Impact Of Human Immunodeficiency Virus Research Articles

Guidelines for Adolescent Health Research*1, *2A position paper of the Society for Adolescent Medicine

Guidelines for Adolescent Health Research*1, *2A position paper of the Society for Adolescent Medicine

Global impact of human immunodeficiency virus and AIDS.

This review provides information on the epidemiology, economic impact, and intervention strategies for the human immunodeficiency virus (HIV)/AIDS pandemic in developing countries. According to the World Health Organization and the Joint United Nations Programme on HIV/AIDS (UNAIDS) at the end of 1999, an estimated 34.3 million people were living with HIV/AIDS. Most of the people living with HIV, 95% of the global total, live in developing countries. Examples of the impact of HIV/AIDS in Africa, Asia, Latin America, the Caribbean, and the Newly Independent States provide insight into the demographics, modes of exposure, treatment and prevention options, and the economic effect of the epidemic on the global community. The epidemic in each region of the world is influenced by the specific risk factors that are associated with the spread of HIV/AIDS and the responses that have evolved to address it. These influences are important in developing HIV/AIDS policies and programs to effectively address the global pandemic.

Impact of Human Immunodeficiency Virus Type-1-Associated Cognitive Dysfunction on Activities of Daily Living and Quality of Life

We examined the impact of neuropsychological (NP) impairment on activities of daily living (ADLs) and quality of life in human immunodeficiency virus type-1 (HIV-1)-infected persons of low socioeconomic status (SES). Thirty-nine patients were stratified into one of three groups: cognitively normal (n = 13), mild cognitive impairment (n = 15), and moderate/severe impairment (n = 11). Quality of life was assessed with the Sickness Impact Profile and ADLs were evaluated via structured interview performed in the patient's residence. While there were no significant differences across groups on disease stage, drug use, depression, or estimated premorbid IQ, cognitively impaired patients were more likely to be unemployed and fail social planning and medication management tasks. Our study confirms a previously reported association between NP impairment and unemployment among HIV-1-infected patients. The data also extend this relationship to a low-SES sample with a high base rate of unemployment, and to instrumental activities of daily living other than work.

Cytokine profile in genital tract secretions from female adolescents: impact of human immunodeficiency virus, human papillomavirus, and other sexually transmitted pathogens.

Quantitative enzyme-linked immunosorbent assays were used to measure interleukin (IL)-2, IL-10, and IL-12 in cervical secretions from female adolescents with and without sexually transmitted infections. Compared with human immunodeficiency virus [HIV]-negative patients, HIV-positive patients had higher concentrations of IL-10 (118.2 pg/mL vs. 34.5 pg/mL; P=.002) and IL-12 (175.5 pg/mL vs. 85.1; P=.03). IL-2 concentrations were not statistically different. Furthermore, genital tract infections were predictors of IL-10 and IL-12 concentrations. Coinfection with HIV and human papillomavirus predicted the highest IL-10 concentrations; coinfection with HIV, human papillomavirus, and other sexually transmitted pathogens predicted the highest IL-12 concentrations. The data indicate that concomitant infection of the genital tract with HIV and other viral, bacterial, or protozoan pathogens influences the local concentrations of some immunoregulatory cytokines.

The impact of HIV infection on Mycobacterium kansasii disease in South African gold miners.

The impact of human immunodeficiency virus (HIV) infection on Mycobacterium kansasii disease in miners was investigated with a retrospective study covering a single workforce. M. kansasii, isolated from 43 HIV-positive and 202 HIV-negative miners, was the most common nontuberculous mycobacterial (NTM) species in both HIV groups. CD4 counts were unusually high for M. kansasii disease (mean 490 x 10(6)/L, from 14 HIV-positive men). Treatment outcomes were similar: mortality during treatment was higher in HIV-positive than in HIV-negative men (9% and 2%, respectively), but not significantly so. The majority of a sample of 31 HIV-positive and 92 HIV-negative men had radiological silicosis and/or old tuberculosis scarring prior to M. kansasii disease. A normal premorbid radiograph was more common in HIV-positive men (45% versus 24%; odds ratio [OR], 2.62; 95% confidence interval [95% CI], 1.01 to 6.67). New cavitation was less common (55% versus 78%; OR, 0.34; 95% CI, 0.13 to 0.88) and new hilar adenopathy more common (OR, 5.07; 95% CI, 1.24 to 21.9) in HIV-positive than in HIV-negative men. Miners, who have additional NTM risk factors, develop M. kansasii disease that occurs at an earlier stage of HIV infection and more closely resembles disease in HIV-negative men than has been found for HIV-associated M. kansasii disease in other settings.

