune complex transfer enzyme immunoassay for antibody IgM to HIV-1 p17 antigen is described. Serum samples containing antibody IgM to HIV-1 p17 antigen were incubated simultaneously with 2,4-dinitrophenyl-bovine serum albumin-recombinant p17 (rp17) conjugate and rp17-β-D -galactosidase conjugate, and the immune complex formed comprising the three components was trapped onto colored polystyrene beads coated with affinity-purified (anti-2,4-dinitrophenyl group) IgG. Subsequently, the immune complex was transferred to white polystyrene beads coated with monoclonal mouse (antihuman IgM) IgG in the presence of excess of ϵN-2,4-dinitrophenyl-L -lysine. The signal for antibody IgM to p17 antigen was the fluorescence intensity by fluorometric assay of β-D -galactosidase activity bound to the white polystyrene beads. The periods of time required for the formation, trapping, and transferring of the immune complex comprising the three components were more than 4 hr, 2 hr, and 3 hr, respectively. The immunoassay developed was shown to be specific by inhibition of transferring the immune complex in the presence of excess of nonspecific IgM but not IgG. Signals for antibody IgM to p17 antigen with serum samples of HIV-1 seroconversion serum panels,—that is, with serum samples in early stages of the infection—tended to be higher than those with serum samples from HIV-1 asymptomatic carriers probably long after the infection and patients with ARC and AIDS. In contrast, signals for antibody IgG to p17 antigen with serum samples of HIV-1 seroconversion serum panels tended to be higher than signals for antibody IgM to p17 antigen but were much lower than signals for antibody IgG to p17 antigen with serum samples from HIV-1 asymptomatic carriers and patients with ARC and AIDS. J. Clin. Lab. Anal. 12:329–336, 1998. © 1998 Wiley-Liss, Inc.     

Recovery of HIV antigen in peritoneal dialysis fluid

We investigated the presence of HIV antigen in dialysis fluid of patients with end-stage renal disease (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD), previously known to be infected with this virus. Sixteen adult patients and 6 adult volunteers were included in the study in 4 groups as follows: Group A: 3 patients on CAPD, previously known to be positive for serum HIV antibodies; Group B: 7 patients on CAPD, serum HIV negative; Group C: 6 AIDS patients without renal disease; and Group D: 6 healthy volunteers. Of the 3 patients of Group A, the HIV-1 Ag was positive in dialysis fluid in only 2. In 1, serum Ab and Ag were present, while in the others only serum Ab was detected. The samples from Group B were all negative for the viral antigen in dialysis fluid. We conclude that dialysis fluid of HIV-infected patients may contain the Ag and is therefore potentially infective. The presence of the HIV antigen was not constant, and was not related to antigenemia. It is possible that the presence of the Ag depends on local factors that influence viral replication or to alterations in the permeability of the peritoneal membrane. We discuss other possible factors that could influence the presence of viral Ag in peritoneal dialysis fluid.     

Quantitation of hiv-1 rna in blood cells of arc and aids patients

Peripheral blood mononuclear cells from HIV-1-infected persons were mixed with 5 M guanidine thiocyanate, and HIV-1-specific probes were hybridized with target RNA directly in the lysate. No RNA purification was needed. Hybrids were purified by repeated capture on superparamagnetic beads coated with oligo(dT) in a device-assisted format, a procedure termed “reversible target capture.” Blood mononuclear cells from 70 ARC and AIDS patients were examined and found to have an average of 1.8 × 10⁵ molecules of HIV-1 RNA per 2 × 10⁶ cells.     

57例抗HIV初筛阳性确认实验带型分析

目的 调查HIV感染初筛实验的准确率及确认抗HIV初筛试验阳性血清的感染和感染型别。方法 调查我国艾滋病高发农村，对部分初筛阳性和可疑的血清进行确认实验。结果 57例初筛为抗HIV阳性和可疑血清进行确认实验，56份为HIV—l阳性，其中1份样本出现HIV—2型反应条带；1份阴性。确认阳性标本的反应条带中，抗外膜蛋白(env)抗体阳性率最高，gpl60为100％，gpl20为94．6％，gp41为91．1％；多聚酶抗原(pol)p66为82．1％；核心抗原(gag)P24为53．6％。提示无症状携带组确认反应条带的pol和gag的阳性率显著高于艾滋病组(P＜0．01)。儿童组gag阳性率显著低于成人组(P＜0．05)。结论 HIV感染初筛实验的准确率较高，但确定感染需靠确认实验。外膜蛋白、p66和p24抗原是HIV感染的重要抗原，对确认HIV的感染具有指导意义。     

Immunogenicity of combined anti-HIV and anti-suppressive vaccine preparations.

