Cytofluorometric analysis of anti-lymphocyte antibodies in AIDS

Anti-lymphocyte antibodies (ALA) have been detected in the plasma of 53.8% of HIV-positive patients tested (CD4/CD8 ratios: mean 0.265; range 0.01 to 0.5) using analytical continuous-flow cytofluorometry. IgG from the AIDS plasma was seen to bind to normal PBL in 53.8% of cases (14/26). In double labelling experiments CD4 + lymphocytes, CD8 + lymphocytes, and B lymphocytes were all bound by the ALA, but monocytes were not bound. Pre-adsorption of the diluted AIDS plasma onto an excess of mouse spleen cells did not remove lymphocyte binding activity. No evidence was found for preferential binding to phytohaemagglutinin-stimulated lymphocytes. ALA could not be detected in the plasma of normal subjects, patients with acute renal failure undergoing renal dialysis, or patients with high levels of circulating immune complexes.     

Semen alloantigens and lymphocytotoxic antibodies in AIDS and ICL

More than 90% of people with AIDS develop circulating immune complexes (CICs) and lymphocytotoxic antibodies (LCTAs). Animals infected with HIV, however, never display CICs or LCTAs, and remain healthy. Similarly, HIV-infected people who do not develop CICs or LCTAs also do not progress to AIDS. The appearance of CICs and LCTAs is, however, highly prognostic for AIDS and death. Since HIV infection does not,per se, lead to the development of CICs and LCTAs, other causes are likely. One such cause, for which both epidemiologic and experimental evidence exists, is semen. Semen components include sperm, seminal fluid, lymphocytes, and sometimes infectious agents, including HIV, mycoplasmas, and herpes and hepatitis viruses, all of which independently cause immune suppression. Extensive evidence demonstrates sperm (and various viruses) contains many proteins mimicking the CD4 protein of T-helper cells, while HIV, mycoplasmas, and seminal fluid mimic class II MHC proteins of other lymphocytes. We identify a large number of protein sequences that display such mimicry using computer homology searching, and demonstrate experimentally that sperm antibodies specifically precipitate antibodies against class II MHC mimics such as mycoplasmas, which in turn precipitate antibodies to lymphocyte antigens. These data prove that immunologic exposure to sperm and lymphocytes (as may occur in receptive anal intercourse, needle sharing, or blood transfusions) is theoretically capable of initiating lymphocytotoxic autoimmunity. Such autoimmunity may play a significant role in the pathogenesis of AIDS, and will need to be addressed clinically in high risk individuals regardless of HIV status and regardless of the success of anti-HIV prophylaxis and treatment.     

Natural antibodies to interferon-gamma

Natural antibodies to interferon (IFN)-γ were detected in the serum of virus-infected patients and also, at a low titre, in the serum of healthy subjects. The increased titre of antibodies to IFN-γ in the sera of virus-infected patients, and its decrease with clinical resolution, indicate that these antibodies are related to viral infection and probably reflect IFN-γ production as a result of antigenic stimulationin vivo. Natural antibodies to IFN-γ were affinity purified and studied for their capability to interferein vitro with the multiple activities of the lymphokine. Data obtained show that these human anti-IFN-γ antibodies have no inhibitory effect on the antiviral and antiproliferative activity of IFN-γ and do not interfere with the binding of the lymphokine to its specific cell receptor. Instead, they can inhibit the expression of HLA-DR antigens induced by IFN-γ on U937 cells and interfere, in mixed lymphocyte culture, with the proliferation of lymphocytes and the generation of cytotoxic lymphocytes. Experiments in animal models suggest that natural antibodies to IFN-γ may have a role in the immunoregulatory process limiting the intensity and/or duration of immune response. As they can interfere only with the immunomodulating activities of IFN-γ, these antibodies might open up new therapeutic approaches to diseases with evidence of activated cell-mediated immunity.     