Human immunodeficiency virus and the outcome of treatment for new and recurrent pulmonary tuberculosis in African patients.

The purpose of this study was to evaluate the impact of human immunodeficiency virus (HIV) infection on treatment for tuberculosis (TB). The study population comprised 28,522 black Southern African gold miners. Patients with sputum culture-positive new or recurrent pulmonary TB diagnosed in 1995 were prospectively enrolled in the cohort. Directly observed therapy (DOT) was practiced and outcomes were assessed at 6 mo after treatment was begun. There were 376 cases of TB (incidence 1,318 per 100,000), of which 190 (50%) were HIV positive and 82 (22%) had recurrent TB. There was no association between HIV status and history of previous TB or drug resistance. Neither the treatment interruption rate (2%) nor the rate at which patients transferred out of the treatment program (1.6%) were associated with HIV status. Excluding deaths, cure rates were similar for HIV-positive and HIV-negative patients (89% versus 88%), but significantly lower in those with recurrent than in those with new TB (77% versus 92%). Mortality was 0.5% in HIV-negative patients versus 13.7% in HIV-positive patients, and in the latter group was associated with CD4(+) lymphocyte depletion. Autopsy examination showed that in HIV-positive patients, early mortality was due to TB whereas late deaths were most commonly due to cryptococcal pneumonia. The study showed that a well-run TB control program can result in acceptable cure rates even in a population with a very high incidence of TB and HIV infection. Particular vigilance is needed for concurrent infections, which may contribute significantly to mortality during treatment of TB in HIV-positive patients.

Alterations in Head and Neck Cancer Occurring in HIV-infected Patients: Results of a Pilot, Longitudinal, Prospective Study

To assess the impact of human immunodeficiency virus (HIV) infection on the presentation and course of head and neck squamous cell carcinoma (HNSCC), we performed a pilot, prospective, longitudinal study of all patients with HNSCC presenting to our institutions over a 6-month period (n=10). A 60% incidence of HIV infection was seen in this study population, with SCC presenting as the initial manifestation of HIV infection in 2 of the 6 patients. In addition, HIV-infected patients were significantly younger than non-infected patients at (p=0.01). None of the HIV-infected patients had acquired immunodeficiency syndrome (AIDS) at the time of presentation, but 5 of 6 patients had an abnormal CD4 count, compared to none of the non-infected patients (p

The epidemiology of infection in childhood

Worldwide infections as a disease group are responsible for most loss of life and good health among children. It was estimated that in 1990, infectious diseases were responsible for 8.3 million of a total of 12.5 million deaths among a global child population (under 5 years-of-age) of 6301 million, and projections to the year 2020 suggest that this burden of mortality is only likely to worsen with the growing impact of human immunodeficiency virus (HIV)? It is estimated that around 4 million children under the age of 5 die annually from acute respiratory tract infections, and diarrhoeal diseases are responsible for approximately 3 million child deaths, while the contribution of HIV to child mortality is poorly quantified but growing? Mortality statistics need to be supplemented by estimates of the burden of disability (morbidity), and to allow for the varying implications of death at different ages. This can be done by use of disabilityadjusted life years (DALY): a measure developed by the World Bank and the World Health Organization (WHO).' Combining estimates of chronic disability and mortality statistics, this measure calculates the likely numbers of healthy years of life lost because of specific diseases and conditions. Also, by 'weighting', an allowance is made for the different significance of illhealth and mortality among infants, elderly persons compared to adults providing for dependants. Estimates of the burden of disease experienced emphasize the importance of infectious disease in developing countries, and the particular role in producing mortality in children under the age of 5 played

Health status assessment for the twenty-first century: item response theory, item banking and computer adaptive testing.

