Acquired Immunodeficiency Syndrome
Acquired Immunodeficiency Syndrome (AIDS) was first recognized in 1981 in a cluster of diseases associated with loss of cellular immunity in adults who had no obvious reason for presenting such immune deficiencies. AIDS was subsequently shown to be the late clinical stage of infection with the human immunodeficiency virus (HIV). Within several weeks after infection with HIV, many persons develop an acute self-limited mononucleosis-like illness lasting for a week or two. They may then be free of clinical signs or symptoms for years before other clinical manifestations develop. The frequency and severity of subsequent HIV-related opportunistic infections or cancers is, in general, directly correlated with the degree of immune system dysfunction.
According to CDC and WHO, HIV infection is defined by laboratory criteria, usually based on detection of HIV antibody, but may also include virological tests for HIV or one of its components. The CDC surveillance AIDS case definition was last revised in 1993, and includes presence of at least one of 23 clinical conditions, provided other causes of immunodeficiency are ruled out. The presence of one of three other clinical conditions or a CD4+ cell count of under 200/mm3 or a CD4+ T-lymphocyte percentage of total lymphocytes under 14%, regardless of clinical status, are also regarded as AIDS cases if laboratory tests showed evidence of HIV infection. The WHO case definition of AIDS is based on laboratory-confirmed HIV infection plus the presence of any of 22 “stage 4” clinical conditions or a CD4+ lymphocyte count of under 200/mm3 or a CD4+ percentage of less than 15. WHO and CDC also have published pediatric AIDS case definitions.
The proportion of HIV-infected persons who, in the absence of anti-HIV treatment, will ultimately develop AIDS has been estimated at over 90%. In the absence of effective anti-HIV treatment, the AIDS case-fatality rate is high: survival time in many developing country studies is often under 1 year; in industrialized countries 80%–90% of untreated patients used to die within 3–5 years after diagnosis. Routine use of prophylactic drugs to prevent Pneumocystis pneumonia and other opportunistic infections, seen in most industrialized countries before effective anti-HIV treatment had become widely available, significantly postponed the development of AIDS-defining clinical conditions and death.
Serological tests for antibodies to HIV have been available commercially since 1985. The most commonly used screening tests (EIA or ELISA) are highly sensitive and specific. Testing strategies depend on the purpose of testing. For surveillance purposes, different strategies are recommended according to the expected level of HIV prevalence in the population tested: a single test is recommended in populations with a prevalence rate above 10%, but lower prevalence levels require a minimum of 2 different tests for reliability. For diagnostic purposes, a 3-test strategy for asymptomatic persons is recommended in populations with an HIV prevalence rate under 10%, and a 2-test strategy in populations with higher rates. Selection of tests depends on such factors as accuracy and local operational characteristics. Different combinations of testing formats, EIA and rapid tests can be used. Confirmatory testing may include the Western blot or indirect fluorescent antibody (IFA) tests. A non-reactive supplemental test negates an initial reactive EIA test; a positive reaction supports it; and an indeterminate result in the Western blot test calls for further evaluation. Rapid testing techniques on blood or oral mucosal transudate facilitate delivery of testing and counseling services.
Most persons infected with HIV develop antibodies detectable with modern tests within one month after infection. The vast majority of people have positive antibody tests by three months after infection. Other tests to detect HIV infection during the period after infection but prior to seroconversion are available; these include tests for circulating HIV antigen (p24) and PCR tests to detect viral nucleic acid sequences. The window period between the time of infection and seroconversion is short, an average of 3–4 weeks with currently available antibody tests. DNA PCR testing plays an important role in pediatric HIV diagnosis, because the presence of passively transferred maternal antibody can result in positive HIV antibody tests in the absence of HIV infection before 18 months of age.