HIV-1 antigens generate in man both a humoral and cellular immune reaction. However, in ARC/AIDS patients, the cellular response is inhibited by HIV-1 which induces an antiproliferative (suppressive) effect on activated T cells. To overcome this inhibition and up-regulate the cellular response, we designed a new vaccine strategy directed both against HIV-1 and immunosuppression and we used an immunizing preparation composed of HIV-1 antigens combined with immunoregulatory peptides prepared in a biologically inactivated but immunogenic form. In mice, this preparation induced anti-HIV-1 antibodies and a cell-mediated cytotoxicity directed against H2 restricted cells carrying HIV-1 antigens.     

Isothiazole derivatives as novel HIV replication inhibitors

A series of 3,4,5-trisubstituted isothiazoles has been screened against HIV-1 (IIIB) and HIV-2 (ROD) at sub-toxic concentrations in acutely infected MT-4 cells. Among the tested compounds, only 3-mercapto-5-phenyl-4-isothiazolecarbonitrile was found to inhibit the replication of HIV-1 (IIIB) and HIV-2 (ROD) at 50% effective concentrations (EC50) of 7.8 and 9.7 microg/ml, respectively. The presence of a thioalkyl chain or dialkylamino function in the 3-position caused a loss of anti-HIV activity. New 4-cyano-5-phenylisothiazoles with other substituents in the 3-position have also been synthesized and studied as potential anti-HIV agents. Our results have demonstrated that 5-phenyl-3-(4-cyano-5-phenylisothiazol-3-yl) disulphanyl-4-isothiazolecarbonitrile and S-(4-cyano-5-phenylisothiazol-3-yl)-O-ethyl thiocarbonate are effective against both HIV-1 (IIIB) (EC50=13.6 and 15.2 microg/ml, respectively) and HIV-2 (ROD) (EC50=17.4 and 13.4 microg/ml, respectively).     

Phenotypic changes in monocytes and alveolar macrophages in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC)

The expression of Class II histocompatibility antigens (HLA-DR and HLA-DQ), leukocyte function associated antigen (LFA-1) and complement receptor type 3 (CR3) on peripheral blood monocytes and alveolar macrophages (M phi) from patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) and age-matched controls was studied. The percentage of HLA-DR+ monocytes from 4 AIDS patients and 12 ARC patients was 52.4 +/- 16.4% (p less than 0.05) and 50.2+21.2% (p less than 0.01) respectively (Controls, 75.4 +/- 12.6%). HLA-DQ expression in monocytes from one AIDS and two ARC patients was 31%, 39% and 18% respectively (in normal individuals, DQ was expressed by approximately 40% monocytes). HLA-DR and HLA-DQ expression on alveolar M phi from one AIDS patient and 2 ARC patients were also depressed. CR3 was expressed by 65.9 +/- 11.1% monocytes from normal controls. Patients with AIDS had a slightly, but significantly lower, proportion of CR3+ monocytes (43.9 +/- 15.9%, p less than 0.05) (in normal controls, CR3 monocytes were 65.9 +/- 11.1%). However, monocytes from ARC patients and alveolar M phi from one AIDS and 2 ARC patients expressed CR3 in a normal range. LFA-1 was significantly depressed in monocytes from both AIDS (45.7 +/- 1%, p less than 0.005) and ARC (57.5 +/- 10.9%, p less than 0.005) patients in comparison with controls (87.4 +/- 8.7%). Only alveolar M phi from one AIDS patient could be studied for LFA-1 antigen and this was into the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)     

Debrisoquin hydroxylation polymorphism among Ghanaians and Caucasians.

The alicyclic and aromatic hydroxylation of debrisoquin was studied in Ghanaians. As in a previously studied Caucasian population, the alicyclic 4-hydroxylation of debrisoquin in Ghanaians was polymorphic. Three phenotypes were observed: homozygous extensive metabolizers (58%), heterozygous extensive metabolizers (36%), and homozygous poor metabolizers (6%). In contrast, British Caucasians are primarily monomorphic extensive metabolizers (92%) and homozygous poor metabolizers comprise 8% of the population. Urinary recovery of the drug and its hydroxylated metabolites was significantly less in the Ghanaian subjects. In both Ghanaian and British populations, aromatic hydroxylation producing 5-, 6-, 7-, and 8-hydroxydebrisoquin was shown to parallel the alicyclic 4-hydroxylation of debrisoquin, and thus to be controlled by the same gene locus. Debrisoquin is advocated as a tool for uncovering polymorphism in drug oxidation and its interethnic variations.     

