Multiple myeloma and human immunodeficiency virus-1 (HIV-1) infection.

Multiple myeloma (MM) in three human immunodeficiency virus (HIV)-infected patients is reported. HIV infection predisposes to the development of high-grade B-cell lymphomas, but few cases of plasma cell tumours in association with HIV have been reported. The coincidence of HIV infection and neoplasia highlights the distinct roles of immunodeficiency and infection with herpesviridae, including HIV itself, in the pathogenesis of HIV-related tumours. In addition, a number of cytokines (e.g., interleukin-6 [IL-6]) and angiogenic factors (e.g., vascular endothelial growth factor [VEGF] and basic fibroblastic growth factor [bFGF]) may play a role in the initiation, maintenance, and progression of multiple myeloma (MM). Infection was the first clinical consideration to the cause of the illness in two of our HIV-seropositive patients. The diagnosis of MM may be difficult in patients with advanced HIV infection as they often have renal failure, bone marrow plasmacytosis, repeated infections, and polyclonal hypergammaglobulinaemia, due to HIV infection itself, opportunistic pathogens, and/or medication.     

Strain-dependent productive infection of a unique eosinophilic cell line by human immunodeficiency virus type 1

Eosinophils are granulocytic leukocytes that function in both protective and pathological immune responses. They can be infected by HIV-1, but characterization of the infection has been hindered by lack of a productive cell culture model. In the present study, the unique eosinophilic cell line AML14.3D10 was used as a model to test the hypothesis that HIV-1 productively infects eosinophilic cells in a strain-dependent fashion. The AML14.3D10 cell line was cultured with one T cell-tropic (T-tropic) strain and two macrophage-tropic (M-tropic) strains of HIV-1 (HTLV-IIIB, HIV-1AdaM, and HIV-1Ba-L strains, respectively). Cytopathic effects were evident in living cultures and in stained slide preparations of AML14.3D10 cells infected with the T-tropic strain of HIV-1. Culture supernatants from infected AML14.3D10 cells contained high levels of HIV-1 p24 protein that peaked at approximately 7-10 days postinfection. A line of AML14.3D10 cells chronically infected with HTLV-IIIB and continuously producing high levels of virus was established. In contrast to the T-tropic strain, the M-tropic strains of HIV-1 did not productively infect the eosinophilic cell line. Thus, the AML14.3D10 eosinophilic cell line was permissive for a T-tropic strain but not for M-tropic strains of HIV-1. Flow cytometry revealed that uninfected AML14.3D10 cells were positive for the HIV-1 receptor CD4 and coreceptors CXCR4 and CCR5; the cell line was negative for CCR3. The lack of productive infection by M-tropic strains despite CCR5 expression indicates that strain-dependent infection may not be determined at the coreceptor level in AML14.3D10 cells.     

Painful neuropathy vasculitis in 2 patients with long-standing human immunodeficiency virus-1 infection

We describe 2 most unusual cases of distal symmetrical painful polyneuropathy in patients with long-standing HIV-1 infection well controlled by HAART. Sural nerve biopsies revealed vasculitis in both cases and steroid therapy led to resolution of symptoms not influenced by analgesics and anti-inflammatory drugs. These unusual cases outline the importance of nerve biopsies in order to reach a diagnosis.     

Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients

AIM: To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico.METHODS: We investigated the presence of OHBI in 49 HIV-1+/HBsAg- patients. Hepatitis B virus (HBV) DNA was analyzed using nested PCR to amplify the Core (C) region and by real-time PCR to amplify a region of the S and X genes. The possible associations between the variables and OHBI were investigated using Pearson’s χ² and/or Fisher’s exact test.RESULTS: We found that the frequency of OHBI was 49% among the group of 49 HIV-1+/HBsAg- patients studied. The presence of OHBI was significantly associated with the HIV-1 RNA viral load [odds ratio (OR) = 8.75; P = 0.001; 95%CI: 2.26-33.79] and with HIV-antiretroviral treatment with drugs that interfere with HBV replication (lamivudine, tenofovir or emtricitabine) (OR = 0.25; P = 0.05; 95%CI: 0.08-1.05).CONCLUSION: The OHBI frequency is high among 49 Mexican HIV-1+/HBsAg- patients and it was more frequent in patients with detectable HIV RNA, and less frequent in patients who are undergoing HIV-ARV treatment with drugs active against HBV.     