The absolute T-helper cell (CD4+) count or percentage is used most often to evaluate the progression of HIV infection and to help clinicians make treatment decisions. Viral load tests serve as a marker of disease activity and response to treatment. The differential window periods of EIA and tests such as p24 antigenemia have served to identify recent infections for surveillance purposes. A person reacting positively on the sensitive test and negatively on the less sensitive is likely to have been infected recently. When HIV testing and treatment history are known, the prevalence of recently infected persons may be used to estimate population-level HIV incidence.
Human immunodeficiency virus (HIV), a retrovirus. Two serologically and geographically distinct species, HIV-1 and HIV-2, have been identified. The transmissibility and pathogenicity of HIV-2 may be lower than that of HIV-1. This chapter refers to HIV-1 except where specified. Three groups of HIV-1 have been identified—M, N and O. Group M is the most prevalent and is subdivided into seven subtypes or clades. Circulating recombinant forms, initially derived from co-infection with different subtypes, are also prevalent. There may be differences between HIV-1 subtypes in rates of disease progression and possibly in transmissibility.
AIDS was first recognized as a distinct clinical entity in 1981. In retrospect, however, isolated cases appear to have occurred during the 1970s, and even earlier in several areas (Africa, Europe, Haiti, USA). Of the estimated 33 million persons (95% confidence interval, 31–36 million) worldwide living with HIV infection or AIDS (HIV/AIDS) in 2007, the largest elements were estimated at 22.5 million in sub-Saharan Africa, 4.0 million in south and southeastern Asia, 1.6 million in Latin America, 1.6 million in eastern Europe and central Asia, and 1.3 million in North America. Globally, AIDS caused an estimated 2.1 million deaths in 2007 (1.9–2.4 million); the epidemic has continued growing, with estimates of 2.5 million new infections (1.8–4.1 million) and 2.1 million children under 15 years (1.9–2.4 million) living with HIV/AIDS. AIDS is now the leading cause of death in persons aged 15 to 59 years old. HIV-1 is the most prevalent HIV species throughout the world; HIV-2 has been found primarily in western Africa, with cases also in countries linked epidemiologically to western Africa.
Sub-Saharan Africa is the most affected region; southern Africa is the worst affected. Unlike other regions, the majority of people (61%) living with HIV in sub-Saharan Africa are women. Prevalence has stabilized or is decreasing in most countries, along with some evidence of decreasing risk behavior. In Asia, prevalence is highest in southeast Asia, with considerable variation in trends – declining in some countries while continuing to grow in others. The Caribbean region has the second-highest prevalence worldwide after sub-Saharan Africa, with two countries, the Dominican Republic and Haiti, accounting for most people with HIV infection in the region. In eastern Europe and central Asia, Russia and Ukraine account for most new HIV diagnoses, but rates are also rising in other countries. Injection drug use is a major factor in the region. Latin America's HIV epidemics are generally stable, with transmission largely in higher-risk populations such as sex workers and men who have sex with men. In North America, Western, Central Europe, Australia and New Zealand, HIV continues to be transmitted mainly through unprotected sex between men.
Humans. HIV-1 evolved from chimpanzee simian immunodeficiency viruses (SIVcpz) that crossed over to humans, presumably from bites or from hunting, butchering, or consumption of bush meat. HIV-2 evolved from cross-species transmission events of sooty mangabey SIV (SIVsm).
Mode of transmission
Person-to-person transmission through unprotected penile-vaginal or penile-anal intercourse; the use of HIV-contaminated needles and syringes, including sharing by intravenous drug users; vertical transmission from mother to infant during pregnancy, delivery, or breastfeeding; transfusion of infected blood or its components. Less common modes of transmission include contact of abraded skin or mucosa with infectious body secretions; and the transplantation of HIV-infected tissues or organs. Transmission though pre-mastication (pre-chewing) of food by HIV-infected pediatric caregivers has also been reported.
The approximate transmission risk per 10 000 exposures with an infected partner for receptive penile-vaginal sex is 10; for insertive penile-vaginal sex, 5; receptive penile-anal sex, 50; insertive penile-anal sex, 6.5; injection drug use with shared injection equipment, 67; and contaminated blood transfusion, 9 000.
