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c Stavudine Stavudine (d4T) has shown good activity as an antiretroviral drug The dose is 40 mg orally twice daily for individuals weighing 60 kg or more However, because of its side effects including lipoatrophy, lipodystrophy, peripheral neuropathy and, rarely, lactic acidosis and hepatitis, this drug should no longer be used except when there is no alternative Patients taking stavudine should be routinely changed to abacavir or tenofovir, both of which are less likely to cause lipoatrophy and lipodystrophy d Lamivudine Lamivudine (3TC) is a safe and well-tolerated agent The dosage is 150 mg orally twice daily or 300 mg orally once a day There are no significant side effects with this agent, and it has activity also against hepatitis B The dose should be reduced with renal insufficiency e Emtricitabine Emtricitabine is a nucleoside analog that is dosed at 200 mg orally It was developed primarily as a once a day alternative to lamivudine However, lamivudine can be dosed daily, eliminating the special indication for emtricitabine As is true of lamivudine, emtricitabine has activity against hepatitis B and its dosage should be reduced in patients with renal insufficiency f Abacavir A daily dose of 300 mg orally twice daily results in potent antiretroviral activity Abacavir retains activity against some HIV strains that have become resistant to other nucleoside drugs Abacavir is formulated with zidovudine and lamivudine in a single pill (Trizivir, one tablet orally twice daily) Although it is a triple-drug regimen, it is not as efficacious as combining two nucleoside/nucleotide analogs with a PI or an NNRTI and should be used only for patients who cannot comply with other regimens Abacavir is also available as a fixed dose combination pill with lamivudine for use as a once daily pill (Epzicom) The main toxicity of abacavir is a hypersensitivity syndrome in about 5% of patients, characterized by a flu-like syndrome with rash and fever that worsens with successive doses; individuals in whom this syndrome develops should not be rechallenged with this agent as reactions with rechallenge can be fatal g Zalcitabine Zalcitabine (ddC) is thought to be one of the least effective antiretroviral agents and is therefore not commonly used Its advantages are that it is inexpensive, easy to administer, and has no known hematologic side effects The usual dosage of zalcitabine is approximately 0005 001 mg/kg orally every 8 hours This drug is formulated in 0375mg and 075-mg tablets Zalcitabine, like didanosine, may cause peripheral neuropathy It is also associated with aphthous ulcers, rash, and rare cases of pancreatitis h Tenofovir Tenofovir is the only licensed nucleotide analog It is given as a single daily oral dose of 300 mg and is generally well tolerated As is true of lamivudine, tenofovir is active against hepatitis B Because HIV variants that are resistant to other nucleoside analogs are often sensitive to tenofovir, it is often included in second- and third-line treatment regimens It is also available in a fixed dose combination pill with emtricitabine (Truvada) for daily dosing A once a day single fixed dose combination pill that contains tenofovir, emtricitabine, and efavirenz (Atripla) is now available.

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2 Protease inhibitors Ten PIs indinavir, nelfinavir, ritonavir, saquinavir, amprenavir, fosamprenavir, lopinavir (in combination with ritonavir), atazanavir, darunavir, and tipranavir are currently available PIs have been shown to potently suppress HIV replication in vitro and in vivo and are administered as part of a combination regimen All the PIs to differing degrees are metabolized by the cytochrome P450 system, and each can inhibit and induce various P450 isoenzymes Therefore, drug interactions are common and difficult to predict Clinicians should consult the product inserts before prescribing PIs with other medications Drugs such as rifampin that are known to induce the P450 system should be avoided The fact that the PIs are dependent on metabolism through the cytochrome P450 system has led to some innovative dosing strategies In particular, ritonavir has been used to boost the drug levels of saquinavir, lopinavir, indinavir, atazanivir, tipranavir, darunavir and amprenavir, allowing use of lower doses and simpler dosing schedules of these PIs In fact, current guidelines recommend that all PI-containing regimens use ritonavir boosting if possible PIs and NRTIs have been linked to a constellation of metabolic abnormalities, including elevated cholesterol levels, elevated triglyceride levels, insulin resistance, diabetes mellitus, and changes in body fat composition (eg, buffalo hump, abdominal obesity) The lipid abnormalities and body habitus changes are referred to as lipodystrophy Its prevalence is known to be increased among persons treated with certain NRTIs (especially stavudine) and most of the PIs (except for unboosted atazanavir), but it has been seen also in HIVinfected persons who have never been treated with these agents Of the different manifestations of lipodystrophy, the dyslipidemias that occur are of particular concern because of the likelihood that increased levels of cholesterol and triglycerides will result in increased prevalence of heart disease All patients taking PIs or NRTIs should have a fasting cholesterol, lowdensity lipoprotein cholesterol, and triglyceride levels performed every 3 6 months Because HIV-infected persons with elevated cholesterol levels are at risk for coronary artery disease, including sudden death, HIV-infected persons who have low-density lipoprotein cholesterol levels > 160 mg/dL after dietary interventions should be started on pravastatin (20 mg daily orally) or atorvastatin (10 mg daily orally) Lovastatin and simvastatin should be avoided because of their interactions with PIs Patients with persistently elevated fasting serum triglyceride levels of 500 mg/dL or more who do not respond to dietary intervention should be treated with gemfibrozil (600 mg twice daily prior to the morning and evening meals) a Indinavir The standard dose of indinavir is 800 mg orally three times a day, although it is usually dosed twice daily in combination with ritonavir Nausea and headache are common complaints with this drug Indinavir crystals are present in the urine in approximately 40% of patients; this results in clinically apparent nephrolithiasis in about 15% of patients receiving indinavir Lower urinary tract symptoms and renal failure also have been reported Patients taking this drug should be instructed to drink at least 48 ounces of fluid.

namespace Example_5_14_ _ _ _The_for_Loop { class Program { public static void Main( ) { for (int counter = 0; counter < 10; counter++) { Console.WriteLine("counter: {0} ", counter); } } } }

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