Limited impact of the thymus on immunological recovery during and after chemotherapy in patients with diffuse large B-cell lymphoma.

To investigate the impact of thymus on immunological recovery after dose-dense chemotherapy a prospective study of 17 patients diagnosed with diffuse large B-cell lymphoma (DLBCL) was conducted. Patients were monitored before, during and until 3 months after chemotherapy. The thymus was visualized using computer tomographic scans. Patients were divided into two groups according to thymic size, one group comprising of patients without detectable thymus and one group of patients with detectable thymus. Naïve CD4 and CD8 counts were measured by flow cytometry, and to measure thymic output determination of CD4+ cells containing T-cell receptor excision circles (TREC) was done. During chemotherapy, the naïve CD4 count decreased significantly as did the CD4-TREC%. Significant difference in recovery of naïve CD4 counts between patients with detectable and undetectable thymic tissue during treatment with chemotherapy was not found. CD4-TREC% was associated with lower age. It was not possible to demonstrate an association between thymic size and recovery of the naïve CD4+ cells. The study terminated 3 months after the last cycle of chemotherapy, and at that time point the naïve CD4 counts and the CD4-TREC% had not returned to pretreatment levels. However, patients with detectable thymic tissue had higher naïve CD4 counts after the first cycles of chemotherapy, suggesting that these patients may be less susceptible to infectious complications related to chemotherapy.

Regulatory T cells in human immunodeficiency virus-infected patients are elevated and independent of immunological and virological status, as well as initiation of highly active anti-retroviral therapy.

Infection with human immunodeficiency virus (HIV) causes a dysregulation of the immune system. This is caused by HIV-specific as well as non-specific mechanisms and has not been explained fully. In particular, knowledge is lacking about the potential role of host-mediated immunosuppressive mechanisms. During recent years it has become evident that a subpopulation of T cells [T regulatory (T(regs))] play a major role in sustaining tolerance to self-antigens. To investigate the influence of initiation of highly active anti-retroviral therapy (HAART) on the T(reg) level in HIV-infected patients we have conducted a prospective study enrolling treatment-naive HIV-infected patients just prior to starting treatment with HAART, measuring levels of T(regs) by flow cytometry and mRNA expression of forkhead box P3 (FoxP3) at weeks 0, 4, 12 and 24 of treatment. In this prospective study neither the percentage of CD4(+)CD25(high+) nor the expression of FoxP3 changed significantly during 24 weeks of HAART. Furthermore, HIV patients have higher T(regs) measured as percentages of CD4(+)CD25(high+) cells paralleled by higher levels of FoxP3 compared with healthy controls. The elevated level of T(regs) was found to be independent of both immunological and virological status, indicating that initiation of HAART has minor effects on the T(reg) level in HIV-infected patients.

Non-adherence to anti-hypertensive medication in low- and middle-income countries: a systematic review and meta-analysis of 92443 subjects.

Hypertension is a rising global burden, and low- and middle-income countries account for 80% of deaths due to complications of hypertension. Hypertension can be controlled by adhering to anti-hypertensive medication. However, non-adherence is an increasing challenge. This review aims to systematically evaluate non-adherence to anti-hypertensive medication among adults in low- and middle-income countries and explore factors affecting non-adherence to anti-hypertensive medication. We performed a systematic search for studies published between 1 January 2000 and 31 August 2015. A selection process was performed for data extraction with a combination of Medical Subject Headings terms: 'hypertension' and 'adherence'. Further search criteria were: language ('english'), species ('humans'), and low- and middle-income countries. A total of 22 studies met the inclusion criteria. The pooled percentage of non-adherence when using the eight-item Morisky Medication Adherence Scale (MMAS) was 63.35% (confidence of interval (CI): 38.78-87.91) and 25.45% (CI:17.23-33.76) when using the 80 and 90% cut-off scales. The factors were classified into the five dimensions of adherence defined by the World Health Organization, and the majority of the studies reported factors from the dimension 'social and economic factors'. This systematic review demonstrated considerable variation of non-adherence to anti-hypertensive medication in low- and middle-income countries depending on the methods used to estimate non-adherence. The results showed a high non-adherence when the MMAS eight-item scale was used and low when the 80 and 90% cut-off scales were used. The majority of factors affecting non-adherence to anti-hypertensive medication fell within the World Health Organization defined dimension 'social and economic factors'.