The risk of sexual HIV transmission is increased by the presence of other sexually transmitted diseases, especially genital ulcerative disease. Lack of male circumcision also substantially increases the risk of female-to-male HIV transmission. At the population level, the frequency of concurrent sex partners (multiple partners in the same time period) is an important determinant of HIV infection rates.
In the absence of prevention interventions, the transmission rate of HIV from infected mothers to their children is about 25% in the absence of breastfeeding and about 35% in breast feeding populations.
After direct exposure of health care workers to HIV-infected blood through injury with needles and other sharp objects, the rate of seroconversion is less than 0.5%, much lower than the risk of hepatitis B virus infection after similar exposures (about 25%). Unsafe injections may account for up to 5% of HIV transmission. The risk to health care workers after mucous membrane exposure has been estimated to be 0.09%; the risk after exposure of non-intact skin has not been quantified, but is estimate to be lower than for mucous membrane exposure.
Carriers are usually asymptomatic; they—and their potential partners—are usually therefore unaware of their potential infection status in the absence of HIV testing.
While the virus has occasionally been found in saliva, tears, urine and bronchial secretions, transmission after contact with these secretions in the absence of blood has not been reported. The risk of transmission from oral sex is not easily quantifiable, but is presumed to be low. No laboratory or epidemiological evidence suggests that biting insects have transmitted HIV infection.
Variable. Although the time from infection to the development of detectable antibodies is generally less than one month, the time from HIV infection to diagnosis of AIDS has an observed range of less than 1 year to 15 years or longer. The median time to development of AIDS in infected infants is shorter than in adults. The increasing availability of effective anti-HIV treatment since the mid-1990s has reduced the development of clinical AIDS, especially in developed countries. Before effective treatment was available, about half of all HIV-infected adults and adolescents in developed countries died within 11 years following infection.
There is some evidence that disease progression from HIV infection to AIDS is more rapid in developing countries than in other populations. The only factor that has been consistently shown to affect progression from HIV infection to the development of AIDS is age at initial infection: adolescent and adults (males and females) who acquire HIV infection at an early age progress to AIDS more slowly than those infected at an older age. Disease progression may also vary by viral subtype.
Period of communicability
Not known precisely; begins early after onset of HIV infection and presumably extends throughout life. Infectiousness is related to viral load. The risk of transmission may be high in the first months after infection when viral load is high, before immune suppression has occurred, and while the high-risk behaviors that led to infection may still be ongoing. Viral load also increases in late symptomatic infection. The presence of STIs has been shown to increase HIV viral load in genital secretions. While use of antiretroviral drugs reduces HIV viral load in blood and genital secretions, individuals on treatment should still be considered infectious.
Unknown, but presumed to be general: race, gender and pregnancy status do not appear to affect susceptibility to HIV infection or AIDS. There is increasing evidence of host factors such as chemokine-receptor polymorphisms that may reduce susceptibility. Lack of male circumcision also increases susceptibility to female-to-male transmission. The presence of other STIs, especially if ulcerative, increases susceptibility.
While HIV infection increases the risk of many opportunistic infections, interactions between HIV and several infectious disease agents have caused particular medical and public health concern. An interaction of major public health importance is with Mycobacterium tuberculosis infection. Persons with latent tuberculous infection who are also infected with HIV develop clinical tuberculosis at an increased rate, with a lifetime risk of developing tuberculosis that is multiplied by a factor of 6–8. This increased risk and the resulting increased transmission have contributed to a parallel pandemic of tuberculosis: in some urban sub-Saharan African populations where 10%–15% of the adult population have dual infections (Mycobacterium tuberculosis and HIV), annual incidence rates for tuberculosis increased 5- to 10-fold during the latter half of the 1990s.
HIV infection may increase rates and severity of malarial infection, and anti-malarial treatment may be less effective in HIV-infected individuals. Other adverse interactions with HIV infection include genital herpes, pneumococcal infection, non-Typhi salmonellosis, and visceral leishmaniasis.
