AIDS is the most epidemic in human history. AIDS is the consequence of a chronic retroviral virus that produces extreme, life-threatening CD4 helper T-lymphocyte dysfunction, opportunistic infections, and malignancy .
Retroviruses include viral RNA transcriptase into double-stranded DNA, which can be integrated into the host genome. Cellular activation leads to transcription of HIV gene items and viral replication. AIDS is defined by serologic evidence of HIV virus with the presence of a range of indicator diseases related to medical immunodeficiency.
HIV is transmitted by coverage to infected body fluids or sexual or perinatal make contact with. Transmissibility from the HIV virus is related to subtype virulence, viral load, and immunologic host factors. Acute HIV virus may present as an acute, self-limited, febrial viral syndrome characterized by exhaustion, pharyngitis, myalgias, rash, lymphadenopathy, and significant viremia without detectable anti-HIV antibodies.
Following an initial viremic phase, individuals seroconvert along with a period of clinical latency is commonly seen. Lymph tissues turn out to be centers for substantive viral replication during a "silent," or asymptomatic, stage of HIV virus despite an absence of detectable trojan in Slow progressive declination in CD4 T lymphocytes, a reversal from the regular CD4: CD8 T-lymphocyte ratio, and numerous other immunologic derangements.
The clinical manifestations are directly related to the development of neurologic complications, opportunistic infections, or malignancy signal marked immunity deficiency. The time course for progress varies, but the median time before appearance of medical illness is about ten many years. Around 10% of individuals infected manifest rapid progress to AIDS within five many years after virus.
A minority of individuals are "long-term nonprogressors." Genetic elements, host cytotoxic immune responses, and viral load and virulence appearance to cause susceptibility to virus and the rate of disease progression. Chemokines (chemoattractant cytokines) regulated leukocyte trafficking to sites of inflammation and have been discovered to play a significant role in the pathogenesis of HIV illness.
All the HIV strains express the envelope protein gp120 that binds to CD4 molecules, but different viral strains display tissue " tropism "or specificity on the basis from the coreceptor that they recognize. These core receptors belong towards the chemokine receptor family.
Viral strains isolated in early stages of infection (eg, R5 viruses) demonstrate tropism toward macrophages. X4 strains of HIV are a lot more commonly seen in later stages of illness.
X 4 viruses bind to chemokine receptor CXCR4, more broadly expressed on T cells, and more related to syncytium formation. A small percentage of individuals possessing nonfunctional alleles for the polymorphic chemokine receptor CCR5 appears to be highly resistant to HIV virus or display delayed progress of disease Mathematical models estimate that through HIV virus billions of virions are produced and cleared each day.
The improvement transcription step of HIV heteroconjugate development and rapid progress of illness, medical drug resistance, and lack of efficacy of HIV heterogeneity develops rapidly. The improvement of antigenically and phenotypically distinct strains early vaccines. Cellular activation is critical for viral infectivity and reactivation of integrated proviral DNA.
Only only 2% of mononuclear cells are found peripherally, lymph nodes from HIV-infected individuals can include include large amounts of trojan sequestered among infected follicular dendritic cells within the germinal centers.
(1) direct HIV-mediated destruction of CD4 T lymphocytes, (2) autoimmune destruction of virus-infected T cells, (1) direct marked decline in CD4 T-lymphocyte counts-characterizing HIV infection-is due to several mechanisms 3) depletion by fusion and development of multinucleated giant cells (4) toxicity of viral proteins to CD4 T lymphocytes and hematopoietic precursors, and (5) induction of apoptosis (programmed cell death).
Ultimately, viral proliferation envelopes host responses, and HIV-induced immunosuppression leads to disease development. Loss of viral containment occurs with lack of adequate helper T purpose and reduced IL-2 production leading to reduction of CD8 + T-cell-dependent cytotoxic responses.
In addition to the cell-mediated immune defects, B-lymphocyte function is altered such that numerous infected individuals have been marked hypergammaglobulinemia but impaired specific antibody responses.
Both anamnestic responses and individuals to humoral immunity in controlling viremia or slowing disease development is unclear. The development of assays to measure viral burden (plasma HIV-RNA quantification) has led to a better understanding of HIV dynamics and has provided a tool for assessing response to therapy.
It is now well well that that viral replication lasts all through the disease, and immunization deterioration occurs regularly clinical latency. The risk of progress to AIDS appears correlated with an individual & # 39; s viral load after seroconversion. Data from a number of large clinical cohorts There is a direct correlation between the CD4 T-lymphocyte count and also the risk of AIDS-defining opportunistic infections.
Thus, the viral load and also the CD4 T-lymphocyte depletion serve as important clinical indicators of immune status in HIV-infected people. Prophylaxis for opportunistic infections such as pneumocystis pneumonia is started when CD4 T-lymphocyte counts reach the 200-250 cells / L variety.
