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Acute HIV SyndromeThe acute HIV syndrome is characterized by an infectious mononucleosis-like syndrome or aseptic meningitis syndrome with fever, lymphadenopathy, meningitis, GI symptoms, and a characteristic infectious exanthem, an enanthem, and genital ulceration. Causes of Acute HIV SyndromeAfter primary HIV infection, billions of virions are produced and destroyed each day; a concomitant daily turnover of actively infected CD4+ cells is also in the billions. HIV infection is relatively unique among human viral infections in that, despite robust cellular and humoral immune responses that are mounted after primary infection, the virus is not cleared completely from the body (with a few exceptions). Chronic infection develops that persists with varying degrees of virus replication for a median of 10 years before an individual becomes clinically ill. Symptoms of Acute HIV Syndrome
DiagnosisDemonstrated seroconversion of anti-HIV antibodies by ELISA, confirmed by Western blot, confirms diagnosis of primary HIV infection. Established HIV infection can be confirmed by these serologic tests as well as by isolation of HIV from blood or CSF or demonstration of p24 antigen. TreatmentHIV Prevention Counseling Sex Education The most common mode of HIV transmission is during sexual intercourse. Currently, in terms of numbers of new HIV infections, female-to-male and male-to-female transmission is much more common than male-to-male. Safer sexual practices must be taught at an early age. Transfusions and Transplantation Blood and blood by-products must be tested before administration. HIV infection must be ruled out in donors of any transplanted organ. Treatment of ARS Symptomatic. Efficacy of antiretroviral therapy at this stage still controversial. Treatment of Asymptomatic HIV Infection Early diagnosis offers the opportunity for counseling and for assistance in preventing the transmission of HIV infection to others. Antiretroviral Therapy Combinations of zidovudine/didanosine and zidovudine/zalcitabine are preferred to zidovudine monotherapy. Protease inhibitors such as indinavir and ritonavir reduce viral load by 2 to 3 logs in some individuals. Combinations of two or more drugs are currently recommended. Recent data on HIV pathogenesis, the development of methods for quantitation of plasma HIV RNA, clinical trial data, and the availability of new drugs have resulted in profound changes of therapeutic approaches. It is now evident that in all stages of the infection the virus replicates at high levels in the lymphoid tissue, as reflected by the amount of HIV RNA in the plasma. This large amount of virus turns over rapidly with a virion half-life of less then 6 h and an estimated 10 billion virus particles produced daily. Shortly after infection, each individual establishes his or her own quasisteady-state level of plasma HIV RNA, which largely determines the rate of CD4 cell destruction and ultimately the natural history of this infection. At any time point of the infection this set-point of plasma HIV RNA correlates inversely with prognosis and, in fact, can be used to predict the natural course of the disease. Inhibition of viral replication with even potent antiretroviral agents either at suboptimal doses and/or as monotherapy by about 70 to 90% is gradually lost within a few months, coincident with the development of resistance. Nevertheless, when antiretroviral agents of different classes with nonoverlapping genetic patterns are used in combination, their genetic barrier to simultaneous resistance is significantly increased. Antiretroviral agents approved for treatment of HIV in one or more countries can be divided into three classes of drugs: nucleoside reverse transcriptase inhibitors (NRTI), nonnucleoside reverse transcriptase inhibitors (NNRTI), and protease inhibitors (PI). They are directed against two target-enzymes-HIV reverse transcriptase and HIV protease-thereby interfering with formation of proviral DNA and virus assembly, respectively. Combination therapy can slow down or even prevent selection of drug-resistant strains and is associated with significant clinical benefit. Current treatment recommendations favor the combined usage of two NRTI and one PI (preferably Indinavir, nelfinavir, or ritonavir) or two NRTI and one NNRTI. Treatment is now recommended for all patients with HIV RNA levels above 5000 to 10,000 copies/mL plasma. For patients at low risk of progression (low plasma HIV RNA level and high CD4+ cell count), particularly those who are not committed to complex antiretroviral regimens, therapy might be safely deferred. These patients should be reevaluated every 3 to 6 months. HAART, with a combination of 3 to 4 drugs, has become the standard of care for treatment of HIV infection. None of the drugs currently available can eradicate HIV infection; but used in combination, the drugs can decrease viral replication, improve immunologic status, and prolong life. |
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