Antiretroviral therapy is recommended for all HIV-infected patients, both to reduce the risk of disease progression and to prevent transmission of the virus to others. Various guidelines for treatment of HIV infection are available.

The FDA has approved dolutegravir (doll-you-TEG-rah-veer; Tivicay – Viiv Healthcare), an integrase strand transfer inhibitor (INSTI), for treatment of HIV-1 infection in adults and in children ≥12 years old who weigh at least 40 kg. It is the third INSTI to be approved by the FDA; raltegravir and elvitegravir were approved earlier.

The FDA has approved rilpivirine (Edurant – Janssen), a non-nucleoside reverse transcriptase inhibitor (NNRTI), for use with other antiretroviral agents for treatment of HIV-1 infection in treatment-naive adults. Rilpivirine is also available in a fixed-dose combination with emtricitabine and tenofovir (Complera – Gilead).

Guidelines for use of antiretroviral agents continue to shift toward earlier and more continuous treatment, both to treat the patient and to prevent transmission of the disease to others. Resistance testing is now recommended when antiretroviral drugs are started. Increases in HIV RNA levels ("viral load") while on therapy may indicate development of drug resistance, requiring further testing and a change in the treatment regimen. Antiretroviral drugs interact with each other and with many other drugs; complete information on these interactions is available at www.aidsinfo.nih.gov.

Even though the incidence continues to decline in the United States, tuberculosis (TB) is still a common cause of death worldwide, and the prevalence of drug-resistant TB poses severe challenges to its treatment and control. Guidelines with detailed management recommendations are available from the Centers for Disease Control and Prevention (CDC), American Thoracic Society and Infectious Diseases Society of America (IDSA).

New guidelines for use of antiretroviral agents have been published, with a shift towards earlier and more continuous treatment. HIV infection is treated with combinations of antiretroviral drugs depending on the patientÆs HIV RNA levels ("viral load") and CD4 cell count. Increases in viral load while on therapy may indicate development of drug resistance, requiring further testing and a change in treatment regimen. Resistance testing is now recommended when a patient is first seen, regardless of when therapy will be started.

Many drugs can cause psychiatric symptoms, but a causal connection is often difficult to establish. Psychiatric symptoms that emerge during drug treatment could also be due to the underlying illness, previously unrecognized psychopathology, or psychosocial factors. The withdrawal of some drugs can cause symptoms such as anxiety, psychosis, delirium, agitation or depression.

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A recent letter to the editor of the Annals of Internal Medicine documented a single case of myopathy apparently due to an interaction between simvastatin (Zocor, and others) and green tea. Since it became available generically, simvastatin has surpassed atorvastatin (Lipitor) as the best selling statin. As such, it is probably the most common cause of statin-induced myopathy, which is often a result of drug interactions.

Etravirine (Intelence - Tibotec), a new non-nucleoside reverse transcriptase inhibitor (NNRTI), has received fast-track FDA approval for use in combination therapy in treatment-experienced adults who have HIV-1 infection resistant to an NNRTI and other antiretroviral agents.

The drugs of choice for treatment of some fungal infections are listed in the tables. Some of the indications and dosages recommended here have not been approved by the FDA. Other guidelines are available from the Infectious Diseases Society of America (www.idsociety.org).

The approval of new drugs and continuing concerns about drug toxicity and resistance have prompted new antiretroviral treatment guidelines. Resistance testing is not recommended before starting antiretroviral therapy. HIV infection is treated with combinations of antiretroviral drugs while monitoring the patient's HIV RNA levels ("viral load") and CD4 cell count. Increases in viral load while on therapy may indicate development of drug resistance requiring further testing and a change in treatment regimen.

Atripla (Gilead/Bristol-Myers Squibb) is the first once daily, single-tablet combination of 3 antiretroviral drugs for treatment of HIV infection. Each tablet contains 600 mg of the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva), 200 mg of the nucleoside reverse transcriptase inhibitor (NRTI) emtricitabine (Emtriva), and 300 mg of the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir DF (Viread). These drugs have been recommended for use together, if resistance testing confirms susceptibility, as an initial regimen of choice for treatment-na∩ve patients.

Serious adverse interactions between drugs continue to be reported. Many of these are due to inhibition or induction of cytochrome P450 (CYP) enzymes, particularly CYP3A4. CYP3A is thought to be involved in the metabolism of more than 50 percent of currently prescribed drugs.2 CYP3A4, which is more abundantly expressed than CYP3A5, accounts for most CYP3A activity in vivo.

The drugs of choice for treatment of some fungal infections are listed in the table that begins on page 8. Some of the indications and dosages recommended here have not been approved by the FDA.

Tuberculosis (TB) is still a problem in the United States, even though the incidence continues to decline in most of the country (MMWR Morbid Mortal Wkly Rep 2004; 53:209). Treatment of TB can be divided into treatment of latent infection diagnosed by a positive PPD and treatment of active clinical TB. Guidelines with detailed management recommendations are available from the US Centers for Disease Control and Prevention (CDC) (MMWR Morbid Mortal Wkly Rep 2003; 52RR-11:1).

New drug approvals as well as continuing concerns about drug toxicity and the development of resistance have prompted new antiretroviral treatment guidelines (Panel on Clinical Practices for Treatment of HIV Infection, November 10, 2003, www.aidsinfo.nih.gov).

Atazanavir (Reyataz - Bristol-Myers Squibb), a new protease inhibitor (PI), and emtricitabine (Emtriva - Gilead), a nucleoside analogue reverse transcriptase inhibitor (NRTI) chemically similar to lamivudine, have been approved by the FDA for treatment of HIV-1 infection. Both are taken once daily, unlike most anti-HIV drugs.

Changes caused by one drug in the absorption, distribution, metabolism or excretion of another may lead to a pharmacokinetic adverse drug interaction (DN Juurlink et al, JAMA 2003; 289:1652). Additive drug interactions, such as vasodilation caused by both sildenafil (Viagra) and nitrates, can also have adverse effects.

Many drugs can cause psychiatric symptoms, but a causal connection is often difficult to establish. Psychiatric symptoms that emerge during drug treatment may also be due to the underlying illness, previously unrecognized psychopathology, or psychosocial factors. The withdrawal of some drugs can cause symptoms such as anxiety, psychosis, delirium, agitation or depression.

Since the last Medical Letter article on this subject, continuing concerns about drug toxicity and development of resistance have prompted new antiretroviral treatment guidelines. The dosage and cost of drugs for HIV infection are listed in the table in this article.

Highly active anti-retroviral therapy (HAART) combining three or four drugs has become the standard of care for treatment of human immunodeficiency virus (HIV) infection

Amprenavir is the fifth protease inhibitor to become available for treatment of HIV infection. It was approved by the FDA for use with other drugs in the treatment of HIV-infected adults and children at least four years old.

Combination antiretroviral therapy including protease inhibitors has dramatically changed the treatment of HIV infection and the prognosis of those affected (Medical Letter Handbook of Antimicrobial Therapy, 1998, page 122). Due to limitations and failures with these drugs in many patients, however, three new drugs, none of them protease inhibitors, have rapidly come into wide use in clinical trials or 'expanded access' programs. They are abacavir (Ziagen - Glaxo Wellcome), adefovir (Preveon - Gilead) and efavirenz (Sustiva - DuPont). Efavirenz was recently approved for treatment of adults and children by the FDA. Abacavir has been recommended for approval by an FDA advisory committee.