In the other direction, infections such as tuberculosis, malaria, and genital herpes may increase HIV viral load and the rate of decline of CD4+ cells. However, the long-term clinical implications of these laboratory findings are less well understood.
Methods of control
Global resources for HIV/AIDS prevention, care and treatment have ramped up considerably in the last several years. An estimated US$10 billion was available for HIV/AIDS worldwide in 2007 with ongoing substantial increases in prevention programs, prevention of mother-to-child transmission, antiretroviral treatment, and other care and support for people with HIV/AIDS, orphans and vulnerable children.
- Preventive measures: HIV/AIDS prevention programs can be effective only with full community and political commitment to change and/or reduce high HIV-risk behaviors. Health education efforts should include both broad-based campaigns to raise awareness of risk, modes of transmission, and prevention measures, and to reduce stigmatization, as well as targeted programs to educate and reduce risk among high-risk groups such as sex workers, injection drug users, and men who have sex with men.
Abstaining from sexual intercourse, while not practical for many, is an absolutely effective way of preventing transmission. Engaging in sex with an uninfected, mutually monogamous partner is also effective, although ensuring mutually monogamy and absence of infection may be challenging. In other cases, correct and consistent use of male condoms is highly effective in preventing transmission. Female condoms, although more costly, are also effective.
Prevention and treatment of injection drug use reduces HIV transmission, as do programs that provide clean injection equipment or instruct users on decontamination of equipment between uses.
Post-exposure prophylaxis with combination antiretroviral drugs is available and recommended in some settings after occupational exposure or non-occupational exposure to HIV infection. If indicated and available, treatment should begin within hours of exposure and is usually recommended to continue for 28 days.
HIV testing and counseling is important to identify infected individuals for referral for care and treatment, and, for pregnant women, to prevent vertical transmission. Risk behavior for HIV-infected persons decreases when infection is identified. HIV testing also provides a setting for condom distribution and delivery of prevention messages for HIV-negative persons. In many settings, the emphasis is on universal, opt-out testing for all individuals, especially in high-prevalence communities.
Mother-to-child HIV transmission can be minimized through primary prevention of HIV infection in women of child-bearing age, prevention of unintended pregnancy in HIV-infected women, and universal screening of pregnant women. An additional HIV test in the third trimester of pregnancy may identify women who seroconverted during pregnancy. With use of maternal and infant antiretrovirals in accordance with national guidelines, vertical transmission rates can be reduced by 50–90% or more. Transmission by breastfeeding may be avoided through use of infant formula, but only where it is acceptable, feasible, affordable, sustainable, and safe. Elective cesarean section may also play a role in resource-rich settings, where use of multiple preventive measures results in transmission rates of under 2%.
Blood donations should be sought from unpaid, volunteer donors. All donated units of blood must be tested for HIV antibody; only donations testing negative can be used. Testing for HIV antigen or nucleic acid can further reduce the risk of contamination. People who have engaged in behaviors that place them at increased risk of HIV infection should not donate plasma, blood, organs for transplantation, tissue or cells (including semen for artificial insemination). Organizations that collect plasma, blood or other body fluids or organs should inform potential donors of this recommendation and test all donors. When possible, donations of sperm, milk or bone should be frozen and stored for 3–6 months before use. Donors who test negative after that interval can be considered not to have been infected at the time of donation. Only strictly medically necessary transfusions should be given. The use of autologous transfusions should be encouraged. Only clotting factor products that have been screened and treated to inactivate HIV should be used.
Only medically necessary injections should be given. Care must be taken in handling, using and disposing of needles or other sharp instruments. Medical waste should be safely stored and destroyed. Health care workers should be provided with and instructed on the proper use of latex gloves, eye protection and other personal protective equipment as needed in order to avoid contact with blood or with fluids. Universal precautions must be taken in the care of all patients and in all laboratory procedures.
