Tags: Delavirdine

Treatment of HIV / AIDS

The goal of antiretroviral therapy is to achieve the maximum suppression of HIV replication (HIV RNA level that is less than the lower limit of quantitation). Secondary goals include an increase in CD4 lymphocytes and an improved quality of life. The ultimate goal is decreased morbidity and mortality.

Infectious disorders

Infectious diseases comprise those illnesses that are caused by microorganisms or their products. Clinical manifestations of infection occur only when sufficient tissue injury has been inflicted directly by microbial products (e.g., endotoxins and exotoxins), or indirectly by host responses (e.g., cytokines and hydrolytic enzymes released by polymorphonuclear leukocytes). Despite the extraordinary recent advances that have occurred in therapeutics for infectious diseases, a number of basic principles should be followed to prescribe antimicrobials and vaccines is an optimal manner.

Antimicrobial therapy: general principles

A wide variety of antimicrobial agents is available to treat established infections caused by bacteria, fungi, viruses, or parasites. This section will cover the general principles of antimicrobial therapy and will also include illustrative clinical problems to emphasize proper decision-making in using antimicrobials.

Toxicity of Antimicrobial Therapy

The mechanisms associated with common adverse reactions to antimicrobials include dose-related toxicity that occurs in a certain fraction of patients when a critical plasma concentration or total dose is exceeded, and toxicity that is unpredictable and mediated through allergic or idiosyncratic mechanisms. For example, certain classes of drugs such as the aminoglycosides are associated with dose-related toxicity.

Antiretroviral Agents General Statement

Decisions regarding when to initiate or modify antiretroviral therapy should be guided by monitoring plasma HIV-1 RNA levels (viral load), CD4+ T-cell counts, and the clinical condition of the patient. Although various other surrogate markers and laboratory parameters were used in the past to assess the risk of progression of HIV infection and evaluate efficacy of antiretroviral agents.

Patient Compliance and Issues Related to Dosage and Administration

Patient compliance with recommended regimens (even when asymptomatic) is essential to the potential benefits of antiretroviral therapy. Adherence to antiretroviral regimens is an important determinant of both the degree and duration of virologic suppression. Excellent adherence has been shown to increase the likelihood of sustained virologic control, which is important for reducing HIV-associated morbidity and mortality. Poor adherence has been shown to increase the likelihood of virologic failure and can lead to the development of resistance and limit the effectiveness of antiretroviral therapy.

HIV Protease Inhibitors

The fact that hyperglycemia, new-onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, and diabetic ketoacidosis have occurred in HIV-infected individuals receiving HIV protease inhibitors should be considered when these drugs are used during pregnancy. Because pregnancy is itself a risk factor for hyperglycemia and it is not known whether use of an HIV protease inhibitor exacerbates this risk, glucose concentrations should be monitored closely in pregnant women receiving these drugs and these women should be advised about the warning signs of hyperglycemia and diabetes (e.g., increased thirst and hunger, unexplained weight loss, increased urination, fatigue, dry or itchy skin).

Antiretroviral Therapy during Pregnancy

Recommendations for use of antiretroviral agents for the treatment of HIV infection in pregnant HIV-infected women generally are the same as those for nonpregnant HIV-infected adults, and women should receive optimal antiretroviral therapy regardless of pregnancy status. Although zidovudine is the only antiretroviral agent currently labeled for use in pregnant women, most clinicians do not consider pregnancy a contraindication for multiple-drug antiretroviral therapy when such therapy is indicated, especially during the second or third trimester.

Antiretroviral Therapy in Pediatric Patients

The same general principles of antiretroviral therapy that apply to HIV-infected adults also apply to HIV-infected pediatric patients; however, the treatment of HIV-infected neonates, children, and adolescents involves unique pharmacologic, virologic, and immunologic considerations. In 1993, the Working Group on Antiretroviral Therapy and Medical Management of HIV-infected Children, a panel convened by the National Pediatric and Family HIV Resource Center (NPHRC), the Health Resources and Services Administration (HRSA), and the National Institutes of Health (NIH) first issued guidelines for the use of antiretroviral agents in the treatment of HIV-infected children. At that time, monotherapy with zidovudine or didanosine was considered an appropriate regimen for initial therapy in HIV-infected pediatric patients.

Antiretroviral Therapy in Previously Treated Adults

A review of the agents that the patient already has received is essential. Resistance testing (performed while the patient is still receiving the old regimen) is useful in maximizing the number of active drugs in the new regimen. Viral resistance is an important, but not the only, reason for treatment failure.