Number Of Human Immunodeficiency Virus Research Articles

New Drug Targets for HIV

A significant number of human immunodeficiency virus (HIV) infections have become resistant to antiretroviral treatment, which means that there is a paramount need for novel drug targets to defeat the virus. Until recently, all HIV drugs inhibited HIV replication by mechanisms operating inside infected cells. In contrast, new antiretroviral drugs operate outside infected cells. Their mechanism of action consists in inhibiting entry of the virus into cells, thereby halting the very first step of HIV replication. Examples of this new class of drugs include entry inhibitors, coreceptor antagonists, and fusion inhibitors. In addition to their novel mechanism of action, this new class of drugs also has potential action against drug-resistant HIV strains, causes minimal adverse effects, and may be administered in a simplified, once-daily dosing regimen. New classes of anti-HIV drugs--and new drugs in existing classes--represent the best hope for people infected with HIV, especially those who have exhausted current therapies.

Assessing the health status of young AIDS and other orphans in Kampala, Uganda

The huge number of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) orphans is an important feature of the epidemic in sub-Saharan Africa. There are few and conflicting data on the effects of being orphaned on health and nutrition in the highly affected HIV endemic areas of Africa. This study reports findings from a cross-sectional survey on associations between orphan status and health and nutrition parameters in young children of urban Uganda. A high prevalence of orphans was reported from a central Kampala community, with 41% being attributed to HIV/AIDS. Although there was a higher prevalence of self-reported morbidity in orphans than non-orphans, there were no differences in reported treatment seeking behaviour and measured anthropometric parameters. Hence it seems that the extended family system still manages to care for young orphans. Paying school fees for older children should be the primary target for HIV/AIDS impact mitigation programs in urban Uganda.

HIV-resistance to viral entry inhibitors.

An increasing number of human immunodeficiency virus (HIV)-infected patients have detectable viraemia despite treatment with multiple-drug combinations or have developed resistance to all available classes of antiretroviral therapy. HIV entry has become an important pharmacological target. Enfuvirtide is the first HIV entry inhibitor to be approved for the treatment of drug-experienced patients but several other agents are progressing through preclinical and clinical trials. However, because different entry inhibitors target different parts of the entry process their combined effects could be synergistic or generate different distinct profiles of drug-resistance. The HIV envelope glycoprotein that drives HIV entry is highly variable. Its plasticity allows HIV to escape the immune system and its variability is associated with HIV tropism, fitness and replicative capacity. Thus, mutations that confer resistance to entry inhibitors will modify these parameters. Therapeutic strategies that aim at blocking virus entry may also be used to alter the natural evolution of HIV in an unprecedented way. Here, we will describe the structure and function of the envelope glycoprotein complex that constitute the basis for the emergence of resistance to HIV entry inhibitors, review those HIV entry inhibitors for which drug-resistance has been evaluated and discuss the interplay between viral resistance to inhibitors of HIV entry and the pathogenicity of HIV and AIDS.

Human Immunodeficiency Virus Risk: Is it Possible to Dissuade People from Having Unsafe Sex?

SummaryThe cumulative number of human immunodeficiency virus (HIV) infections worldwide has reached 60 million in little over 30 years. HIV continues to spread despite a detailed understanding of the manner in which it spreads and measures which can prevent spread. Some governments have been highly successful in containing the spread of HIV through blood products and from mother to child and among injecting drug users. Lack of political will, lack of resources or challenges to widely accepted scientific evidence have held back similar interventions in other countries. It has proved much more difficult to reduce the sexual transmission of HIV in both high and low income countries. A wide range of strategies has been identified but it remains unclear which strategies deserve priority and what methods of promoting them have the greatest effect. There is ample evidence that awareness of HIV and changes in sexual behaviour have occurred widely but the penetration of information remains poor in some vulnerable groups especially adolescents and women in poorer countries. Further obstacles face those who have information about the risk. The subordinate position of women and a desire for large families are important obstacles to condom negotiation and use. Urbanization, poverty, conflict and declining public services all exacerbate unsafe sexual behaviour. We argue that so-called ‘structural’ interventions directed at these wider contexts of unsafe behaviour merit greater attention. Such approaches have the added benefit of being less susceptible to ‘risk compensation’ which has the potential to undermine strategies directed at reducing the transmission efficiency of HIV.

