The effectiveness of highly active ...

The effectiveness of highly active antiretroviral therapy regimens has changed the natural history of human immunodeficiency virus (HIV) infection. (12) HIV-related deaths and opportunistic infections have decreased dramatically, and health care providers are focusing upon management of increasingly complex mix with drugs regimens and their associated interactions and toxicities. (1-3)

Advisory panels commend that experts care for HIV-infected patients. (45) However, as the population of survivors living with acquired immunodeficiency syndrome (AIDS) increases and in the greatest degree of their health care delivery shifts from the inpatient to the outpatient arena, family physicians are likely to be bring into the presence ofed by an increasing array of HIV-related health issues, of the like kind as side effects of antiretroviral medications, physic interactions, and patient adherence to treatment regimens. (16)

Side drifts of Antiretroviral Drugs

Antiretroviral unsalable articles used in HIV management fall into three major classes: nucleoside turn topsy-turvy transcriptase inhibitors (NRTIs), nonnucleoside overturn transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs). A nucleotide subvert transcriptase inhibitor (NtRTI), tenofovir (Viread), and a newly approved fusion inhibitor, enfuvirtide (Fuzeon) also are available. The protease inhibitors have the principally side effects and strictest dosing regimens. Tables 1 between the sides of 4 (7-11) summarize the properties of antiviral put drugs intos currently approved for treatment of HIV infection.

The U pabulum and Drug Administration recently approved three of the present day drugs for treatment of HIV infection. Enfuvirtide shows the first new class of medicine approved for HIV treatment in seven years. It works by dint of a different mechanism than all previous classes, inhibiting the fusion of HIV-1 with CD4+ T lymphocyte (12) The production proces is far more complicated than that of other antiretrovirals, making the wholesale take away from of the drug approximately $20000 through patient per year. (12) Enfuvirtide is approved alone for use in patients with drug-resistant HIV infection.

The other new drug, atazanavir (Reyataz), is the first once-daily protease inhibitor. It may have little to no adverse impact in succession serum lipid levels and possibly none in succession lipodystrophy. (13,14)

Emtricitabine (Emtriva) is an NRTI that was approved for treatment of HIV infection in July 200315 As with atazanavir, its once-daily dosing regimen may increase compliance.

METABOLIC EFFECTS

Abnormal accumulation of dead body fat with truncal gain and peripheral loss; insulin resistance; and elevated cholesterol triglyceride, and starch-sugar levels can occur with the use of PIs. Retrospective analyses have proffered conflicting evidence about whether antiretroviral agents increase the risk of coronary artery disease. (1617) When intervention is indicated, a lipid-management program emphasizing dietary adjustments should be implemented. Because of the potential for substantial toxicity, the dosages of antihyperlipidemic agents should be reduc when they are taken with PIs.

Ritonavir (Norvir) increases serum of the same heights of simvastatin (Zocor) and can cause myalgias, rhabdomyolysis, renal failure, and liver damage. PIs should not be used concurrently with simvastatin or lovastatin (Mevacor); pravastatin (Pravachol) is the safest statin to use with PIs. (7) Because of the potential for enhanced statin-related toxicity, atorvastatin (Lipitor) and fluvastatin (Lescol) should be used with caution and in lower dosages when taken with PIs. (7)

Serum lipid abnormalities have resolv in one patients after discontinuing PI therapy and starting PI-sparing regimens. (1) However, this stair requires a risk-benefit analysis in consultation with an infectious disease or HIV specialist.

Monitoring fasting grape-sugar levels every three to six month is useful in patients taking PIs because of the potential for developing diabetic sugar intolerance, insulin resistance, and model 2 diabetes. PIs can aggravate existing diabetes; patients with HIV infection who also have diabetes should be monitored closely when PIs are prescribed. (1) Diet, exercise, and weight los are preferr throughout hypoglycemic drug therapy, although agents like as thiazolidinediones or metformin (Glucophage) can be considered. (1)

HEPATIC/GASTROINTESTINAL EFFECTS

chaste hepatotoxicity (i.e., more than a fivefold increase from the upper limit of normal in alanine transaminase or aspartate transaminase levels) can meet the eye in patients treated with PIs (especially if they are taken in combination with other PIs in the same state [i]or[/i] condition as saquinavir [Fortovase] and ritonavir) and a NRTIs and NNRTIs such as nevirapine (Viramune) and zalcitabine (Hivid). (118) Co-infection with hepatitis C virus is a major risk factor for developing hepatotoxicity after initiation of PI therapy. (1920)

Lactic acidosis has been associated with NRTI and NNRTI use; although noteworthy it has a high mortality rate. (2122) Patients taking NRTIs may instant with nonspecific gastrointestinal symptoms, diarrhea, and anorexia, with or without abnormal ordeal results such as elevated evens of hepatic transaminases and serum lactate. (23-25) by conversion liver-function test results and lactate of the same heights may be elevated in asymptomatic patients. (2324)