WHO recommends immunization of asymptomatic HIV-infected children with the EPI vaccines; those who are symptomatic should not receive BCG vaccine. Live Measles-Mumps-Rubella and Polio vaccines are recommended for all HIV-infected children. CDC does not recommend use of OPV for HIV-infected children.
- Control of patient, contacts and the immediate environment:
- Report to local health authority: Official reporting of AIDS cases is obligatory in most countries. Official reporting of HIV infections is required in some areas, Class 2 (see Reporting). Whether or not name-based reporting is the rule, care must be taken to protect patient confidentiality.
- Isolation: Isolation of the HIV-positive person is unnecessary, ineffective and unjustified. Universal precautions apply to all hospitalized patients. Observe additional precautions appropriate for specific infections that occur in AIDS patients.
- Concurrent disinfection: Of equipment contaminated with blood or body fluids, and with excretions and secretions visibly contaminated with blood and body fluids according to universal precautions guidelines, by using bleach solution or germicides effective against M. tuberculosis.
- Quarantine: Not applicable. Patients and their sexual partners should not donate blood, plasma, organs for transplantation, tissues, cells, or breast milk for human milk banks. Although not widely recommended, some centers have reported safe impregnation of women by HIV-infected male partners through semen processing or viral suppression in the men with antiretroviral treatment.
- Immunization of contacts: Not applicable.
- Notification of contacts and source of infection: Sex and needle-sharing partners should be notified of their exposure. Notification may be done by the index patient or by health staff with strict confidentiality.
- Specific treatment: Early diagnosis of infection and referral for medical evaluation are indicated. Consult current sources of information for appropriate drugs, schedules and doses, including WHO and UNAIDS websites. Ongoing education and counseling to maintain the patient's health, adherence to treatment, and prevention of transmission are indicated.
- Prophylaxis of opportunistic infections. Prophylactic use of oral cotrimoxazole is recommended to prevent Pneumocystis pneumonia and other infections. Isoniazid preventive treatment is given in some settings, with our without use of tuberculin skin tests. Other primary or secondary prophylactic medications may be recommended in specific situations.
- AIDS must be managed as a chronic disease; antiretroviral treatment is complex, involving a combination of drugs: resistance will rapidly appear if only one or two effective drugs are used. The drugs may have toxic side effects, and treatment must be life-long. Adherence is critical for the success of the treatment. A successful treatment is not a cure, although it results in suppression of viral replication. Ideally, decisions to initiate or change antiretroviral treatment should be guided by the laboratory parameters of both plasma HIV RNA (viral load) and CD4+ T cell count where available, and by assessing the clinical condition of the patient. Laboratory results provide important information about the virological and immunological status of the patient and the risk of progression to AIDS. Once the decision to initiate antiretroviral treatment has been made, treatment should be aggressive with the goal of maximal viral suppression. In general, two nucleoside reverse transcriptase inhibitors and either a non-nucleoside reverse transcriptase inhibitor or protease inhibitors should be used initially. Special considerations apply to pediatric patients and pregnant women, with specific treatment regimens for these patients.
- Epidemic measures: HIV is currently pandemic, with large numbers of infections reported in Africa, Asia, Americas, and Europe. See 9A (Preventive measures) for recommendations.
- Disaster implications: Emergency personnel should follow the same universal precautions as health workers. If latex gloves are not available and skin surfaces come into contact with blood, this should be washed off as soon as possible. Surgical masks, visors and protective clothing are indicated when performing procedures that may involve spurting or splashing of blood or bloody fluids. Emergency transfusion services should use blood donations screened for HIV antibody; when it is not possible to test donated blood, donations should be accepted only from donors who have engaged in no HIV-risk behaviors, and preferably from donors who have previously tested negative for HIV.
- International measures: Neither the United Nations Joint Program on HIV/AIDS (UNAIDS, the body that coordinates HIV- and AIDS-related UN activities) nor WHO endorse measures such as requirements for AIDS or HIV examinations for foreign travelers prior to entry into a country.
[CCDM19: P. Kilmarx, T. Boerma]
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