Nortriptyline and debrisoquine hydroxylations in Ghanaian and Swedish subjects

Eleven Ghanaian and 12 Swedish subjects phenotyped with a debrisoquine (D) hydroxylation test were given a single oral dose of nortriptyline (NT). Much the same percentage of the given NT dose was excreted as 10-hydroxy-NT (10-OH-NT) by Ghanaians (43.1%) and Swedes (49.2%). There was a close correlation between plasma clearance of NT by 10-hydroxylation and the D metabolic ratio (D/4-OH-D in urine) in the Ghanaians (rs = -0.95; P less than 0.01) and Swedes (rs = -0.84; P less than 0.01). The E-isomer of 10-OH-NT is the major isomer in both Ghanaians (76% to 92% of total 10-OH-NT) and Swedes (78% to 95%). It is suggested that the E-10-hydroxylation of NT and the 4-hydroxylation of D are similarly coregulated in Ghanaians and Swedes.     

中国南方畲族人群中艾滋病感染相关等位基因基质细胞衍生因子1的频率和多态性分布

背景基质细胞衍生因子是嗜淋巴细胞人类免疫缺陷病毒1感染的体外潜在抑制因子,可阻断人类免疫缺陷病毒1侵入人体的通路.目的了解人类免疫缺陷病毒1感染相关等位基因基质细胞衍生因子-3'A在我国南方畲族人群中的频率和多态性分布,探讨畲族人未感染人类免疫缺陷病毒1的基因水平的可能原因.设计单一样本研究.单位赣南医学院生化与分子生物学教研室.对象于1995-01/12从畲族主要居住地江西省铅山县、福建省宁德地区和浙江省景宁畲族自治县随机选择3代均为畲族的186名无人类免疫缺陷病毒1感染的无关个体作为观察对象.方法随机采集血样186份,提取基因组DNA.经PCR-RFLP分析,计算基因突变频率;并对群体分布和性别分布进行统计分析.主要观察指标中国畲族人群基质细胞衍生因子1基因型构成.结果186人的数据均进入结果分析,无脱落者.基质细胞衍生因子-3'A频率为19.6%,群体分布符合Hardy-Weinberg平衡,性别之间无差异.结论南方畲族人的基质细胞衍生因子-3'A基因突变可能延缓艾滋病的发病进程,这一发现对于我国南方畲族人的艾滋病防治具有积极意义.     

The Efficacy and Toxicity of Azidothymidine (AZT) in the Treatment of Patients with AIDS and AIDS-related Complex (ARC): An Open Uncontrolled Treatment Study

SUMMARY The efficacy and toxicity of oral azidothymidine has been studiedin 145 patients with the acquired immunodeficiency syndrome(AIDS) or AIDS-related complex (ARC). The median survival time of AIDS patients on azidothymidinewas 4. 5 times higher when compared to a historical AIDS groupwho had not received the drug. This result must be interpretedwith caution because of changes in treatment of HIV infectionand growing awareness of AIDS which may have led to earlierdiagnosis in the group treated with azidothymidine. The mortality was significantly higher in those patients whoreceived transfusions and was particularly high in those whowere transfused before azidothymidine. There was a significantdifference in the occurrence of opportunistic infections inthe patients who received transfusions compared with those whodid not. AIDS patients treated immediately after an episode of Pneumocystiscarinii pneumonia survived significantly longer than those inwhom treatment was delayed for three months or more, and longerthan those who were treated with azidothymidine because of anotheropportunistic infection or Kaposi's sarcoma. The T4 cell median counts increased in patients treated withazidothymidine reaching a peak at the end of the fourth monthof treatment in the ARC group and at the end of the first monthin the AIDS group with a subsequent fall in both groups. Sixty percent of patients were p24 viral antigen positive atthe start of treatment and 19 percent of these patients hada fall of more than 50 percent in antigen level while 32 percentbecame antigen negative following treatment with azidothymidene.The mortality in the patients where the antigen disappearedor in whom there was a major fall of more than 50 percent inantigen level was significantly less than in those where therewas no change in antigen level. Twenty-nine patients were treated with azidothymidine becauseof skin Kaposi's sarcoma and in 17 tumour regressed or was stable. Thirty-two percent of patients treated with azidothymidine becameanaemic. Neutropenia occurred in 3 percent of patients. Plateletsincreased initially after treatment but subsequently fell tothrombocytopenic levels in eight patients. Nine of 12 patientswith thrombocytopenia before azidothymidine was commenced respondedwith an increased platelet count.     

