Definition AIDS or acquired immunodeficiency syndrome – was originally defined empirically by the Centers for Disease Control and Prevention(CDC) as “the presence of a reliably diagnosed disease that is at least moderately indicative of an underlying defect in cell-mediated immunity. ” Following the recognition of the causative virus, HIV, and the development of the sensitive and specific tests for HIV infection, the definition of AIDS has undergone substantial revision.
The current surveillance definition categorizes HIV-infected persons on the basis of clinical conditions associated with HIV infection and CD4+T lymphocyte counts. Etiology AIDS is caused by the infection with the human retroviruses HIV-1 or HIV-2. HIV-1 is the most common cause worldwide; HIV-2 has about 405 sequence homology with HIV-1, is more closely related to simian immunodeficiency viruses, and has been identified predominantly in western Africa. HIV-2 infection has now, however, been reported in europe, south america, canada, and the united states.
These viruses are passed through sexual contact; through contact with blood, blood products, or contaminated intravenous needles; intrapartum or perinatally from mother to infant; or via breast milk. Ther e is no evidence that the virus can be passed through casual or family contact or by insect bites such as mosquitoes. There is a definite, though small, occupational risk of infection for health care workers and laboratory personnel who work with HIV-infected specimens. The risk of transmission of HIV from an infected health care worker to his or her patients throug invasive procedures is extremely low.
Epidemiology By january 1, 1997, a cumulative total of approximately 570,000 cases of AIDS has been reported in the United States; approximately 60% of those had died. It has been estimated that there are between 630,000 and 897,000 HIV-infected people in the U. S. Major risk groups continue to be men who have had sex with men and men and women injection drug users; however, the numbers of the cases that are transmitted heterosexually, particularly among women, are increasing rapidly. These women also transmit the infection to their children.
As the majority of IDU-associated cases are among inner-city minority populations, the burden of HIV infection and AIDS falss increasingly and disproportionately on minorities, especially in the cities of the Northeast and Southeast U. S. Cases of AIDS are still being found among individuals who have received contaminated blood products in the past, although the risk of acquiring new infection through this route is extremely small in the U. S. HIV infection/AIDS is a global pandemic, especially in developing countries. Pathophysiology and Immunopathogenesis.
The hallmark of HIV disease is a profound immunodeficiency resulting from a progressive quantitative and qualitative deficiency of the subset of T lymphocytes referred to as helper or inducer T cells. This subset of T cells is defined phenotypically by the expression on the cell surface of the CD4 molecule, which serves as the primary cellular receptor for HIV. Recently, it has been demonstrated that a coreceptor must be present with CD4 for efficient entry of HIV-1 into target cells. These coreceptors belong to the seven-transmembrane-domain G protein-coupled family of receptors.
The molecule termed CXCR4, or fusin, is the coreceptor for T cell-tropic strains of HIV-1, and the B-chemokine receptor CCR-5 is the coreceptor for the macrophage-tropic starins of HIV-1. Although the CD4+T lymphocyteband CD4+ monocyte lineage are the pricipal cellular targets of HIV, virtually any cell that expresses CD4 along with one of the coreceptors can potentially be infected by HIV. Primary infection Following the initial transmission, the virus infects CD4 + cells, probably T lyphocytes, monocytes, or bone marrow-derived dendritic cells.
Both during this initial stage and later in infection, the lymphoid system is a major site for the establishment and propagation of HIV infection. Initially, lymph node architecture is preserved, but ultimately it is completely disrupted and the efficiency of the node in trapping virions declines, leading to the equilibration of the viral burden between peripheral blood cells and lymph node cells. Most patients undergo a viremic stage during primary infection, in some patients associated with the acute retroviral syndrome, a mononucleosis-like illness.
This phase is important in disseminating virus to lymphoid and other organs throughout the body, and it is ultimately contained partially by the development of an HIV specific immune response and the trapping of virions in the lymphoid tissue. Establishment of chronic and persistent infection Despite the robust immune response that s mounted following primary infection, the virus, with very few exceptions, is not cleared from the body. Instead, a chronic infection develops that persists for a median time of 10 years before the patient becomes clinically ill.
During this period of clinical latency, the number of CD4+ T cells gradually declines but few, if any, clinical findings are evident; however, active viral replication can almost always be detected by measurable plasma viremia and the demonstration of virus replication in lymphoid tissue. Advanced HIV disease After some period of time, CD4+T cells counts will fall below some critical level and patients become highly susceptible to opportunistic diseases. Immune response to HIV infection Both humoral and cellular immune responses to HIV develop soon after primary infection.
Humoral responses include antibodies participating in antibody-dependent cellular cytotoxicity. Cellular immune responses include the generation of HIV-specific CD4+ and CD8+ T lymphocytes, as well as NK cells and mononuclear cells mediating ADCC. CD8+ T lymphocytes may also suppress HIV replication in a noncytolytic, non-MHC restricted by soluble factors such as the B-chemokines RANTES, as well as other as yet unidentified factors secreted by CD8+ T lyphocytes. Diagnosis of HIV infection Laboratory diagnosis of HIV infection depends on the demonstration of anti-HIV antibodies and/or the detection of HIV or one of its components.