Predictive value of soluble haemoglobin scavenger receptor CD163 serum levels for survival in verified tuberculosis patients.

Pre-treatment serum levels of sCD163 were measured in a cohort of 236 suspected tuberculosis (TB) cases from Guinea-Bissau, with a median follow-up period of 3.3 years (range 0-6.4 years). In 113 cases, the diagnosis of TB was verified by positive sputum microscopy and/or culture. Among the verified TB cases, a decreased survival rate was found in 27 patients with sCD163 levels above the upper reference limit (3.95 microg/mL). The difference in survival was significant during TB treatment (log rank, p<0.02) and after long-term follow-up (log rank, p<0.001). The decrease in survival rate during TB treatment remained significant in a multivariate Cox model controlling for human immunodeficiency virus (HIV) status, age and gender, with a mortality increase of 1.19 (95% CI, 1.04-1.36) per microg of sCD163, and a hazard ratio (HR) for sCD163 levels above the upper reference limit of 4.18 (95% CI, 1.06-16.4). The difference was not significant after excluding patients with concomitant HIV-1 and HIV-2 infection in Kaplan-Meier analyses (log rank, p 0.11). In contrast, the difference in survival remained significant in Kaplan-Meier analyses after long-term follow-up, even after excluding patients with concomitant HIV-1 and HIV-2 infection (log rank, p 0.002). In the Cox model, the mortality increase per microg of sCD163 was 1.27 (95% CI, 1.14-1.40), with an HR for elevated sCD163 levels of 2.85 (95% CI, 1.44-5.63). The HRs for concomitant HIV-1 and HIV-2 infection were 6.92 (95% CI, 3.28-14.58) and 2.48 (95% CI, 1.09-5.67), respectively. Thus, sCD163 levels appeared to be an independent predictor of survival in verified TB patients.

Suppression of p24 antigen in sera from HIV-infected individuals with low-dose alpha-interferon and zidovudine: a pilot study.

On the basis of the observations that HIV antigenaemia indicates a high risk of progression to AIDS and that zidovudine and alpha-interferon act synergistically against HIV replication in vitro, we performed a pilot trial including 12 HIV-infected asymptomatic patients with detectable p24 antigen in serum. The patients received low-dose lymphoblastoid alpha-interferon alone for 4 weeks followed by a combination of interferon and low-dose zidovudine for a further 16 weeks. The median p24 antigen level decreased significantly (P less than 0.01), the decrease being most pronounced at week 5. Decreases in haemoglobin and neutrophil counts were observed. Four patients required reduction of the zidovudine dose and three patients were transfused. In conclusion, the drug combination was capable of reducing the serum level of HIV p24 antigen and it was tolerated by the patients. Further studies are required to evaluate the clinical implications of these observations.

CD4 lymphocyte counts and serum p24 antigen of no diagnostic value in monitoring HIV-infected patients with pulmonary symptoms.

The diagnostic value of the CD4 cell counts and the HIV p24 antigen were evaluated in a consecutive series of 105 HIV-infected patients experiencing 128 episodes of pulmonary symptoms which required bronchoscopy. One-third of patients with opportunistic infection (OI) had CD4 counts greater than 0.200 x 10(9)/l, and 60% of patients without OI had CD4 counts less than 0.200 x 10(9)/l; 47 and 42% of patients with and without OI, respectively, had detectable p24 antigen in serum. Only 36% of the patients with OI presented the combination of CD4 cells less than 0.200 x 10(9)/l and p24 in serum. In conclusion, the CD4 cell counts and the presence of p24 antigen in serum had a very limited predictive value for the presence of OI in HIV-infected patients with pulmonary symptoms.

Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors.

Three virus isolates HTLV-IIIB/lyA, HTLV-IIIB/lyB and HTLV-IIIB/lyO, obtained by passaging and propagating the HTLV-IIIB/H9 isolate in three separate cultures of mixed peripheral blood mononuclear cells (PBMC) from donors of blood type A, B or O, respectively, were tested for susceptibility for virus neutralization by the monoclonal antibody (MAb) AH16 directed against the blood group A epitope. MAb AH16 was previously shown to inhibit cell-free virus infection using HTLV-IIIB propagated in H9 cells. AH16 showed a concentration-dependent inhibition of the HTLV-IIIB/lyA isolate but did not inhibit the HTLV-IIIB/lyB or the HTLV-IIIB/lyO isolate. Specificity of the MAb-mediated inhibition was shown using A-antigen (tetrasaccharide). Thus, HIV infection of PBMC from donors with blood type A appears to induce expression of host-cell-encoded carbohydrate blood group A epitope on HIV which can be a target for MAb-mediated virus neutralization.