Child-rearing practices of primary caregivers of HIV-infected children: An integrative review of the literature

The number of human immunodeficiency virus (HIV)-infected children has increased because of the HIV and acquired immunodeficiency syndrome epidemic. Yet little is known about the child-rearing practices of these children's primary caregivers. The purpose of this article is to describe what is known about the child-rearing practices of primary caregivers of HIV-infected children. The review covers a 10-year period from 1990 to 2000. Three electronic bibliographic databases (MEDLINE, CINAHL, and AIDSLINE) were explored. Key words used were HIV-positive children, caregivers, and child-rearing. A total of 50 papers were examined. Using the Matrix Method, each paper was evaluated according to five frames of reference: journal, purpose, sample, method, and findings. Content analysis was used to identity salient themes. Themes that emerged were: caregiver, child, and interactions or child-rearing practices. These findings affirm the parent-child interaction model generated by Kathryn E. Barnard and support this framework as a tool for investigating the relationships between these children and their caregivers. Copyright 2002, Elsevier Science (USA). All rights reserved.

Parkinsonism in HIV dementia.

A great number of human immunodeficiency virus (HIV)-infected patients develop a central nervous system disorder, commonly called HIV dementia or AIDS dementia complex (ADC). HIV dementia is independent of opportunistic infections and is due to the virus itself. Symptoms include psychomotor slowing, apathy and motor disorders similar to the bradykinesia and postural and gait abnormalities observed in late Parkinson's disease. Consequently, HIV has been discussed during the last few years as an additional cause for parkinsonism, and parkinsonian syndromes as manifestations of HIV dementia. Moreover, the early phase of HIV infection gains increasing interest because of studies which report subtle neurological symptoms at this stage. Accordingly, we found in SIV-infected monkeys that dopamine is reduced by 44% within as few as two months of infection, indicating that changes during early infection must be thoroughly evaluated. In this short review, we discuss alterations in the nigrostriatal dopaminergic system during early and late immunodeficiency virus infection and the common clinical and biochemical features shared by HIV dementia and Parkinson's disease.

SINUSITIS IN HIV INFECTION

The number of human immunodeficiency virus (HIV)–infected outpatients is growing rapidly because of the widespread use of antiretroviral therapy, earlier recognition of HIV infection and prophylaxis, and earlier treatment of opportunistic infections. 56 As a result, new HIV-associated medical problems are being encountered with increasing frequency. Among the most important of these are chronic and recurrent sinusitis. Based on several prospective studies, the incidence of sinusitis in HIV-infected patients is estimated to be as high as 60% to 80%. 27,53 In addition, HIV-infected patients may have an atypical presentation of sinusitis that makes recognition difficult for many practitioners. Because of the associated immunodeficiency in HIV infection, sinusitis often tends to be more severe and difficult to treat than in non–HIV-infected subjects. For these reasons, sinusitis has become a major source of morbidity in HIV-infected patients and is likely to become more of a problem for as long as the HIV epidemic persists. This article reviews the current state of knowledge about sinusitis in HIV infection, including its epidemiology, clinical presentation, pathophysiology, and current recommendations for treatment and management.