Effects of glycyrrhizin (SNMC: Stronger Neo-Minophagen C) in hemophilia patients with HIV-1 infection

Forty-two hemophiliacs with HIV infection were treated with high-dose glycyrrhizin, Stronger Neo-Minophagen C (SNMC). The dose was 100-200 ml of SNMC in 21 patients and 400-800 ml in the other 21. The patients were divided into an asymptomatic carrier (AC) group and AIDS related-complex (ARC)/AIDS group. SNMC was administered intravenously daily for the first 3 weeks, and every second day for the following 8 weeks to the 42 HIV-infected hemophilia patients, in accordance with the protocol proposed by the Japanese National Research Committee. The CD4/CD8 ratio and CD4 positive lymphocyte counts did not change during the treatment period. However, significant improvement was noted in some cases. A slight increase in mitogenic responsiveness to phytohemagglutinin, Concanavalin A and pokeweed mitogen was noted in most patients of both groups, especially significant improvement was seen in the AC group administered over 400 ml of SNMC. Furthermore, complete improvement was noted in liver dysfunction, which has been thought to be one of the major problems for hemophiliacs treated with blood products. Thus, prophylactic administration of high-dose SNMC to HIV positive hemophiliacs who have impaired immunological ability and liver dysfunction was considered to be effective in preventing the development from AC/ARC to AIDS.     

CGP 53437, an orally bioavailable inhibitor of human immunodeficiency virus type 1 protease with potent antiviral activity.

CGP 53437 is a peptidomimetic inhibitor of human immunodeficiency virus type 1 (HIV-1) protease containing a hydroxyethylene isostere. The compound inhibited recombinant HIV-1 protease with a Ki of 0.2 nM. The inhibition constant versus human cathepsin D and human cathepsin E was 4 nM. Human pepsin and gastricsin were inhibited with Kis of 8 and 500 nM, respectively, and human renin was inhibited with a Ki of 190 microM. The replication of HIV-1/LAV, HIV-1/Z-84, and HIV-1/pLAI was inhibited with a 90% effective dose of 0.1 microM in acutely infected MT-2 cells. The 50% cytotoxic dose was 100 microM. Similar antiviral activity was observed when the compound was added up to 10 h after infection. At the effective concentration, processing of Gag precursor protein p55 was greatly reduced, confirming an action on the late stage of the virus life cycle, as expected. The efficacy of the inhibitor was also demonstrated by using primary human peripheral blood lymphocytes infected with the HIV-1/LAV strain, low-passage clinical isolates obtained from HIV-1-seropositive individuals (including a zidovudine-resistant strain), and HIV-2/ROD. In these cells, CGP 53437 delayed the onset of HIV replication in a dose-dependent fashion (substantial effects with concentrations of > or = 0.1 microM) as long as the inhibitor was maintained in the culture. CGP 53437 was orally bioavailable in mice. Concentrations in plasma 10-fold in excess of the in vitro antiviral 90% effective dose could be sustained for several hours after oral application of 120 mg/kg. Therefore, CGP 53437 has the potential to be a therapeutically useful anti-HIV agent for the treatment of AIDS.     

Detection of human immunodeficiency virus type 1 p24 antigen and plasma RNA: relevance to indeterminate serologic tests

