Incidence and trends in Kaposi's sarcoma in the era of effective antiretroviral therapy.

OBJECTIVE: To evaluate the impact of antiretroviral and antiherpesvirus therapies on the incidence of KS and assess trends in incidence of Kaposi's sarcoma (KS) in a large multicenter HIV/AIDS surveillance system between 1990 and 1998. METHODS: Incidence was calculated per 100 person-years (py); the effects of therapies on risk for KS were calculated by using multivariate Poisson regression controlling for gender, race/ethnicity, age, HIV exposure mode, CD4+ cell count, and calendar year. Antiretroviral therapy was defined as monotherapy, dual therapy, or triple therapy (95% of triple therapy regimens contained a protease inhibitor). Acyclovir, ganciclovir, and foscarnet were the antiherpesvirus therapies evaluated. RESULTS: There were 37,303 HIV-infected people in the study contributing 70,238 py. Those prescribed triple antiretroviral therapy had a 50% reduction in the incidence of KS (95% confidence interval, 20%-70%) compared with those who were not prescribed antiretroviral therapy and there was a reduction in risk for KS among persons prescribed foscarnet (p =.05). Overall, KS incidence declined an estimated 8.8% per year (observed incidence 4. 1 per 100 py in 1990 to 0.7 per 100 py in 1998; p <.001). CONCLUSION: Incidence of KS is declining in this large U.S. population and may continue to decline as new, more effective antiretroviral agents are developed and used widely.

Human herpesvirus 8 and Kaposi's sarcoma in persons infected with human immunodeficiency virus.

Human herpesvirus 8 (HHV-8) was detected in 1994 in biopsies of Kaposi's sarcoma (KS) tissues from a patient with AIDS. The evidence that HHV-8 infection is etiologically related to the development of KS is compelling. Essentially all patients with KS of any epidemiological type have serological evidence of HHV-8 infection. About 30%-40% of homosexual men infected with human immunodeficiency virus (HIV) are seropositive for HHV-8; rates are lower (<10%) among HIV-infected women, hemophiliacs, and injection drug users. Among homosexual men, the probability of HHV-8-seropositivity is directly proportional to the numbers of previous male sex partners, which suggets that HHV-8 is a sexually transmitted infection. Although HHV-8 is detectable in saliva and semen, the exact mechanism of transmission is not known. A reduction in KS incidence among patients with AIDS in the 1980s has been attributed to lower rates of HHV-8 transmission that resulted from alterations in sexual behaviors. A further decline in KS incidence has been associated with the use of antiretroviral therapy. Antiretroviral therapy to control HIV replication and to limit the associated immunodeficiency is currently the best approach for preventing KS in persons infected with HHV-8 and HIV.

Effect of antiretroviral therapy on recent trends in selected cancers among HIV-infected persons. Adult/Adolescent Spectrum of HIV Disease Project Group.

We examined incidence trends in seven HIV-associated cancers (Kaposi's sarcoma [KS], invasive cervical cancer, immunoblastic lymphoma, primary brain lymphoma [PBL], Burkitt's lymphoma, other non-Hodgkin's lymphomas, and Hodgkin's lymphoma) and the effects of antiretroviral therapy on these trends. Data were abstracted from medical records in 89 hospitals and clinics in nine U.S. cities from January 1994 through June 1997. The stratified Cochran-Mantel-Haenszel statistic was used to test for trend. There were 19,684 HIV-infected persons representing 26,638 years of follow-up. Decreases in incidence per 1000 person-years were observed for KS (January through June 1994, 49.9; January through June 1997, 25.7; p = .001) and PBL (January through June 1994, 8.0; January through June 1997, 2.3; p = .01), especially during time on antiretroviral therapy, but changes in the incidence of other cancers were not significant. During the study, prescription of combination antiretroviral therapy increased from 16% to 57%. The incidences of KS and PBL are decreasing. Although for KS the decline occurred in both treated and untreated groups (difference in rate of decline not significant, p = .08), it was sharper in the treated group; additionally, KS declined faster in the era after highly active antiretroviral agents were introduced. Thus, these decreases may be due in part to the effect of antiretroviral therapy slowing the progression of HIV disease.

Group O human immunodeficiency virus-1 infections.

Human immunodeficiency viruses (HIV), the cause of AIDS, have remarkable genetic diversity. Among the HIV-1 viruses are the "major" (group M) HIV-1 subtypes and genetic "outliers" that have been designated as group O viruses. Group O viruses are most prevalent in parts of Africa, although they have also been reported in Europe and the United States and are associated with AIDS. Because group O viruses are so highly divergent, tests designed to detect group M viruses may be unreliable in the diagnosis of group O infection. Modification of these tests are needed to protect the safety of the blood supply.

