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Biomedical subjects

D J Hu

Publications and source records attributed to D J Hu.

At least 19 recordsLinked to original sources

The development and evaluation of a probe hybridization method for subtyping HIV type 1 infection in Uganda.

We developed a method for large-scale screening of HIV-1 genotypic variation based on DNA probe hybridization. Nested PCR amplifications were performed to generate fragments in the env C2-V3 region and also in the gp41 region, which encompasses the immunodominant domain. The proviral DNA sequences were derived from 68 samples and phylogenetically analyzed. For comparison, the C2-V3 fragment was used in DNA probe hybridization to rapidly determine the infecting HIV subtype. The hybridizing probes were designed on the basis of the two most prevalent subtypes in Uganda, A and D. The results were compared to evaluate the feasibility of using this hybridization method for large-scale genotypic screening. Sequence analysis of the 68 amplified PCR fragments showed that 39 were subtype A and 29 were subtype D. The results of DNA hybridization to the amplified products with A and D subtype-specific probes were more than 90% concordant with the subtypes determined by sequence analysis. Our findings suggest that probe hybridization with subtype-specific probes is effective for large-scale screening of HIV-infected populations. Application of this method will significantly reduce the time needed for large, population-based investigations.

DNA Probes

A molecular epidemiologic survey of HIV in Uganda. HIV Variant Working Group.

OBJECTIVE: Previous data, based on a small sampling of convenience, reported subtypes A, B, C, D, and G in Uganda, but neither the extent nor the proportion of these subtypes could be evaluated. To establish correctly the prevalence and distribution of HIV-1 subtypes, we analysed viral clades in 739 HIV-1-seropositive specimens from different areas of Uganda. METHODS: Blood specimens from 1100 patients were collected in five districts of Uganda. Within this collection, 929 HIV-1-seroreactive samples underwent analysis of viral DNA, and 739 were selected for further subtyping in env or pol regions. RESULTS: Using a combination of subtype A- and D-specific probes to C2-V3 region and DNA sequencing, HIV-1 env subtypes were determined in 594 specimens: 341 were of subtype A (57.4%), 250 of subtype D (42.1%), and three of subtype C (0.5%). Sixty-two samples showed reactivity with both probes, suggesting potential mixed infections, cross-reactivity to probes, or possibly other subtypes. Subsequent sequence analysis of 19 randomly selected specimens revealed subtypes A (n = 4), D (n = 12), and C (n = 3). Sequence analysis of the 27 samples chosen from the remaining 83 samples, which could be amplified only with viral gp41 or protease gene primers, classified them as subtypes A (n = 13) and D (n = 14). No significant clinical, demographic, or geographic differences were found between HIV-1 infections with viruses of subtypes A and D, despite considerable genetic diversity within these clades. CONCLUSIONS: This is the first major population-based study of the prevalent HIV-1 strains in an African country selected for vaccine trials. The subtyping methods we describe should be of use to investigators seeking to conduct large-scale screening for HIV variants in other populations.

Adult

Presence of human immunodeficiency virus (HIV) type 1 subtype A infection in a New York community with high HIV prevalence: a sentinel site for monitoring HIV genetic diversity in North America. Centers for Disease Control and Prevention-Bronx Lebanon HIV Serosurvey Team.

To determine whether US residents are infected with subtypes of human immunodeficiency virus (HIV) type 1 other than subtype B (Western), the predominant North American subtype with a unique GPGR genetic sequence in the V3 loop, viruses from 22 HIV-infected adults were serotyped and subtyped. Twenty patients had subtype B (Western), of whom 15 had serotype B (Western), 3 had serotype A/C, 1 had serotype B (Thai), and 1 had a nontypeable serotype. Two had subtype A, both serotype A/C. Both subtype A-infected patients, only 1 of whom had been outside the United States, reported sex with persons traveling abroad, suggesting possible acquisition in the United States. Because US residents are infected with non-subtype B (Western) strains, US surveillance for HIV-1 diversity is needed to elucidate subtype-specific transmission patterns and pathogenesis and to guide evaluation and development of HIV diagnostic tests and vaccines.

