HIV infection primary

UNTOWARD EFFECTS Rifabutin generally is well tolerated in persons with HIV infection primary reasons for discontinuation of therapy include rash (4%), GI intolerance (3%), and neutropenia (2%). Overall, neutropenia occurred in 25% of patients with severe HIV infection who received rifabutin. Uveitis and arthralgias have occurred in patients receiving rifabutin doses >450 mg daily in combination with clarithromycin or fluconazole. Patients should be cautioned to discontinue the drug if visual symptoms occur. Like rifampin, the drug causes an orange-tan discoloration. Rarely, thrombocytopenia, a flu-like syndrome, hemolysis, myositis, chest pain, and hepatitis have occurred. 

The pathogenesis of AIDS (10,12,13) following HIV infection may be separated into primary and secondary effects. The primary effects are (/) quantitative and quahtative decreases in infected cells, ie, the T-lymphocytes (2) impaked cellular immunity (J) impaked immune surveillance and... 

Brengel-Pesce K, Innocenti-Francillard P, Morand P, Chanzy B, Seigneurin JM (1997) Transient infection of astrocytes with HIV-1 primary isolates derived from patients with and without AIDS dementia complex. J Neurovirol 3 449-454 Budka H, Costanzi G, Cristina S, Lechi A, Parravicini C, Trabattoni R, Vago L (1987) Brain pathology induced by infection with the human immunodeficiency virus (HIV). A histological, immunocytochemical, and electron microscopical study of 100 autopsy cases. Acta Neuropathol (Berl) 75 185-198... 

Sugimoto H, Konno S et al (2006) [A case of primary HIV infection presenting as mononeuritis multiplex]. Rinsho Shinkeigaku 46(8) 561-563... 

HIV infection occurs through three primary modes of transmission sexual, parenteral, and perinatal. The most common method for transmission is receptive anal and vaginal intercourse, with the probability of transmission up to 3% per sexual contact for the former, and up to 0.2% per sexual contact for the latter. The probability of transmission increases when the index partner has a high level of viral replication (which occurs at the very beginning of infection or late in disease), or when the uninfected partner has ulcerative disease, compromised mucosal surfaces, or (in the case of men) has not been circumcised. 

Panel on Clinical Practices for Treatment of HIV Infection Convened by the Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents. 2006. Available at http //aidsinfo.nih.gov Public Health Service Task Force. Recommendations for use of antiretroviral drugs in pregnant HIV-1 infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States. October 12,2006. (http //aidsinfo.nih.gov) Smith DE, Walker BD, Cooper DA, et al. Is antiretroviral treatment of primary HIV infection clinically justified on the basis of current evidence AIDS 2004 18 709-718. 

Clinical presentations of primary HIV infection vary, but patients often have a viral syndrome or mononucleosis-like illness with fever, pharyngitis, and adenopathy (Table 40-3). Symptoms may last for 2 weeks. 

Persons with acute primary HIV infections should be treated with combination antiretroviral therapy to suppress virus replication to levels below the limit of detection of sensitive plasma HIV RNA assays. 

Inhibiting viral replication with combination of potent antiretroviral therapy has been the most clinically successful strategy in the treatment of HIV infection. There have been three primary groups of drugs used nucleoside and nonnucleoside reverse transcriptase inhibitors and protease inhibitors (Pis) (Table 40-5). 

Intravenous Immune Globulin (IGIV) IGIV is a product derived from blood plasma from a donor pool similar to the immune globulin (IG) pool, but prepared so it is suitable for intravenous use. IGIV does not transmit infectious diseases. It is primarily used for replacement therapy in primary antibody-deficiency disorders, for the treatment of Kawasaki disease, immune thrombocytopenic purpura, hypogammaglobulinemia in chronic lymphocytic leukemia, and in some cases of HIV infection. 

Nearly 40 million people are infected with the human immunodeficiency virus (HIV). Over half of those infected reside in sub-Saharan Africa. Worldwide during 2004, it is estimated that nearly 14,000 people a day were infected. Human immunodeficiency virus type 1 is the primary etiological source for the acquired immunodeficiency syndrome (AIDS). Fortunately, people infected with HIV are leading longer and more productive lives due to the availability of more effective therapies. Better medicines have evolved due to the efforts of scientists worldwide who find targets and compounds that inhibit the virus life-cycle. The current treatment for HIV infection is via a drug cocktail that usually includes a protease inhibitor (PI), a nucleoside reverse transcriptase inhibitor (NRTI), and a non-nucleoside reverse transcriptase inhibitor (NNRTI). 

The reverse transcriptase enzyme (RT) is the primary enzyme responsible for the conversion of the viral single-strand RNA to the double-strand DNA. The reverse transcriptase enzyme is a component of the virion and is encoded by the pol gene. The RT is manufactured in the HIV-infected cells as a gag-pol fusion polyprotein. The RT is not the only enzyme necessary for the translation of RNA to DNA. The other enzymes for this conversion include RNA-dependent DNA polymerase, DNA-dependent DNA polymerase, and RNase H (Gilboa and Mitra, 1978 Prasad and Gogg, 1990). The reverse transcriptase enzyme has a high error rate (1 in 2000 bases), which produces higher incidents of mutation. Some of these mutations make the virus resistant to NNRTI treatment. 

Primary HIV infection Asymptomatic Acnte retroviral syndrome Clinical stage I... 

Treatment of primary immunodeficiency states in which severe impairment of antibody forming capacity idiopathic thrombocytopenic purpura (IPT) bone marrow transplantation pediatric HIV infection... 

Finally, we would like to reiterate our own view, that however much we may deplore the abuse of drugs, our primary aim should be to promote a healthier life-style in our clients and minimise the risk of HIV infection. 

After oral administration, the bioavailability of zalcitabine is more than 80%. Food slightly interferes with its absorption. Sixty to eighty percent of the compound is excreted unchanged in the urine. Its (dideoxycytidine S -triphosphate) peak concentrations are at 2-3 h. The primary metabolite is dideoxyuridine, which is <15% of the administered dose. Zalcitabine is indicated in combination with other antiretroviral agents for the treatment of HIV infection. 

After oral administration, nevirapine is rapidly absorbed with a bioavailability of 93%, and peak plasma concentrations are achieved in 4h. Food or antacids do not interfere with its absorption. It is very lipophilic, crosses the placenta and its presence has been reported in breast milk. Nevirapine is mainly metabolized by the cytochrome P-450 system (CYP3A4 and CYP2B6) to hydroxy-lated metabolites, and after metabolism, the primary route of excretion is through urine. It has an elimination half-life of 25-30 h. Nevirapine can induce its own metabolism by stimulating the cytochrome P-450 system, which results in the reduction of the half-life of subsequent doses. In combination with other antiretroviral agents, nevirapine is recommended for the treatment of HIV infection in adults and children. It should not be administered alone since resistance develops rapidly. 

Chun TW, Engel D, Berrey MM, Shea T. et al. 1998. Early establishment of a pool of latently infected, resting CD4(+) T cells during primary HIV infection. Proc Natl. Acad Sci USA. 95 8869-8873... 

Protease inhibitors are often incorporated into the comprehensive treatment of people with HIV infection. Use of these drugs in combination with other anti-HIV agents is discussed in more detail later in this chapter (see HIV and the Treatment of AIDS ). In addition, a specific protease inhibitor can be combined with a low dose of ritonavir—a process known as protease-inhibitor boosting. 34,69 Ritonavir inhibits the hepatic breakdown of the other (primary) protease drug, thereby enabling the primary drug to exert better therapeutic effects at a lower dose.34... 

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