Effects of neutralizing antibodies on escape from CD8+ T-cell responses in HIV-1 infection

Despite substantial advances in our knowledge of immune responses against HIV-1 and of its evolution within the host, it remains unclear why control of the virus eventually breaks down. Here, we present a new theoretical framework for the infection dynamics of HIV-1 that combines antibody and CD8⁺ T-cell responses, notably taking into account their different lifespans. Several apparent paradoxes in HIV pathogenesis and genetics of host susceptibility can be reconciled within this framework by assigning a crucial role to antibody responses in the control of viraemia. We argue that, although escape from or progressive loss of quality of CD8⁺ T-cell responses can accelerate disease progression, the underlying cause of the breakdown of virus control is the loss of antibody induction due to depletion of CD4⁺ T cells. Furthermore, strong antibody responses can prevent CD8⁺ T-cell escape from occurring for an extended period, even in the presence of highly efficacious CD8⁺ T-cell responses.     

Anti-R7V antibodies as therapeutics for HIV-infected patients in failure of HAART

Many attempts to use therapeutic antibodies to treat HIV have been unsuccessful owing to the high variability of the viral proteins, the multiplicity of the cellular targets, and the conformational changes of the gp120 glycoprotein during cell binding. A new concept of identifying a cellular antigen associated with the HIV envelope was investigated. The characterized epitope, R7V, is responsible for the formation of antibodies protective against HIV in non-progressor patients. The purified anti-R7V antibodies neutralize all HIV isolates, including the escape mutants after highly active antiretroviral therapy, creating a new therapeutic tool for the treatment of HIV-infected patients.     

A summary of the workshop on passive immunization using monoclonal antibodies for HIV/AIDS, held at the National Institute of Allergy and Infectious Diseases, Bethesda, 10 March 2006

Passive immunization with monoclonal antibodies (MAbs) has been shown to prevent a wide variety of diseases. Currently, there are no MAb products that are licensed for use for immunotherapy or immunoprophylaxis against infection by HIV. However, there are several rational arguments that can be advanced for the use of a passive immunization approaches for counteracting HIV much as for other diseases especially with respect to mother-to-child transmission (MTCT) of HIV and immediate post-exposure situations. Several arguments questioning the feasibility of the approach based on availability of effective drugs, high cost of production and distribution of the MAbs among others, also get raised. It seems that the field now is looking at some promising MAbs as well as several alternate ways to manufacture antibodies and which hopefully may positively affect cost-related issues. This summary of a workshop held to assess the role of MAbs in the treatment and prevention of HIV/AIDS provides a fairly comprehensive analysis of the usefulness of MAb technology for future HIV/AIDS research.     

The Progress on the Studies of HIV/AIDS Vaccine

人类控制HIV感染长远的目标是发展安全、有效、廉价的HIV AIDS疫苗。但经 2 0多年的努力 ,人类探索HIV AIDS疫苗之路仍在继续。分析了疫苗研究的复杂性和发展HIV AIDS疫苗过程中所面临的挑战 ,并对发展HIV AIDS疫苗的可能性从实验和临床方面进行了阐述。同时结合HIV感染的免疫应答原理对现有的各种HIV AIDS疫苗研究策略作一综述 ,并根据以往HIV AIDS疫苗研究的经验和教训提出未来疫苗的发展思路及展望。     

MSM and HIV/AIDS in China

This article profiles current status of spread and control of HIV/AIDS in China. China has a significant population of MSM （men who have sex with men） and they have been becoming very much alive in many ways since 1990s due to recent social changes. Some surveys indicate that great many of MSM are engaged in high-risk behaviors. In addition, majority of MSM have also experienced sexual encounters with women sometimes in their lives, which possibly contribute to spread of HIV to women. Some reports documented that HIV is becoming rampant among MSM since more than 1% of them are now infected. Political, cultural and custom elements could hinder intervention activities against HIV spread among MSM. Fortunately, many cities in China have seen that MSM were in cooperation with responsible institutions carrying out certain intervention measures. The general situation is promising. The authors forecast that the fast HIV spread among MSM of China could possibly be halted within several years when the authorities become more sensible to this issue, health service institutions offer unswerving efforts toward the MSM community and those who involve in MSM undertakes necessary responsibilities.     

