Immune impairment in HIV infection: Existence of risky and immunodeficiency thresholds

Results of several studies show that some DC populations are susceptible to HIV. Modulation of DCs by HIV infection, in particular interference of the antigen-presenting function of DCs, is a key aspect in viral pathogenesis and contributes to viral evasion from immunity because the loss of the DC function engenders some impairment effects for a proliferation of CTL responses, which play an important role in the immune response to HIV. As described herein, we use a simple mathematical model to examine virus-immune dynamics over the course of HIV infection in the context of the immune impairment effects. A decrease of the DC number and function during the course of HIV-1 infection is observed. Therefore, we simply assumed that the immune impairment rate increases over the HIV infection. Under the assumption, four processes of the disease progression dynamics of our model are classifiable according to their virological properties. It is particularly interesting a typical disease progression presents a “risky threshold” and an “immunodeficiency threshold”. Regarding the former, the immune system might collapse when the impairment rate of HIV exceeds a threshold value (which corresponds to a transcritical bifurcation point). For the latter, the immune system always collapses when the impairment rate exceeds the value (which corresponds to a saddle-node bifurcation point). To test our theoretical framework, we investigate the existence and distribution of these thresholds in 10 patients.     

Mechanisms and ways of regulation of lipoic acid penetration into biological structures]

Experimental evidence of the penetration of low doses (100--120 mkM) of lipoic acid (LA) into cells and mitochondria by means of transport systems, involving proteins was obtained. The functioning of those systems is regulated by hormones, is dependent of redox states, is disturbed in the presence of energy metabolism inhibitors and is stimulated by repeated injections of LA. The penetration of LA into erythrocytes is facilitated by a concentration gradient K+ and Na+ and the high activity of transport ATPases. In case of high (over 120 mkM) content of lipoate in the incubation medium, its penetration into the cells and mitochondria occurs largely due to ordinary diffusion. Such penetration of LA predominantly occurs also under conditions of transversely directed gravitational overloading (6g). The rate of LA penetration into the biological structures of the organism is regulated by complicated and efficient mechanisms, involving hormonal control of protein biosynthesis.     

New ways of preventing HIV infection: thinking simply, simply thinking

HIV infection is the greatest health crisis in human history. It continues to spread unchecked among the poor in the developing world because we have failed to design simple preventative methods that are available and affordable to those living on under Dollars 2 a day. Five new methods are discussed. (i) A natural microbicide. Intravaginal lime or lemon juice has been used for centuries as a traditional contraceptive. The juice can also kill HIV in the laboratory, but clinical trials are needed to see if vaginal application is acceptable, safe and effective. (ii) Intravaginal oestrogen. Monkeys can be protected from Simian immunodeficiency virus (SIV) infection by keratinizing the vagina with topical oestrogen. If women take the oral contraceptive pill vaginally it retains its contraceptive efficacy, and the oestrogen it contains should thicken the vagina and protect against HIV infection. Clinical trials are needed. (iii) Male circumcision. Removal of the inner foreskin removes the main site of HIV entry into the penis, resulting in a sevenfold reduction in susceptibility to infection. The practice needs to be promoted. (iv) Post-coital penile hygiene. Wiping the penis immediately after intercourse with lime or lemon juice or vinegar should kill the virus before it has had a chance to infect. A clinical trial of efficacy is needed. (v) PhotoVoice. Asking schoolchildren in developing countries to photograph their impressions of HIV/AIDS is a powerful way of getting them to discuss the subject openly, and develop their own preventative strategies.     

HIV infection in the Warsaw Clinic of Infectious Hepatology]

An epidemiological survey of patients in the Warsaw Clinic of Infectious Hepatology, the Polish National Center of AIDS Control, has been made. The epidemiological evaluation of risk groups and the age of HIV-infected persons has revealed that in Poland they are similar to those in Europe and in the USA (homosexuals and addicts aged 26-30 years). In 12% of the hospitalized patients the full clinical picture of AIDS, in 11.3% pre-AIDS (ARC) and in 58.1% lymphadenopathy (LAS) have been registered. In 18.4% of the patients only antibodies to HIV have been detected. The necessity of timely laboratory examinations for the determination of antibodies to HIV, whose presence may be signalled by any clinical symptom of the disease, has been shown.     