Obstacles and progress toward development of a preventive HIV vaccine.

AIDS: Researchers have been seeking an HIV vaccine almost since the disease was first discovered, and while a number of phase I trials have been carried out, few have been extended to phase II trials and none have progressed to phase III trials. AIDS advocates agree that an HIV vaccine is not only necessary, but should also be safe, effective, stable, affordable, orally administered, and able to create long-lasting immunity. However, not everyone can agree on whether it should induce humoral, cell-mediated, or mucosal immune responses, or if it should induce all three of the immune responses. Other questions remain regarding the animals' roles in testing, how to work in the global genetic variability of HIV, and whether the vaccine should prevent infection. Despite the scientific uncertainties and inherent social difficulties, several candidate vaccines have been developed. However, the debate on how to proceed to large-scale phase III trials, designed to evaluate protective efficacy, is still unresolved. Concluding comments offer observations about continuing vaccine development to phase III trials.^ieng

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.

PIP: Worldwide, there are more than 18 million persons infected with HIV, the cause of AIDS. As HIV disease progresses, HIV-infected persons become vulnerable to various opportunistic infections that tend to vary from region to region. Tuberculosis is the most frequent serious opportunistic infection in sub-Saharan Africa. It is more prevalent in Latin America and in Asia than in the US. Bacterial and parasitic infections are common in sub-Saharan Africa. Toxoplasmosis, cryptosporidiosis, isosporiasis, and other fungal diseases are prevalent in Latin America. Fungal diseases, particularly cryptococcoses, and Penicillium marneffei infection, seem to also be prevalent in Asia. These regions have limited health resources. Regimens designed to prevent opportunistic infections that prolong and improve the quality of life of HIV-infected persons include trimethoprim-sulfamethoxazole to prevent Pneumocystis carinii pneumonia, toxoplasmosis, and bacterial infections; isoniazid to prevent tuberculosis; and 23-valent pneumococcal vaccine to Streptococcus pneumonia pneumonia. Scientists need to conduct research to identify the spectrum of opportunistic infections and the efficacy of different prevention measures in resource-poor countries. Health officials need to develop a minimum standard of care for HIV-infected patients. Since HIV/AIDS continues to grow in developing countries, scientists and health providers should pay as much attention to HIV/AIDS as to other tropical diseases.

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

More than 18 million persons in the the world are estimated to have been infected with human immunodefeiciency 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 infections such as toxoplasmosis, cryptosporidiosis, and isosporaisis 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 pnemococcal 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 (AU).

Kaposi's sarcoma-associated herpesvirus infection prior to onset of Kaposi's sarcoma.

OBJECTIVES: Kaposi's sarcoma-associated herpesvirus (KSHV), a newly discovered human gammaherpesvirus, is found in the majority of KS lesions from patients with and without AIDS. Peripheral blood mononuclear cells (PBMC) were examined for KSHV DNA to determine whether viral infection precedes onset of this neoplasm. DESIGN: Randomized and blinded case-control study of prospectively collected PBMC samples from ongoing cohort studies. METHODS: Paired PBMC drawn before and after KS onset from 21 AIDS-KS patients were compared to paired PBMC from 23 high-risk HIV-infected homo-/bisexual patients who did not develop KS and to a single PBMC sample from 19 low-risk, HIV-infected hemophiliac patients. Extracted DNA samples were amplified by polymerase chain reaction (PCR) using two non-overlapping nested primer sets to control for potential PCR contamination. RESULTS: In all comparisons, patients who went on to develop KS were significantly more likely to show evidence of KSHV infection prior to onset of KS than either control group. Of PBMC samples from AIDS-KS patients drawn prior to KS, 52% were positive for KSHV DNA whereas both high- and low-risk control groups had lower rates of PBMC infection (9-13%). KSHV infection can precede KS onset by up to 21 months among AIDS-KS patients. CONCLUSIONS: AIDS-KS patients are significantly more likely to show evidence of KSHV infection in PBMC prior to KS onset than control HIV-infected patients. Because identical PBMC samples from cases and controls were examined blindly, these results are not caused by a bias in tissue sampling. Homo-/bisexual and hemophiliac AIDS patients who do not develop KS appear to have a low prevalence of infection. These findings indicate that KSHV infection is specifically associated with the subsequent development of KS in AIDS patients.

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.