Annual Summary of Vital Statistics—1995

Recent trends in the vital statistics of the United States continued in 1995, including decreases in the number of births, the birth rate, the age-adjusted death rate, and the infant mortality rate; life expectancy at birth increased to a level equal to the record high of 75.8 years in 1992. Marriages and divorces both decreased. An estimated 3,900,089 infants were born during 1995, a decline of 1% from 1994. The preliminary birth rate for 1995 was 14.8 live births per 1000 total population, a 3% decline, and the lowest recorded in nearly two decades. The fertility rate, which relates births to women in the childbearing ages, declined to 65.6 live births per 1000 women 15 to 44 years old, the lowest rate since 1986. According to preliminary data for 1995, fertility rates declined for all racial groups with the gap narrowing between black and white rates. The fertility rate for black women declined 7% to a historic low level (71.7); the preliminary rate for white women (64.5) dropped just 1%. Fertility rates continue to be highest for Hispanic, especially Mexican-American, women. Preliminary data for 1995 suggest a 2% decline in the rate for Hispanic women to 103.7. The birth rate for teenagers has now decreased for four consecutive years, from a high of 62.1 per 1000 women 15 to 19 years old in 1991 to 56.9 in 1995, an overall decline of 8%. The rate of childbearing by unmarried mothers dropped 4% from 1994 to 1995, from 46.9 births per 1000 unmarried women 15 to 44 years old to 44.9, the first decline in the rate in nearly two decades. The proportion of all births occurring to unmarried women dropped as well in 1995, to 32.0% from 32.6% in 1994. Smoking during pregnancy dropped steadily from 1989 (19.5%) to 1994 (14.6%), a decline of about 25%. Prenatal care utilization continued to improve in 1995 with 81.2% of all mothers receiving care in the first trimester compared with 78.9% in 1993. Preliminary data for 1995 suggests continued improvement to 81.2%. The percent of infants delivered by cesarean delivery declined slightly to 20.8% in 1995. The percent of low birth weight (LBW) infants continued to climb in 1994 rising to 7.3%, from 7.2% in 1993. The proportion of LBW improved slightly among black infants, declining from 13.3% to 13.2% between 1993 and 1994. Preliminary figures for 1995 suggest continued decline in LBW for black infants (13.0%). The multiple birth ratio rose to 25.7 per 1000 births for 1994, an increase of 2% over 1993 and 33% since 1980. Age-adjusted death rates in 1995 were lower for heart disease, malignant neoplasms, accidents, and homicide. Although the total number of human immunodeficiency virus (HIV) infection deaths increased slightly from 42,114 in 1994 to an estimated 42,506 in 1995, the age-adjusted death rate for HIV infection did not increase, which may indicate a leveling off of the steep upward trend in mortality from HIV infection since 1987. Nearly 15,000 children between the ages of 1-14 years died in the United States (US) in 1995. The death rate for children 1 to 4 years old in 1995 was 40.4 per 100,000 population aged 1 to 4 years, 6% lower than the rate of 42.9 in 1994. The 1995 death rate for 5- to 14-year-olds was 22.1, 2% lower than the rate of 22.5 in 1994. Since 1979, death rates have declined by 37% for children 1 to 4 years old, and by 30% for children 5 to 14 years old. For children 1 to 4 years old, the leading cause of death was injuries, which accounted for for an estimated 2277 deaths in 1995, 36% of all deaths in this age group. Injuries were the leading cause of death for 5- to 14-year-olds as well, accounting for an ever higher percentage (41%) of all deaths. In 1995, the preliminary infant mortality rate was 7.5 per 1000live births, 6% lower than 1994, and the lowest ever recorded in the US. The decline occurred for neonatal as well as postneonatal mortality rates, and among white and black infants alike.

An estimate of the number of human immunodeficiency virus (HIV)-positive blood donations by HIV-seronegative donors in a northern Thailand HIV epicenter.

Despite mandatory antibody testing, human immunodeficiency virus (HIV) can be transmitted from HIV-infected blood that is seronegative. The objective of this study was to estimate the probability of HIV-infected blood donations during the seronegative "window period" in a northern Thailand HIV epicenter. Thus, a retrospective cohort of repeat blood donors was created. With the assumptions that the probability of HIV seroconversion is distributed uniformly between the last HIV-negative and the first HIV-positive donation and that the seronegative window is 45 days, the rate of window-period donations was calculated by multiplying the incidence by the window duration. Of 11,232 repeat donors, 273 seroconverted during 9,518,863 person-days of observation (i.e., a window-period donation rate of 1/775). There were more window-period donations among 21- to 30-year-old men and in donors replacing blood of friends or relatives. Additional measures are needed to reduce the high number of HIV-infected window-period donations.