MSM and HIV/AIDS in China

This article profiles current status of spread and control of HIV/AIDS in China. China has a significant population of MSM (men who have sex with men) and they have been becoming very much alive in many ways since 1990s due to recent social changes. Some surveys indicate that great many of MSM are engaged in high-risk behaviors. In addition,majority of MSM have also experienced sexual encounters with women sometimes in their lives, which possibly contribute to spread of HIV to women. Some reports documented that HIV is becoming rampant among MSM since more than 1% of them are now infected. Political, cultural and custom elements could hinder intervention activities against HIV spread among MSM. Fortunately, many cities in China have seen that MSM were in cooperation with responsible institutions carrying out certain intervention measures. The general situation is promising. The authors forecast that the fast HIV spread among MSM of China could possibly be halted within several years when the authorities become more sensible to this issue, health service institutions offer unswerving efforts toward the MSM community and those who involve in MSM undertakes necessary responsibilities.     

MSM and HIV/AIDS in China

INTRODUCTION The term MSM (men who have sex with men) was introduced into mainland China in 2000. Homosexuals, without identifying gender, were used previously to de- scribe MSM by authorities, the public and even professionals. The first confirmed MSM ca…     

Apoptosis in AIDS

Infection with the human immunodeficiency virus type 1 (HIV-1) leads to progressive immunodeficiency and onset of opportunistic infections and neoplasms. The loss of immune competence is associated with declines in both the functionality and the number of CD4+ lymphocytes. Multiple mechanisms have been proposed to explain death and dysfunction of CD4+ T-cells. The mechanisms of HIV-1-mediated cell death which are relevant in vivo are unclear at present. However, in vitro explorations on the cytopathic effects of HIV-1 have yielded a wealth of potential triggering events, and signaling and effector pathways leading to apoptosis. The types of pro- and anti-apoptotic stimuli that have been associated with HIV-1 are multiple and often appear overlapping or even contradictory. This review focuses on the various molecular determinants from HIV-1 that play a role in induction of apoptosis in T-lymphocytes.Special attention is devoted to the viral genes, env, nef, tat and vpr, for which a significant body of literature on apotosis-related effects is available.     

Chinese NGOs in action against HIV/AIDS

Chinese nongovernmental organizations （NGOs） have played a significant role in the battle against AIDS in the People＇s Republic of China. This article provides a brief overview of the structure of these organizations, as well as an analysis of their principle accomplishments. Of great significance in this analysis is the fact that Chinese NGOs have effectively dealt with many sensitive health education areas that government authorities have felt reluctant to handle directly. As such, they have provided an indispensable component in the HIV/AIDS prevention and control calculus on the mainland.     

The Relationship Between Scientific Knowledge and Behaviour: An HIV/AIDS Case

Debates on the role of scientific knowledge to affect behaviour are continuing. The theory of planned behaviour suggests that behaviour is influenced by attitudes, subjective norms and perceived behavioural control and not by knowledge. However, a large body of knowledge argues that increased HIV/AIDS-related knowledge leads to the adoption of safe behavioural practices. The purpose of this non-experimental survey study, therefore, was to investigate the correlation between academic HIV/AIDS knowledge, functional HIV/AIDS knowledge and self-reported behavioural preferences of 300 biology and 243 non-biology students from nine South African schools. Results suggest a correlation between students’ understanding of academic and functional HIV/AIDS knowledge. The behavioural preferences of both biology and non-biology students were generally the same and safe. Among biology students, correlation was observed between academic HIV/AIDS knowledge and self-reported safe behavioural preferences, which was not the case for non-biology students, where functional HIV/AIDS knowledge correlated with self-reported safe behavioural preferences. Within schools, however, no correlation was found between both forms of HIV/AIDS knowledge and self-reported safe behavioural preferences. There were indications that context-specific local factors have a greater influence on behavioural preferences. These findings suggest that the type of knowledge that could influence behaviour is informed by context-specific dynamics.     

Catalytic antibodies from HIV-infected patients specifically hydrolyzing viral integrase suppress the enzyme catalytic activities