Human immunodeficiency virus gag and pol-specific CD8 T cells in perinatal HIV infection.

BACKGROUND: Binding of fluorochrome-conjugated MHC class I tetramers is a powerful means to detect antigen-specific CD8 T lymphocytes. In human immunodeficiency virus (HIV) infection, cellular immune response is essential in curtailing HIV disease progression but gaps persist in our understanding of HIV-specific cells during the disease course. In this study, we evaluated tetramer binding HIV-specific CD8 T cells in HIV-infected children. METHODS: Fluorescently labeled tetramers for HIV gag and pol were utilized to quantify antigen-specific cells by flow cytometry using a whole blood labeling method in a cohort of 19 HLA-A2+ HIV-infected children (age range 1 month to 17 years). RESULTS: Fourteen children had detectable gag (median 0.4%) and pol (median 0.1%) binding CD8 T cells, three children had gag binding cells only, and two had neither. Numbers of gag and pol binding cells correlated with each other and each correlated independently with total CD8 T cells and total CD4 T cells. CONCLUSIONS: HIV gag and pol-specific CD8 T cells are maintained during the chronic phase of HIV infection in children and CD4 lymphocytes appear to be important for sustaining their levels.     

Isolation of human immunodeficiency virus (HIV) from whole blood]

The authors describe a simple and sensitive technique for HIV isolation from small amounts of heparinized whole blood. This method demonstrated a high efficiency in detecting HIV at all stages of disease and appeared more sensitive with respect to viral isolation from peripheral blood mononuclear cells. Although further studies are needed to better understand the biological significance of a positive cultural result obtained by this method, HIV isolation from whole blood can be routinely employed, especially when small amounts of blood are available.     

Diagnosis of mycobacterial infection in acquired immunodeficiency syndrome (AIDS) patients and HIV carriers.

Differences in tuberculosis diagnosis between infected and non-infected HIV patients were described. In Barcelona, tuberculosis is present in 41.6% of 851 patients in whom AIDS was detected between 1981 and the first quarter of 1990. We reviewed the results of the methods used for tuberculosis diagnosis in 270 AIDS patients controlled in our hospital, in whom tuberculosis was detected (33.3%), and we compared these data with the results obtained in HIV carriers with tuberculosis and with tuberculous patients without HIV infection. Statistically significant differences were found between the three groups with respect to sex, age, results of Ziehl-Neelsen stain in pulmonary specimens and skin test reaction; between AIDS patients and the non-HIV infected population differences were observed in tuberculosis site. Positive skin test reaction diminished from tuberculous individuals non-HIV infected (95%), to HIV carriers with tuberculosis (71.8%) and AIDS patients with tuberculosis (21.8%). Acid-fast smears from pulmonary specimens were positive in 35.7%, 23.5% and 43.7% respectively. Statistically significant differences were found in tuberculosis localization between tuberculous patients non-HIV infected and tuberculous patients with AIDS, in the last group tuberculosis lymphadenitis was the most frequent localization (33.3%) of extrapulmonary tuberculosis, followed by abdominal tuberculosis (15.5%). The incidence of HIV infection among tuberculous patients was 4.6 in our study, but could be higher if patients between 19 and 30 years old were always checked for anti-HIV antibodies.     

Radiologic pulmonary manifestations in patients with HIV virus infection]

Altogether 155 patients with a newly detected positive reaction to HIV (a human immunodeficiency virus) were investigated in the Republic of Burundi. Chest x-ray was done in 80 of them. Pulmonary tuberculosis was diagnosed in 2 of them, pneumonia (chronic, interstitial and bronchial)--in 15. Enhancement and deformity of lung marking were detected in 45 patients (coincidence with clinical signs of acute bronchitis was found but in 5 of them). A conclusion has been made of interstitial pneumonias being typical of HIV-infected patients and of frequent enhancement of lung marking in the preclinical stage of AIDS.     

Prevalence of human immunodeficiency virus (HIV) infection among hemophiliacs in Fukuoka, Japan

To determine when the hemophiliacs in Fukuoka prefecture, Japan, first became positive for antibodies, we tested human immunodeficiency virus (HIV) antibodies on serum samples obtained from 1976-1987 stored at -30 C. Fifteen out of 64 hemophilia A patients (23.4%), five out of 11 hemophilia B patients (45.5%), but none of 17 patients with von Willebrand's disease (0%) were positive for HIV antibodies. In this series, two with hemophilia A became positive for HIV antibodies for the first time in 1983, and in 1984 another four with hemophilia A and one with hemophilia B became positive.     