Human immunodeficiency virus infection in an emergency hand service

A study prompted by the high number of human immunodeficiency virus (HIV) patients in the South African population was performed to evaluate the incidence of HIV in patients attending our Emergency Hand Service. Over a 6-month period, more than 500 consecutive emergency patients were tested for HIV. In our series, 24 patients tested HIV-positive. Of these, 14 presented with hand sepsis and 10 with hand injuries. Bacteriology was performed on all patients with sepsis to document bacteria type and sensitivity. CD4 counts (T4 lymphocyte counts) were done on 12 patients to assess immunocompetence. Other factors examined included hospital stay, number of operations, postoperative morbidity, and mechanism of injury. Results indicate that septic HIV patients spent more time in the hospital and required more operations than septic non-HIV patients. Furthermore, of all of the population of emergency hand patients, a larger percentage of HIV-positive persons than HIV-negative persons was likely to be seen for infection.

Identification of multirestricted immunodominant regions recognized by cytolytic T lymphocytes in the human immunodeficiency virus type 1 Nef protein.

Peripheral blood mononuclear cells from a large number of human immunodeficiency virus (HIV)-seropositive donors were used to analyze the CD8+ T-cell response to each part of the Nef protein of HIV-1/LAI. This report identifies an immunodominant region (amino acids 73 to 144) in the Nef protein that was recognized by 97% of the NEF responder donors. This peptide sequence was dissected into four epitopic regions (amino acids 73 to 82, 83 to 97, 113 to 128, and 126 to 144), each of which was recognized under different HLA class I restrictions. Short overlapping peptides were used to sensitive the target cells for cytolysis and so to determine if these epitopic regions were multirestricted. Each region was found to contain several epitopes recognized with different HLA molecules. Thus, the central region of the Nef protein, a regulatory protein expressed early in HIV-infected cells, is rich in epitopic sequences which are found to be similar in many infected individuals and which can be recognized in association with at least ten HLA class I molecules. Their implications for the vaccination of humans with peptide sequences are discussed.

An Estimate of the Prevalence of Human Immunodeficiency Virus Infection in England and Wales by using a Direct Method

Knowledge of the number of human immunodeficiency virus (HIV) seropositive people in a country and of their distribution in different transmission categories is important for health care planning, for risk estimations and for targeting public health interventions. We used data on seroprevalence of antibody to HIV in defined subgroups of the population attained from unlinked anonymous HIV testing surveys and combined these with estimates of the respective sizes of these subgroups from an interview study on sexual attitudes and lifestyles. Seroprevalence in those subgroups not covered by the HIV testing surveys was derived from a series of assumptions and approximations. The estimated numbers of HIV seropositive subjects in each subgroup were added to give an overall total for England and Wales at the end of 1991. The overall estimate was 27180 HIV seropositive people, with lower and upper bounds of 20200 and 34300 respectively. Homosexual and bisexual men were estimated to constitute about half of the total number who were seropositive, and heterosexually infected people constituted approximately a quarter. The greatest numerical uncertainties applied to the number of HIV seropositive men who have had a male partner, but not in the last 5 years, and to the number of HIV seropositive heterosexual men and women who have no recognized risk behaviour. Overlap between the various subgroups defined by unlinked anonymous testing programmes is substantial, but could partly be adjusted for with data from the interview study. The estimates of this study are in the same range as those made earlier with this and other modelling strategies.

Continuous ambulatory peritoneal dialysis and survival of HIV infected patients with end-stage renal disease

