Role of human immunodeficiency virus infection in the pathogenesis of human papillomavirus-associated cervical neoplasia.

Although many basic questions about the relationship between HIV and HPV infection remain unresolved, epidemiological studies have consistently shown a strong association between HIV infection and the development of HPV-related squamous intraepithelial neoplasia. This work indicates that HIV infection may promote the clinical manifestation of subclinical or latent HPV infection. Recent technical advances localizing virus DNA and gene products in situ will provide new avenues for investigation, allowing us to go beyond correlations and to clarify the mechanisms of interaction between the two viruses in individual patients. With improved antiretroviral therapy and prophylaxis for HIV-associated opportunistic infection and prolonged survival of women with HIV, HPV infection and its most serious consequence, cervical cancer, are likely to assume greater significance in the clinical management of HIV-infected women throughout the world. A better understanding of the role of HIV in promoting the clinical manifestation of HPV infection will be essential to the control of this disease.     

Chronic basal meningitis and vasculitis in acquired immunodeficiency syndrome. A possible role for human immunodeficiency virus

We describe the clinical and postmortem findings in a 57-year-old man with human immunodeficiency virus who presented with neurologic symptoms attributed to stroke. In addition to multiple foci of ischemic necrosis, pathologic examination of the brain showed chronic basal meningitis and vasculitis. No microorganisms were found. The association of meningitis and vasculitis in patients with acquired immunodeficiency syndrome is unusual and the possibility that these conditions may be due to primary human immunodeficiency virus infection is raised.     

Quantification of mast cells in the uterine cervix of women infected with human immunodeficiency virus

The objective of the study was to identify mastocytosis in the chorionic epithelium of the uterine cervix in HIV-infected and non–HIV-infected women in autopsy specimens using histochemistry and immunohistochemistry techniques. Sixteen cervical tissue specimens were collected, of which 10 (62.50%) were from HIV-infected women. Histochemical and immunohistochemical techniques were used to evaluate mast cell density using Giemsa stain and anti-mast cell tryptase and anti-mast cell chymase antibodies, respectively. The study of the sheets and counting of mast cells with blue (Giemsa) or brown staining (anti-mast cell tryptase or chymase antibodies) were performed by 3 examiners, and 10 consecutive fields were examined under a light microscope at 400× magnification. A significant difference was found in mast cell density in the chorionic epithelium of the cervix in HIV-infected compared with non–HIV-infected women. The present study may contribute to the characterization of genital mucosa abnormalities and help better understand the potential role of mast cells in HIV-infected women.     

Pediatric human immunodeficiency virus infection.

In the past decade, an increase in pediatric human immunodeficiency virus (HIV) infection has had a substantial impact on childhood morbidity and mortality worldwide. The vertical transmission of HIV from mother to infant accounts for the vast majority of these cases. Identification of HIV-infected pregnant women needs to be impoved so that appropriate therapy can be initiated for both mothers and infants. While recent data demonstrate a dramatic decrease in HIV transmission from a subset of women treated with zidovudine during pregnancy, further efforts at reducing transmission are desperately needed. This review focuses on vertically transmitted HIV infection in children, its epidemiology, diagnostic criteria, natural history, and clinical manifestations including infectious and noninfectious complications. An overview of the complex medical management of these children ensues, including the use of antiretroviral therapy. Opportunistic infection prophylaxis is reviewed, along with the important role of other supportive therapies.     

Human immunodeficiency virus receptor and coreceptor expression on human uterine epithelial cells: regulation of expression during the menstrual cycle and implications for human immunodeficiency virus infection

Human immunodeficiency virus-1 (HIV-1) is primarily a sexually transmitted disease. Identification of cell populations within the female reproductive tract that are initially infected, and the events involved in transmission of infection to other cells, remain to be established. In this report, we evaluated expression of HIV receptors and coreceptors on epithelial cells in the uterus and found they express several receptors critical for HIV infection including CD4, CXCR4, CCR5 and galactosylceramide (GalC). Moreover, expression of these receptors varied during the menstrual cycle. Expression of CD4 and CCR5 on uterine epithelial cells is high throughout the proliferative phase of the menstrual cycle when blood levels of oestradiol are high. In contrast, CXCR4 expression increased gradually throughout the proliferative phase. During the secretory phase of the cycle when both oestradiol and progesterone are elevated, CD4 and CCR5 expression decreased whereas CXCR4 expression remained elevated. Expression of GalC on endometrial glands is higher during the secretory phase than during the proliferative phase of the menstrual cycle. Because epithelial cells line the female reproductive tract and express HIV receptors and coreceptors, it is likely that they are one of the first cell types to become infected. The hormonal regulation of HIV receptor expression may affect a woman's susceptibility to HIV infection during her menstrual cycle. Moreover, selective coreceptor expression could account for the preferential transmission of R5-HIV-1 strains to women. In addition, these studies provide evidence that the uterus, and potentially the entire upper reproductive tract, are important sites for the initial events involved in HIV infection.     