Adolescent

Cost-effectiveness of short-course zidovudine to prevent perinatal HIV type 1 infection in a sub-Saharan African Developing country setting.

OBJECTIVE: To evaluate the cost-effectiveness of a short-course zidovudine program to prevent perinatal transmission of human immunodeficiency virus (HIV) type 1 in sub-Saharan African country settings. DESIGN AND SETTING: Several clinical trials of short-course zidovudine during pregnancy for prevention of perinatal transmission of HIV are under way in developing countries in sub-Saharan Africa. A decision model was used to examine the cost-effectiveness of zidovudine programs in a hypothetical 1-year birth cohort in a sub-Saharan African setting from the perspective of the health care system and of society. A completed short course of zidovudine was assumed to reduce perinatal HIV transmission from 25% to 16.5%, approximately one half of the effect of the longer-course zidovudine. Estimates of program costs, lifetime HIV-related health care costs, and lost productivity costs were derived from the published literature and from preliminary data available from sites of planned clinical trials. Sensitivity analyses were conducted on all relevant parameters. MAIN OUTCOME MEASURES: Medical costs, lost productivity costs, program costs, cost savings, and incremental cost-effectiveness, expressed as cost per infant HIV infection prevented. RESULTS: The model estimated that a national zidovudine program in a setting with 12.5% HIV seroprevalence would reduce perinatal HIV incidence by 12% (4.9 infections per 1000 births). The costs to the health care system would be $3748 per infant HIV infection prevented. When productivity losses were included in the model, the cost decreases to $1115 per infant HIV infection prevented. The cost to implement a national zidovudine program including the cost of counseling, testing, and drugs, would be $2 million per 100,000 births or $20 per pregnant woman. In the base case, decreases in the cost of counseling and testing and increases in maternal HIV prevalence, zidovudine efficacy, and medical and lost productivity costs improved cost-effectiveness of the zidovudine program. CONCLUSIONS: Assuming demonstrable efficacy of short-course zidovudine prevention of perinatal HIV, a national perinatal HIV prevention program with zidovudine in most sub-Saharan African country settings would reduce the incidence of infant HIV infection and, in some settings, provide societal savings; however, substantial initial investment in such programs will be required. Where health care resources are limited, as in these regions, allocation of resources to a perinatal zidovudine program will need to be considered in the context of resources required for other pressing medical care needs.

Africa South of the Sahara

The emerging genetic diversity of HIV. The importance of global surveillance for diagnostics, research, and prevention.

The discovery of highly divergent strains of human immunodeficiency virus (HIV) not reliably detected by a number of commonly used diagnostic tests has underscored the need for effective surveillance to track HIV variants and to direct research and prevention activities. Pathogens such as HIV that mutate extensively present significant challenges to effective monitoring of pathogens and to disease control. To date, relatively few systematic large-scale attempts have been made to characterize and sequence HIV isolates. For most of the world, including the United States, information on the distribution of HIV strains among different population groups is limited. We describe herein the implications resulting from the rapid evolution of HIV and the need for systematic surveillance integrated with laboratory science and applied research. General surveillance guidelines are provided to assist in identifying population groups for screening, in applying descriptive epidemiology and systematic sampling, and in developing and evaluating efficient laboratory testing algorithms. Timely reporting and dissemination of data is also an important element of surveillance efforts. Ultimately, the success of global surveillance network depends on collaboration and on coordination of clinical, laboratory, and epidemiologic efforts.

AIDS Vaccines

Surveillance for human immunodeficiency virus type 1 group O infections in the United States.