Kaposi's sarcoma-associated herpesvirus and Kaposi's sarcoma in Africa. Uganda Kaposi's Sarcoma Study Group.

BACKGROUND: Endemic Kaposi's sarcoma (KS) is a clinically and epidemiologically distinct human immunodeficiency virus negative form of KS occurring in Africa. Kaposi's sarcoma is now the most frequently reported cancer in some areas of Africa. OBJECTIVE: To determine if a KS-associated herpesvirus (KSHV) is present in both endemic HIV-seronegative and HIV-seropositive KS lesions from African patients. METHODS: Paraffin-embedded tissue specimens from Ugandan patients with KS and non-KS tumor control patients attending a university-based oncology clinic were examined in a blinded case-control study. Tissue DNA specimens were examined for detectable KSHV genome by nested polymerase chain reaction performed at two independent laboratories. RESULTS: We identified KSHV in 17 (85%) of 20 KS tissue specimens from HIV-seronegative patients and 22 (92%) of 24 KS tissue specimens from HIV-infected persons. Kaposi's sarcoma lesions from four HIV-infected persons and four HIV-seronegative persons were positive for KSHV. Unlike previous studies in North America and Europe, three (14%) of 22 non-KS cancer control patients' tissue specimens were also positive for KSHV that resulted in an overall odds ratio of 49.2 (95% confidence interval, 9.1 to 335) for detecting KSHV in KS lesions from patients in Uganda. CONCLUSION: As in North America and Europe, KSHV infection is strongly associated with both HIV-seropositive and HIV-seronegative KS in Africa. However, it is likely that infection with this virus is more highly prevalent in Uganda.

Investigations of patients of health care workers infected with HIV. The Centers for Disease Control and Prevention database.

OBJECTIVE: To assess the risk for transmission of the human immunodeficiency virus (HIV) from an infected health care worker to patients. DESIGN: Survey of investigators from health departments, hospitals, and other agencies who had elected to notify patients who had received care from health care workers infected with HIV. MEASUREMENTS: Information was collected about infected health care workers, their work practices, their patients' HIV test results, procedures that they did on those of their patients who were tested for HIV, and patient notification procedures. RESULTS: As of 1 January 1995, information about investigations of 64 health care workers infected with HIV was reported to the Centers for Disease Control and Prevention; HIV test results were available for approximately 22,171 patients of 51 of the 64 health care workers. For 37 of the 51 workers, no seropositive patients were reported among 13,063 patients tested for HIV. For the remaining 14 health care workers, 113 seropositive patients were reported among 9108 patients. Epidemiologic and laboratory follow-up did not show any health care worker to have been a source of HIV for any of the patients tested. CONCLUSION: Despite limitations, these data are consistent with previous assessments that state that the risk for transmission of HIV from a health care worker to a patient is very small. These data also support current recommendations that state that retrospective patient notification need not be done routinely.

Lack of HIV transmission in the practice of a dentist with AIDS.

OBJECTIVE: To determine whether dentist-to-patient or patient-to-patient transmission of human immunodeficiency virus (HIV) occurred in the practice of a dentist who had the acquired immunodeficiency syndrome (AIDS). DESIGN: Retrospective epidemiologic investigation supported by molecular virology studies. SETTING: The practice of a dentist with AIDS in an area with a high AIDS prevalence. PARTICIPANTS: A dentist with AIDS, his former employees, and his former patients, including 28 patients with HIV infection. MEASUREMENTS: Identification of potential risks for acquisition of HIV infection, genetic relatedness among HIV strains, and infection-control practices. RESULTS: A dentist with known behavioral risks for HIV infection, who was practicing in an area of Miami, Florida, that had a high rate of reported AIDS cases, disclosed that he frequently did invasive procedures and did not always follow recommended infection-control procedures. Of 6474 patients who had records of receiving care from the dentist during his last 5 years of practice, 1279 (19.8%) were known to have been tested for HIV infection and 24 of those (1.9%) were seropositive. Four other patients with HIV infection were identified through additional case-finding activities. Of these 28 patients with HIV infection, all but 4 had potential behavioral risk factors for infection. Phylogenetic tree analysis of HIV genetic sequences from the dentist and 24 of the patients with HIV infection showed an absence of strong bootstrap support for any grouping and therefore did not indicate that the virus strains were linked. CONCLUSIONS: Despite identifying numerous patients with HIV infection, we found no evidence of dentist-to-patient or patient-to-patient transmission of HIV during dental care. Our findings are consistent with those of all previous studies in this area, with the exception of one that did identify such transmission.