Low prevalence of human immunodeficiency virus-1 (HIV-1), HIV-2, and human T cell lymphotropic virus-1 infection in Somalia.

A seroepidemiologic survey was conducted to determine the prevalence of human immunodeficiency virus type 1 (HIV-1), HIV-2, human T cell lymphotropic virus type I (HTLV-I), and Treponema pallidum infection among southern Somalis. Sera were collected from 1,269 study subjects in the urban area of the capital city, Mogadishu, and in the rural towns of Merka, Qoryoley, and Kismayo. The subjects included 57 prostitutes, 79 sexually transmitted disease (STD) patients, and 1,133 others, including outpatient and hospitalized patients with leprosy, tuberculosis, other infectious diseases, individuals from rehabilitation camps and secondary schools, and Ethiopian immigrants. Results indicated that none of the sera were positive for HIV-1 and HIV-2 by Western blot, but one was positive for HTLV-I. The prostitutes had a significantly higher prevalence of treponemal antibody (50.8%; P less than 0.0001) than either the STD patients (12.6%) or the other subjects (5.2%). Epidemiologic data indicated that 94% of the males and females were circumcised and only 2.6% of the males used condoms. Overall, the results of this study suggested a very low prevalence of HIV-1, HIV-2, and HTLV-I infections, especially among prostitutes and STD patients, who were considered at greatest risk of contracting these retroviral infections.     

T-cell progenitor function during progressive human immunodeficiency virus-1 infection and after antiretroviral therapy

Impairment of T-cell renewal has been proposed as contributing to CD4(+) T-cell depletion in persons infected with human immunodeficiency virus-1. We analyzed the T-cell development capacity of progenitors using fetal thymus organ culture. Those who progressed to AIDS had a dramatic loss in T-cell development capacity shortly after seroconversion. In contrast, long-term nonprogressors retained progenitor capacity 8 years after seroconversion. Approximately 70% of patients experienced an improvement in T-cell development capacity after receiving 6 months of potent antiretroviral therapy. Improvement in T-cell development in fetal thymus organ culture correlated with an increase in the number of naive CD4(+) T cells in peripheral blood. Numbers of progenitors in blood and bone marrow after seroconversion or during therapy did not correlate with the change observed in T-cell development capacity. These data provide evidence that HIV-1 infection can interfere with T-cell renewal at the level of the progenitor cell. Interference with T-cell renewal may contribute to CD4(+) T-cell depletion.     

In vitro reactivation of human immunodeficiency virus-1 upon stimulation with scrub typhus rickettsial infection

While a number of microbial infections induce a transient burst in viral load in individuals infected with human immunodeficiency virus-1 (HIV-1), a recent study has suggested that scrub typhus may suppress HIV-1 infection. We investigated the effects of Orientia tsutsugamushi on HIV-1 infection. In vitro HIV-1 infection experiments were conducted using peripheral blood mononuclear cells (PBMC) acutely infected with R5 and X4 HIV-1 or PBMC derived from patients receiving highly active antiretroviral therapy (HAART) whose plasma viral load was undetectable. Stimulation of PBMC with O. tsutsugamushi induced production of proinflammatory cytokines and beta-chemokines, and markedly down-regulated expression of CCR5. Although pretreatment with O. tsutsugamushi rendered PBMC resistant to R5 HIV-1, it otherwise enhanced HIV-1 replication. Stimulation by O. tsutsugamushi induced HIV-1 replication in PBMC from patients receiving HAART. These findings suggest that scrub typhus does not necessarily suppress HIV-1 infection and does have potential to enhance HIV-1 replication.     

Serum Vpr regulates productive infection and latency of human immunodeficiency virus type 1.