BACKGROUND: Reports that the human immunodeficiency virus type 1 (HIV-1) group O variants are not reliably detected by some commercial diagnostic tests have raised concerns about the sensitivity of existing screening tests, especially with regard to blood safety. Although it is unlikely that these divergent strains are prevalent in North America, systematic, continuous surveillance is needed to monitor the potential spread of HIV variants into that region. STUDY DESIGN AND METHODS: Stored serum samples (n = 1072) from both high- and low-risk population groups at several sites in the United States and Puerto Rico were tested by peptide enzyme immunoassays specific for the prototypic HIV-1 group O strains, MVP5180 and ANT70. RESULTS: None of the 1072 samples examined had peptide reactivity that was consistent with HIV-1 group O infection. CONCLUSION: While no evidence of specific HIV-1 group O (MVP5180 or ANT70) infection was found in this study, the sensitivity of current tests has not been fully evaluated against the wide range of genetic variation of HIV. Therefore, it is important to continue active surveillance for HIV-1 and HIV type 2 strains, to characterize any divergent strains, and to judiciously modify tests to correct for any deficiencies in sensitivity.

Acquired Immunodeficiency Syndrome

Preventing opportunistic infections in human immunodeficiency virus-infected persons: implications for the developing world.

More than 18 million persons in the world are estimated to have been infected with human immunodeficiency virus (HIV), the cause of the acquired immunodeficiency syndrome (AIDS). As immunodeficiency progresses, these persons become susceptible to a wide variety of opportunistic infections (OIs) The spectrum of OIs varies among regions of the world. Tuberculosis is the most common serious OI in sub-Saharan Africa and is also more common in Latin America and in Asia than in the United States. Bacterial and parasitic infections are prevalent in Africa; protozoal infections such as toxoplasmosis, cryptosporidiosis, and isosporiasis are also common in Latin America. Fungal infections, including cryptococcosis and Penicillium marneffei infection, appear to be prevalent in Southeast Asia. Despite limited health resources in these regions, some measures that are recommended to prevent OIs in the United States may be useful for prolonging and improving the quality of life of HIV-infected persons. These include trimethoprim-sulfamethoxazole to prevent Pneumocystis carinii pneumonia, toxoplasmosis, and bacterial infections; isoniazid to prevent tuberculosis; and 23-valent pneumococcal vaccine to prevent disease due to Streptococcus pneumoniae. Research is needed to determine the spectrum of OIs and the efficacy of various prevention measures in resource-poor nations, and health officials need to determine a minimum standard of care for HIV-infected persons. An increasing problem in the developing world, HIV/AIDS should receive attention comparable to other tropical diseases.

AIDS-Related Opportunistic Infections

How important is race/ethnicity as an indicator of risk for specific AIDS-defining conditions?

In order to examine differences in the prevalence of AIDS-defining conditions by race/ethnicity, we analyzed U.S. surveillance data for 203,470 adolescents and adults diagnosed with AIDS from 1988 through 1992. A number of AIDS-indicator conditions were more common among certain racial/ethnic groups. The prevalence of extrapulmonary tuberculosis was higher among blacks, Hispanics, Asians/Pacific Islanders, and American Indians/Alaskan Natives than among whites. The prevalence of isosporiasis and toxoplasmosis was higher among Hispanics than among blacks or whites. Furthermore, the likelihood of being diagnosed with extrapulmonary tuberculosis (TB), toxoplasmosis, or isosporiasis was generally higher among foreign-born than among U.S.-born persons of all racial/ethnic groups. The prevalence of all malignancies was higher among whites than among blacks or Hispanics. However, the magnitude of prevalence differences by race/ethnicity was reduced when we controlled for other demographic and exposure risk categories. Although race/ethnicity was significantly associated with the prevalence of a number of conditions, the relative frequency and patterns of AIDS-indicator conditions in different populations are probably most influenced by differences in (1) underlying prevalence or exposure to various etiologic agents causing these conditions, (2) diagnosis and reporting of conditions, and (3) access to care and therapy for HIV-related conditions.

Acquired Immunodeficiency Syndrome

Model-based estimates of the risk of human immunodeficiency virus and hepatitis B virus transmission through unsafe injections.