BACKGROUND: Most enzyme immunoassay-reactive specimens producing indeterminate Western blot results belong to individuals who are not infected with human immunodeficiency virus type 1 (HIV-1). However, a small percentage may correspond to early seroconversion or advanced disease, at which stage partial reactivity on Western blot may be observed. STUDY DESIGN AND METHODS: To determine the utility of HIV-1 p24 antigen and cell-free RNA detection for the resolution of Western blot-indeterminate serologic results, several types of enzyme immunoassay-positive, sero-indeterminate specimens were analyzed. Samples were obtained from infected individuals at the time of seroconversion (n = 20), from patients with AIDS (n = 2), as specimens from clinical samples obtained for diagnostic testing (n = 57), from blood donors producing persistent indeterminate results (n = 47), and from random blood donors (n = 72). RESULTS: HIV-1 p24 antigen was detected in 10 of 20 specimens collected from 9 of 12 individuals who seroconverted and in 2 of 2 AIDS patients. HIV-1 plasma RNA was positive in 22 of 22 samples from those 14 individuals. All of 57 diagnostic specimens and 47 samples obtained from persistently indeterminate donors were negative for HIV-1 p24 antigen and plasma HIV- 1 RNA. One of 72 blood donor specimens was positive for HIV-1 plasma RNA and had borderline reactivity for p24 antigen. CONCLUSION: The detection of plasma RNA appears to be sensitive and specific; negative test results may be used to identify false-positive serologic reactions. The detection of p24 antigen and plasma RNA can also be used to confirm HIV-1 infection in persons with indeterminate serologic results associated with early seroconversion or late-stage disease.     

Changes in the clinical symptomatology of initial manifestations of aids

We analysed the clinical spectrum of AIDS manifestations of HIV positive patients treated between 1985 and 1988 at the University Hospital of Düsseldorf, West-Germany. In 1985 32 patients with HIV infection (16 asymptomatic, eleven PGL/ARC, five AIDS), 1986 49 patients (17 asymptomatic, 19 PGL/ARC, 13 AIDS), 1987 104 patients (13 asymptomatic, 54 PGL/ARC, 37 AIDS) and 1988 206 patients (23 asymptomatic, 111 PGL/ARC, 72 AIDS) were treated on a in- and out-patient basis. In 1985 five, in 1986 13, in 1987 36 and in 1988 48 patients developed AIDS. Kaposi-sarcoma was seen in 1985 in 40%, in 1986 in 31%, in 1987 in 12% and in 1988 in 9% of these cases. At the same time the rate of patients with opportunistic infections as the primary manifestation of AIDS grew from 60% (1985), 69% (1986), 88% (1987) to 91% (1988). Concomitantly the rate of homosexual patients dropped from 90% (1985), 82% (1986), 60% (1987) to 62% (1988). The rate of i.v. drug abuser rose from 10% (1985) to 24% (1988). In 1985 10% of HIV patients were female. This rate rose up to 18% in 1988. 1987 and 1988 the main opportunistic infections as the primary manifestation of AIDS were pneumocystis carinii pneumonia, toxoplasma encephalitis and candida esophagitis. In summary there is an alteration in the HIV positive population in the last years and concomitantly the clinical spectrum of AIDS is changing.     

Effect of foscarnet on quantities of cytomegalovirus and human immunodeficiency virus in blood of persons with AIDS.

Four intravenous dosages of foscarnet given for 10 days were compared with no therapy in persons with AIDS who had asymptomatic cytomegalovirus (CMV) viremia. CMV viremia was quantitated by endpoint cell dilution microcultures, pp65 antigenemia assay, and measurement of CMV DNA in peripheral blood leukocytes by a quantitative-competitive PCR. Human immunodeficiency virus type 1 (HIV-1) viremia was quantitated by endpoint cell dilution microculture, serum p24 antigen assay, and PCR for HIV-1 RNA in plasma. Twenty-seven subjects who had received a median of 22 months of nucleoside antiretroviral therapy were enrolled. Twenty-two subjects received foscarnet, which was well tolerated and decreased the CMV burden, as reflected by all three indicator assays. During the 10 days of dosing, the level of CMV viremia, as measured by 50 percent tissue culture infective doses, decreased from 117.5 to 12.7 (P = 0.001), the amount of CMV DNA decreased from 20,328 copies to 622 copies per 150,000 leukocytes (P = 0.02), and the level of CMV pp65 antigenemia decreased from 14.9 to 1.6 positive peripheral blood mononuclear cells per 50,000 leukocytes (P = 0.008). A significant pharmacodynamic relationship was found between the peak foscarnet concentration and a decrease in the level of CMV antigenemia (P < 0.05). Foscarnet had no effect on quantitative HIV-1 microcultures during the 10 days of treatment, but the HIV-1 p24 antigen level in serum decreased significantly, from 454 to 305 pg/ml (P = 0.01). Also, a significant pharmacodynamic relationship was seen between plasma HIV-1 RNA concentrations and both peak foscarnet concentration (P < 0.01) and the area under the foscarnet time-concentration curve (P < 0.05). Reductions in the levels of CMV and HIV-1 viremia correlated quantitatively with systemic exposure to foscarnet, whereas control subjects actually experienced an increase in CMV and HIV-1 burdens. The dual antiviral activity of foscarnet shown in this trial encourages investigation of its use in combination with other antiretroviral therapies for persons with AIDS.     