Mechanisms of lipid elevations associated with the treatment of patients with HIV infection

OBJECTIVE: Dyslipidemia and other metabolic abnormalities, which are associated with the use of highly active antiretroviral therapy (HAART) for the treatment of HIV infection, are of concern to patients and healthcare providers. The objective of this review is to present the current understanding of the dyslipidemia associated with the protease inhibitor (PI)-component of HAART: its possible origin, potential consequences, and management techniques. DATA SOURCES, STUDY SELECTION: Peer-reviewed, published literature was identified via MEDLINE. Other sources included abstracts from recent HIV-related conferences that presented data pertinent to the topic. Studies were selected based on their impact on our understanding of HIV infection and its treatment. DATA EXTRACTION, SYNTHESIS: Relevant portions of the publications considered were compiled and conclusions were drawn based on the clinical experience of the author. CONCLUSION: Dyslipidemia associated with current PIs should be a serious consideration when initiating long-term treatment of HIV infection. Current management techniques that include lipid-lowering agents may be improved and streamlined by incorporating a lipid-friendly PI into HAART.     

Prevalence of HIV antigens in cerebrospinal fluid and in serum of patients with both asymptomatic and symptomatic HIV infection]

Prevalence of HIV-Ag in both serum and CSF has been determined in 19 HIV infected patients, including 7 patients without any symptoms or only generalized lymphadenopathy, 5 patients with ARC and 7 patients with AIDS. The results have been correlated with clinically evident neurological disorders. HIV-Ag have been detected in 9 out of 12 patients with ARC (AIDS Related Complex) and AIDS. In 8 of them neurological disorders have been present. Out of the remaining 7 patients in only one HIV-Ag has been detected in CSF (p < 025). No correlation between the presence of HIV antigen in CSF and serum has been noted.     

Foreign-protein-mediated immunodeficiency in hemophiliacs with and without HIV

Hemophilia-AIDS has been interpreted in terms of two hypotheses: the foreign-protein-AIDS hypothesis and the Human Immunodeficiency Virus (HIV)-AIDS hypothesis. The foreign-protein-AIDS hypothesis holds that proteins contaminating commercial clotting factor VIII cause immunosuppression. The foreign-protein hypothesis, but not the HIV hypothesis, correctly predicts seven characteristics of hemophilia-AIDS: 1) The increased life span of American hemophiliacs in the two decades before 1987, although 75% became infected by HIV —because factor VIII treatment, begun in the 1960s, extended their lives and simultaneously disseminated harmless HIV. After 1987 the life span of hemophiliacs appears to have decreased again, probably because of widespread treatment with the cytotoxic anti-HIV drug AZT. 2) The distinctly low, 1.3–2%, annual AIDS risk of hemophiliacs, compared to the higher 5–6% annual risk of intravenous drug users and male homosexual aphrodisiac drug users — because transfusion of foreign proteins is less immunosuppressive than recreational drug use. 3) The age bias of hemophilia-AIDS, i.e. that the annual AIDS risk increased 2-fold for each 10-year increase in age —because immunosuppression is a function of the lifetime dose of foreign proteins received from transfusions. 4) The restriction of hemophilia-AIDS to immunodeficiency diseases — because foreign proteins cannot cause non-immunodeficiency AIDS diseases, like Kaposi's sarcoma. 5) The absence of AIDS diseases above their normal background in sexual partners of hemophiliacs — because transfusion-mediated immunotoxicity is not contagious. 6) The occurrence of immunodeficiency in HIV-free hemophiliacs — because foreign proteins, not HIV, suppress their immune system. 7) Stabilization, even regeneration, of immunity of HIV-positive hemophiliacs by long-term treatment with pure factor VIII. This shows that neither HIV nor factor VIII plus HIV are immunosuppressive by themselves. Therefore, AIDS cannot be prevented by elimination of HIV from the blood supply and cannot be rationally treated with genotoxic antiviral drugs, like AZT. Instead, hemophilia-AIDS can be prevented and has even been reverted by treatment with pure factor VIII.