Human immunodeficiency virus type 1 integrase (IN) catalyzes integration of a DNA copy of the viral genome into the host genome. It was shown previously that IN preincubation with various oligodeoxynucleotides (ODNs) induces formation of dimers and oligomers of different gyration radii; only specific ODNs stimulate the formation of catalytically active dimers. Here we have shown that preincubation of IN with specific and nonspecific ODNs leads to a significant and comparable decrease in its hydrolysis by chymotrypsin, while nonspecific ODNs protect the enzyme from the hydrolysis by trypsin worse than specific ODNs; all ODNs had little effect on the IN hydrolysis by proteinase K. In contrast to canonical proteweases, IgGs from HIV‐infected patients specifically hydrolyze only IN. While d(pT)_n markedly decreased the IgG‐dependent hydrolysis of IN, d(pA)_n and d(pA)_n?d(pT)_n demonstrated no detectable protective effect. The best protection from the hydrolysis by IgGs was observed for specific single‐ and especially double‐stranded ODNs. Although IN was considerably protected by specific ODNs, proteolytic IgGs and IgMs significantly suppressed both 3′‐processing and integration reaction catalyzed by IN. Since anti‐IN IgGs and IgMs can efficiently hydrolyze IN, a positive role of abzymes in counteracting the infection cannot be excluded. Copyright © 2011 John Wiley & Sons, Ltd.     

Five myths about AIDS that have misdirected research and treatment

A number of widely repeated and factually incorrect myths have pervaded the AIDS research literature, misdirecting research and treatment. Five of the most outstanding are: 1) that all risk groups develop AIDS at the same rate following HIV infection; 2) that there are no true seroreversions following HIV infection; 3) that antibody is protective against HIV infection; 4) that the only way to treat AIDS effectively is through retroviral therapies; and 5) that since HIV is so highly correlated with AIDS incidence, it must be the sole necessary and sufficient cause of AIDS. A huge body of research, reviewed in this paper, demonstrates the falsity of these myths. 1) The average number of years between HIV infection and AIDS is greater than 20 years for mild hemophiliacs, 14 years for transfussion severe hemophiliacs, 10 years for old severe hemophiliacs, 10 years for homosexual men, 6 years for transfusion patients of all ages, 2 years for transplant patients, and 6 months for perinatally infected infants. These differences can only be explained in terms of risk-group associated cofactors. 2) Seroreversions are common. Between 10 and 20 percent of HIV-seronegative people in high risk groups have T-cell immunity to HIV, and may have had one or more verified positive HIV antibody tests in the past. 3) Antibody, far from being protective against HIV, appears to be highly diagnostic of loss of immune regulation of HIV, and some evidence of antibody-enhancement of infection exists. 4) Non-retroviral treatments of HIV infection, including safer sex practices, elimination of drug use, high nutrient diets, and limited reexposure to HIV and its cofactors have proven to be effective means of preventing or delaying onset of AIDS. 5) Many immunosuppressive factors, including drug use, multiple concurrent infections, and exposure to alloantigens, are as highly correlated with AIDS risk groups as HIV. These data are more consistent with AIDS being a multifactorial or synergistic disease than a monofactorial one.     

Change and Chisungu in Zambia's Time of AIDS

Through an examination of amafunde – a Bemba word meaning ‘instruction’, which refers to the training given to a young woman before her marriage – this article explores the social changes that have followed widespread HIV infection on the Zambian Copperbelt. Amafunde today are marked by openness between senior women and those they train for marriage, an openness that they encourage their charges to adopt in married life. This emphasis on direct or ‘straight’ speech stands in stark contrast to earlier accounts of female initiation in Zambia, which highlight ‘obscure’ modes of communication. An analysis of this change reveals the increased importance of both secrecy and disclosure in Zambia's time of AIDS, as well as the influence of Pentecostal Christianity. Most importantly, it indexes changes in the social forms that the interplay of secrecy and disclosure has traditionally produced.     

Chinese NGOs in action against HIV/AIDS

INTRODUCTION The AIDS epidemic continues its seemingly inexorable spread throughout the world. It is now very clear that the virus represents not only a medical problem, but also a challenging and multifaceted social problem. Because of this fact, it is imperative that nongovernmental organiza- tions outside of, or tangential to, the medical arena be- come involved in prevention and control efforts. The Chinese government is supportive of the development of such organizations on the mai…     

Chinese NGOs in action against HIV/AIDS

Chinese nongovernmental organizations (NGOs) have played a significant role in the battle against AIDS in the People‘s Republic of China. This article provides a brief overview of the structure of these organizations, as well as an analysis of their principle accomplishments. Of great significance in this analysis is the fact that Chinese NGOs have effectively dealt with many sensitive health education areas that government authorities have felt reluctant to handle directly. As such, they have provided an indispensable component in the HIV/AIDS prevention and control calculus on the mainland.