In human immunodeficiency virus (HIV)-positive individuals, the vast majority of infected peripheral blood cells and lymph node cells may be latently or nonproductively infected. The vpr open reading frame of HIV-1 encodes a 15-kDa virion-associated protein, Vpr. The vpr gene has been shown to increase virus replication in T cells and monocyte/macrophages in vitro. We have previously reported that vpr expression in various tumor lines leads to growth inhibition and differentiation, indicating that Vpr may function as a regulator of cellular permissiveness to HIV replication. Here we show that Vpr protein is present in significant amounts in the serum of AIDS patients. Purified serum Vpr activated virus expression from five latently infected cell lines, U1, OM.10.1, ACH-2, J1.1, and LL58. Serum Vpr also activated virus expression from resting peripheral blood mononuclear cells of HIV-infected individuals. Together, these findings implicate serum Vpr in the activation of HIV replication in vivo and in the control of latency. Anti-Vpr antibodies inhibited Vpr activity, suggesting that humoral immunity modulates Vpr activity in vivo. These results have broad implications for the virus life cycle and for the prospective control of HIV replication and pathogenesis.     

Rapid loss of specific antibodies after pneumococcal vaccination in patients with human immunodeficiency virus-1 infection

Pneumococcal infections are frequently observed in patients with human immunodeficiency virus (HIV) infection and active immunization has been recommended as prophylaxis in this patient group. We studied 103 out-patients with asymptomatic or mildly symptomatic HIV infection with respect to specific IgG and IgG2 pneumococcal antibodies before and after vaccination with a 23-valent pneumococcal polysaccharide vaccine. A significant increase ( > 2-fold) in IgG and IgG2 antibody levels was observed after 1 month in 69/103 patients (67%) with no correlation with the CD4 cell count at the time of vaccination. The response rate was not influenced by concurrent treatment with anti-retroviral monotherapy, or by age or gender. After immunization a strong correlation between IgG and IgG2 anti-pneumococcal antibodies was demonstrated. Nevertheless, 12 months after vaccination the specific antibody titres were not significantly different from pre-vaccination values. In conclusion, antibodies induced by pneumococcal vaccination in patients with HIV infection have a short duration. This raises the question as to whether vaccination will have any impact on clinical end-point in this group of patients.     

T-cell non-Hodgkin lymphoma in human immunodeficiency virus-1-infected individuals

We present two patients with human immunodeficiency virus-1 (HIV-1) infection in whom T-cell non-Hodgkin lymphoma developed, based on pathologic diagnosis, immunophenotyping, and T-cell receptor gene rearrangement. Both cases were positive for human immunodeficiency virus-1 by enzyme-linked immunosorbent assay and immunoblot methods. Histologic sections from each patient showed a high-grade pleomorphic T-cell non-Hodgkin lymphoma, and immunophenotyping demonstrated a prevalence of reactivity for CD4 (helper) over CD8 (suppressor) antigens. T-cell receptor beta-chain gene rearrangement studies revealed a rearranged pattern with either the HindIII or BamHI enzymes, whereas immunoglobulin heavy chain genes retained a germ-line configuration. Viral sequences specific for human T-cell leukemia virus-I, human T-cell leukemia virus-II, or HIV-1 were not detected. Thus, although rare, T-cell non-Hodgkin lymphoma may be observed in HIV-1-infected individuals.     

Infection by human immunodeficiency virus-1 is not a risk factor for amebiasis

The purpose of this study was to determine whether HIV-1 infected patients in our community were more susceptible to Entamoeba histolytica and Entamoeba dispar infection than non-HIV-infected individuals. The prevalence and frequency of invasive amebiasis was determined in 203 HIV+/AIDS subjects and 140 close relatives or sexual partners, all of whom were HIV-. Anti-E. histolytica antibodies (IgG, IgA) were assessed as indicators of E. histolytica invasive infection. Polymerase chain reaction (PCR) was used for the characterization of the Entamoeba species. The prevalence estimated with PCR data showed that E. histolytica infection was more common in the HIV+/AIDS group (25.32%), than in HIV- contacts (18.46%). E. histolytica + E. dispar infection was more frequent in HIV+/AIDS patients (13.3%), than in HIV- contacts (0.7%). E. histolytica and/or E. dispar infection was highly prevalent in HIV+/AIDS patients (34.1%) without evidence of recent or current invasive disease. Contacts of HIV+/AIDS patients who were infected with E. histolytica were asymptomatic cyst passers. Our results suggest that E. histolytica strains prevalent in the studied community appear to be of low pathogenic potential.     