Acute human immunodeficiency virus infection.

Human immunodeficiency virus type 1 (HIV-1) infection has a broad spectrum of clinical manifestations, ranging from asymptomatic seroconversion to a severe symptomatic illness resembling infectious mononucleosis or other medical conditions including hepatitis, meningoencephalitis, or pneumonitis. Without clinical alertness, the illness is usually misdiagnosed or even not considered. Here we report 3 cases of acute HIV-1 infection with either a negative HIV-1 antibody assay or an indeterminate Western blot result, but high plasma levels of HIV-1 RNA. The initial presentations included fever, skin rash, sore throat, neck lymphadenopathy, cough and headache. One patient presented with infectious mononucleosis-like illness, 1 with aseptic meningitis, and 1 with acute tonsillitis. Physicians should be alert to the possibility of acute HIV-1 infection, especially in cases with unexplained fever, lymphadenopathy or rash.     

Screening hospital patients for uterine cervical cancer.

Women patients admitted to a district general hospital with non-gynaecological conditions were offered a cervical smear test. In three years 2296 women were tested. Serious uterine pathology was detected in 13 patients (5.7 per 1000) and significant cytological abnormalities (dyskaryosis of all grades) in 46 (20.0 per 1000). Of the women screened 963 (41.9%) had never had a smear test before and 1608 (70.0%) were over 39 yr. The results show that cervical screening of non-gynaecological patients in hospital reaches many of the women at risk for cervical cancer who do not otherwise have smears taken and reveals considerable uterine pathology.     

The role of oxidative stress in disease progression in individuals infected by the human immunodeficiency virus.

This review describes the potential role of oxidative stress as a cofactor of disease progression from asymptomatic human immunodeficiency virus (HIV) infection to the acquired immunodeficiency syndrome (AIDS). Oxidative stress is a known activator of HIV replication in vitro through the activation of a factor that binds to a DNA-binding protein, NF-kappa B, which in turn stimulates HIV gene expression by acting on the promoter region of the viral long terminal repeat. Tumor necrosis factor alpha (TNF-alpha), an essential cytokine produced by activated macrophages, is also involved in the activation of HIV infection through similar mechanisms. TNF-mediated cytotoxicity of cells exposed to this substance is related to the generation of intracellular hydroxyl radicals. An indirect argument in favor of the role of oxidative stress in HIV-associated disease progression is the consumption of glutathione (GSH), a major intracellular antioxidant, during HIV infection and progression. GSH is known to play a major role in regulation of T cell immune functions. Oxidative stress may also play an important role in the genesis of cellular DNA damage and, in this context, may be related to HIV-associated malignancies and disease progression. Finally, the role of antioxidants as components of therapeutic strategies to combat HIV disease progression is discussed.     

Review of human immunodeficiency virus (HIV) and squamous lesions of the uterine cervix

With heterosexual transmission becoming the primary mode of transmission, more women are being infected with human immunodeficiency virus (HIV). Accrued data from around the world indicate that these HIV-infected women exhibit higher rates of persistent HPV infection with multiple oncogenic viruses, more abnormal Pap tests, more prevalent cervical intraepithelial neoplasia (CIN) lesions, and aggressive invasive cervical cancer compared with their HIV-negative counterparts. In countries where HAART was introduced more than a decade ago, HPV-related disease is increasing among ageing HIV-positive women. The high rate of cervical disease seen in HIV-positive women has prompted recommendations for more aggressive surveillance. The best strategy to screen HIV-infected women, particularly in resource-poor nations, remains challenging. This article reviews the collective literature regarding HIV and squamous lesions of the cervix and highlights these key issues.     