Raised serum beta 2 microglobulin levels in different stages of human immunodeficiency virus infection

Serum beta 2 microglobulin (beta 2-M) levels were determined in patients with Acquired Immunodeficiency Syndrome (AIDS), AIDS Related Complex (ARC), Persistent Generalized Lymphadenopathy (PGL), healthy intravenous drug addicts (IVDA) and heterosexual controls. Seventy-eight out of 79 AIDS patients (98.7%) exhibited elevated beta 2-M levels. High levels of beta 2-M were also found in 83 of 100 (83%) of PGL/ARC patients and in 24 of 56 (42.8%) healthy IVDA. Patients with AIDS had significantly higher mean beta 2-M levels when compared with all other groups. The mean levels of PGL/ARC patients were significantly higher than those of healthy IVDA and the mean levels for healthy IVDA significantly differ from those of the heterosexual controls. After 2-24 months of follow up three out of four PGL/ARC patients whose serum beta 2-M was greater than 8.0 mg/l developed AIDS.     

Human immunodeficiency virus type 1 activation after blood transfusion

BACKGROUND: Anemia and transfusion are predictors of disease progression in AIDS patients. This study was designed to examine the effects of blood transfusion on human immunodeficiency virus type 1 (HIV-1) expression. STUDY DESIGN AND METHODS: Assays of plasma viral load were performed before and after transfusion in nine HIV-1-infected patients who required blood transfusion for refractory anemia. RESULTS: There was a modest rise in plasma HIV-1 p24 antigen and plasma HIV-1 RNA beginning 1 to 2 weeks after the blood transfusion. The mean change in plasma p24 antigen for all patients was 9.3 +/− 5.1 (mean +/− SE) pg per mL at Week 2 after transfusion and 18 +/− 11.1 pg per mL at Week 4. Plasma HIV-1 RNA levels were unchanged immediately after transfusion and exceeded pretransfusion levels with a mean rise of 84 +/− 40 percent (SE) at Week 1, 70 +/− 27 percent at Week 2, and 67 +/− 38 percent at Week 4 (p equals; 0.006, exact permutation test). There was no increase in spontaneous or interleukin 2-induced lymphocyte proliferation or p24 antigen production by patients' lymphocytes that were examined immediately after blood transfusion. CONCLUSION: The transfusion of blood to persons with advanced HIV-1 infection modestly increases plasma levels of HIV-1. The activation of HIV-1 expression by transfusion may help to explain the accelerated course of HIV-1 disease in recipients of blood transfusion.     

Retrospective study correlating clinical infectious history and peripheral blood T-cell subpopulations in cancer, GvH and HIV+ patients.

The CD4+ CD8- inducer helper cell and the CD4- CD8+ cytotoxic/suppressor cell absolute numbers were measured in the peripheral blood of patients with various pathological conditions: with leukemia-lymphomas or solid tumors, patients with bone marrow grafts suffering from GvH, HIV-1 asymptomatic carriers, ARC and AIDS patients. The study was carried out during observation periods when they were not suffering from opportunistic infections and were untreated. In all the groups a decrease of the CD4+ CD8- cell absolute number was observed. In the leukemia-lymphoma and solid tumor bearing patients the CD4- CD8+ absolute value was lower than normal, while in the GvH- and HIV-infected patients, it was significantly higher. The clinical follow-up of each group indicates that GvH, ARC and AIDS patients developed infection in 40-68% of the cases, ie the only groups at risk of infection are those in which the CD4- CD8+ absolute values are high: we suggest that the balance CD4+ versus CD8+ should be considered rather the absolute CD4+ when discussing appropriate use of immuno-regulators.     

Synthesis and screening for anti-HIV activity of some N-Mannich bases of isatin derivatives

The effect of about 12 new compounds of Mannich bases of isatin against HIV-1 (IIIB) and HIV-2 (ROD) strains in MT 4 cells was studied. The screening method employed was MTT. In initial studies, one compound has shown maximum protection of 16% in subtoxic concentration.