Pairs of 11 antimicrobial agents were tested in vitro for their ability to act synergistically against three strains of Mycobacterium avium complex isolated from patients with acquired immune deficiency syndrome. From the combinations tested, four drugs (ethambutol, rifampin, ciprofloxacin, and erythromycin) were selected for more extensive study against 20 strains of M. avium complex. The inhibitory and killing synergism obtained with combinations of two, three, or four drugs was assessed by determining the fractional inhibitory concentration index and fractional bactericidal concentration index. Inhibitory synergism occurred against 90 to 100% of the strains for all drug combinations in which ethambutol was included. Killing synergism occurred against 85 to 95% of the strains when ethambutol was used in combinations which included either rifampin or ciprofloxacin. However, killing synergism occurred against only 45% of the strains when drugs were tested at concentrations that can be obtained in patient serum. In other experiments, rifabutin (Ansamycin) gave results that were comparable to those obtained with rifampin. Clofazimine did not show synergistic killing activity at a concentration that is achievable in serum for any of the drugs tested. Our results indicate that there is considerable variability in the antimicrobial susceptibility of M. avium isolates obtained from patients with acquired immune deficiency syndrome. This variability could have significant impact on the clinical response to various therapies.
A new serotype of simian acquired immune deficiency syndrome (SAIDS) retrovirus (type 2) belonging to the D genus of retroviruses is associated with a SAIDS occurring spontaneously in a colony of Celebes macaques (Macaca nigra) and rhesus macaques (Macaca mulatta) at the Oregon Regional Primate Research Center. This syndrome resembles SAIDS in M. mulatta at the California Primate Research Center, which is associated with a similar type D retrovirus (type 1). However, at the Oregon Center, SAIDS is distinguished by the occurrence of retroperitoneal fibromatosis in some of the affected monkeys. Type 2 virus was isolated from seven of seven macaques with SAIDS, retroperitoneal fibromatosis, or both and from one of six healthy macaques. The new strain is closely related to SAIDS retrovirus type 1 and Mason-Pfizer monkey virus but can be distinguished by competitive radioimmunoassay for minor core (p10) antigen and by genomic restriction endonuclease cleavage patterns. Neutralization tests indicate that type 1 and type 2 SAIDS retroviruses are distinct serotypes. Therefore, separate vaccines may be necessary to control these infections in colonies of captive macaques.
Immunoglobulin G (IgG) and IgM antibodies to human T-cell leukemia/lymphoma virus-I (HTLV-I)-associated membrane antigens (HTLV-I-MA) were assayed by indirect cytospin immunofluorescence, and IgG and IgM antibodies to purified HTLV-I were assayed by enzyme-linked immunosorbent assay in sera from 119 immunologically well-characterized promiscuous male homosexuals in The Netherlands, of whom 9 suffered from acquired immune deficiency syndrome (AIDS), 18 suffered from lymphadenopathy syndrome (LAS), and 5 suffered from gay bowel syndrome. Antibodies to HTLV-I-MA were present in four of nine AIDS patients, including one patient with antibodies to purified HTLV-I. Antibodies to HTLV-I-MA were present in 6 of 18 LAS patients, including 3 patients with antibodies to purified HTLV-I. Of five patients with gay bowel syndrome, one had IgG and IgM antibodies to HTLV-I-MA. Of the four HTLV-I seropositive AIDS patients, two had IgG and IgM antibodies to HTLV-I or HTLV-I-MA, one had only IgG antibodies, and one had only IgM antibodies. Of the six HTLV-I seropositive LAS patients, four had IgG and IgM antibodies to HTLV-I or HTLV-I-MA, and two had only IgM antibodies. In the sera from 27 healthy homosexuals with and 60 without T-cell subset imbalances...