BACKGROUND: Patient-to-patient transmission through contaminated medical equipment may be the principal route of nosocomial blood-borne infections globally. Quantifying cross infection risks could facilitate efforts to ensure safe injections in developing countries. METHOD: A mathematical model was developed to evaluate the risk of cross infection due to unsafe injections. The model was applied to immunization programmes with a fixed number of injections and in which unsterile needle and syringe reuse rates were specified. Risk estimates were generated using a range of human immunodeficiency virus (HIV) and hepatitis B (HBV) prevalences. RESULTS: The risk of cross infection is zero when properly sterilized equipment is used. With unsafe injections, the risk of cross infection with HBV is consistently higher than HIV for comparable levels of endemicity. A single reuse of each needle and syringe in areas with an HBeAg prevalence of 4% results in 980 cases of HBV/100,000 infants; reuse four times results in 3740 cases. When the HIV prevalence is 1% and the reuse rate is 4, 14 to 35 cases of HIV/100,000 women could occur. Contamination of multidose vaccine vials could considerably increase these estimates. CONCLUSIONS: Neither HIV nor HBV transmission has been reported with injections administered through the Expanded Programme on Immunization. However, ample evidence exists that reuse of unsterile needles and syringes is common in developing countries. Ongoing efforts to ensure safe practices and improve injection technologies are required to protect these populations from both medical and traditional skin-piercing procedures.

Adult

Coccidioidomycosis among persons with AIDS in the United States.

Adults and adolescents diagnosed with AIDS from 1987 through 1992 residing in counties endemic (selected counties in California, Arizona, Texas, New Mexico, Nevada, Utah) and not endemic for Coccidioides immitis were assessed to determine the frequency of and risk factors for disseminated coccidioidomycosis. Of 602 AIDS patients reported with disseminated coccidioidomycosis, 323 (1.1% of AIDS patients) resided in C. immitis-endemic counties and 279 (0.1% of AIDS patients) resided in C. immitis-nonendemic counties in 35 states. In multivariate analysis, patients with disseminated coccidioidomycosis in C. immitis-endemic counties were more likely to be injecting drug users (odds ratio, 2.6; 95% confidence interval, 1.8-3.7) and blood product recipients (odds ratio, 3.6; 95% confidence interval, 1.5-8.3) than to be homosexual or bisexual men. Of patients with disseminated coccidioidomycosis, 63% had died by 1 year after AIDS diagnosis. Disseminated coccidioidomycosis should be considered in AIDS patients in all areas of the United States.

AIDS-Related Opportunistic Infections

HIV risk behaviors but absence of infection among drug users in detoxification centers outside Yunnan province, China, 1993.

OBJECTIVES: To date, HIV spread in China has occurred principally among injecting drug users (IDU) in remote border regions of Yunnan province. We therefore sought to better understand the risks for and prevalence of HIV infection among drug users in parts of China outside Yunnan province. METHODS: A behavioral survey of drug use and AIDS-related knowledge was conducted among all consenting drug users who entered treatment from 1 November to 31 December 1993 in seven provincial drug detoxification centers outside Yunnan province. After giving verbal informed consent, all drug users were tested for HIV. RESULTS: Of the 1293 study participants, 207 (16%) reported injecting drugs. The proportion of IDU among all drug users varied widely by region, from 1% in Sha'anxi and Gansu provinces in the northwest region to 58% in Guangxi province in the south. IDU were more likely than non-IDU to be single and unemployed or self-employed, but did not differ in other demographic aspects. Among all drug users, 2% reported sharing needles without cleaning equipment, while 5% shared with some cleaning. Although 1060 (82%) drug users had heard of AIDS and most knew about its sexual (79%), parenteral (77%), and perinatal (60%) modes of transmission, many had misconceptions about its spread by casual contact. Of the 207 IDU tested for HIV, none were HIV-positive (95% confidence interval, 0--1.4). CONCLUSION: The absence of HIV infections detected in this study suggests that the prevalence of HIV is currently low among IDU in China outside the Yunnan province. However, the behavior of these IDU puts them at high risk for HIV infection. Prevention efforts are needed to prevent the spread of HIV among IDU throughout China and to avoid the experience of neighboring countries in Asia.

Adolescent

Income and AIDS rates in Los Angeles County.