Health status assessment is frequently used to evaluate the combined impact of human immunodeficiency virus (HIV) disease and its treatment on functioning and well-being from the patient's perspective. No single health status measure can efficiently cover the range of problems in functioning and well-being experienced across HIV disease stages. Item response theory (IRT), item banking and computer adaptive testing (CAT) provide a solution to measuring health-related quality of life (HRQoL) across different stages of HIV disease. IRT allows us to examine the response characteristics of individual items and the relationship between responses to individual items and the responses to each other item in a domain. With information on the response characteristics of a large number of items covering a HRQoL domain (e.g. physical function, and psychological well-being), and information on the interrelationships between all pairs of these items and the total scale, we can construct more efficient scales. Item banks consist of large sets of questions representing various levels of a HRQoL domain that can be used to develop brief, efficient scales for measuring the domain. CAT is the application of IRT and item banks to the tailored assessment of HRQoL domains specific to individual patients. Given the results of IRT analyses and computer-assisted test administration, more efficient and brief scales can be used to measure multiple domains of HRQoL for clinical trials and longitudinal observational studies.

The impact of human immunodeficiency virus (HIV) infection on quality of life in a multiracial South African population.

We set out to document quality of life in South African HIV subjects, using the Medical Outcomes Survey (MOS) SF-36 instrument, and to determine whether this was affected by race, gender or clinical stage of disease. A cross-sectional survey of 134 HIV outpatients (42 White, 49 Mixed race, 43 Black) and 114 healthy non-medical hospital personnel (36 White, 37 Mixed race, 42 Black) was carried out at a referral centre for HIV patients in the Western Cape region of South Africa. Scores on eight scales measuring different aspects of quality of life were calculated. Black female controls scored significantly lower on all scales (p < 0.05) except physical function. HIV-infected subjects of Mixed race (both genders) reported poorer physical function (p < 0.05) but no other scale was affected by race. HIV subjects scored significantly lower than controls on all scales (p < 0.01); the majority of the decline in function occurred early in disease by WHO stages 1 and 2. We conclude that HIV-infection impacts early on all aspects of quality of life and that this impact is largely independent of racial origin.

Predictors of mortality in the Amsterdam cohort of human immunodeficiency virus (HIV)-positive and HIV-negative drug users.

The impact of human immunodeficiency virus (HIV) infection and other risk factors on mortality was studied in a cohort of Dutch injection drug users and drug users who did not inject. Participants were recruited between 1985 and 1992 and followed up through 1993. Vital status was ascertained through repeat visit information, supplemented by population register data. A total of 77 deaths were recorded among 632 drug users, for a mortality rate per 1,000 person-years of 7 for HIV-negative noninjection drug users, 18 for HIV-negative injection drug users, and 64 for HIV-positive injection drug users. In multivariate analyses, limited to injection drug users, a positive HIV serostatus, age above 40 years, and using benzodiazepines several times daily were significantly associated with an elevated risk of death, both for death from all causes and for death preceding acquired immunodeficiency syndrome (AIDS) diagnosis (pre-AIDS). For pre-AIDS death, the adjusted relative risk associated with HIV infection was 2.2 (95% confidence interval 1.3-3.7). Only 38% of HIV-infected injection drug users who died were diagnosed with AIDS. However, 76% of HIV-infected injection drug users who died without AIDS diagnosis had evidence of immunosuppression (CD4 count < 500/microliters). Daily use of methadone and participation in needle and syringe exchange schemes were not associated with lower mortality rates. This study illustrates in a group of injection drug users with a 30% HIV seroprevalence and a high background mortality the profound influence on mortality that HIV infection has gained.

Zidovudine kinetics in the pregnant baboon.