Natural killer cell activity of peripheral blood mononuclear cells against K562 myeloid cells was studied in 8 normal heterosexual men, 5 healthy homosexual men, and 11 homosexual men with acquired immune deficiency syndrome. The overall natural killer cell activity was lower in healthy homosexual men and in homosexual men with acquired immune deficiency syndrome. Peripheral blood mononuclear cells from four normal heterosexual men were preincubated overnight in complete medium supplemented with various concentrations of lectin-free interleukin 2 lacking interferon. Cells from these cultures exhibited a dose-dependent augmentation of natural killer cell activity. Peripheral blood mononuclear cells obtained from 8 normal heterosexuals, 5 healthy homosexuals, and 11 homosexual men with acquired immune deficiency syndrome were preincubated overnight in complete medium supplemented with 20% interleukin 2. Natural killer cell activity cultured in 20% interleukin 2 increased to 78.4 +/- 8.4 (mean +/- standard deviation) from 30.8 +/- 11.0 in normal heterosexual men, to 68.3 +/- 17.6 from 16.8 +/- 13.6 in healthy homosexual men and to 49.3 +/- 15.3 from 11.6 +/- 6.1 in homosexual men with acquired immune deficiency syndrome at a 100:1 effector/target cell ratio. These results suggest that interleukin 2 is capable of directly stimulating natural cell-mediated cytotoxicity. Consideration of the use of interleukin 2 as a potential therapeutic agent to modify immune responses in disorders such as acquired immune deficiency syndrome appears warranted.
Mycobacterium haemophilum was isolated from wrist and ankle aspirates as the organism responsible for tenosynovitis in a patient with acquired immune deficiency syndrome. Mycobacterium isolates recovered from synovial fluid were identified as hemin requiring by their failure to grow on subculture unless the medium was supplemented with hemin. M. haemophilum is of low virulence and rarely associated with infections in humans. This is the first documented case of M. haemophilum infection in a patient with acquired immune deficiency syndrome.
Significantly higher proportions of patients with acquired immune deficiency syndrome (AIDS) or lymphadenopathy syndrome (LAS) were positive for antibodies to cytomegalovirus (CMV) and herpes simplex virus (HSV) compared with control groups of commercial blood donors. In contrast, no differences were found in the incidence of individuals positive for antibodies to rubella in these groups of subjects. Of those positive for antibodies to CMV and HSV in each group, the mean antibody levels were significantly higher in AIDS-LAS patients compared with the controls. The entire distribution of antibody concentrations to CMV and HSV in AIDS patients was shifted upward, so that significantly more patients showed high values and significantly fewer showed low values, indicating hyperactive humoral immune responses to these viruses. In sharp contrast, the AIDS patients with antibody levels for rubella showed the same distribution of antibody levels as did two groups of controls. No correlation was found between concentrations of CMV and HSV antibodies in individual AIDS-LAS patients.
We evaluated the cellular immunity of 408 clinically stratified subjects at risk for acquired immune deficiency syndrome (AIDS), to define the role of interferon-alpha production deficits in the pathogenesis of opportunistic infections (OI). We followed 115 prospectively for up to 45 mo. Onset of OI was associated with, and predicted by, deficiency both of interferon-alpha generation in vitro, and of circulating Leu-3a+ cells. Interferon-alpha production is an index of the function of certain non-T, non-B, large granular lymphocytes (LGL) that are independent of T cell help. Leu-3a+ cell counts are a marker of T cell function. OI did not usually develop until both of these mutually independent immune functions were simultaneously critically depressed, leading to a synergistic interaction. These data suggest that the AIDS virus affects a subset of LGL, and that cytokine production by these cells is an important component of the host defense against intracellular pathogens that becomes crucial in the presence of severe T cell immunodeficiency.
To determine whether healthy homosexual men are immunologically impaired, peripheral blood leukocytes (PBL) from 20 male homosexuals were compared prospectively with PBL from 14 age-matched male heterosexual donors with respect to: (a) the capacity of their PBL to generate functional T cell immune responses in vitro; and (b) the content of total T cells and T cell subsets in their peripheral blood. The homosexual donors studied indicated moderate sexual life styles in that all but one of the donors had less than five current sexual partners. The percentages of OKT3+, OKT4+, and OKT8+ T cells were similar to those of heterosexual controls. T cell function was assessed by measuring cytotoxic T cell responses to influenza virus and to allogeneic cells. Approximately one-third of the homosexual donors consistently exhibited weak cytotoxic T lymphocyte (CTL) responses to influenza virus, whereas all of the heterosexual donors generated strong CTL responses to influenza. There was no correlation between the strength of CTL responsiveness to influenza virus and the strength of CTL responses to allogeneic cells. These results suggest that the influenza-specific CTL response may be a sensitive indicator of immunologic defects in asymptomatic homosexuals. If acquired immune deficiency syndrome results from an infectious agent...