Similarly, patients with HIV virus with fewer than 50 CD4 T lymphocytes / L are at a significantly increased risk for cytomegalovirus (CMV) retinitis and Mycobacterium avium complex (MAC) infection. Cells other than CD4 T lymphocytes contribute to the pathogenesis of HIV infection.
HIV-infected monocytes will also release large quantities from the acute-phase reactant cytokines, including IL-1 monocytes, macrophages, and dendritic cells can be infected with HIV and facilitate transfers of trojan to lymphoid tissues and immunoprivileged sites. , IL-6, and TNF, contributing to constitutional symptomatology.
TNF, in particular, has been implicated in the severe wasting syndrome observed in patients with advanced illness. Concomitant infections may serve as cofactors for HIV infection, increasing expression of HIV through enhanced cytokine production, coreceptor surface expression, or increased cellular activation mechanisms.
Common nonspecific symptoms consist of fever, Patients are susceptible to a wide variety of atypical or opportunistic infections with bacterial, viral, protozoal, and fungal pathogens. Weight loss and cachexia can be due to nausea, vomiting, anorexia, or diarrhea.
They often portend a poor prognosis. Lung virus with Pneumocystis jiroveci is the most common opportunistic infection, affecting 75% of individuals. Patients present clinically with fevers, cough, shortness of breath, and hypoxemia ranging in severity from mild to existence threatening.
A negative diagnosis of pneumocystis pneumonia could have been made a strong sputum staining does not rule out disease in patients in whom there is a feeling of grimes. susceptibility of disease, and further diagnostic maneuvers such as bronchoalveolar lavage or fiberoptic transbronchial biopsy may be required to establish the diagnosis.
Issues of pneumocystis pneumonia include pneumothorace, progressive parenchymal disease with severe respiratory insufficiency, and most commonly, adverse reactions to the medications used for treatment and prophylaxis.
Mycobacterial infections with M tuberculosis or M avium intracellulare (MAC); and fungal infections with C neoformans, H capsulatum, or C immitis. Medical suspicion followed by early diagnosis of these infections should lead to aggressive treatment.
The improvement of active tuberculosis is not accelerated in HIV virus as a result of compromised cellular immunity. The risk of reactivation is estimated to be 5-10% per year in HIV-infected patients by a lifetime risk of 10% in those having having HIV. Yet, diagnosis may be delayed due to anergic skin responses.
Extrapulmonary manifestations occurring in up to 70% of HIV - infected individuals with tuberculosis, and the emergence of multidrug resistance may compound the problem. MAC is really a less virulent pathogen than M tuberculosis, and disseminated infections only occur only with extreme medical immunodeficiency.
The presence on physical examination of oral candidacy (thrush) and hairy leukoplakia is highly correlated with HIV infection and portends rapid development to AIDS.
HIV-infected people with oral candidiasis are at least greater risk for esophageal candidiasis, which may exist as substancesal persimasis, whereas perspiration from oral candidiasis, whereas perspiration and dysphagia. This infection and its characteristic medical presentation are so common that most practitioners treat with empiric oral antifungal therapy.
Persistent diarrhea, especially when accompanied by high fevers and abdominal pain, may signal infectious enterocolitis. The patient should not respond quickly, others explanations for the esophageal symptoms should be explored, including herpes simplex and CMV infections.
HIV-associated gastropathy and malabsorption are commonly noted in these individuals. The list of potential pathogens in these cases is lengthy and including bacteria, MAC, protozoans (cryptosporidium, microsporidia, Isospora belli, Entamoeba histolytica, Giardia lamblia), and even HIV itself.
Co-infection with viral hepatitis (HBV, HCV, CMV) can lead to end-stage liver disease, but fortunately, an institution of highly active antiretroviral therapy (HAART) can lead to a reduction in medical HBV illness.
Herpes simplex virus (HSV) and herpes zoster virus (HZV) may cause chronic persistent or progressive lesions in individuals with compromised cellular (viral, bacterial, fungal), neoplastic, or nonspecific. immunity.
The risk of disseminated HSV or HZV virus and the presence of molluscum contagiosum appear to be correlated using the amount of immunoincompetence.
Seborrheic dermatitis caused by Pityrosporum ovale and fungal skin infections (Candida albicans, dermatophyte species) are also commonly observed in HIV-infected patients. Staphylococcus including methacillin-resistant S aureus can cause the folliculitis, furunculosis, and bullous impetigo commonly observed in HIV-infected individuals, which require aggressive treatment to prevent dissemination and sepsis.