Correlation between carbohydrate structures on the envelope glycoprotein gp120 of HIV-1 and HIV-2 and syncytium inhibition with lectins.

The binding of 13 different lectins to gp120 partially purified from two HIV-1 isolates and one HIV-2 isolate was studied by in situ staining on electrophoretically separated and electroblotted HIV antigens. The lectins concanavalin A, wheat germ agglutinin, Lens culinaris agglutinin, Vicia faba agglutinin, Pisum sativum agglutinin and phytohaem(erythro)agglutinin bound to gp120 of all three isolates. The carbohydrate of gp120 recognized by lectins was thus arranged in at least four types of glycans: a high mannose type glycan, a bisected hybrid or complex type glycan, a biantennary fucosylated complex type glycan and a triantennary bisected complex type glycan. Only lectins which bound at least one of the four types of glycans were capable of inhibiting fusion of HIV-infected cells with CD4 cells by a carbohydrate-specific interaction with the HIV-infected cells. Thus, several different glycan structures may be implicated in CD4-gp120 binding.

Trends in survival of Danish AIDS patients from 1981 to 1989.

Length of survival was analysed in relation to year of diagnosis, AIDS-indicative disease, age, risk behaviour, zidovudine therapy, and CD4 cell count and serum immunoglobulin (Ig) levels at the time of diagnosis in a group of 231 consecutive adult Danish AIDS patients reported before 1 January 1988. The cumulative survival rate was 53% (95% confidence interval 47-59%) at 1 year, 29% (22-36%) at 2 years and 18% (10-26%) at 3 years. Length of survival increased significantly (P less than 0.001) over time for patients who were initially diagnosed with Pneumocystis carinii pneumonia (PCP), 17% (3-31%) at 2 years prior to 1986, 32% (16-49%) in 1986 and 52% (34-69%) in 1987, whereas survival remained stable for patients with other AIDS-indicative diseases. Survival was similar for patients who were diagnosed with Kaposi's sarcoma alone and PCP alone. Independent predictors of a shortened survival were a CD4 cell count less than 200 x 10(6)/l, a serum IgA level greater than 4 g/l, and an initial diagnosis with opportunistic infections other than PCP. In addition, the multivariate analysis suggested an improved survival in recent years for patients diagnosed with PCP, independent of other factors examined. We conclude that length of survival in AIDS patients is highly variable. Determinants of progression include CD4 cell count, serum IgA level, and presenting disease. Survival has increased markedly for patients with PCP and median survival now exceeds 24 months.

Buspirone, a serotonin receptor agonist, increases CD4 T-cell counts and modulates the immune system in HIV-seropositive subjects.

OBJECTIVE: We have previously shown that drugs that decrease intracellular cAMP levels increase/restore the proliferative and cytotoxic capacity of T cells from HIV-seropositive subjects in vitro. Buspirone, a serotonin receptor agonist, indirectly decreases intracellular cAMP levels in T cells and has the same increasing/restoring effect on T-cell proliferation in lymphocytes from HIV-seropositive subjects in vitro. DESIGN: Buspirone was given as a single high dose to six HIV-seropositive subjects, or as continuous medication with increasing dosage over 6 weeks to nine HIV-seropositive subjects, with CD4 T-cell counts of 150-300 x 10(6)/l. RESULTS: Significant increases in CD4 T cells, CD4 percentage and CD4/CD8 ratio were found 1 week after a single high dose of buspirone was administered. With continuous administration, a significant increase in CD4 T cells was observed after 1 and 4 weeks. Serum HIV RNA showed a significant decrease 1 h after a single dose of buspirone was administered. With continuous administration of buspirone, plasma HIV RNA first increased within the first 2 weeks of treatment and then decreased towards and below baseline concurrently with a significant decrease in CD8T cells. The proliferative T-cell response to poke weed mitogen and membrane expression of IL-2R increased significantly during continuous treatment with a significant decrease in expression of HLA-DR on CD8+ T cells. Development of "flu-like' symptoms, so severe that two patients withdrew from the study and two patients ceased medication before time, was a clinical indication of modulation of the immune system by buspirone. CONCLUSION: The study shows that buspirone modulates the immune system and leads to changes in the CD4 and CD8 T-cell numbers, functional capacity, cell maturation and viral load.