We have investigated the respective role of quantitative T lymphocyte subset abnormalities, interleukin-2 (IL-2) production and responsiveness to IL-2, in the proliferative deficiency that is observed in acquired immune deficiency syndrome (AIDS) and Lymphadenopathy syndrome (LAS) patients or even in some apparently healthy male homosexuals. 83 subjects were evaluated: 35 symptom free male homosexuals (HC), 24 LAS and 24 AIDS patients. As expected, many HC and most patients presented with T lymphocyte subset imbalance. These quantitative defects were associated with decreased reactivity to PHA and reduced production of IL-2 by PHA stimulated lymphocytes. No correlation however could be found between these two functions and variations in the T lymphocyte subset distribution. On the other hand, PHA responsiveness appeared to closely depend on IL-2 activity. Addition of exogenous IL-2 to lymphocytes from patients with low proliferative responses, stimulated with suboptimal PHA concentration, enhanced proliferation in some but not all the cases. In most instances this increase never reached the levels observed with similarly treated cells from normal individuals. In these patients, the limited number of lymphocytes which express IL-2 receptors upon PHA stimulation may explain both low PHA reactivity and reduced IL-2 responsiveness. These data indicate some possible mechanisms of immunodeficiency in AIDS and LAS.
Peripheral blood mononuclear cells from male homosexuals with acquired immune deficiency syndrome (AIDS) and with AIDS related complex (ARC) were examined for the autologous mixed lymphocyte reaction (AMLR) between responder T and irradiated autologous non-T cells and in vitro influence of purified human interleukin-1 (IL-1) and -2 (IL-2) on the AMLR. The AMLR was significantly (P less than 0.001) deficient in both ARC and AIDS; the deficiency of the AMLR was of the similar magnitude in two groups when compared to asymptomatic homosexuals and healthy heterosexuals. In vitro addition of IL-2 enhanced the AMLR to the baseline levels of control subjects in most patients in ARC group (P less than 0.01) and in four of 15 patients in AIDS group (P less than 0.01). Addition of IL-1 to IL-2 containing cultures resulted in no further increase in the AMLR response over those with IL-2 alone. This study demonstrates deficiency of the AMLR in patients with ARC and AIDS that is corrected by purified IL-2 in the majority of cases with ARC but only a subset of patients with AIDS. The significance of these findings is discussed.
This report aims to provide an overview
of selected likely development impact of Human
Immunodeficiency Virus (HIV) and Acquired Immune Deficiency
Syndrome (AIDS) for Lesotho. The purpose is to engage in a
dialogue with the Government, relevant stakeholders and the
donor community on the appropriate actions to pursue in
support of the Government's recently developed strategy
on the epidemic. This report is to assist policy makers in
Lesotho in their effort to incorporate HIV/AIDS into the
planning process on a regular basis. As such, it is directed
at officials at the ministries of finance and development
planning. It employs conventional demographic and economic
models to analyze selected development impacts of HIV/AIDS
on the economy, thereby providing an illustration of how
these impacts can be incorporated in the regular planning
processes (including annual budgeting) in the finance and
development ministries of the Government. It points out the
need for monitoring the progression of the epidemic through
further research and improvements in existing instruments.
The report identifies three areas where the HIV/AIDS impact
is severe and need further appropriate studies: a)
household; b) public sector; and c) integration of HIV/AIDS
into planning models and decision making.
In June 2002, the countries of
Southeastern Europe (SEE) recommitted themselves to scale up
action on the prevention and treatment of Human
Immunodeficiency Virus (HIV) and Acquired Immune Deficiency
Syndrome (AIDS). Given the rapid increase in the rate of HIV
infection in Eastern Europe in general, and the generally
similar risk conditions for low HIV prevalence SEE
populations, this commitment is timely in terms of
preventing a more widespread epidemic. It should also be
recognized by the World Bank as a call to action to support
these countries through the application of its comparative
advantage in both lending and non-lending activities. The
purpose of this paper is to review the current status of the
AIDS epidemics in three countries of the Sub-region
(Bulgaria, Croatia, and Romania - which constitute the ECC05
Country Department of the World Bank), to evaluate the
approaches and strategies currently being used in each
country, and to make recommendations both for government
strategies and for the Bank's current and potential
future involvement in relation to these strategies. The
current low levels of HIV infection in SEE present a
challenge in gaining recognition of the potential impact of
HIV/AIDS on health systems...