Bacillary angiomatosis is a potentially fatal dermatologic disorder of tumor-like proliferating vascular endothelial cell lesions, the result of infection by Bartonella quintana or Bartonella henselae. The lesions may resemble those of Kaposi & # 39; s sarcoma but respond to treatment with erythromycin or tetracycline. CNS manifestations in HIV-infected patients consist of infections and malignancies.
Cryptococcal meningitis commonly manifests as headache and fever. Up to 90% of patients with cryptococcal meningitis exhibit a positive serum test for Cryptococcus neoformans antigen .
HIV-associated cognitive-motor complex, or AIDS dementia complex, is the most frequently diagnosed cause of altered mental status in HIV-infected patients. Patients normally have difficulty with cognitive tasks, poor short-term memory, slowed motor purpose, personality changes, and waxing and waning dementia. Up to 50% of patients with AIDS suffer from this disorder, due caused by glial or macrophage infection by HIV resulting in destructive inflammatory changes within the CNS.
Other differential diagnosis can be broad, including metabolic disturbances and toxic encephalopathy occurred from drugs. Consist of neurosyphilis, CMV or herpes simplex encephalitis, lymphoma, and progressive multifocal leukoencephalopathy, a progressive demyelinating disease caused by a JC papovavirus.
Perceptual nervous system manifestations of HIV virus include sensory, motor, and inflammatory polyneuropathies. Almost 33% of individuals with advanced HIV disease develop peripheral tingling, numbness, and pain in these extremities. direct neuronal HIV infection.
Alcoholism, thyroid disease, syphilis, vitamin B12 deficiency, drug toxicity (ddI, ddC), CMV-associated ascending polyradiculopathy, and transverse myelitis also cause peripheral neuropathies. Less commonly, HIV-infected patients can develop an inflammatory demyelinating polyneuropathy similar to Guillain- Barré syndrome; however, unlike the sensory neuropathies, this inflammatory demyelinating polyneuropathy usually presents before the onset of clinically appropriate immunodeficiency.
The diagnosis could be difficult to make because Toxoplasma gondii virus, microinfarction, and HIV-related malignancies commonly seen in AIDS include Kaposi & # 39; s sarcoma, non-Hodgkin & # 39; s lymphoma, primary CNS lymphoma, invasive cervical carcinoma, and anal squamous cell carcinoma.
Kaposi & # 39; s sarcoma is the most typical HIV-associated cancer. In San Francisco, 15-20% of HIV-infected homosexual men This this tumor during the progress of their disease.
Unlike classic Kaposi & # 39; s sarcoma, which affects older men within the Mediterranean, the illness in HIV-infected individuals may present with either localized cutaneous lesions or promulgated visceral involvement.
It is often a progressive disease, and pulmonary involvement could be fatal. Histologically, the lesions of Kaposi & # 39; s sarcoma consist of a mixed cell population that includes vascular endothelial cells and spindle cells within a collagen network.
Human herpesvirus 8 is associated with Kaposi & # 39; s sarcoma in patients with AIDS. Human herpesvirus 8 is associated with Kaposi & # 39; s sarcoma normally presents as a purplish nodular skin lesion or painless oral lesion.
In the GI tract, Kaposi & # 39; s sarcoma can produce chronic blood loss or acute hemorrhage. In the lung, it often presents as coarse nodular infiltrates bilaterally, frequently related to pleural effusions.
The CNS is frequently involved either as a primary site or as an extranodal site of widespread disease.
Anal dysplasia and squamous cell carcinoma are also commonly found in HIV-infected homosexual men. These tumors appear to be related to concomitant anal or rectal infection with human papillomavirus (HPV). In HIV-infected women, the incidence of HPV-related cervical dysplasia is as high as 40%, and dysplasia can progress rapidly to invasive cervical carcinoma.
Adherence to multidrug regimens remains a challenge, but clearly antiretroviral therapy improves immune purpose. HIV-infected patients have an unusually high rate of adverse reactions to a wide variety of antibiotics and frequently developed severe debilitating cutaneous reactions.
Drug hypersensitivity and toxicity can be severe, potentially life-threatening, and limiting with certain agents. Immune reconstitution syndrome is really a descriptive occurrence days to weeks following initiation of HAART.
Medical relapse or worsening of mycobacterial, pneumocystis, hepatitis, or neurological infections occurs as a result of a resurgence of immune activity, caused paradoxical worsening of inflammation, possibly as residual antigens or subclinical pathogens are attacked.
Other issues of HIV-infection include arthritides, myopathy, GI syndromes, dysfunction of the adrenal and thyroid glands, hematologic cytopenias, and nephropathy. Since the illness was first described in 1981, medical knowledge of the underlying pathogenesis of AIDS has increased at a rate unprecedented in medical background.
This knowledge has led towards the rapid improvement of therapies directed at controlling HIV virus as well as the multitude of complicating opportunistic infections and cancers.