Heterozygosity for a deletion in the CKR-5 gene leads to prolonged AIDS-free survival and slower CD4 T-cell decline in a cohort of HIV-seropositive individuals.

OBJECTIVE: Recently, it has been shown that a homozygous 32 base-pair deletion in the gene encoding CKR-5, a major coreceptor for HIV-1, leads to resistance to infection with HIV-1. We have investigated whether HIV-seropositive individuals who were heterozygous for the CKR-5 deletion had a different course of the disease. DESIGN: Thirty-five high-risk HIV-seronegative and 99 HIV-seropositive Danish homosexual men followed form 1985 to 1996 and 37 blood donors were analysed for their CKR-5 genotype by polymerase chain reaction. RESULTS: Two (6%) of the 35 HIV-seropositive subjects at high-risk of infection were homozygous and seven (20%) were heterozygous for the CKR-5 deletion. This was not significantly different from the distribution in normal donors. Twenty-two (22%) of the 99 HIV-seropositive subjects were heterozygous and none was homozygous. Two subgroups of patients who had an opposite course of the HIV disease were identified. Of nine long-term non-progressors, six (66%) were heterozygous for the deletion. This frequency is significantly higher than in nine rapid progressors of whom non was heterozygous. The frequency of heterozygotes in long-term non-progressors was also significantly higher than in the cohort as a whole. A Kaplan-Meier plot of the HIV-seropositive subjects, of whom 57 developed AIDS, showed a significantly better prognosis within the first 7 years of follow-up for those who were heterozygous for the deletion. Heterozygous individuals also had a significantly slower decrease in CD4 T-cell count per year. CONCLUSION: Individuals who are heterozygous for the 32-base-pair deletion in the CKR-5 gene have a slower decrease in their CD4 T-cell count and a longer AIDS-free survival than individuals with the wild-type gene for up to 11 years of follow-up.

High incidence of hepatitis B infection and evolution of chronic hepatitis B infection in patients with advanced HIV infection.

Two hundred eleven HIV-seropositive patients with AIDS, AIDS-related complex, or a CD4+ cell count less than 200 x 10(6) were examined for the presence of hepatitis B virus markers during the course of their HIV infection (median follow-up of 18 months; range of 1 to 107 months). Anti-HBs was detected initially in 138 patients (65%). Sixteen patients (8%) were HBsAg positive at entry. Fourteen had chronic HBV infection of whom 12 initially were positive for HBeAg and HBV DNA; 11 remained positive during follow-up, whereas one seroconverted to anti-HBe and lost HBV DNA. Two patients with chronic HBV infection were initially negative for HBeAg and HBV DNA: one later had reactivated HBV replication and one cleared HBeAg following onset of hepatitis D infection. The last two HBsAg-positive patients had resolving acute HBV infection. Six of the 57 patients who initially were negative for HBV markers acquired HBV infection during follow-up. Four of these six patients developed chronic infection whereas two patients had acute subclinical resolving hepatitis. In addition, four patients became HBsAg positive with their last serum samples, possibly indicating reactivation of HBV infection following progressive immunological and clinical deterioration. None of the patients developed clinical symptoms that could be ascribed to HBV infection, and transaminase elevations were only sporadically recorded. It is concluded that acquisition of HBV infections is not infrequent in HIV-seropositive patients with immune deficiency. Furthermore, the course of both previously established chronic HBV infection and newly acquired HBV infection is modified in such patients, whereas reactivation of past HBV infection seems to be a rare event.

Autologous HIV-1 neutralizing antibodies: emergence of neutralization-resistant escape virus and subsequent development of escape virus neutralizing antibodies.