We have isolated a molecular clone of the full-length integrated provirus of simian acquired immune deficiency syndrome retrovirus serotype 1 (SRV-1) from a fatal case of simian acquired immune deficiency syndrome in a juvenile rhesus macaque. An integrated SRV-1 provirus was cloned, sequenced, and found to contain four large open reading frames encoding gag-precursor protein, protease, polymerase, and envelope. The proviral clone was transfected into D17 canine osteosarcoma cells and found to produce infectious virus. A comparison of the sequences of this clone with a noninfectious clone showed 20 differences, resulting in 10 amino acid changes. Also, a cluster of exchanges, short insertions, and deletions in the 5' leader sequences resulted in extension of the tRNA(Lys) primer-binding site from 14 to 19 nucleotides. Virus isolated from transfected cells was shown to be infectious and pathogenic, resulting in disease that followed the same time course and mortality as disease induced by uncloned, in vitro cultivated virus isolated from diseased animals. These results unequivocally show that a type D retrovirus (SRV-1) causes a fatal immunosuppressive syndrome in rhesus monkeys.
Sera from patients with adult T-cell leukemia and asymptomatic carriers of human T-cell lymphotropic virus type I (HTLV-I) from widely separated areas of the world reacted strongly in a standardized quantitative enzyme-linked immunosorbent assay procedure with HTLV-I viral antigen prepared from a strain isolated in the United States. There was a sharp differentiation of the values seen in the patients as compared with a normal population. Of the 35 acquired immune deficiency syndrome patients with Kaposi's sarcoma, only 2 were positive for HTLV-I antibodies in this test, and the distribution of the negative assay values in the other acquired immune deficiency syndrome patient sera was similar to that seen in the normal sera. Sera which contained extremely high levels of antibodies to other unrelated viruses (rubella virus, cytomegalovirus, and herpes simplex virus) all showed negative anti-HTLV-I results, in a pattern similar to the normal sera. Sera from patients with several autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis, thyroiditis) as well as those with infectious mononucleosis or myeloma all also showed the normal distribution of negative results, in spite of the presence of very high levels of the autoantibodies...
Human T-lymphotropic virus type III or lymphoadenopathy associated virus (HTLV-III/LAV) is the cause of acquired immune deficiency syndrome (AIDS). In addition to the conventional retroviral genes involved in virus replication, namely, gag, pol, and env genes, DNA sequence analysis of HTLV-III genome predicted two additional open reading frames termed by us short open reading frame (sor) and 3' open reading frame (3' orf). Furthermore, functional analysis revealed another gene with transactivating function, termed tat. We have now structurally identified and functionally characterized these HTLV-III specific genes by way of cDNA cloning. DNA sequence analysis of the clones shows that the tat and 3' orf genes contain three exons and their transcription into functional mRNA involves two splicing events and that the sor gene contains at least two exons. In vitro transcription and translation of the cloned spliced sequences show that the sor, tat, and 3' orf genes code for polypeptides with apparent mobility of 24-25 kDa, 14-15 kDa, and 26-28 kDa, respectively. All three polypeptides are immune reactive and are immunogenic in the natural host. The results demonstrate that the three extra open reading frames of HTLV-III, two of which are unique to HTLV-III...
Increased levels of 3% PEG precipitable circulating immune complexes (CIC) were found in healthy homosexual men, in homosexual patients with the acquired immune deficiency syndrome (AIDS), and in the AIDS related lymphadenopathy syndrome (LAS). The degree of CIC elevation increases from healthy homosexual men to LAS and AIDS. Patients suffering from AIDS associated with opportunistic infections had a more pronounced increase in CIC than patients with AIDS associated Kaposi's sarcoma. In LAS and AIDS the amount of CIC correlated with the degree of inversion of the T4/T8 lymphocyte ratio, whereas in healthy homosexual men with increased levels of CIC the T4/T8 ratio was not significantly altered. Laser nephelometric partial components analysis revealed that these complexes were of a complement poor subtype with low component levels of C4, C1q and C3c. IgM and IgG were found to be the major components. It is suggested that these CIC might represent a marker of the total antigenic burden of the immune system. Possibly, they are of prognostic and monitoring value for clinical handling of patients at risk for AIDS.