Key role of human leukocyte antigen in modulating human immunodeficiency virus progression: An overview of the possible applications

Host and viral factors deeply influence the human immunodeficiency virus (HIV) disease progression. Among them human leukocyte antigen (HLA) locus plays a key role at different levels. In fact, genes of the HLA locus have shown the peculiar capability to modulate both innate and adaptive immune responses. In particular, HLA class I molecules are recognized by CD8⁺ T-cells and natural killers (NK) cells towards the interaction with T cell receptor (TCR) and Killer Immunoglobulin Receptor (KIR) 3DL1 respectively. Polymorphisms within the different HLA alleles generate structural changes in HLA class I peptide-binding pockets. Amino acid changes in the peptide-binding pocket lead to the presentation of a different set of peptides to T and NK cells. This review summarizes the role of HLA in HIV progression toward acquired immunodeficiency disease syndrome and its receptors. Recently, many studies have been focused on determining the HLA binding-peptides. The novel use of immune-informatics tools, from the prediction of the HLA-bound peptides to the modification of the HLA-receptor complexes, is considered. A better knowledge of HLA peptide presentation and recognition are allowing new strategies for immune response manipulation to be applied against HIV virus.     

The role of viral and cellular proteins in the budding of human immunodeficiency virus

For over two decades, research on Human immunodeficiency virus (HIV), which is responsible for AIDS, has aimed at understanding of the molecular mechanisms used by this virus during its life cycle. An essential step in the HIV life cycle is the budding, which promotes the release of viral particles from the host cell. It has recently been revealed that HIV in the process of budding uses besides one viral protein also the machinery of the infected cell, in particular the proteins Tsg101 and ubiquitin. The viral protein is the p6 domain of the Gag precursor polyprotein. In normal cells, Tsg101 functions as a regulator of endocytic trafficking that recognizes ubiquitinated cargo and directs its delivery to degradative compartments. In HIV-infected cells, Tsg101 and ubiquitin interact with Gag p6 to promote the release of new viral particles from the host cell. Molecular mechanisms underlying the process of HIV budding from infected cells suggests a whole new range of drug targets that could prove useful in AIDS suppression in HIV-positive patients.     

Transmission of the human immunodeficiency virus

The accumulated data strongly support the conclusion that transmission of HIV occurs through blood, sexual activity, and perinatal events. Nevertheless, the fear of transmission by other routes may continue to increase with the anticipated increase in the number of cases of AIDS over the next few years. An unrealistic requirement for absolute certainty about the lack of transmission by other routes persists, despite the knowledge that it is not scientifically possible to prove that an event cannot occur. It remains difficult to believe that a virus that is spreading rapidly and may cause a cruel, frightening, and fatal disease is not highly contagious and easily transmitted. The available data indicate that HIV transmission is not highly efficient in a single or a few exposures, unless one receives a very large inoculum. The widespread dissemination of HIV is more likely the result of multiple, repeated exposures over time by routes of transmission that are strongly related to personal and cultural patterns of behavior--particularly, sexual activity and the use of drugs. Isolated transmission events should be placed in full perspective by examining the results of population-based studies that provide rates of risk. It is from these studies that rational approaches and public policy should be developed.     

Chemical inactivation of human immunodeficiency virus in vitro.

Most chemicals with potential virucidal activity are extremely cytotoxic even at very small concentrations, thus introducing a number of technical problems and uncertainties in the evaluation of the net virucidal effect. In the present study, an attempt was made to confirm the reported virucidal activity of certain well-known chemicals and a number of new compounds were investigated. The results suggest that HIV inactivation is dependent on the viral concentration, the time of incubation in presence of the putative disinfectant and the degree of virucidal activity of the latter. The data illustrate methodological problems arising from residual cytotoxicity of the chemical which may mask or mimic the presence of a true virucidal activity and lead to erroneous conclusions. Alcohol, the most commonly used disinfectant, was found to be ineffective for high viral concentrations, whilst sodium hypochlorite was the most efficient.     

How human immunodeficiency virus ravages the immune system.

The immune system of individuals infected with human immunodeficiency virus is affected in two distinct ways: by loss of CD4+ cells and by loss of T-helper-cell function. Neither of these processes is yet fully understood. Research during 1991 that investigated the interaction between human immunodeficiency virus and the immune system has raised as many questions as it answered. Nevertheless, many of the issues raised are relevant to mechanisms responsible for the ravaging of the immune system by human immunodeficiency virus.     

Ultrastructural pathology of human immunodeficiency virus infection.

The electron microscope has been used with great skill in many aspects of the acquired immunodeficiency syndrome. It has played a critical role in classifying the human immunodeficiency virus, in characterizing the morphogenesis and gene products of the virus, and in elucidating the host cell targets and interactions. With the aid of the electron microscope, new opportunistic pathogens are being identified, and particularly difficult diagnoses are being made. Extrapolations from observations made at the ultrastructural level to the light microscopic level have provided criteria for the diagnosis of several infectious agents. As with any powerful scientific tool, observations must be interpreted with great care by scientists experienced in electron microscopy.