As the number of human immunodeficiency virus (HIV) infected patients has increased in the U.S., the number of infected patients treated for end-stage renal disease (ESRD) has stabilized at about 1 to 2% of the hemodialyzed population. Little has been written regarding the role of continuous ambulatory peritoneal dialysis (CAPD) in the treatment of HIV infected patients with ESRD. To evaluate the effectiveness of CAPD as a long term therapy for HIV infected patients with ESRD, we reviewed our ESRD program's experience. We entered 392 patients from its inception in February 1984 until April 1992. Thirty-one, or 7.9% of our population were HIV infected. Twenty, or 64.5% had stage IV infection. Patients were entered into our chronic hemodialysis (HD) or CAPD program according to standard clinical criteria. Eight HIV infected patients elected to start CAPD, while 23 patients were treated exclusively with HD. The proportion of stage IV infected patients was similar in both treatment modality groups. HIV infected ESRD patients were younger than non-HIV infected patients (37.5 +/- 9.7 vs. 49.8 +/- 15.7 years, respectively, P < 0.0001) at the start of treatment. We used Cox regression techniques to analyze survival data. Mean survival time for our entire non-HIV infected ESRD population (N = 361) was 44.0 +/- 33.9 months. Mean survival time for HIV infected patients with ESRD was 15.5 +/- 9.9 months. Median survival for HIV infected ESRD patients was 13 months compared to 38 months for the non-infected population. As expected, mean survival time in HIV infected ESRD patients was significantly diminished compared to non-infected ESRD patients (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of herpesvirus infections in the future.

Numerous diverse, often opposing, trends will determine the frequency (and severity) of herpesvirus infections in the future. A major factor is the growing population of iatrogenically immunocompromised patients, accruing especially from large increases in organ and autologous bone marrow transplantation. Of even greater importance is the immense number of human immunodeficiency virus (HIV)-infected patients for whom herpesviruses may: (1) have been a cofactor in acquisition of HIV infection; (2) contribute to in vivo activation of HIV; (3) cause severe infections. Another factor influencing severe herpesvirus infections is the aging of populations in developed countries; this will be associated with a greater prevalence, and more morbid manifestations, of herpes zoster. Sociologic changes will also be important. The consequences of these, such as attempts to influence sexual practices, will be difficult to predict. Other changes, such as more frequent use of early child care facilities, will predictably lead to early acquisition of most herpesviruses, thereby decreasing the incidence of severe disease in adulthood. Factors that will reduce the incidence and/or severity of herpesvirus infections include vaccines (varicella, herpes simplex, cytomegalovirus); prophylactic strategies for immunocompromised hosts (passive immunization, antiviral drugs, blood product selection); more rapid and sensitive diagnostic methods; and suppressive or early antiviral therapy for common infections, such as genital herpes simplex and varicella.(ABSTRACT TRUNCATED AT 250 WORDS)

Interactions between HIV-infected monocytes and the extracellular matrix: increased capacity of HIV-infected monocytes to adhere to and spread on extracellular matrix associated with changes in extent of virus replication and cytopathic effects in infected cells.

Monocytes express cell surface receptors for extracellular matrix (ECM) proteins of basement membranes. These receptors are engaged during extravasation of cells through capillary endothelium into tissue. The number of human immunodeficiency virus (HIV)-infected monocytes that adhered to ECM over 2 h was threefold higher than that of uninfected control cells. This difference was ECM specific and was not observed with a bovine serum albumin substrate. Enhanced adhesion to ECM was evident in monocytes by 4 days after HIV infection and increased through 10 days. Monocytes exposed to a T cell-tropic HIV strain that binds to but does not replicate in monocytes showed no changes in adherence to ECM. Thus, productive infection of monocytes by HIV induces a significant increase in the capacity of these cells to interact with ECM. Enhanced adhesion of HIV-infected monocytes to ECM was associated with increased spreading: at 12 h, sixfold more HIV-infected monocytes were spread on ECM than were uninfected control cells. Cell processes of HIV-infected monocytes formed a complex network on ECM: many of these cells expressed HIV proteins as detected by indirect immunofluorescence. HIV-associated cytopathic effects and levels of virion-associated reverse transcriptase activity depended on the substrate to which monocytes were attached. Virus replication and cytopathic effects in monocytes adhered to ECM, fibronectin, or plastic alone were comparable. In contrast, HIV-infected monocytes attached to laminin showed a significant increase in virus replication and in extent of cytopathic effects through 2 weeks after infection. The lowest levels of HIV replication and cytopathic effects were in monocytes attached to collagen IV. Interactions between monocytes and ECM profoundly affect the manner in which these cells control HIV infection: HIV infection changes the capacity of infected monocytes to attach and spread on ECM; attachment to ECM alters the extent of virus replication in infected cells.