The standard screening test for HIV infection is the detection of anti-HIV antibodies using enzyme-linked immunosorbent assay). This test is highly sensitive and is quite specific. Western blot is the most commonly used confirmatory test and detects antibodies to HIV antigens of specific molecular weights. Antibodies to HIV begin to appearnwithin 2 weeks of infection, and the period of time between initial infection and the development of detectable antibodies is rarely longer than 3 months. The HIV p24 antigen can be measured using a capture assay, an ELISA-type assay.
Plasma p24 antigen levels rise during the first few weeks following infection, prior to the appearance of anti-HIV antibodies. HIV can be cultured directly from tissue, peripheral blood cells, or plasma. HIV genetic material can be detected using PCR. This is useful test in patients witha positive or indeterminate ELISA and an indeterminate western blot or in patients in whom serological testing may be unreliable. Laboratory monitoring of patients with HIV infection Measurement of the CD4+ T cell count and level of plasma HIV RNA are important parts of the routine evaluation and monitoring of HIV-infected individuals.
The CD4+ T cell count is a generally accepted indicator of the immunologic competence of the patient with HIV infection, and there is a close relationship between the CD4+ T cell count and the clinical manifestations of AIDS. While the CD4+ T cell counts provides information on the current immunologic status of the patient, the HIV RNA level predicts what will happen to the CD4+ T cell count in the near future and hence predicts the clinical prognosis. A level of HIV RNA > 20,000 copies/ml is felt by many experts to be an indication for initiation of antiretroviral therapy regardless of the CD4+ T cell count.
Clinical manifestations of HIV infection Group 1: Acute HIV syndrome(acute retroviral sysndrome) Group 2: Asymptomatic infection Group 3: Persistent generalized adenopathy Group 4: Other diseases: Subgroup A: Constitutional disease(fever, diarrhea, weight loss) Subgroup B: Neurologic disease Subgroup C: Secondary infectious diseases Subgroup D: Secondary neoplasms Subgroup E: Other conditions Group 1: Acute HIV syndrome(acute retroviral sysndrome). Approximately 50-70 % of infected individuals experience an acute syndrome following primary infection.
Acute syndrome follows infection by 3-6 weeks. Characterized by fever, rigors, cramps, diarrhea, and aseptic meningitis; lasts 1-2 weeks and resolves spontaneouly as immune response to HIV develops. Most patients will then enter a phase of clinical latency, although an occasional patient will experience progressive immunologic and clinical deterioration. Group 2: Asymptomatic infection. Length of time between infection and development of disease varies greatly, but the median is estimated to be 10 years.
HIV disease with active viral replication usually progresses during this asymptomatic period, and CD4+ T cell counts fall. The rate of disease progression is directly correlated with plasma HIV RNA levels. Patients with high levels of HIV RNA progress to symptomatic disease faster than to those with low levels of HIV RNA. Group 3: Persistent generalized lymphadenopathy. Palpable adenopathy at two or more extrainguinal sites that persists for more than 3 months without explanation other than HIV infection. Many patients will go on to disease progression. Group 4: Other diseases:
Subgroup A-Constitutional symptoms: fever persisting for more than 1 month, involuntary weight loss of more than10% of baseline, diarrhea for longer than 1 month in absence of explainable cause. Subgroup B-Neurologic disease: most common is HIV encephalopathy(AIDS dementia complex); other neurologic complications include oppotunistic infections, primary CNS lymphoma, CNS Kaposi’s sarcoma, aseptic meningitis, myelopathy, peripheral neuropathy and myopathy. Subgroup C-Secondary infectious diseases: Pneumonia is the most common opportunistic infection, occuring in approximately 80% of individuals during the course of their illness.
Other common infections include chorioretinitis, colitis, pneumonitis, adrenalitis, oral thrush, esophagitis, meningitis and disseminated infections, encephalities, and intracerebral mass lesion. Subgroup D-Secondary neoplasms: Kaposi’s sarcoma(cutaneous and visceral, more fulminant course than in non HIV-infected patients), lymphoid neoplasms(especially B cell lymphomas of brain, marrow, GI tract). Subgroup E-Other conditions: A variety of organ-specific syndromes can be seen in HIV-infected patients, either as primary manifestations of the HIV infection or as complications of treatment.
Treatment of HIV infection General principles of patient management include counseling, psychosocial support, and screening for infections and require comprehensive knowledge of the disease processes associated with HIV infection. Antiretroviral therapy Nucleoside analogues Nonnucleoside reverse transcriptase inhibitors Protease inhibitors Medical management of clinical symptomatic manifestations Treatment and prevention of opportunistic infections Antidiarrheal therapy Chemotherapy Antidepressant therapy Nutrition therapy.