低水平病毒载量长期不进展人类免疫缺陷病毒-1感染者的人类免疫缺陷病毒-1的遗传分析

目的 分析低水平病毒载量长期不进展(LTNP)HIV-1感染者HIV-1的遗传特征.方法 采用有限稀释套式PCR、终点PCR和序列确证分析等技术对5例低病毒载量LTNP HIV-1感染者不同随访时间点HIV-1前病毒enw基因c2-v3-c3区域和gag基因p17区域进行扩增和序列分析.分别计算不同时间点内以及不同时间点与用于分析的最早时间点之间上述两个基因区域的基因多样性和基因离散率,依据基因离散率计算基因的进化率,统计学分析用GraphPad Prism 5软件.结果 5例患者在21个随访时间点共获得115条c2-v3-c3序列和173条p17序列.进化树分析表明,不同患者的序列分开,同一患者的序列特异地聚集,序列质量可靠.5例患者env基因c2-v3-c3区域不同时间点基因多样性为0～6.38%,平均为2.1%,病例1、3和5基因多样性随感染时间的增加逐渐升高(r=0.7257、0.4954、0.3288),病例2和4基因多样性随感染时间的增加逐渐下降(r=-0.3759、-0.5028);基因离散率为0.1%～6.5%,平均为2.9%,除病例1外,基因离散率均随感染时间间隔的增加逐渐升高,进化率分别为每年每位点-0.13%、0.81%、0.09%、0.14%和0.16%,平均为0.21%.gag基因p17区域基因多样性为0～2.5%,平均为1.2%,基因离散率为0.2%～2.7%,平均为1.4%,除病例3基因多样性和基因离散率随感染时间或时间间隔的增加下降外,其余病例均随感染时间或时间间隔的增加而逐渐升高,进化率分别为每年每位点0.087%、0.064%、-0.014%、0.081%和0.087%,平均为0.061%.结论 低水平病毒载量LTNP HIV-1感染者HIV-1有复制能力,病毒基因维持较低水平的进化;HIV-1 env基因变化的程度大于gag基因.     

Sicca syndrome in patients infected with human immunodeficiency virus-1

We investigated human immunodeficiency virus-1 (HIV-1)-associated sicca syndrome. The average saliva production in HIV-infected patients was 15.9 ± 6.3?ml, and the average tear production was 9.8 ± 4.5?mm. In particular, 6 patients (42.9%) showed a significant decrease in tear production. This sicca syndrome mimicked autoimmune Sjögren's syndrome (SS) because of the presence of dry eye, dry mouth, hyperamylasemia, and hypergammaglobulinemia; however, no antinuclear antibodies, anti-SS-A, or anti-SS-B were detected in sera from HIV-1-infected patients. In addition, no relationship was observed between saliva and tear production and CD4, HIV-RNA. Hepatitis C virus (HCV) and human T-lymphotrophic virus (HTLV-1) are considered to be possible causative agents of SS. However, coinfection with HCV did not affect the decrease of saliva and tear production, and only one patient was coinfected with HTLV-1. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are also potential causative agents of SS, and they are sometimes detected in the saliva of HIV-1-infected patients. However, the detection of EBV and CMV in the saliva was not related to the decrease in saliva production. Furthermore, HIV therapy (highly active anti-retroviral therapy; HAART) did not affect the state of sicca syndrome.The pathogenesis of sicca syndrome in HIV-1-infected patients is not clear, but we did find some infiltration of CD8 lymphocytes in salivary gland biopsy. Usually, CD8 lymphocytosis is found in peripheral blood in HIV-infected patients. Diffuse infiltrative lymphocytosis syndrome by predominant CD8 lymphocytes is occasionally found in HIV-infected patients. Such CD8 infiltration may induce the destruction of both the salivary and lacrimal glands.