The devastating impact of human immunodeficiency virus (HIV) infection during pregnancy has made the pharmacologic evaluation of potentially therapeutic agents of high priority. The results presented here are the maternal pharmacokinetics from a series of experiments to delineate more clearly the complex maternal-fetal pharmacokinetics and the effects of AZT in the chronically instrumented maternal and fetal baboon during both steady state intravenous infusion and oral bolus dosage regimens. Two results of major clinical importance were found. First, during pregnancy, both the clearance and volume of distribution of AZT were increased. Plasma clearance in the pregnant animals was 51 +/- 10 ml/min/kg compared with 37 +/- 2 ml/min/kg in the nonpregnant animals, and steady state volume of distribution was 3.7 +/- 1.21/kg compared with 2.2 +/- 0.61/kg. Second, with continuous intravenous infusion plasma drug concentrations were easily maintained in the therapeutic range, whereas with oral administration plasma concentration fell below therapeutic levels within 2 h of the dose being given. Because maternal plasma concentrations are a major determinant of drug concentration achieved in the fetus, an understanding of drug kinetics in pregnancy is of vital importance when making recommendations regarding optimal drug therapy during pregnancy to maximize the beneficial effect--the prevention of HIV infection in children.

The impact of human immunodeficiency virus on mortality of patients treated for tuberculosis in a cohort study in Zambia

We have examined the impact of human immunodeficiency virus (HIV) on mortality of patients treated for tuberculosis in a prospective study in Lusaka, Zambia. Patients with sputum smear-positive, miliary, or meningeal tuberculosis were prescribed 2 months' daily streptomycin, thiacetazone, isoniazid, rifampicin, and pyrazinamide followed by 6 months thiacetazone and isoniazid; others, 2 months streptomycin, thiacetazone and isoniazid followed by 10 months thiacetazone and isoniazid. 239 patients (65 HIV-negative and 174 HIV-positive) were followed to 2 years from start of treatment. The crude mortality rate ratio for HIV-positive compared with HIV-negative patients over 2 years was 5.00 (95% confidence interval 2.30–10.86). Median survival for HIV-positive patients from the start of treatment was 22 months. At least 34% of HIV-positive patients for whom cause of death was known died from tuberculosis, three-quarters of these during the first month of treatment. Risk factors for death in HIV-positive patients included multi-site tuberculosis, history of prolonged diarrhoea or fever, oral thrush, splenomegaly, anergy to tuberculin, low weight, anaemia or lymphopenia, and poor compliance with regimens containing rifampicin and pyrazinamide. Tuberculosis, even treated, was a major cause of death in patients with HIV infection.

HIV status does not affect microbiologic spectrum or neurologic outcome in spinal infections

The impact of human immunodeficiency virus (HIV) on the clinical presentations, causative organisms, and neurologic outcomes of patients with spinal infections is reviewed. Thirty-two patients with spinal epidural abscesses, vertebral osteomyelitis, or both were treated at an urban hospital over a 42-month period. Thirteen of these patients were confirmed by serologic analysis to be HIV seropositive. The diagnoses were confirmed by 30 open surgical procedures (14 anterior, 16 posterior) and seven percutaneous biopsies. Twenty-seven intraoperative cultures were positive and the remaining three patients had positive blood cultures prior to the surgical procedure. In both the HIV (+) and HIV (−) groups, Staphylococcus aureus predominated as the causative organism (overall rate: 72%). Mycobacterium tuberculosis was the second most common organism. The clinical presentations in both groups were similar with pain as the most frequent symptom and objective neurologic abnormalities on physical examination in 29 of the 32 patients (91%). The results of this analysis show that the clinical presentations and organisms cultured do not differ depending upon a concurrent HIV infection. Furthermore, the ultimate neurologic outcome of patients with spinal infections depends on their neurologic status at the time of treatment and not on their HIV status.