The capacity of consecutive human sera to neutralize sequentially obtained autologous virus isolates was studied. HIV-1 was isolated three times over a 48-164-week period from three individuals immediately after seroconversion and from two individuals in later stages of infection. Development of neutralizing antibodies to the primary virus isolates was detected 13-45 weeks after seroconversion. Emergence of escape virus with reduced sensitivity to neutralization by autologous sera was demonstrated. The patients subsequently developed neutralizing antibodies against the escape virus but after a delay. Titers of neutralizing antibodies against late virus isolates were generally low compared to initial neutralizing titers against primary virus isolates. The delay in appearance of neutralizing antibodies to the dominant viral strain at any time in the patient and the emergence of neutralization resistant escape virus may be part of the explanation of the apparent failure of the immune system to control HIV infection.

Aerosolized pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia: a controlled, randomized trial.

The objective was to assess the efficacy of a biweekly dose of 60 mg aerosolized pentamidine (AP) for primary prophylaxis (PP) of Pneumocystis carinii pneumonia (PCP) and the impact of prophylaxis on survival in HIV-infected patients. Participants were AIDS patients with no history of PCP, patients with a CD4 count < or = 0.200 x 10(9)/L, or patients belonging to the CDC group IVC2, irrespective of CD4 count. It was an open, randomized, controlled trial. Patients were assigned to receive AP, 60 mg biweekly via a System 22 nebulizer, or to a control group not receiving any prophylaxis. Incidence curves for PCP and survival were generated using the Kaplan-Meier method, stratified by treatment group, and compared using the log-rank test. Data were analyzed according to intention to treat. There were 15 cases of PCP among 105 patients in the AP group and 32 cases among 104 patients in the control group. The cumulative incidence of PCP by 18 months was 13% (95% CI 5-21%) in the AP group and 30% (95% CI 18-41%) in the control group, (p = 0.002). During the study period 19 patients (18%) in the AP group died and 24 patients (23%) in the control group (NS; p = 0.28). We conclude that a biweekly dose of 60 mg AP is efficient as primary PCP prophylaxis when a System 22 nebulizer is used. There was, however, no difference in survival between the groups, suggesting that AP has an impact on morbidity only.

Neutralization epitopes on HIV pseudotyped with HTLV-I: conservation of carbohydrate epitopes.

One mechanism for expanding the cellular tropism of human immunodeficiency virus (HIV) in vitro is through formation of phenotypically mixed particles (pseudotypes) with human T lymphotropic virus type I (HTLV-I). In this study we found that pseudotypes allow penetration of HIV particles into CD4-negative cells, previously nonsusceptible to HIV infection. The infection of CD4-negative cells with pseudotypes could be blocked with anti-HTLV-I serum but failed to be significantly inhibited with anti-HIV serum or a V3-neutralizing anti-gp120 monoclonal antibody. This may represent a possibility for pseudotypes to escape neutralization by the immune system in vivo. Previous reports have suggested that carbohydrate structures may be conserved neutralization epitopes on retroviruses. In this study, the neutralizing capacity of lectins and anti-carbohydrate monoclonal antibodies was found to block infection by cell-free pseudotypes in CD4-negative cells. We suggest that although viral cofactors might expand the tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate neutralization epitopes.

Ranitidine improves certain cellular immune responses in asymptomatic HIV-infected individuals.

Human immunodeficiency virus (HIV) infection is characterized by a progressive impairment in immunocompetence leading to severe opportunistic infections and malignancies. In a double-blind, placebo-controlled study, the potential impact of immunomodulation by oral ranitidine, 600 mg daily, for 28 days was studied in 18 HIV-positive patients (CDC group II). All were without clinical signs of infections and were not treated with other known immunomodulating agents. Several immunological parameters related to HIV infection were studied and confirmed to be impaired early in HIV infection. Spontaneous and in vitro interleukin-2- and interferon-alpha-stimulated natural killer cell activity improved in the ranitidine-treated patients in contrast to a decrease in nontreated patients (#p less than 0.03, #p less than 0.01, #p less than 0.02 between groups, respectively). Furthermore, T-cell blastogenesis to phytohemagglutinin stimulation and soluble interleukin-2 receptors in serum increased in ranitidine-treated patients compared with nontreated patients (#p less than 0.01). However, ranitidine treatment did not change CD4+ cell counts. Although the significant improvement in immunocompetence shown in this study is small, the present result indicates the need for further trials with immunomodulation by ranitidine in HIV-infected individuals.

In vitro separation and expansion of CD4 lymphocytes from HIV-infected individuals without activation of HIV infection.

