ACQUISITION AND TRANSMISSION OF HIV
Infection associated with HIV has been recognized for almost two decades, and morbidity and mortality have taken enormous tolls worldwide. The best estimates are that a total of about 42 million persons throughout the world have acquired HIV since inception of the epidemic, of whom about 12 million have died. Estimates for selected AIDS data, which demonstrate the profound impact of this disease on the global population, are shown in Table 82-1. Unfortunately, despite the availability of life-prolonging medications, up to 60 million cases will have developed by the millennium. Two thirds of all cases have occurred in sub-Saharan Africa. Almost 25% of those who have died have been children. Estimates are that 8 million children have become orphans on account of this disease. Table 82-2 summarizes international data by region.
Table 82-1. Global HIV/AIDS estimates, 1997
Table 82-2. International epidemiology of HIV/AIDS
In the United States, the first 50,000 cases were reported between 1981 and 1987. The second 50,000 cases were reported by 1989, and by the beginning of 1998, a total of 641,000 cases of AIDS had been reported to the Centers for Disease Control and Prevention. Current estimates are that up to 900,000 persons are HIV-positive. Blacks (40%), Caucasians (38%), and Hispanics (19%) are most notably involved. Dramatic changes have occurred among selected groups at risk for HIV. Currently, 84% of cases have occurred in men, 15% in women, and about 1% in children. However, between 1985 and 1996, the percentage of AIDS cases in women increased from 7% to 20%, mostly associated with heterosexual sex or IV drug use. AIDS among heterosexuals increased from 5% (1988) to 18% (1995). In male subjects, homosexuality (48%), IV drug use (20%), or both (7%) are the most prominent associations; acquisition through heterosexual sex accounts for 5% of cases. Similar data for women demonstrate IV drug use (8%) and heterosexual sex (10%) to be the most frequent associations. Among hospitalized patients, seroprevalence ranges from 0.2% to 14.2%.
Among persons ages 18 to 22, approximately 33,000 are HIV-positive. Homosexual contact was the most common mode of spread among white men of this age, whereas heterosexual contact was most common among women. This is especially noted within minorities. In 1996, about 7,500 persons above age 50 were reported with AIDS. Of these, 12% were above age 65. Homosexuality and an absence of acknowledged risk factors were most common in persons above age 50. In this group, persons had a higher risk for death within 1 month of an AIDS diagnosis, and the diagnosis of an AIDS-defining opportunistic infection was more common in this group.
Globally, major disparities in mortality from AIDS are being recognized between developing countries and the United States. This is mostly related to the availability of antiretroviral medications. Data from the United States demonstrate that HIV-related deaths declined in 1996 by 23% in comparison with deaths in 1995. This was noted among all risk groups and in all geographic regions. Similarly, 1996 data demonstrate substantial decreases in the diagnosis of AIDS-related opportunistic infections. During that year, about 57,000 opportunistic infections were diagnosed, representing a decline of 6% from the previous year.
The rate of progression to AIDS following seroconversion can be gauged from the baseline CD4-cell count and viral load (HIV RNA). This information has been generated from a cohort of male homosexuals, and it is uncertain how to extrapolate it to others. Data have been provided in chart form (Table 82-3). As an example, the risk for AIDS within 3 years in persons with CD4-cell counts above 750 and HIV RNA below 500 is nil, and it rises to only 3.6% after 9 years. Alternatively, for patients with baseline CD4-cell counts above 750 but with viral loads above 3,000, the risk for AIDS rises to 3% at 3 years and 40% at 9 years. Up to 11% of patients infected with HIV demonstrate prolonged survivorship. Such persons demonstrate ongoing viral replication, and virus can regularly be cultured from their lymph nodes. Characteristics of patients with long-term survival include low viral load, noncytopathogenicity of HIV strains, absence of enhancing antibodies, a cytokine response characterized by elevated amounts of interleukin-2 (the TH1 response), and an enhanced CD8-cell response. Thus, a combination of decreased viral virulence and enhanced immune response probably contributes to prolonged survival in this subset.
Table 82-3. Risk for development of AIDS
Health care workers comprise an important subset at risk for HIV infection because of their potential exposure to HIV-infected body fluids, most notably blood. The risk for seroconversion following exposure to HIV-infected blood is approximately 0.3%. The risk after mucous membrane exposure is about 0.09%. HIV seroconversion after skin exposure has occurred; the risk is thought to be less than that following exposure to mucous membranes. Seroconversion occurs at a mean of 46 days following exposure; in 95%, seroconversion occurs within 6 months. In most persons (81%), primary HIV syndrome develops within 1 month after seroconversion. Through June 1997, 52 health care workers with documented HIV seroconversion following occupational exposure had been reported. Most of these exposures were to blood and were percutaneous. Enhanced risks for seroconversion include deep injury, exposure into a vein or artery, or visible contamination. Currently, the benefit of assessing risk by measurement of viral load from the source is unknown.