Delayed somatic growth and pubertal development in human immunodeficiency virus-infected hemophiliac boys: Hemophilia Growth and Development Study

As part of the Hemophilia Growth and Development Study, we investigated the impact of human immunodeficiency virus (HIV) infection on statural growth, weight gain, and skeletal and sexual maturity in more than 300 boys with moderate to severe hemophilia, of whom 62% were infected with HIV. Age-adjusted height and weight were reduced in the HIV-infected subjects (p < 0.001). However, mean weight for height and triceps skin-fold thickness of the infected-boys closely resembled those of the uninfected group. In HIV-infected boys, height for age was positively related to the CD4+ lymphocyte count when the count was < 200 cells/mm3. Age-adjusted serum testosterone levels did not differ by HIV status, but in the infected participants the mean age-adjusted bone age was significantly reduced (p = 0.038) and the distribution of Tanner stages, adjusted for age, differed significantly (p = 0.003). The probability of advancing one or more Tanner stages in the first study year was significantly slowed in HIV-infected boys more than 14 years of age (p = 0.0003). We conclude that linear growth was significantly impaired in boys with hemophilia and HIV infection, but the wasting of malnutrition was not found. The delays in bone age and pubertal maturation strongly suggest that part of the growth failure seen in acquired immunodeficiency syndrome can be attributed to pubertal delay. We speculate that the lack of demonstrable difference in age-adjusted testosterone concentrations might reflect subtle differences in the pattern of secretion of testosterone or in the concentration of sex-hormone binding globulin.

Tropical respiratory medicine. 2. Impact of human immunodeficiency virus on tuberculosis in developing countries.

Mycobacterium tuberculosis is present in approximately 50% of 15-49 year olds in the developing world, while infection in Europe and North America is limited largely to the elderly and some disadvantaged groups. The authors concentrate upon the interaction of HIV infection and tuberculosis (TB) in developing countries with a particular focus upon research data from sub-Saharan Africa. They discuss HIV infection and predisposition for TB, epidemiological determinants of the TB-HIV interaction, HIV-2 and TB, the impact of HIV on TB treatment services, treatment regimes, and prevention. They note that HIV greatly increases a person's risk of contracting TB by reactivation or recent infection or both, and that HIV-associated TB is not more infectious. The efficacy of most diagnostic procedures is compromised by HIV and anti-TB drug resistance is associated with HIV infection in industrialized countries. TB responds well to optimal treatment, but death from other causes during treatment and recurrence of TB are common with the suboptimal regimens applied in most developing countries. Thiacetazone should be removed from treatment regimens because of its high incidence of toxicity. A need also exists to determine the duration of anti-TB treatment needed for HIV-infected patients. More effective drugs are needed, while short-course chemotherapy needs to be made available where it is currently in short supply or unavailable. The authors also recommend adherence to International Union against Tuberculosis and Lung Disease program guidelines.

Hepatitis B Virus Activation among Central Africans Infected with Human Immunodeficiency Virus (HIV) Type 1: Pre-s2 Antigen Is Predominantly Expressed in HIV Infection

To evaluate the impact of human immunodeficiency virus (HIV) type 1 on the natural history of hepatitis B virus (HBV) infection, sera from Central Africans with and without antibodies to HIV were examined for HBV markers of ongoing replication, recovery from infection, and reactivation or reinfection. The prevalence of HBV infection and HBV surface antigen (HBsAg) was similar for HIV-positive and -negative persons. AIDS patients were more likely to be HBsAg positive and have markers of viral replication. Unlike pre-surface (pre-s) 1 antigen (Ag), which did not differ significantly with respect to HIV infection, pre-s2Ag was more common among HIV-positive persons than among HIV-negative ones and was more common among AIDS patients than among HIV-positive asymptomatic carriers. HIV-positive persons had more markers consistent with HBV reactivation and lower levels of antibody to HBsAg.