Entry of acquired immune deficiency syndrome virus into the host immune cell involves the participation of various components of host and viral cell unit. These components may be categorized as attachment of the viral surface envelope protein subunit, gp120, to the CD4+ receptor and chemokine coreceptors, CCR5 and CXCR4, present on T cell surface. The viral fusion protein, gp41, the second cleaved subunit of Env undergoes reconfiguration and the membrane fusion reaction itself. Since the CD4+ T cell population is actively involved; the ultimate outcome of human immunodeficiency virus infection is total collapse of the host immune system. Mathematical modeling of the stages in viral membrane protein-host cell receptor-coreceptor interaction and the effect of antibody vaccine on the viral entry into the susceptible host cell has been carried out using as impulsive differential equations. We have studied the effect of antibody vaccination and determined analytically the threshold value of drug dosage and dosing interval for optimum levels of infection. We have also investigated the effect of perfect adherence of drug dose on the immune cell count in extreme cases and observed that systematic drug dosage of the immune cells leads to longer and improved lives.
Feline immunodeficiency virus (FIV), formerly called feline T-lymphotropic lentivirus, causes an immune deficiency in cats that is very similar to the acquired immune deficiency syndrome in humans (N. C. Pedersen, E. M. Ho, M. L. Brown, and J. K. Yamamoto, Science 235:790-793, 1987). We have examined the reverse transcriptase of this virus to determine whether it is similar enough to the reverse transcriptase of the human immunodeficiency virus type 1 (HIV-1) to enable its use as a model for chemotherapy for acquired immune deficiency syndrome. The FIV reverse transcriptase is similar to that of HIV-1 in sensitivity to the noncompetitive inhibitor phosphonoformate (Ki, 0.3 microM) and relative insensitivity to phosphonoacetate. This enzyme was also sensitive to two competitive inhibitors, the 5'-triphosphates of 2', 3'-dideoxythymidine (Ki, 3.4 nM) and 3'-azido-3'-deoxythymidine (AZT; Ki, 6.2 nM). The ratios of Ki/Km for these two competitive inhibitors are similar to the ratios calculated from previously reported data for the HIV-1 enzyme assayed under identical conditions. In contrast, the FIV enzyme is different from the reverse transcriptase of avian myeloblastosis virus in sensitivity to those inhibitors. The replication of FIV in Crandell feline kidney cells was inhibited by AZT; virus production was inhibited more than 95% by 1.0 microM AZT.
INTRODUCTION: Survival of patients with acquired immune deficiency syndrome has improved with combination antiretroviral therapy; mortality due to liver diseases, however, has also increased in these patients. OBJECTIVES: To estimate the accumulated probability of survival in human immunodeficiency virus-hepatitis C virus coinfected and non-coinfected patients and to investigate factors related to acquired immune deficiency syndrome patients' survival. METHODS: Non-concurrent cohort study using data from surveillance information systems of acquired immune deficiency syndrome patients over 13 years of age. Hepatitis C and B, human immunodeficiency virus exposure category, CD4+ T cell count, age group, schooling, race, sex, and four acquired immune deficiency syndrome diagnosis periods were studied. Kaplan-Meier survival analysis and Cox model with estimates of the hazard ratio and 95% confidence interval were used. RESULTS: Of the total 2864 individuals included, with median age was 35 years, 219 died (7.5%), and 358 (12.5%) were human immunodeficiency virus-hepatitis C virus coinfected. The accumulated probability of survival in human immunodeficiency virus-hepatitis C virus coinfected patients, after acquired immune deficiency syndrome diagnosis...
Human Immune Deficiency Virus (HIV) and Acquired Immune-Deficiency Syndrome (AIDS) still carry a stigma in the community. Many people do not know their status and they are still reluctant to be tested including pregnant women despite the fact that Voluntary Counselling and Testing (VCT) is offered for free in South Africa. In South Africa VCT for HIV and AIDS is offered by lay counsellors in public hospitals and clinics. The study conducted by Mate, Bennet, Mphatswe, Barker and Rollins (2009:5483) outlined that in South Africa the prevention of mother-to-child transmission (PMTCT) of HIV guidelines have raised hope that the national goal of reducing perinatal HIV transmission rates to less than 5% can be attained. A qualitative, exploratory, descriptive and contextual study was conducted in 15 public clinics of the Polokwane Municipality in the Capricorn District, Limpopo Province. The purpose of the study was to determine the experiences of the lay counsellors who provide VCT for the PMTCT of HIV and AIDS in the Capricorn District, Limpopo Province. Data were collected through one-to-one interviews using a semi-structured guide (De Vos et al, 2006:296). The findings of the study reflected the following: the content of training and counselling skills received by lay counsellors were satisfactory...