Rapid In Situ Detection of PCR-Amplified HIV-1 DNA

The low copy number of human immunodeficiency virus 1 (HIV-1) DNA infected cells precludes routine detection by in situ hybridization. The inability to detect cells latently infected by HIV-1 makes difficult the study of factors that induce viral transcription, an essential factor in the development of the acquired immune deficiency syndrome (AIDS). A sensitive and rapid technique to detect HIV-1 DNA could be used as a diagnostic test for AIDS and to differentiate latent versus active viral infection. We describe a 3-h technique whereby HIV-1 DNA is amplified by hot start polymerase chain reaction (PCR) and detected directly in infected cells. The specificity of the assay was demonstrated by double labeling the positive cells with CD4. Using a CR10 HIV-1-infected cell line, the 90% of cells that were HIV-1 DNA positive could be distinguished from the 10% that were actively expressing HIV-1 RNA. The PCR in situ technique should allow for the direct localization of DNA sequences in cells that would otherwise be undetectable by conventional in situ analysis.

Cryptococcal meningitis associated with acquired immunodeficiency syndrome (AIDS) in African patients: treatment with fluconazole.

Cryptococcal meningitis associated with acquired immunodeficiency syndrome (AIDS) is particularly common in tropical Africa. This could be explained by the dramatic increase in the number of human immunodeficiency virus (HIV) infections and the high prevalence of Cryptococcus neoformans var. neoformans in the domestic and general environment of HIV-positive and AIDS patients Meningoencephalitis is the usual and dominant clinical feature of cryptococcal infection in AIDS patients and 'slim disease', tuberculosis and candidiasis are the most common opportunistic infections associated with cryptococcal meningitis. In a group of 64 African patients with AIDS and cryptococcosis treatment with a daily dose of 400 mg fluconazole (FCA) during the acute phase showed a clinical cure in 63% of the evaluable patients. Mycological response to treatment with negative culture was found in 76% of our patients (at day 60-90). The overall tolerance of FCA was excellent. This treatment was also used successfully for relapse of cryptococcal meningitis.

Intracerebral hodgkin's disease in a human immunodeficiency virus-seropositive patient

Intracerebral involvement of Hodgkin's disease (HD) is rarely described, with only 42 cases in the literature. Since the outbreak of the acquired immune deficiency syndrome (AIDS) epidemic, there has been an increasing number of human immunodeficiency virus (HIV)-infected (HIV+) persons who have diffuse non-Hodgkin's lymphoma and, more recently, atypical aggressive HD. The authors report the case of a patient with a history of intravenous drug abuse (IVDA) and Stage IVB HD who, after a drug-induced clinical remission, had intracerebral mixed-cellularity HD. This appears to be the first report of intracerebral HD in a person who is HIV+.

Projection of AIDS incidence in women in New York State.

The results of the Newborn HIV Seroprevalence Study in New York State for 1988 were used to estimate the number of human immunodeficiency virus (HIV)-infected women of childbearing age in 1988. The estimate was accomplished for each of 80 age, racial/ethnic, and geographic strata by dividing the number of seropositive newborns by the 1988 estimated fertility rate. Summing across strata yielded a total of 23,430 infected women age 15 to 44 years in 1988. From this estimate a tree model was used to estimate the number of women infected during 1981-88. Back calculation was used to distribute these infections over time, and the selected incubation distribution was used to estimate future AIDS cases for this population: 8,295 cases by 1993.

Quantitation of human immunodeficiency virus DNA by using the polymerase chain reaction

The polymerase chain reaction was used to measure the DNA copy number of human immunodeficiency virus (HIV). Differences in polymerase chain reaction amplification efficiency were controlled by amplifying known amounts of HIV DNA in parallel with samples. This technique is a sensitive, accurate, and reproducible method for the quantitation of HIV DNA.