Antiviral agents

Antiviral Drugs

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Antiretroviral Agents General Statement

Abacavir Sulfate, Amprenavir, Atazanavir Sulfate, Delavirdine Mesylate, Didanosine, Efavirenz, Emtricitabine, Enfuvirtide, Indinavir Sulfate, Lamivudine, Lopinavir and Ritonavir, Nelfinavir Mesylate, Nevirapine, Ritonavir, Saquinavir, Stavudine, Tenofovir Disoproxil Fumarate, Zalcitabine, Zidovudine Laboratory Monitoring Plasma HIV-1 RNA Levels and CD4+ T-cell Counts 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 (e.g., peripheral blood mononuclear cell [PBMC] HIV-1 titers, plasma concentrations or levels of HIV p […]

Antiretroviral Therapy in Previously Treated Pediatric Patients

Consideration should be given to altering the initial antiretroviral regimen in HIV-infected pediatric patients if there is clinical, immunologic, or virologic evidence of disease progression; if there are signs of toxicity or intolerance; or if new data become available indicating that a drug or regimen is superior to the current regimen. Clinical events that may indicate disease progression in an HIV-infected child and warrant consideration of a change in antiretroviral therapy include progressive neurodevelopmental deterioration or growth failure (i.e., persistent, unexplained decline in weight growth velocity despite adequate nutritional support). Progressive neurodevelopmental deterioration is defined as persistence or progression of deterioration documented on repeated testing as demonstrated by the presence of […]

Patient Compliance and Issues Related to Dosage and Administration

Patient Compliance 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. There is evidence that nonadherence in patients receiving HAART is the strongest predictor of failure to achieve suppression of viral load to levels below the limits […]

Drug Interactions

Drug Interactions Among the Antiretroviral Agents While further study is needed, data are accumulating regarding pharmacokinetic interactions among the various antiretroviral agents, especially those involving the HIV protease inhibitors and NNRTIs, and the need for dosage adjustments as a result of these interactions. While some pharmacokinetic interactions between antiretroviral agents can be used for therapeutic advantage (e.g., use of low-dose ritonavir to boost plasma concentrations of some other HIV protease inhibitors), other interactions can result in suboptimal drug concentrations and reduced therapeutic effects and should be avoided. The pharmacokinetic interaction between ritonavir and other HIV protease inhibitors is now used for therapeutic advantage in various antiretroviral regimens. Low-dose ritonavir (100-400 mg […]

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). Because hyperbilirubinemia (generally reported as an increase in indirect bilirubin) has been […]

CDC Recommendations for Postexposure Prophylaxis following Occupational Exposure to HIV

Since most occupational exposures to HIV do not result in transmission of the virus, the potential toxicity of PEP regimens must be considered carefully and, whenever possible, prophylaxis should be implemented in consultation with clinicians who have expertise in antiretroviral therapy and HIV transmission. Modification of the recommended regimens may be appropriate based on factors such as whether the source patient is known or suspected of being infected with drug-resistant strains of HIV; the local availability of antiretroviral agents; and the medical condition, concurrent drug therapy, and drug toxicity in the exposed health-care worker. The CDC has made the following recommendations for PEP following occupational exposure to HIV: The recommended basic […]

Nucleoside Reverse Transcriptase Inhibitors

Safety and efficacy of zidovudine in pregnant women have been established and the drug appears to be well tolerated during pregnancy. In addition to zidovudine, data are available from clinical trials in pregnant women for didanosine, lamivudine, and stavudine; data regarding use of abacavir or tenofovir disoproxil fumarate (a nucleotide reverse transcriptase inhibitor) are not available to date. Follow-up of uninfected children born to women enrolled in study PACTG 076 (from birth to a median age of 4.2 years) has not revealed any difference in growth, neurodevelopment, or immunologic status among infants born to women who received zidovudine for prevention of maternal-fetal transmission of HIV compared with those born to women […]

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. Therefore, multiple-drug antiretroviral therapy should be discussed with and offered to all HIV-infected pregnant women for their own health. In addition, because there is evidence that use of a regimen that includes both antepartum and intrapartum […]

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. However, […]