Impact of Human Immunodeficiency Virus on Medical and Surgical Residents

Background.— Previous surveys of resident physicians on human immunodeficiency virus (HIV) matters have tended to focus on urban programs serving a patient population with an expected high prevalence of HIV infection. The objective of this study was to survey a community hospital residency program in a nonurban area with a perceived low HIV patient seroprevalence. Methods.— A 32-question survey was completed on an anonymous basis by the entire 74 member multidisciplinary resident physician group at a two-campus university-affiliated hospital program in southeastern Pennsylvania in May 1991. Results.— Residents perceived their patient population's HIV seroprevalence rate to be low although they believed their personal risk of occupational exposure to blood-borne infection was moderate to high. House staff most often complied with universal precautions for fear of acquiring a blood-borne illness and most often did not comply because of time constraints. Not perceiving the exposure as a health risk was the primary reason for nonreporting of exposures. Occupational exposure rates were alarmingly high, with suturing using a curved needle being the most common exposure method. Most residents were unfamiliar with HIV legislation. A majority of the house staff wanted improved HIV patient management training and life and disability insurance against occupationally acquired HIV. Many other important issues were addressed in this survey. Conclusion.— Residents even in low seroprevalence environments do fear occupationally acquired HIV. A great need exists for improved training in universal precautions, acquired immunodeficiency syndrome legislation, and HIV patient management as well as for insurance against occupationally acquired HIV. ( Arch Intern Med . 1992;152:1788-1796)

Hemophilia Growth and Development Study

The study design, research questions, and baseline data are presented from a multicenter longitudinal epidemiologic investigation of the impact of human immunodeficiency virus (HIV) infection on three areas of functioning in children and adolescents with hemophilia: physical growth and sexual maturation, immune function, and neurological and neuropsychological functioning. Sixty-nine percent (n = 333) of a population of males between the ages of 6 and 19 years with moderate to severe hemophilia participated in a comprehensive baseline examination. Approximately 62% of the study group was HIV seropositive and 38% HIV seronegative. Adjusted for age, HIV-positive participants were three times as likely as HIV-negative participants to exhibit declines in height-for-age attainment (p = 0.05), twice as likely to have delays in sexual maturation (p = 0.414), and more than three times as likely to exhibit antibody levels that were not indicative of prior exposure or vaccination (p < 0.001). In addition, analysis of a comprehensive battery of neuropsychological tests showed that HIV-positive participants were 50% more likely to show scores approximately 1 SD below expected levels in three of nine functional areas (p = NS) compared with HIV-negative participants. Entry data for this study reveal a greater likelihood for HIV-positive children and adolescents with moderate to severe hemophilia to have abnormal growth, and to exhibit antibody levels not indicative of prior exposure to disease or vaccination, which could be attributed to HIV infection. Lowered neuropsychological test performance in both groups may be attributable to the deleterious effects of chronic illness. Data are being collected from a group of non-HIV infected non-hemophiliac siblings for comparison.

Cost of Care for Patients With Human Immunodeficiency Virus Infection

The increasing impact of human immunodeficiency virus (HIV) infection on the health care delivery system requires surveillance of current patterns of HIV-related health care utilization to adequately plan for future needs. Most studies to date have concentrated on inpatient care for patients with the acquired immunodeficiency syndrome (AIDS). Outpatient utilization has been less well studied and there are few data regarding HIV-infected patients without a diagnosis of AIDS. Denver Health and Hospitals is a public system delivering comprehensive health care to mostly indigent residents of the city and county of Denver. Patients with HIV infection in this system were identified through multiple surveillance sources, and billing system records for these patients were analyzed. During 1990, 812 patients with HIV infection of 13 years or more were accessed in the Denver Health and Hospitals. During that year, the total HIV-related health care charges were $7,858,690, of which 57% were for inpatient care and 43% for ambulatory care. Patients with AIDS (34% of patients) accounted for 62% of all charges, and patients with HIV infection but without a diagnosis of AIDS (66% of patients) for 38% of charges. Compared with national predictions, patients with AIDS in our system had lower inpatient and higher outpatient utilization. These results are consistent with a shift from inpatient to outpatient health care services in patients with AIDS. A significant proportion of HIV-related health care costs are incurred by patients who have not yet developed AIDS.