Antiretroviral therapy is indicated for health care workers following possible actual HIV exposure. Medications should be initiated as soon as feasible, preferably within hours. However, treatment begun after many days should still be considered in the setting of high risk, as it may favorably affect the acute retroviral syndrome. The basic regimen is zidovudine (AZT) 300 mg and 3 lamivudine (3TC) 150 mg both twice daily. For health care workers with more severe exposures (e.g., large-bore needle, deep puncture), the addition of either 750 mg of nelfinavir thrice daily or 800 mg of indinavir every 8 hours is indicated. Therapy is continued for 4 weeks. Exposed health care workers should be checked for seroconversion at 6 weeks and then at 3, 6, and 12 months.
Studies of HIV in pregnancy provide excellent documentation of the feasibility of preventing the spread of disease by antiretroviral therapy. Aids Clinical Trials Group (ACTG) 076, a federally funded investigation, demonstrated a decline in spread of HIV to the newborn from approximately 24% to 8% (i.e., a 70% reduction) with the use of zidovudine during pregnancy, the peripartum period, and the first 6 weeks of life. This regimen may be initiated in the naive patient after 10 to 12 weeks of gestation. The recommendations for additional agents are inconclusive, and administration should be based on stage of disease, medications risks, and other relevant factors. For patients with known HIV infection who are on therapy and become pregnant, medications should generally be continued. (R.B.B.)
Centers for Disease Control and Prevention. Update: trends in AIDS incidence—United States, 1996. MMWR Morb Mortal Wkly Rep 1997;46:861–867.
Recent data concerning the incidence of AIDS in the United States. The information demonstrates decreases in AIDS-related opportunistic infections and deaths in comparison with data from 1995. This in turn reflects the positive impact of antiretroviral and antiopportunistic medications. Unfortunately, such trends are not seen worldwide.
Centers for Disease Control and Prevention. Public Health Service guidelines for the management of health-care worker exposures to HIV and recommendations for post-exposure prophylaxis MMWR Morb Mortal Wkly Rep 1998;(RR7):1–35.
An excellent in-depth review of the problems and recommendations for management. All issues—identification, treatment, and counseling—are addressed. The authors stress the need for rapid initiation of antiretroviral treatment when indicated, and this requires the availability of appropriate facilities within the health care system.
Centers for Disease Control and Prevention. Public Health Service Task Force recommendations for the use of antiretroviral drugs in pregnant women infected with HIV-1 for maternal health and for reducing perinatal HIV-1 transmission in the United States. MMWR Morb Mortal Wkly Rep 1998;47(RR2):1–30.
This document provides the most recent recommendations for the management of HIV in pregnancy. At least zidovudine is indicated, and for patients who have been on antiretroviral therapy and then become pregnant, medications should generally be continued. These recommendations should be available to and followed by all health care workers dealing with pregnant women.
Janssen RS, et al. HIV infection among patients in U.S. acute-care hospitals. N Engl J Med 1992;327:445–452.
A multiple-hospital survey based on anonymous blood samples from 20 hospitals in 15 U.S. cities. Almost 5% of 195,829 specimens were HIV-positive. Seroprevalence rates were 0.2% to 14.2%. Most patients were hospitalized for non–HIV-related reasons. The authors estimate that 225,000 patients with HIV infection were hospitalized in 1990 in the United States, and they recommend voluntary HIV testing for persons ages 15 to 54 in hospitals with more than one newly diagnosed AIDS case per 1,000 discharges annually.
Marcus R, CDC Cooperative Needlestick Surveillance Group. Surveillance of health care workers exposed to blood from patients infected with the human immunodeficiency virus. N Engl J Med 1988;319:1118–1123.
Approximately 1,200 health care workers with blood exposures, more than 60% of them nurses, were followed. Most exposures resulted from needlestick injuries, and about a third were potentially preventable. The seroprevalence rate was 0.4%.
Pantaleo G, et al. Studies in subjects with long-term, nonprogressive human immuno-deficiency virus infection. N Engl J Med 1995;332:209–216.
This and a companion article provide insights regarding a small subset of HIV-infected patients who are nonprogressors. Such persons continue to demonstrate viral replication, albeit with low viral loads. Lymph nodes and general immune function remain intact. The virus appears to be attenuated.
Rosenberg PS, Biggar RJ. Trends in HIV incidence among young adults in the United States. JAMA 1998;279:1894–1899.
Estimates are that about 33,000 persons ages 18 to 22 are HIV-positive. Male acquisition is primarily homosexual, whereas female acquisition is primarily heterosexual. The latter is increasing, and the former is decreasing.
Vlahov D, et al. Prognostic indicators for AIDS and infectious death in HIV-infected injection drug users. JAMA 1998;279:35–40.
The authors studied a cohort of more than 500 HIV-infected drug users for up to 8 years. As has been previously noted for male homosexuals, there was a direct correlation between baseline CD4-cell count, HIV RNA, and progression to AIDS-defining disease or infectious death. Of the two parameters, HIV RNA showed the more direct correlation. Simple assessments can be used to gauge the prognosis in IV drug users and male homosexuals.