OBJECTIVE: To examine the relationship between income and AIDS rates in Los Angeles County (LAC) by race/ethnicity. METHODS: 1990 US census data were used to classify LAC postal zones (zip codes) by median household income into low-, middle-, and high-income strata. AIDS rates were calculated for each income stratum based on 15,805 AIDS cases diagnosed from 1987 through 1992 and reported to the county health department. RESULTS: The AIDS rate was highest among residents of low-income areas (252.8 per 100,000), intermediate among residents of middle-income areas (161.2 per 100,000), and lowest among residents of high-income areas (82.0 per 100,000). This trend in rates was present in all racial/ethnic groups examined and was most pronounced among whites (675.1, 226.7, and 88.4 per 100,000, respectively). Residents of low-income areas accounted for 78% of AIDS cases among blacks, 67% among Hispanics, and 47% among whites. CONCLUSIONS: These findings suggest a strong inverse relationship between income and AIDS rates in LAC that is consistent across racial/ethnic groups. Prevention programs and treatment services should be directed most intensively to low-income neighborhoods in this county.

Acquired Immunodeficiency Syndrome

The expanding regional diversity of the acquired immunodeficiency syndrome epidemic in the United States.

BACKGROUND: The geographic spread of the human immunodeficiency virus (HIV) epidemic reflects multiple subepidemics in different regions and population groups. METHODS: To describe regional trends in the acquired immunodeficiency syndrome (AIDS) in the United States, we analyzed national surveillance data for persons with AIDS diagnosed from 1988 through 1991. RESULTS: Highest annual AIDS incidence rates were in the US territories (52.7 per 100,000) and the Northeast (27.7 per 100,000). The greatest percentage increases were in the US territories (68.8%), the South (60.1%), and the Midwest (52.4%). Men who have sex with men constituted the majority of AIDS cases nationally (54.6%), as well as in the Midwest (67.8%), the South (57.4%), and the West (75.3%). Among injecting drug users, the greatest rates of increase in AIDS cases were observed among blacks in the South. Although large increases in the number of persons with HIV transmitted through heterosexual contact were reported from almost all regions, the largest increase was in the South. CONCLUSION: High rates of increase in AIDS cases from the Midwest, South, and US territories probably reflect later entry of HIV into these regions compared with the earlier HIV epidemics in large metropolitan areas of the Northeast and West. In particular, because the South has the largest population of the regions, and sexually transmitted disease surveillance data suggest that substantial populations in the South are at risk, the marked increase in AIDS incidence in this region suggests that the major impact of the epidemic may yet be seen. The continuing spread of HIV and AIDS in different communities and regions demonstrates the need to expand preventive and therapeutic services.

Acquired Immunodeficiency Syndrome

Surveillance of AIDS-defining conditions in the United States. Adult/Adolescent Spectrum of HIV Disease Project Group.

OBJECTIVE: To examine the reporting of AIDS-defining illnesses using two national surveillance systems. METHODS: Comparison of AIDS indicator diseases reported to the national AIDS reporting system (ARS) for AIDS cases diagnosed from January 1990-December 1992 among individuals aged > 13 years in 10 metropolitan areas, with that observed in the Adult/Adolescent Spectrum of HIV Disease (ASD) project, a surveillance project that monitors the clinical diagnoses of HIV-infected individuals receiving medical care. RESULTS: In the 10 metropolitan areas, 39,265 individuals with AIDS were reported to ARS, and 5969 with AIDS had medical record reviews as part of ASD. At initial AIDS diagnosis, the number of indicator diseases reported to ARS was almost identical to the number observed in ASD (mean number of diagnoses, ARS 1.3; ASD 1.2). However, ASD recorded a greater number of diagnoses over time than ARS (mean number of indicator diagnoses > 12 months after initial diagnosis, ASD 2.3; ARS 1.4). Conditions that typically occur late in the course of AIDS such as Mycobacterium avium infection and cytomegalovirus disease, were more frequently recorded by ASD than by ARS. CONCLUSION: ARS provides complete, population-based information on the frequency of AIDS-defining conditions at initial diagnosis. However, specialized surveillance projects such as ASD are needed to accurately describe subsequent AIDS-defining conditions.

AIDS-Related Opportunistic Infections