In order to offer a gene therapy-based treatment against AIDS, it is likely to be necessary to harvest and culture CD4 cells from HIV-positive patients without activating the HIV infection. We have used a magnetic cell sorting (MACS) system to enrich CD4 cells. Using positive selection, CD4 cells from a total of 14 patients were enriched from a mean percentage of CD4 cells in PBMC of 18% to 91% CD4 cells in the enriched cell fraction. Furthermore, we found that this separation did not lead to an increase in viral load. The MACS performed equally well on cells from HIV-positive patients and HIV-negative donors. CD4 cells from HIV-positive patients were readily expanded with PHA; 19-fold by day 10, 50-fold by day 20, and 156-fold by day 25. However, CD4 cells from HIV-positive patients grew at a slower rate than CD4 cells from HIV-negative donors. The expanded CD4 cells showed a high degree of CD4 expression and no loss of polyclonality. Only in two of six cultures were we able to detect HIV-antigen production, and using an LTR-PCR and an RT assay, we did not find activation of the HIV infection during the culture period. Thus, the method described separates and expands CD4 cells from HIV-positive patients without activation of the HIV infection.

Sumatriptan increases the proliferation of peripheral blood mononuclear cells from HIV-infected individuals and healthy blood donors in vitro.

HIV infection is characterized by the loss of CD4+ T cells as well as the loss of T-cell function, leading to severe immunodeficiency. The proliferative capacity of T cells measured in vitro as responses to antigens and mitogens is severely reduced during HIV infection. An increased level of the intracellular second messenger adenosine 3',5'-cyclic monophosphate (cAMP) has been shown to cause impaired proliferative capacity of peripheral blood mononuclear cells (PBMC) from HIV-infected individuals in vitro. Sumatriptan, a 5HT1d receptor agonist, inhibits the activity of adenylyl cyclases, the enzymes responsible for regulation of the intracellular levels of cAMP. In a preliminary study sumatriptan increased the proliferative responses of PBMC to a polyclonal activator in vitro in 9 of 10 HIV-seropositive individuals (p=0.007), and in 7 of 9 healthy blood donors (p=0.05). This was probably due to a decrease in the intracellular level of cyclic AMP.

Tubuloreticular inclusions in skin biopsies from patients with HIV infection.

Skin biopsies obtained from apparently normal skin from 15 HIV infected patients and 6 anti-HIV negative patients were examined by electron microscopy. Tubuloreticular inclusions (TRI) were detected within the cytoplasm of capillary endothelial cells in 5/5 AIDS patients and in 2/5 patients with AIDS related conditions. Biopsies from 5 asymptomatic HIV positive patients and the 6 control subjects were without ultrastructural alterations. The occurrence of TRI was related to low numbers of CD 4+ lymphocytes. 5/7 patients with TRI had elevated serum interferon activity, and in all of the patients without TRI, interferon activity was below detection level. The occurrence of TRI was not dependent on the presence of free p24 antigen in serum. It is concluded that the occurrence of TRI in entothelial cells of skin capillaries is associated with late stages of HIV infection and this may indicate a generalization of this change.

Tumour necrosis factor and eicosanoid production from monocytes exposed to HIV in vitro.

We investigated the hypothesis that exposure of monocytes to human immunodeficiency virus (HIV) augments production of proinflammatory mediators. The production of tumour necrosis factor alpha (TNF-alpha) and the eicosanoids PGE2 and LTB4 from human monocytes was evaluated after exposure to two strains of HIV (SSI-002 or HIV-1IIIB). After 16 h incubation with low doses of SSI-002, lipopolysaccharide-stimulated TNF-alpha production was enhanced 70-85% while PGE2 production was decreased. Heat-inactivated virus failed to alter the production of these mediators. Higher viral doses tended to decrease TNF-alpha and PGE2 production concomitantly, but this might be due to toxicity. HIV-1IIIB had no effect on either TNF-alpha or PGE2 production. Calcium ionophore-stimulated LTB4 production was doubled by HIV-1IIIB, but significantly decreased by SSI-002. Three or seven days after exposure to both HIV strains, increased PGE2 production was found. In conclusion, HIV only modestly altered the production of mediators from monocytes. The effects were strain-specific. In most experiments a second stimulus was required to demonstrate differences.